Fluoxetine versus other types of pharmacotherapy for depression

Laura R Magni; Marianna Purgato; Chiara Gastaldon; Davide Papola; Toshi A Furukawa; Andrea Cipriani; Corrado Barbui

doi:10.1002/14651858.CD004185.pub3

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Figure 1

Study flow diagram, 2005 version.

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Figure 2

Study flow diagram, 2012 version.

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Figure 3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 4

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Analysis 1.1

Comparison 1 Fluoxetine versus TCAs, Outcome 1 Failure to respond ‐ HDRS (‐50%).

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Analysis 1.2

Comparison 1 Fluoxetine versus TCAs, Outcome 2 End‐point score on rating scale.

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Analysis 1.3

Comparison 1 Fluoxetine versus TCAs, Outcome 3 Failure to complete ‐ Total.

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Analysis 1.4

Comparison 1 Fluoxetine versus TCAs, Outcome 4 Failure to complete ‐ Inefficacy.

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Analysis 1.5

Comparison 1 Fluoxetine versus TCAs, Outcome 5 Failure to complete ‐ Side Effects.

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Analysis 2.1

Comparison 2 Fluoxetine versus heterocyclics, Outcome 1 Failure to respond ‐ HDRS (‐50%).

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Analysis 2.2

Comparison 2 Fluoxetine versus heterocyclics, Outcome 2 End‐point score on rating scale.

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Analysis 2.3

Comparison 2 Fluoxetine versus heterocyclics, Outcome 3 Failure to complete ‐ Total.

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Analysis 2.4

Comparison 2 Fluoxetine versus heterocyclics, Outcome 4 Failure to complete ‐ Inefficacy.

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Analysis 2.5

Comparison 2 Fluoxetine versus heterocyclics, Outcome 5 Failure to complete ‐ Side Effects.

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Analysis 3.1

Comparison 3 Fluoxetine versus other SSRIs, Outcome 1 Failure to respond ‐ HDRS (‐50%).

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Analysis 3.2

Comparison 3 Fluoxetine versus other SSRIs, Outcome 2 End‐point score on rating scales.

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Analysis 3.3

Comparison 3 Fluoxetine versus other SSRIs, Outcome 3 Failure to complete ‐ Total.

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Analysis 3.4

Comparison 3 Fluoxetine versus other SSRIs, Outcome 4 Failure to complete ‐ Inefficacy.

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Analysis 3.5

Comparison 3 Fluoxetine versus other SSRIs, Outcome 5 Failure to complete ‐ Side Effects.

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Analysis 4.1

Comparison 4 Fluoxetine versus SNRIs, Outcome 1 Failure to respond ‐ HDRS (‐50%).

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Analysis 4.2

Comparison 4 Fluoxetine versus SNRIs, Outcome 2 End‐point score on rating scale.

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Analysis 4.3

Comparison 4 Fluoxetine versus SNRIs, Outcome 3 Failure to complete ‐ Total.

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Analysis 4.4

Comparison 4 Fluoxetine versus SNRIs, Outcome 4 Failure to complete ‐ Inefficacy.

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Analysis 4.5

Comparison 4 Fluoxetine versus SNRIs, Outcome 5 Failure to complete ‐ Side Effects.

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Analysis 5.1

Comparison 5 Fluoxetine versus MAOIs or newer ADs, Outcome 1 Failure to respond ‐ HDRS (‐50%).

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Analysis 5.2

Comparison 5 Fluoxetine versus MAOIs or newer ADs, Outcome 2 End‐point score on rating scales.

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Analysis 5.3

Comparison 5 Fluoxetine versus MAOIs or newer ADs, Outcome 3 Failure to complete ‐ Total.

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Analysis 5.4

Comparison 5 Fluoxetine versus MAOIs or newer ADs, Outcome 4 Failure to complete ‐ Inefficacy.

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Analysis 5.5

Comparison 5 Fluoxetine versus MAOIs or newer ADs, Outcome 5 Failure to complete ‐ Side Effects.

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Analysis 6.1

Comparison 6 Fluoxetine versus other conventional psychotropic drugs, Outcome 1 Failure to respond ‐ HDRS (‐50%).

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Analysis 6.2

Comparison 6 Fluoxetine versus other conventional psychotropic drugs, Outcome 2 End‐point score on rating scales.

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Analysis 6.3

Comparison 6 Fluoxetine versus other conventional psychotropic drugs, Outcome 3 Failure to complete ‐ Total.

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Analysis 6.4

Comparison 6 Fluoxetine versus other conventional psychotropic drugs, Outcome 4 Failure to complete ‐ Inefficacy.

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Analysis 6.5

Comparison 6 Fluoxetine versus other conventional psychotropic drugs, Outcome 5 Failure to complete ‐ Side Effects.

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Analysis 7.1

Comparison 7 Fluoxetine versus other non‐conventional AD agents, Outcome 1 Failure to respond ‐ HDRS (‐50%).

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Analysis 7.2

Comparison 7 Fluoxetine versus other non‐conventional AD agents, Outcome 2 End‐point score on rating scales.

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Analysis 7.3

Comparison 7 Fluoxetine versus other non‐conventional AD agents, Outcome 3 Failure to complete ‐ Total.

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Analysis 7.4

Comparison 7 Fluoxetine versus other non‐conventional AD agents, Outcome 4 Failure to complete ‐ Inefficacy.

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Analysis 7.5

Comparison 7 Fluoxetine versus other non‐conventional AD agents, Outcome 5 Failure to complete ‐ Side Effects.

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Analysis 8.1

Comparison 8 Subgroup analysis for fluoxetine versus TCAs: failure to respond, Outcome 1 follow‐up <6 weeks.

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Analysis 8.2

Comparison 8 Subgroup analysis for fluoxetine versus TCAs: failure to respond, Outcome 2 follow‐up 6‐16 weeks.

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Analysis 9.1

Comparison 9 Subgroup analysis for fluoxetine versus TCAs: endpoint score, Outcome 1 follow‐up <6 weeks.

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Analysis 9.2

Comparison 9 Subgroup analysis for fluoxetine versus TCAs: endpoint score, Outcome 2 follow‐up 6‐16 weeks.

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Analysis 9.3

Comparison 9 Subgroup analysis for fluoxetine versus TCAs: endpoint score, Outcome 3 follow‐up >16 weeks.

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Analysis 10.1

Comparison 10 Subgroup analysis for fluoxetine versus TCAs: failure to complete ‐ total, Outcome 1 follow‐up <6 weeks.

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Analysis 10.2

Comparison 10 Subgroup analysis for fluoxetine versus TCAs: failure to complete ‐ total, Outcome 2 follow‐up 6‐16 weeks.

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Analysis 11.1

Comparison 11 Subgroup analysis for fluoxetine versus TCAs: failure to complete ‐ inefficacy, Outcome 1 follow‐up <6 weeks.

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Analysis 11.2

Comparison 11 Subgroup analysis for fluoxetine versus TCAs: failure to complete ‐ inefficacy, Outcome 2 follow‐up 6‐16 weeks.

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Analysis 12.1

Comparison 12 Subgroup analysis for fluoxetine versus TCAs: failure to complete ‐ side effects, Outcome 1 follow‐up <6 weeks.

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Analysis 12.2

Comparison 12 Subgroup analysis for fluoxetine versus TCAs: failure to complete ‐ side effects, Outcome 2 follow‐up 6‐16 weeks.

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Analysis 13.1

Comparison 13 Subgroup analysis for fluoxetine versus heterocyclics: endpoint score, Outcome 1 follow‐up <6 weeks.

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Analysis 13.2

Comparison 13 Subgroup analysis for fluoxetine versus heterocyclics: endpoint score, Outcome 2 follow‐up 6‐16 weeks.

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Analysis 14.1

Comparison 14 Subgroup analysis for fluoxetine versus heterocyclics: failure to complete ‐ total, Outcome 1 follow‐up <6 weeks.

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Analysis 14.2

Comparison 14 Subgroup analysis for fluoxetine versus heterocyclics: failure to complete ‐ total, Outcome 2 follow‐up 6‐16 weeks.

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Analysis 15.1

Comparison 15 Subgroup analysis for fluoxetine versus heterocyclics: failure to complete ‐ inefficacy, Outcome 1 follow‐up <6 weeks.

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Analysis 15.2

Comparison 15 Subgroup analysis for fluoxetine versus heterocyclics: failure to complete ‐ inefficacy, Outcome 2 follow‐up 6‐16 weeks.

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Analysis 16.1

Comparison 16 Subgroup analysis for fluoxetine versus heterocyclics: failure to complete ‐ side effects, Outcome 1 follow‐up <6 weeks.

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Analysis 16.2

Comparison 16 Subgroup analysis for fluoxetine versus heterocyclics: failure to complete ‐ side effects, Outcome 2 follow‐up 6‐16 weeks.

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Analysis 17.1

Comparison 17 Subgroup analysis for fluoxetine versus other SSRIs: failure to respond, Outcome 1 follow‐up <6 weeks.

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Analysis 17.2

Comparison 17 Subgroup analysis for fluoxetine versus other SSRIs: failure to respond, Outcome 2 follow‐up 6‐16 weeks.

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Analysis 17.3

Comparison 17 Subgroup analysis for fluoxetine versus other SSRIs: failure to respond, Outcome 3 follow‐up >16 weeks.

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Analysis 18.1

Comparison 18 Subgroup analysis for fluoxetine versus other SSRIs: endpoint score, Outcome 1 follow‐up <6 weeks.

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Analysis 18.2

Comparison 18 Subgroup analysis for fluoxetine versus other SSRIs: endpoint score, Outcome 2 follow‐up >16 weeks.

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Analysis 18.3

Comparison 18 Subgroup analysis for fluoxetine versus other SSRIs: endpoint score, Outcome 3 follow‐up 6‐16 weeks.

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Analysis 19.1

Comparison 19 Subgroup analysis for fluoxetine versus other SSRIs: failure to complete ‐ total, Outcome 1 follow‐up <6 weeks.

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Analysis 19.2

Comparison 19 Subgroup analysis for fluoxetine versus other SSRIs: failure to complete ‐ total, Outcome 2 follow‐up 6‐16 weeks.

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Analysis 19.3

Comparison 19 Subgroup analysis for fluoxetine versus other SSRIs: failure to complete ‐ total, Outcome 3 follow‐up >16 weeks.

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Analysis 20.1

Comparison 20 Subgroup analysis for fluoxetine versus other SSRIs: failure to complete ‐ inefficacy, Outcome 1 follow‐up <6 weeks.

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Analysis 20.2

Comparison 20 Subgroup analysis for fluoxetine versus other SSRIs: failure to complete ‐ inefficacy, Outcome 2 follow‐up >16 weeks.

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Analysis 20.3

Comparison 20 Subgroup analysis for fluoxetine versus other SSRIs: failure to complete ‐ inefficacy, Outcome 3 follow‐up 6‐16 weeks.

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Analysis 21.1

Comparison 21 Subgroup analysis for fluoxetine versus other SSRIs: failure to complete ‐ side effects, Outcome 1 follow‐up <6 weeks.

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Analysis 21.2

Comparison 21 Subgroup analysis for fluoxetine versus other SSRIs: failure to complete ‐ side effects, Outcome 2 follow‐up 6‐16 weeks.

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Analysis 21.3

Comparison 21 Subgroup analysis for fluoxetine versus other SSRIs: failure to complete ‐ side effects, Outcome 3 follow‐up >16 weeks.

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Analysis 22.1

Comparison 22 Subgroup analysis for fluoxetine versus MAOIs or newer ADs: failure to respond, Outcome 1 follow‐up <6 weeks.

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Analysis 22.2

Comparison 22 Subgroup analysis for fluoxetine versus MAOIs or newer ADs: failure to respond, Outcome 2 follow‐up 6‐16 weeks.

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Analysis 23.1

Comparison 23 Subgroup analysis for fluoxetine versus MAOIs or newer ADs: endpoint score, Outcome 1 follow‐up <6 weeks.

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Analysis 23.2

Comparison 23 Subgroup analysis for fluoxetine versus MAOIs or newer ADs: endpoint score, Outcome 2 follow‐up 6‐16 weeks.

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Analysis 24.1

Comparison 24 Subgroup analysis for fluoxetine versus MAOIs or newer ADs: failure to complete ‐ total, Outcome 1 follow‐up <6 weeks.

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Analysis 24.2

Comparison 24 Subgroup analysis for fluoxetine versus MAOIs or newer ADs: failure to complete ‐ total, Outcome 2 follow‐up 6‐16 weeks.

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Analysis 25.1

Comparison 25 Subgroup analysis for fluoxetine versus MAOIs or newer ADs: failure to complete ‐ inefficacy, Outcome 1 follow‐up <6 weeks.

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Analysis 25.2

Comparison 25 Subgroup analysis for fluoxetine versus MAOIs or newer ADs: failure to complete ‐ inefficacy, Outcome 2 follow‐up 6‐16 weeks.

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Analysis 26.1

Comparison 26 Subgroup analysis for fluoxetine versus MAOIs or newer ADs: failure to complete ‐ side effects, Outcome 1 follow‐up <6 weeks.

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Analysis 26.2

Comparison 26 Subgroup analysis for fluoxetine versus MAOIs or newer ADs: failure to complete ‐ side effects, Outcome 2 follow‐up 6‐16 weeks.

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Summary of findings for the main comparison. Fluoxetine compared to TCAs

Fluoxetine compared to TCAs
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: TCAs
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	TCAs	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	471 per 1000	463 per 1000 (406 to 520)	OR 0.97 (0.77 to 1.22)	2124 (24 studies)	⊕⊕⊕⊝ moderate¹
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0.03 higher (0.07 lower to 0.14 higher)		3393 (50 studies)	⊕⊕⊕⊝ moderate¹	This effect approaches zero
Failure to complete ‐ total ‐	335 per 1000	284 per 1000 (246 to 326)	OR 0.79 (0.65 to 0.96)	4194 (49 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ side effects ‐	193 per 1000	116 per 1000 (87 to 152)	OR 0.55 (0.40 to 0.75)	3647 (40 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐	68 per 1000	87 per 1000 (66 to 112)	OR 1.29 (0.96 to 1.72)	2911 (33 studies)	⊕⊕⊕⊝ moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in study design: no details on randomisation procedures and allocation concealment. Blinding stated but not tested.

Summary of findings for the main comparison. Fluoxetine compared to TCAs

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Summary of findings 2. Fluoxetine compared to ABT‐200

Fluoxetine compared to ABT 200
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: ABT 200
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	ABT 200	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)		0 per 1000 (0 to 0)	Not estimable	0 (0)
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 1.85 standard deviations lower (2.25 to 1.45 lower)		141 (1 study)	⊕⊕⊝⊝ low¹	This corresponds to a large effect according to conventions proposed by Cohen 1992. However, only one study contributed to this analysis
Failure to complete ‐ total ‐	528 per 1000	167 per 1000 (82 to 304)	OR 0.18 (0.08 to 0.39)	144 (1 study)	⊕⊕⊝⊝ low¹
Failure to complete ‐ inefficacy ‐	56 per 1000	14 per 1000 (2 to 115)	OR 0.24 (0.03 to 2.20)	144 (1 study)	⊕⊕⊝⊝ low¹
Failure to complete ‐ side effects ‐	361 per 1000	43 per 1000 (11 to 132)	OR 0.08 (0.02 to 0.27)	144 (1 study)	⊕⊕⊝⊝ low¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in study design: no details on randomisation procedures and allocation concealment. Blinding stated but not tested. Only one study included in the analysis.

Summary of findings 2. Fluoxetine compared to ABT‐200

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Summary of findings 3. Fluoxetine compared to agomelatine

Fluoxetine compared to agomelatine
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: agomelatine
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Agomelatine	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	282 per 1000	361 per 1000 (280 to 450)	OR 1.44 (0.99 to 2.09)	515 (1 study)	⊕⊕⊝⊝ low^1,2
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0.02 standard deviations higher (0.18 lower to 0.23 higher)		1213 (3 studies)	⊕⊕⊕⊝ moderate¹	This effect approaches zero
Failure to complete ‐ total ‐	135 per 1000	170 per 1000 (122 to 233)	OR 1.31 (0.89 to 1.94)	785 (2 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐	55 per 1000	59 per 1000 (23 to 142)	OR 1.08 (0.41 to 2.88)	785 (2 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ side effects ‐	34 per 1000	50 per 1000 (25 to 97)	OR 1.51 (0.74 to 3.07)	785 (2 studies)	⊕⊕⊕⊝ moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested. ² Only one study included in this analysis.

Summary of findings 3. Fluoxetine compared to agomelatine

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Summary of findings 4. Fluoxetine compared to amineptine

Fluoxetine compared to amineptine
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: amineptine
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Amineptine	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	719 per 1000	486 per 1000 (249 to 727)	OR 0.37 (0.13 to 1.04)	63 (1 study)	⊕⊕⊕⊝ moderate¹
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0 standard deviations higher (0 to 0 higher)		0 (0)		No data available on this outcome
Failure to complete ‐ total ‐	210 per 1000	140 per 1000 (43 to 370)	OR 0.61 (0.17 to 2.21)	232 (2 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐	94 per 1000	97 per 1000 (19 to 366)	OR 1.04 (0.19 to 5.57)	63 (1 study)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ side effects ‐ (Copy)	84 per 1000	46 per 1000 (3 to 418)	OR 0.52 (0.03 to 7.82)	232 (2 studies)	⊕⊕⊕⊝ moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested.

Summary of findings 4. Fluoxetine compared to amineptine

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Summary of findings 5. Fluoxetine compared to amisulpride

Fluoxetine compared to amisulpride
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: amisulpride
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Amisulpride	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)		0 per 1000 (0 to 0)	Not estimable	0 (0)
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0.17 standard deviations higher (0.07 lower to 0.41 higher)		268 (1 study)	⊕⊕⊝⊝ low¹	This corresponds to a very small effect according to conventions proposed by Cohen 1992
Failure to complete ‐ total ‐	225 per 1000	288 per 1000 (191 to 409)	OR 1.39 (0.81 to 2.38)	281 (1 study)	⊕⊕⊝⊝ low¹
Failure to complete ‐ inefficacy ‐	56 per 1000	65 per 1000 (25 to 156)	OR 1.16 (0.43 to 3.10)	281 (1 study)	⊕⊕⊝⊝ low¹
Failure to complete ‐ side effects ‐	92 per 1000	72 per 1000 (32 to 155)	OR 0.77 (0.33 to 1.82)	281 (1 study)	⊕⊕⊝⊝ low¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested. Only one study included in the analysis.

Summary of findings 5. Fluoxetine compared to amisulpride

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Summary of findings 6. Fluoxetine compared to bupropion

Fluoxetine compared to bupropion
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: bupropion
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Bupropion	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	493 per 1000	447 per 1000 (318 to 582)	OR 0.83 (0.48 to 1.43)	436 (2 studies)	⊕⊕⊕⊝ moderate¹
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0 standard deviations higher (0 to 0 higher)		0 (0)		No data available on this outcome
Failure to complete ‐ total ‐	356 per 1000	356 per 1000 (270 to 450)	OR 1.00 (0.67 to 1.48)	436 (2 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐	23 per 1000	0 per 1000 (0 to 87)	OR 1.16 (0.33 to 4.10)	436 (2 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ side effects ‐	59 per 1000	60 per 1000 (28 to 124)	OR 1.01 (0.45 to 2.25)	436 (2 studies)	⊕⊕⊕⊝ moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested.

Summary of findings 6. Fluoxetine compared to bupropion

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Summary of findings 7. Fluoxetine compared to citalopram

Fluoxetine compared to citalopram
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: citalopram
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Citalopram	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	379 per 1000	268 per 1000 (109 to 522)	OR 0.60 (0.20 to 1.79)	59 (1 study)	⊕⊝⊝⊝ very low^1,2
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0.06 standard deviations higher (0.10 lower to 0.21 higher)		661 (3 studies)	⊕⊕⊕⊝ moderate¹	This effect approaches zero
Failure to complete ‐ total ‐	211 per 1000	189 per 1000 (138 to 254)	OR 0.87 (0.60 to 1.27)	732 (3 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐	75 per 1000	66 per 1000 (37 to 112)	OR 0.87 (0.48 to 1.56)	732 (3 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ side effects ‐	75 per 1000	49 per 1000 (27 to 89)	OR 0.64 (0.34 to 1.20)	732 (3 studies)	⊕⊕⊕⊝ moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested. ² Only one study included in the analysis and less than 100 patients.

Summary of findings 7. Fluoxetine compared to citalopram

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Summary of findings 8. Fluoxetine compared to Crocus sativus

Fluoxetine compared to Crocus sativus
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison:Crocus sativus
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Crocus sativus	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	250 per 1000	150 per 1000 (35 to 464)	OR 0.53 (0.11 to 2.60)	40 (1 study)	⊕⊝⊝⊝ very low¹
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0 standard deviations higher (0 to 0 higher)		0 (0)		No data available on this outcome
Failure to complete ‐ total ‐	50 per 1000	50 per 1000 (3 to 475)	OR 1.00 (0.06 to 17.18)	40 (1 study)	⊕⊝⊝⊝ very low¹
Failure to complete ‐ inefficacy ‐		0 per 1000 (0 to 0)	Not estimable	0 (0)
Failure to complete ‐ side effects ‐		0 per 1000 (0 to 0)	Not estimable	0 (0)
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested. Only one study included in the analysis and less than 50 patients.

Summary of findings 8. Fluoxetine compared to Crocus sativus

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Summary of findings 9. Fluoxetine compared to duloxetine

Fluoxetine compared to for duloxetine
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: duloxetine
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
		Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	400 per 1000	485 per 1000 (289 to 684)	OR 1.41 (0.61 to 3.25)	103 (1 study)	⊕⊕⊝⊝ low^1,2
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0 standard deviations higher (0 to 0 higher)		0 (0)		No data available on this outcome
Failure to complete ‐ total ‐	281 per 1000	260 per 1000 (171 to 372)	OR 0.90 (0.53 to 1.52)	532 (2 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐	15 per 1000	47 per 1000 (14 to 152)	OR 3.33 (0.93 to 12.11)	432 (2 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ side effects ‐	66 per 1000	19 per 1000 (5 to 80)	OR 0.28 (0.07 to 1.23)	532 (2 studies)	⊕⊕⊕⊝ moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested. ² Only one study included in the analysis.

Summary of findings 9. Fluoxetine compared to duloxetine

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Summary of findings 10. Fluoxetine compared to escitalopram

Fluoxetine compared to escitalopram
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: escitalopram
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Escitalopram	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	236 per 1000	239 per 1000 (147 to 363)	OR 1.02 (0.56 to 1.85)	240 (1 study)	⊕⊕⊝⊝ low^1,2
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0.07 standard deviations higher (0.19 lower to 0.33 higher)		231 (1 study)	⊕⊕⊝⊝ low^1,2	This effect approaches zero
Failure to complete ‐ total ‐	148 per 1000	210 per 1000 (148 to 292)	OR 1.53 (1.00 to 2.37)	578 (2 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐	13 per 1000	23 per 1000 (6 to 82)	OR 1.74 (0.46 to 6.53)	578 (2 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ side effects ‐	77 per 1000	89 per 1000 (51 to 151)	OR 1.17 (0.64 to 2.12)	578 (2 studies)	⊕⊕⊕⊝ moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested. ² Only one study included in the analysis.

Summary of findings 10. Fluoxetine compared to escitalopram

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Summary of findings 11. Fluoxetine compared to fluvoxamine

Fluoxetine compared to fluvoxamine
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: fluvoxamine
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Fluvoxamine	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	605 per 1000	592 per 1000 (443 to 727)	OR 0.95 (0.52 to 1.74)	177 (1 study)	⊕⊕⊝⊝ low^1,2
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0 standard deviations higher (0 to 0 higher)		0 (0)		No data available on this outcome
Failure to complete ‐ total ‐	170 per 1000	936 per 1000 (69 to 219)	OR 071 (0.36 to 1.37)	284 (2 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐		0 per 1000 (0 to 0)	Not estimable	0 (0)
Failure to complete ‐ side effects ‐	39 per 1000	41 per 1000 (6 to 239)	OR 1.04 (0.14 to 7.71)	100 (1 study)	⊕⊕⊝⊝ low^1,2
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested. ² Only one study included in the analysis.

Summary of findings 11. Fluoxetine compared to fluvoxamine

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Summary of findings 12. Fluoxetine compared to hypericum

Fluoxetine compared to hypericum
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: hypericum
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Hypericum	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	490 per 1000	485 per 1000 (346 to 625)	OR 0.98 (0.55 to 1.73)	717 (6 studies)	⊕⊕⊕⊝ moderate¹
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0.13 standard deviations higher (0.02 lower to 0.29 higher)		648 (5 studies)	⊕⊕⊕⊝ moderate¹	This corresponds to a very small effect according to conventions proposed by Cohen 1992
Failure to complete ‐ total ‐	129 per 1000	133 per 1000 (88 to 189)	OR 1.04 (0.65 to 1. 68)	679 (5 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐			OR 4.70 (0.22 to 99.39)	401 (2 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ side effects ‐	35 per 1000	42 per 1000 (20 to 88)	OR 1.21 (0.56 to 2.64)	679 (5 studies)	⊕⊕⊕⊝ moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested.

Summary of findings 12. Fluoxetine compared to hypericum

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Summary of findings 13. Fluoxetine compared to maprotiline

Fluoxetine compared to maprotiline
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: maprotiline
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Maprotiline	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	398 per 1000	563 per 1000 (984 to 734)	OR 1.95 (0.91 to 4.18)	163 (2 studies)	⊕⊕⊕⊝ moderate
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0.04 standard deviations higher (0.15 lower to 0.23 higher)		433 (5 studies)	⊕⊕⊕⊝ moderate¹	This effect approaches zero
Failure to complete ‐ total ‐	92 per 1000	151 per 1000 (84 to 257)	OR 1.75 (0.90 to 3.41)	351 (4 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ side effects ‐	67 per 1000	36 per 1000 (11 to 121)	OR 0.53 (0.15 to 1.93)	209 (3 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐	19 per 1000	47 per 1000 (6 to 279)	OR 2.54 (0.33 to 19.9)	209 (3 studies)	⊕⊕⊕⊝ moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested.

Summary of findings 13. Fluoxetine compared to maprotiline

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Summary of findings 14. Fluoxetine compared to mianserin

Fluoxetine compared to mianserin
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: mianserin
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Mianserin	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	593 per 1000	538 per 1000 (282 to 776)	OR 0.80 (0.27 to 2.38)	53 (1 study)	⊕⊝⊝⊝ very low^1,2
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0.43 standard deviations higher (0.38 lower to 1.23 higher)		128 (3 studies)	⊕⊕⊕⊝ moderate¹	This corresponds to a small effect according to conventions proposed by Cohen 1992
Failure to complete ‐ total ‐	362 per 1000	263 per 1000 (93 to 560)	OR 0.63 (0.18 to 2.25)	93 (2 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐	74 per 1000	154 per 1000 (30 to 522)	OR 2.27 (0.38 to 13.63)	53 (1 study)	⊕⊝⊝⊝ very low^1,2
Failure to complete ‐ side effects ‐	148 per 1000	154 per 1000 (38 to 450)	OR 1.05 (0.23 to 4.70)	53 (1 study)	⊕⊝⊝⊝ very low^1,2
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested. ² Only one study included in the analysis and less than 100 patients.

Summary of findings 14. Fluoxetine compared to mianserin

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Summary of findings 15. Fluoxetine compared to milnacipran

Fluoxetine compared to milnacipran
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: milnacipran
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Milnacipran	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	473 per 1000	518 per 1000 (412 to 623)	OR 1.20 (0.78 to 1.84)	370 (2 studies)	⊕⊕⊕⊝ moderate¹
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0.36 standard deviations lower (0.63 to 0.08 lower)		213 (2 studies)	⊕⊕⊕⊝ moderate¹	This corresponds to a small effect according to conventions proposed by Cohen 1992
Failure to complete ‐ total ‐	411 per 1000	406 per 1000 (322 to 497)	OR 0.98 (0.68 to 1.42)	560 (3 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐	137 per 1000	165 per 1000 (97 to 267)	OR 1.25 (0.68 to 2.30)	560 (3 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ side effects ‐	71 per 1000	103 per 1000 (59 to 175)	OR 1.50 (0.81 to 2.76)	560 (3 studies)	⊕⊕⊕⊝ moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested.

Summary of findings 15. Fluoxetine compared to milnacipran

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Summary of findings 16. Fluoxetine compared to mirtazapine

Fluoxetine compared to mirtazapine
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: Fluoxetine Comparison: mirtazapine
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Mirtazapine	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	354 per 1000	444 per 1000 (363 to 527)	OR 1.46 (1.04 to 2.04)	600 (4 studies)	⊕⊕⊕⊝ moderate¹
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0.57 standard deviations higher (0.15 lower to 1.29 higher)		31 (1 study)	⊕⊝⊝⊝ very low^1,2	This corresponds to a medium effect according to conventions proposed by Cohen 1992
Failure to complete ‐ total ‐	327 per 1000	304 per 1000 (211 to 416)	OR 0.90 (0.55 to 1.47)	301 (3 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐	44 per 1000	62 per 1000 (31 to 119)	OR 1.45 (0.71 to 2.96)	600 (4 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ side effects ‐	98 per 1000	93 per 1000 (56 to 151)	OR 0.95 (0.55 to 1.64)	600 (4 studies)	⊕⊕⊕⊝ moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested. ² Only one study included in the analysis and less than 100 patients.

Summary of findings 16. Fluoxetine compared to mirtazapine

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Summary of findings 17. Fluoxetine compared to moclobemide

Fluoxetine compared to moclobemide
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: moclobemide
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Moclobemide	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	436 per 1000	496 per 1000 (416 to 575)	OR 1.27 (0.92 to 1.75)	721 (7 studies)	⊕⊕⊕⊝ moderate¹
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0.13 standard deviations higher (0.04 lower to 0.30 higher)		540 (6 studies)	⊕⊕⊕⊝ moderate¹	This corresponds to a very small effect according to conventions proposed by Cohen 1992
Failure to complete ‐ total ‐	207 per 1000	209 per 1000 (155 to 275)	OR 1.01 (0.70 to 1.45)	721 (7 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐	62 per 1000	44 per 1000 (21 to 93)	OR 0.70 (0.32 to 1.56)	679 (6 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ side effects ‐	86 per 1000	91 per 1000 (57 to 144)	OR 1.07 (0.64 to 1.80)	721 (7 studies)	⊕⊕⊕⊝ moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested.

Summary of findings 17. Fluoxetine compared to moclobemide

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Summary of findings 18. Fluoxetine compared to nefazodone

Fluoxetine compared to nefazodone
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: nefazodone
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Nefazodone	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)		0 per 1000 (0 to 0)	Not estimable	0 (0)
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0.06 standard deviations lower (0.30 lower to 0.18 higher)		271 (4 studies)	⊕⊕⊕⊝ moderate¹	This effects approaches zero
Failure to complete ‐ total ‐	220 per 1000	132 per 1000 (58 to 269)	OR 0.54 (0.22 to 1.31)	161 (3 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐	24 per 1000	17 per 1000 (1 to 211)	OR 0.71 (0.05 to 10.71)	161 (3 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ side effects ‐	96 per 1000	75 per 1000 (33 to 161)	OR 0.76 (0.32 to 1.81)	286 (4 studies)	⊕⊕⊕⊝ moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested.

Summary of findings 18. Fluoxetine compared to nefazodone

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Summary of findings 19. Fluoxetine compared to paroxetine

Fluoxetine compared to paroxetine
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: paroxetine
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Paroxetine	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	426 per 1000	477 per 1000 (408 to 550)	OR 1.23 (0.93 to 1.65)	1574 (9 studies)	⊕⊕⊕⊝ moderate¹
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0.01 standard deviations lower (0.25 lower to 0.24 higher)		2061 (11 studies)	⊕⊕⊕⊝ moderate¹	This effect approaches zero
Failure to complete ‐ total ‐	317 per 1000	313 per 1000 (273 to 358)	OR 0.98 (0.81 to 1.20)	1848 (10 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐	52 per 1000	39 per 1000 (22 to 71)	OR 0.75 (0.41 to 1.39)	1005 (4 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ side effects ‐	133 per 1000	115 per 1000 (87 to 151)	OR 0.85 (0.62 to 1.16)	1509 (9 studies)	⊕⊕⊕⊝ moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested.

Summary of findings 19. Fluoxetine compared to paroxetine

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Summary of findings 20. Fluoxetine compared to phenelzine

Fluoxetine compared to phenelzine
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: phenelzine
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Phenelzine	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	150 per 1000	200 per 1000 (45 to 564)	OR 1.42 (0.27 to 7.34)	40 (1 study)	⊕⊝⊝⊝ very low¹
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0.05 standard deviations lower (0.67 lower to 0.57 higher)		40 (1 study)	⊕⊝⊝⊝ very low¹	This effect approaches zero
Failure to complete ‐ total ‐	100 per 1000	20 per 1000 (1 to 308)	OR 0.18 (0.01 to 4.01)	40 (1 study)	⊕⊝⊝⊝ very low¹
Failure to complete ‐ inefficacy ‐		0 per 1000 (0 to 0)	Not estimable	0 (0)
Failure to complete ‐ side effects ‐	50 per 1000	17 per 1000 (1 to 303)	OR 0.32 (0.01 to 8.26)	40 (1 study)	⊕⊝⊝⊝ very low¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested. Only one study included in the analysis and less than 50 patients.

Summary of findings 20. Fluoxetine compared to phenelzine

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Summary of findings 21. Fluoxetine compared to pramipexole

Fluoxetine compared to pramipexole
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: pramipexole
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Pramipexole	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	657 per 1000	513 per 1000 (315 to 707)	OR 0.55 (0.24 to 1.26)	105 (1 study)	⊕⊕⊝⊝ low¹
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0 standard deviations higher (0 to 0 higher)		0 (0)		No data available on this outcome
Failure to complete ‐ total ‐	443 per 1000	87 per 1000 (23 to 250)	OR 0.12 (0.03 to 0.42)	105 (1 study)	⊕⊕⊝⊝ low¹
Failure to complete ‐ inefficacy ‐	57 per 1000	29 per 1000 (3 to 215)	OR 0.49 (0.05 to 4.51)	105 (1 study)	⊕⊕⊝⊝ low¹
Failure to complete ‐ side effects ‐	314 per 1000	27 per 1000 (5 to 186)	OR 0.06 (0.01 to 0.50)	105 (1 study)	⊕⊕⊝⊝ low¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested. Only one study included in the analysis.

Summary of findings 21. Fluoxetine compared to pramipexole

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Summary of findings 22. Fluoxetine compared to reboxetine

Fluoxetine compared to reboxetine
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: reboxetine
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Reboxetine	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	566 per 1000	501 per 1000 (418 to 589)	OR 0.77 (0.55 to 1.10)	721 (3 studies)	⊕⊕⊕⊝ moderate¹
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0.04 standard deviations higher (0.31 lower to 0.40 higher)		205 (2 studies)	⊕⊕⊕⊝ moderate¹	This effect approaches zero
Failure to complete ‐ total ‐	361 per 1000	253 per 1000 (199 to 316)	OR 0.60 (0.44 to 0.82)	764 (4 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐	88 per 1000	82 per 1000 (43 to 146)	OR 0.92 (0.47 to 1.77)	464 (3 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ side effects ‐	129 per 1000	57 per 1000 (22 to 139)	OR 0.41 (0.15 to 1.09)	211 (2 studies)	⊕⊕⊕⊝ moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested.

Summary of findings 22. Fluoxetine compared to reboxetine

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Summary of findings 23. Fluoxetine compared to sertraline

Fluoxetine compared to sertraline
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: sertraline
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Sertraline	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	416 per 1000	494 per 1000 (435 to 554)	OR 1.37 (1.08 to 1.74)	1188 (6 studies)	⊕⊕⊕⊝ moderate¹
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0.09 standard deviations higher (0.03 lower to 0.20 higher)		1160 (7 studies)	⊕⊕⊕⊝ moderate¹	This corresponds to a very small effect according to conventions proposed by Cohen 1992
Failure to complete ‐ total ‐	229 per 1000	258 per 1000 (217 to 307)	OR 1.17 (0.93 to 1.49)	1591 (9 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐	70 per 1000	76 per 1000 (49 to 118)	OR 1.09 (0.68 to 1.77)	1056 (5 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ side effects ‐	110 per 1000	134 per 1000 (102 to 174)	OR 1.25 (0.92 to 1.70)	1591 (9 studies)	⊕⊕⊕⊝ moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested.

Summary of findings 23. Fluoxetine compared to sertraline

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Summary of findings 24. Fluoxetine compared to tianeptine

Fluoxetine compared to tianeptine
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: tianeptine
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Tianeptine	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	534 per 1000	562 per 1000 (462 to 657)	OR 1.12 (0.75 to 1.67)	387 (3 studies)	⊕⊕⊕⊝ moderate¹
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0.15 standard deviations lower (0.40 lower to 0.10 higher)		730 (3 studies)	⊕⊕⊕⊝ moderate¹	This corresponds to a very small effect according to conventions proposed by Cohen 1992
Failure to complete ‐ total ‐	225 per 1000	218 per 1000 (167 to 279)	OR 0.96 (0.69 to 1.33)	830 (3 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐	47 per 1000	39 per 1000 (13 to 110)	OR 0.82 (0.27 to 2.53)	830 (3 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ side effects ‐	91 per 1000	101 per 1000 (66 to 152)	OR 1.13 (0.71 to 1.80)	830 (3 studies)	⊕⊕⊕⊝ moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested.

Summary of findings 24. Fluoxetine compared to tianeptine

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Summary of findings 25. Fluoxetine compared to trazodone

Fluoxetine compared to trazodone
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: trazodone
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Trazodone	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	642 per 1000	467 per 1000 (189 to 769)	OR 0.49 (0.13 to 1.86)	110 (3 studies)	⊕⊕⊕⊝ moderate¹
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0.25 standard deviations lower (0.76 lower to 0.26 higher)		203 (4 studies)	⊕⊕⊕⊝ moderate¹	This corresponds to a small effect according to conventions proposed by Cohen 1992
Failure to complete ‐ total ‐	250 per 1000	145 per 1000 (71 to 274)	OR 0.51 (0.23 to 1.13)	230 (4 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐	147 per 1000	38 per 1000 (7 to 207)	OR 0.23 (0.04 to 1.51)	70 (2 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ side effects ‐	151 per 1000	105 per 1000 (34 to 280)	OR 0.66 (0.20 to 2.19)	110 (3 studies)	⊕⊕⊕⊝ moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested.

Summary of findings 25. Fluoxetine compared to trazodone

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Summary of findings 26. Fluoxetine compared to venlafaxine

Fluoxetine compared to venlafaxine
Patient or population: patients with depression Settings: in‐ and outpatients Intervention: fluoxetine Comparison: venlafaxine
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Venlafaxine	Fluoxetine
Failure to respond (reduction ≥ 50% on HDRS)	341 per 1000	400 per 1000 (363 to 439)	OR 1.29 (1.10 to 1.51)	3387 (12 studies)	⊕⊕⊕⊝ moderate¹
Endpoint score (HDRS or MADRS)		The mean endpoint score in the intervention groups was 0.10 standard deviations higher (0.0 to 0.19 higher)		3097 (13 studies)	⊕⊕⊕⊝ moderate¹	This corresponds to a very small effect according to conventions proposed by Cohen 1992
Failure to complete ‐ total ‐	256 per 1000	234 per 1000 (203 to 267)	OR 0.89 (0.74 to 1.06)	2683 (14 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ inefficacy ‐	43 per 1000	56 per 1000 (40 to 79)	OR 1.31 (0.91 to 1.89)	2640 (13 studies)	⊕⊕⊕⊝ moderate¹
Failure to complete ‐ side effects ‐	116 per 1000	87 per 1000 (69 to 110)	OR 0.72 (0.56 to 0.94)	2640 (13 studies)	⊕⊕⊕⊝ moderate¹
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Limitations in studies designs: no details on randomisation procedures and allocation concealment. Blinding stated but not tested.

Summary of findings 26. Fluoxetine compared to venlafaxine

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Comparison 1. Fluoxetine versus TCAs

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to respond ‐ HDRS (‐50%) Show forest plot	24	2124	Odds Ratio (M‐H, Random, 95% CI)	0.97 [0.77, 1.22]

1.1 Fluoxetine vs Amitriptyline	11	777	Odds Ratio (M‐H, Random, 95% CI)	0.93 [0.68, 1.28]
1.2 Fluoxetine vs Clomipramine	1	94	Odds Ratio (M‐H, Random, 95% CI)	0.63 [0.27, 1.45]
1.3 Fluoxetine vs Desipramine	2	84	Odds Ratio (M‐H, Random, 95% CI)	1.70 [0.56, 5.15]
1.4 Fluoxetine vs Dothiepin/dosulepin	2	144	Odds Ratio (M‐H, Random, 95% CI)	2.13 [1.08, 4.20]
1.5 Fluoxetine vs Doxepine	1	40	Odds Ratio (M‐H, Random, 95% CI)	1.0 [0.28, 3.54]
1.6 Fluoxetine vs Imipramine	5	761	Odds Ratio (M‐H, Random, 95% CI)	0.74 [0.41, 1.35]
1.7 Fluoxetine vs Lofepramine	1	183	Odds Ratio (M‐H, Random, 95% CI)	0.99 [0.55, 1.78]
1.8 Fluoxetine vs Trimipramine	1	41	Odds Ratio (M‐H, Random, 95% CI)	2.05 [0.56, 7.45]
2 End‐point score on rating scale Show forest plot	50	3393	Std. Mean Difference (IV, Random, 95% CI)	0.03 [‐0.07, 0.14]

2.1 Fluoxetine vs Amiptriptyline	19	1023	Std. Mean Difference (IV, Random, 95% CI)	0.10 [‐0.09, 0.29]
2.2 Fluoxetine vs Clomipramine	5	372	Std. Mean Difference (IV, Random, 95% CI)	‐0.10 [‐0.31, 0.10]
2.3 Fluoxetine vs Desipramine	4	147	Std. Mean Difference (IV, Random, 95% CI)	0.27 [‐0.32, 0.86]
2.4 Fluoxetine vs Dothiepin/dosulepin	4	266	Std. Mean Difference (IV, Random, 95% CI)	0.16 [‐0.27, 0.59]
2.5 Fluoxetine vs Imipramine	12	1063	Std. Mean Difference (IV, Random, 95% CI)	‐0.01 [‐0.21, 0.19]
2.6 Fluoxetine vs Lofepramine	1	183	Std. Mean Difference (IV, Random, 95% CI)	0.13 [‐0.16, 0.42]
2.7 Fluoxetine vs Nomifensine	1	28	Std. Mean Difference (IV, Random, 95% CI)	‐0.37 [‐1.12, 0.38]
2.8 Fluoxetine vs Nortriptyline	2	251	Std. Mean Difference (IV, Random, 95% CI)	‐0.48 [‐1.20, 0.24]
2.9 Fluoxetine vs Trimipramine	2	60	Std. Mean Difference (IV, Random, 95% CI)	0.41 [‐0.10, 0.92]
3 Failure to complete ‐ Total Show forest plot	49	4194	Odds Ratio (M‐H, Random, 95% CI)	0.79 [0.65, 0.96]

3.1 Fluoxetine vs Amitriptyline	18	1089	Odds Ratio (M‐H, Random, 95% CI)	0.62 [0.46, 0.85]
3.2 Fluoxetine vs Clomipramine	2	263	Odds Ratio (M‐H, Random, 95% CI)	0.65 [0.38, 1.14]
3.3 Fluoxetine vs Desipramine	2	104	Odds Ratio (M‐H, Random, 95% CI)	0.44 [0.16, 1.24]
3.4 Fluoxetine vs Dothiepin/dosulepin	5	478	Odds Ratio (M‐H, Random, 95% CI)	1.57 [0.92, 2.69]
3.5 Fluoxetine vs Doxepine	4	323	Odds Ratio (M‐H, Random, 95% CI)	0.81 [0.49, 1.32]
3.6 Fluoxetine vs Imipramine	12	1225	Odds Ratio (M‐H, Random, 95% CI)	0.79 [0.51, 1.21]
3.7 Fluoxetine vs Lofepramine	1	183	Odds Ratio (M‐H, Random, 95% CI)	0.50 [0.24, 1.04]
3.8 Fluoxetine vs Nomifensine	1	40	Odds Ratio (M‐H, Random, 95% CI)	6.33 [0.67, 60.16]
3.9 Fluoxetine vs Nortriptyline	3	448	Odds Ratio (M‐H, Random, 95% CI)	0.73 [0.36, 1.47]
3.10 Fluoxetine vs Trimipramine	1	41	Odds Ratio (M‐H, Random, 95% CI)	2.0 [0.41, 9.78]
4 Failure to complete ‐ Inefficacy Show forest plot	33	2911	Odds Ratio (M‐H, Random, 95% CI)	1.29 [0.96, 1.72]

4.1 Fluoxetine vs Amitriptyline	13	835	Odds Ratio (M‐H, Random, 95% CI)	0.91 [0.44, 1.88]
4.2 Fluoxetine vs Clomipramine	1	120	Odds Ratio (M‐H, Random, 95% CI)	7.37 [0.37, 145.75]
4.3 Fluoxetine vs Desipramine	2	104	Odds Ratio (M‐H, Random, 95% CI)	1.03 [0.20, 5.35]
4.4 Fluoxetine vs Dothiepin/dosulepin	3	271	Odds Ratio (M‐H, Random, 95% CI)	1.34 [0.49, 3.66]
4.5 Fluoxetine vs Doxepine	3	283	Odds Ratio (M‐H, Random, 95% CI)	1.72 [0.60, 4.92]
4.6 Fluoxetine vs Imipramine	10	1093	Odds Ratio (M‐H, Random, 95% CI)	1.41 [0.97, 2.05]
4.7 Fluoxetine vs Nortriptyline	1	205	Odds Ratio (M‐H, Random, 95% CI)	0.38 [0.07, 2.03]
5 Failure to complete ‐ Side Effects Show forest plot	40	3647	Odds Ratio (M‐H, Random, 95% CI)	0.55 [0.40, 0.75]

5.1 Fluoxetine vs Amitriptyline	16	1038	Odds Ratio (M‐H, Random, 95% CI)	0.41 [0.23, 0.71]
5.2 Fluoxetine vs Clomipramine	2	263	Odds Ratio (M‐H, Random, 95% CI)	0.30 [0.12, 0.79]
5.3 Fluoxetine vs Desipramine	2	104	Odds Ratio (M‐H, Random, 95% CI)	0.27 [0.04, 1.68]
5.4 Fluoxetine vs Dothiepin/dosulepin	5	478	Odds Ratio (M‐H, Random, 95% CI)	2.05 [0.59, 7.16]
5.5 Fluoxetine vs Doxepine	3	283	Odds Ratio (M‐H, Random, 95% CI)	0.82 [0.44, 1.53]
5.6 Fluoxetine vs Imipramine	10	1093	Odds Ratio (M‐H, Random, 95% CI)	0.47 [0.26, 0.86]
5.7 Fluoxetine vs Lofepramine	1	183	Odds Ratio (M‐H, Random, 95% CI)	0.16 [0.02, 1.38]
5.8 Fluoxetine vs Nortriptyline	1	205	Odds Ratio (M‐H, Random, 95% CI)	0.86 [0.42, 1.77]

Comparison 1. Fluoxetine versus TCAs

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Comparison 2. Fluoxetine versus heterocyclics

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to respond ‐ HDRS (‐50%) Show forest plot	3		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Maprotiline	2	163	Odds Ratio (M‐H, Random, 95% CI)	1.95 [0.91, 4.18]
1.2 Fluoxetine vs Mianserin	1	53	Odds Ratio (M‐H, Random, 95% CI)	0.80 [0.27, 2.38]
2 End‐point score on rating scale Show forest plot	8		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only

2.1 Fluoxetine vs Maprotiline	5	433	Std. Mean Difference (IV, Random, 95% CI)	0.04 [‐0.15, 0.23]
2.2 Fluoxetine vs Mianserin	3	128	Std. Mean Difference (IV, Random, 95% CI)	0.43 [‐0.38, 1.23]
3 Failure to complete ‐ Total Show forest plot	6		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

3.1 Fluoxetine vs Maprotiline	4	351	Odds Ratio (M‐H, Random, 95% CI)	1.75 [0.90, 3.41]
3.2 Fluoxetine vs Mianserin	2	93	Odds Ratio (M‐H, Random, 95% CI)	0.63 [0.18, 2.25]
4 Failure to complete ‐ Inefficacy Show forest plot	4		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

4.1 Fluoxetine vs Maprotiline	3	209	Odds Ratio (M‐H, Random, 95% CI)	2.54 [0.33, 19.19]
4.2 Fluoxetine vs Mianserin	1	53	Odds Ratio (M‐H, Random, 95% CI)	2.27 [0.38, 13.63]
5 Failure to complete ‐ Side Effects Show forest plot	4		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

5.1 Fluoxetine vs Maprotiline	3	209	Odds Ratio (M‐H, Random, 95% CI)	0.53 [0.15, 1.93]
5.2 Fluoxetine vs Mianserin	1	53	Odds Ratio (M‐H, Random, 95% CI)	1.05 [0.23, 4.70]

Comparison 2. Fluoxetine versus heterocyclics

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Comparison 3. Fluoxetine versus other SSRIs

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to respond ‐ HDRS (‐50%) Show forest plot	17		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Citalopram	1	59	Odds Ratio (M‐H, Random, 95% CI)	0.60 [0.20, 1.79]
1.2 Fluoxetine vs Escitalopram	1	240	Odds Ratio (M‐H, Random, 95% CI)	1.02 [0.56, 1.85]
1.3 Fluoxetine vs Fluvoxamine	1	177	Odds Ratio (M‐H, Random, 95% CI)	0.95 [0.52, 1.74]
1.4 Fluoxetine vs Paroxetine	9	1574	Odds Ratio (M‐H, Random, 95% CI)	1.23 [0.93, 1.65]
1.5 Fluoxetine vs Sertraline	6	1188	Odds Ratio (M‐H, Random, 95% CI)	1.37 [1.08, 1.74]
2 End‐point score on rating scales Show forest plot	21		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only

2.1 Fluoxetine vs Citalopram	3	661	Std. Mean Difference (IV, Random, 95% CI)	0.06 [‐0.10, 0.21]
2.2 Fluoxetine vs Escitalopram	1	231	Std. Mean Difference (IV, Random, 95% CI)	0.07 [‐0.19, 0.33]
2.3 Fluoxetine vs Paroxetine	11	2061	Std. Mean Difference (IV, Random, 95% CI)	‐0.01 [‐0.26, 0.24]
2.4 Fluoxetine vs Sertraline	7	1160	Std. Mean Difference (IV, Random, 95% CI)	0.09 [‐0.03, 0.20]
3 Failure to complete ‐ Total Show forest plot	25		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

3.1 Fluoxetine vs Citalopram	3	732	Odds Ratio (M‐H, Random, 95% CI)	0.87 [0.60, 1.27]
3.2 Fluoxetine vs Escitalopram	2	578	Odds Ratio (M‐H, Random, 95% CI)	1.53 [1.00, 2.37]
3.3 Fluoxetine vs Fluvoxamine	2	284	Odds Ratio (M‐H, Random, 95% CI)	0.71 [0.36, 1.37]
3.4 Fluoxetine vs Paroxetine	10	1848	Odds Ratio (M‐H, Random, 95% CI)	0.98 [0.81, 1.20]
3.5 Fluoxetine vs Sertraline	9	1591	Odds Ratio (M‐H, Random, 95% CI)	1.17 [0.93, 1.49]
4 Failure to complete ‐ Inefficacy Show forest plot	13		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

4.1 Fluoxetine vs Citalopram	3	732	Odds Ratio (M‐H, Random, 95% CI)	0.87 [0.48, 1.56]
4.2 Fluoxetine vs Escitalopram	2	578	Odds Ratio (M‐H, Random, 95% CI)	1.74 [0.46, 6.53]
4.3 Fluoxetine vs Paroxetine	4	1005	Odds Ratio (M‐H, Random, 95% CI)	0.75 [0.41, 1.39]
4.4 Fluoxetine vs Sertraline	5	1056	Odds Ratio (M‐H, Random, 95% CI)	1.09 [0.68, 1.77]
5 Failure to complete ‐ Side Effects Show forest plot	23		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

5.1 Fluoxetine vs Citalopram	3	732	Odds Ratio (M‐H, Random, 95% CI)	0.64 [0.34, 1.20]
5.2 Fluoxetine vs Escitalopram	2	578	Odds Ratio (M‐H, Random, 95% CI)	1.17 [0.64, 2.12]
5.3 Fluoxetine vs Fluvoxamine	1	100	Odds Ratio (M‐H, Random, 95% CI)	1.04 [0.14, 7.71]
5.4 Fluoxetine vs Paroxetine	9	1509	Odds Ratio (M‐H, Random, 95% CI)	0.85 [0.62, 1.16]
5.5 Fluoxetine vs Sertraline	9	1591	Odds Ratio (M‐H, Random, 95% CI)	1.25 [0.92, 1.70]

Comparison 3. Fluoxetine versus other SSRIs

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Comparison 4. Fluoxetine versus SNRIs

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to respond ‐ HDRS (‐50%) Show forest plot	15		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Duloxetine	1	103	Odds Ratio (M‐H, Random, 95% CI)	1.41 [0.61, 3.25]
1.2 Fluoxetine vs Milnacipran	2	370	Odds Ratio (M‐H, Random, 95% CI)	1.20 [0.78, 1.84]
1.3 Fluoxetine vs Venlafaxine	12	3387	Odds Ratio (M‐H, Random, 95% CI)	1.29 [1.10, 1.51]
2 End‐point score on rating scale Show forest plot	15		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only

2.1 Fluoxetine vs Milnacipran	2	213	Std. Mean Difference (IV, Random, 95% CI)	‐0.36 [‐0.63, ‐0.08]
2.2 Fluoxetine vs Venlafaxine	13	3097	Std. Mean Difference (IV, Random, 95% CI)	0.10 [0.00, 0.19]
3 Failure to complete ‐ Total Show forest plot	19		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

3.1 Fluoxetine vs Duloxetine	2	532	Odds Ratio (M‐H, Random, 95% CI)	0.90 [0.53, 1.52]
3.2 Fluoxetine vs Milnacipran	3	560	Odds Ratio (M‐H, Random, 95% CI)	0.98 [0.68, 1.42]
3.3 Fluoxetine vs Venlafaxine	14	2683	Odds Ratio (M‐H, Random, 95% CI)	0.89 [0.74, 1.06]
4 Failure to complete ‐ Inefficacy Show forest plot	18		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

4.1 Fluoxetine vs Duloxetine	2	432	Odds Ratio (M‐H, Random, 95% CI)	3.33 [0.92, 12.11]
4.2 Fluoxetine vs Milnacipran	3	560	Odds Ratio (M‐H, Random, 95% CI)	1.25 [0.68, 2.30]
4.3 Fluoxetine vs Venlafaxine	13	2640	Odds Ratio (M‐H, Random, 95% CI)	1.31 [0.91, 1.89]
5 Failure to complete ‐ Side Effects Show forest plot	18		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

5.1 Fluoxetine vs Duloxetine	2	532	Odds Ratio (M‐H, Random, 95% CI)	0.28 [0.07, 1.23]
5.2 Fluoxetine vs Milnacipran	3	560	Odds Ratio (M‐H, Random, 95% CI)	1.50 [0.81, 2.76]
5.3 Fluoxetine vs Venlafaxine	13	2640	Odds Ratio (M‐H, Random, 95% CI)	0.72 [0.56, 0.94]

Comparison 4. Fluoxetine versus SNRIs

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Comparison 5. Fluoxetine versus MAOIs or newer ADs

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to respond ‐ HDRS (‐50%) Show forest plot	16		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Agomelatine	1	515	Odds Ratio (M‐H, Random, 95% CI)	1.44 [0.99, 2.09]
1.2 Fluoxetine vs Mirtazapine	4	600	Odds Ratio (M‐H, Random, 95% CI)	1.46 [1.04, 2.04]
1.3 Fluoxetine vs Moclobemide	7	721	Odds Ratio (M‐H, Random, 95% CI)	1.27 [0.92, 1.75]
1.4 Fluoxetine vs Phenelzine	1	40	Odds Ratio (M‐H, Random, 95% CI)	1.42 [0.27, 7.34]
1.5 Fluoxetine vs Reboxetine	3	721	Odds Ratio (M‐H, Random, 95% CI)	0.77 [0.55, 1.10]
2 End‐point score on rating scales Show forest plot	13		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only

2.1 Fluoxetine vs Agomelatine	3	1213	Std. Mean Difference (IV, Random, 95% CI)	0.02 [‐0.18, 0.23]
2.2 Fluoxetine vs Mirtazapine	1	31	Std. Mean Difference (IV, Random, 95% CI)	0.57 [‐0.15, 1.29]
2.3 Fluoxetine vs Moclobemide	6	540	Std. Mean Difference (IV, Random, 95% CI)	0.13 [‐0.04, 0.30]
2.4 Fluoxetine vs Phenelzine	1	40	Std. Mean Difference (IV, Random, 95% CI)	‐0.05 [‐0.67, 0.57]
2.5 Fluoxetine vs Reboxetine	2	205	Std. Mean Difference (IV, Random, 95% CI)	0.04 [‐0.31, 0.40]
3 Failure to complete ‐ Total Show forest plot	17		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

3.1 Fluoxetine vs Agomelatine	2	785	Odds Ratio (M‐H, Random, 95% CI)	1.22 [0.59, 2.49]
3.2 Fluoxetine vs Mirtazapine	3	301	Odds Ratio (M‐H, Random, 95% CI)	0.92 [0.51, 1.68]
3.3 Fluoxetine vs Moclobemide	7	721	Odds Ratio (M‐H, Random, 95% CI)	1.01 [0.70, 1.47]
3.4 Fluoxetine vs Phenelzine	1	40	Odds Ratio (M‐H, Random, 95% CI)	0.18 [0.01, 4.01]
3.5 Fluoxetine vs Reboxetine	4	764	Odds Ratio (M‐H, Random, 95% CI)	0.60 [0.44, 0.83]
4 Failure to complete ‐ Inefficacy Show forest plot	16		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

4.1 Fluoxetine vs Agomelatine	2	785	Odds Ratio (M‐H, Random, 95% CI)	1.08 [0.41, 2.88]
4.2 Fluoxetine vs Mirtazapine	4	600	Odds Ratio (M‐H, Random, 95% CI)	1.45 [0.71, 2.96]
4.3 Fluoxetine vs Moclobemide	6	679	Odds Ratio (M‐H, Random, 95% CI)	0.70 [0.32, 1.56]
4.4 Fluoxetine vs Phenelzine	1	40	Odds Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4.5 Fluoxetine vs Reboxetine	3	464	Odds Ratio (M‐H, Random, 95% CI)	0.92 [0.47, 1.77]
5 Failure to complete ‐ Side Effects Show forest plot	16		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

5.1 Fluoxetine vs Agomelatine	2	785	Odds Ratio (M‐H, Random, 95% CI)	1.50 [0.73, 3.08]
5.2 Fluoxetine vs Mirtazapine	4	600	Odds Ratio (M‐H, Random, 95% CI)	0.95 [0.54, 1.66]
5.3 Fluoxetine vs Moclobemide	7	721	Odds Ratio (M‐H, Random, 95% CI)	1.04 [0.54, 2.01]
5.4 Fluoxetine vs Phenelzine	1	40	Odds Ratio (M‐H, Random, 95% CI)	0.32 [0.01, 8.26]
5.5 Fluoxetine vs Reboxetine	2	211	Odds Ratio (M‐H, Random, 95% CI)	0.40 [0.10, 1.61]

Comparison 5. Fluoxetine versus MAOIs or newer ADs

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Comparison 6. Fluoxetine versus other conventional psychotropic drugs

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to respond ‐ HDRS (‐50%) Show forest plot	8		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Amineptine	1	63	Odds Ratio (M‐H, Random, 95% CI)	0.37 [0.13, 1.04]
1.2 Fluoxetine vs Bupropion	2	436	Odds Ratio (M‐H, Random, 95% CI)	0.83 [0.48, 1.43]
1.3 Fluoxetine vs Pramipexole	1	105	Odds Ratio (M‐H, Random, 95% CI)	0.55 [0.24, 1.26]
1.4 Fluoxetine vs Tianeptine	1	387	Odds Ratio (M‐H, Random, 95% CI)	1.12 [0.75, 1.67]
1.5 Fluoxetine vs Trazodone	3	110	Odds Ratio (M‐H, Random, 95% CI)	0.49 [0.13, 1.86]
2 End‐point score on rating scales Show forest plot	13		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only

2.1 Fluoxetine vs ABT‐200	1	141	Std. Mean Difference (IV, Random, 95% CI)	‐1.85 [‐2.25, ‐1.45]
2.2 Fluoxetine vs Amisulpride	1	268	Std. Mean Difference (IV, Random, 95% CI)	0.17 [‐0.07, 0.41]
2.3 Fluoxetine vs Nefazodone	4	271	Std. Mean Difference (IV, Random, 95% CI)	‐0.06 [‐0.30, 0.18]
2.4 Fluoxetine vs Tianeptine	3	730	Std. Mean Difference (IV, Random, 95% CI)	‐0.15 [‐0.40, 0.10]
2.5 Fluoxetine vs Trazodone	4	203	Std. Mean Difference (IV, Random, 95% CI)	‐0.25 [‐0.76, 0.26]
3 Failure to complete ‐ Total Show forest plot	17		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

3.1 Fluoxetine vs ABT‐200	1	144	Odds Ratio (M‐H, Random, 95% CI)	0.18 [0.08, 0.39]
3.2 Fluoxetine vs Amineptine	2	232	Odds Ratio (M‐H, Random, 95% CI)	0.61 [0.17, 2.21]
3.3 Fluoxetine vs Amisulpride	1	281	Odds Ratio (M‐H, Random, 95% CI)	1.39 [0.81, 2.38]
3.4 Fluoxetine vs Bupropion	2	436	Odds Ratio (M‐H, Random, 95% CI)	1.00 [0.67, 1.48]
3.5 Fluoxetine vs Nefazodone	3	161	Odds Ratio (M‐H, Random, 95% CI)	0.54 [0.22, 1.31]
3.6 Fluoxetine vs Pramipexole	1	105	Odds Ratio (M‐H, Random, 95% CI)	0.12 [0.03, 0.42]
3.7 Fluoxetine vs Tianeptine	3	830	Odds Ratio (M‐H, Random, 95% CI)	0.96 [0.69, 1.33]
3.8 Fluoxetine vs Trazodone	4	230	Odds Ratio (M‐H, Random, 95% CI)	0.51 [0.23, 1.13]
4 Failure to complete ‐ Inefficacy Show forest plot	14		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

4.1 Fluoxetine vs ABT‐200	1	144	Odds Ratio (M‐H, Random, 95% CI)	0.24 [0.03, 2.20]
4.2 Fluoxetine vs Amineptine	1	63	Odds Ratio (M‐H, Random, 95% CI)	1.04 [0.19, 5.57]
4.3 Fluoxetine vs Amisulpride	1	281	Odds Ratio (M‐H, Random, 95% CI)	1.16 [0.43, 3.10]
4.4 Fluoxetine vs Bupropion	2	436	Odds Ratio (M‐H, Random, 95% CI)	1.16 [0.33, 4.10]
4.5 Fluoxetine vs Nefazodone	3	161	Odds Ratio (M‐H, Random, 95% CI)	0.71 [0.05, 10.71]
4.6 Fluoxetine vs Pramipexole	1	105	Odds Ratio (M‐H, Random, 95% CI)	0.49 [0.05, 4.51]
4.7 Fluoxetine vs Tianeptine	3	830	Odds Ratio (M‐H, Random, 95% CI)	0.82 [0.27, 2.53]
4.8 Fluoxetine vs Trazodone	2	70	Odds Ratio (M‐H, Random, 95% CI)	0.23 [0.04, 1.51]
5 Failure to complete ‐ Side Effects Show forest plot	17		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

5.1 Fluoxetine vs ABT‐200	1	144	Odds Ratio (M‐H, Random, 95% CI)	0.08 [0.02, 0.27]
5.2 Fluoxetine vs Amineptine	2	232	Odds Ratio (M‐H, Random, 95% CI)	0.52 [0.03, 7.82]
5.3 Fluoxetine vs Amisulpride	1	281	Odds Ratio (M‐H, Random, 95% CI)	0.77 [0.33, 1.82]
5.4 Fluoxetine vs Bupropion	2	436	Odds Ratio (M‐H, Random, 95% CI)	1.01 [0.45, 2.25]
5.5 Fluoxetine vs Nefazodone	4	286	Odds Ratio (M‐H, Random, 95% CI)	0.76 [0.32, 1.81]
5.6 Fluoxetine vs Pramipexole	1	105	Odds Ratio (M‐H, Random, 95% CI)	0.06 [0.01, 0.50]
5.7 Fluoxetine vs Tianeptine	3	830	Odds Ratio (M‐H, Random, 95% CI)	1.13 [0.71, 1.80]
5.8 Fluoxetine vs Trazodone	3	110	Odds Ratio (M‐H, Random, 95% CI)	0.66 [0.20, 2.19]

Comparison 6. Fluoxetine versus other conventional psychotropic drugs

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Comparison 7. Fluoxetine versus other non‐conventional AD agents

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Failure to respond ‐ HDRS (‐50%) Show forest plot	7		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Crocus Sativus	1	40	Odds Ratio (M‐H, Random, 95% CI)	0.53 [0.11, 2.60]
1.2 Fluoxetine vs Hypericum	6	717	Odds Ratio (M‐H, Random, 95% CI)	0.98 [0.55, 1.73]
2 End‐point score on rating scales Show forest plot	5		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only

2.1 Fluoxetine vs Hypericum	5	648	Std. Mean Difference (IV, Random, 95% CI)	0.13 [‐0.02, 0.29]
3 Failure to complete ‐ Total Show forest plot	6		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

3.1 Fluoxetine vs Crocus Sativus	1	40	Odds Ratio (M‐H, Random, 95% CI)	1.0 [0.06, 17.18]
3.2 Fluoxetine vs Hypericum	5	679	Odds Ratio (M‐H, Random, 95% CI)	1.04 [0.58, 1.85]
4 Failure to complete ‐ Inefficacy Show forest plot	2		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

4.1 Fluoxetine vs Hypericum	2	401	Odds Ratio (M‐H, Random, 95% CI)	4.70 [0.22, 99.39]
5 Failure to complete ‐ Side Effects Show forest plot	5		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

5.1 Fluoxetine vs Hypericum	5	679	Odds Ratio (M‐H, Random, 95% CI)	1.21 [0.56, 2.64]

Comparison 7. Fluoxetine versus other non‐conventional AD agents

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Comparison 8. Subgroup analysis for fluoxetine versus TCAs: failure to respond

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 follow‐up <6 weeks Show forest plot	5	341	Odds Ratio (M‐H, Random, 95% CI)	0.67 [0.35, 1.27]

1.1 Fluoxetine vs Amitriptyline	3	207	Odds Ratio (M‐H, Random, 95% CI)	0.56 [0.19, 1.65]
1.2 Fluoxetine vs Clomipramine	1	94	Odds Ratio (M‐H, Random, 95% CI)	0.63 [0.27, 1.45]
1.3 Fluoxetine vs Imipramine	1	40	Odds Ratio (M‐H, Random, 95% CI)	1.42 [0.27, 7.34]
2 follow‐up 6‐16 weeks Show forest plot	18	1742	Odds Ratio (M‐H, Random, 95% CI)	1.02 [0.80, 1.31]

2.1 Fluoxetine vs Amitriptyline	8	570	Odds Ratio (M‐H, Random, 95% CI)	1.06 [0.75, 1.50]
2.2 Fluoxetine vs Desipramine	2	84	Odds Ratio (M‐H, Random, 95% CI)	1.70 [0.56, 5.15]
2.3 Fluoxetine vs Dothiepin/dosulepin	2	144	Odds Ratio (M‐H, Random, 95% CI)	2.13 [1.08, 4.20]
2.4 Fluoxetine vs Doxepine	1	40	Odds Ratio (M‐H, Random, 95% CI)	1.0 [0.28, 3.54]
2.5 Fluoxetine vs Imipramine	4	721	Odds Ratio (M‐H, Random, 95% CI)	0.69 [0.36, 1.34]
2.6 Fluoxetine vs Lofepramine	1	183	Odds Ratio (M‐H, Random, 95% CI)	0.99 [0.55, 1.78]

Comparison 8. Subgroup analysis for fluoxetine versus TCAs: failure to respond

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Comparison 9. Subgroup analysis for fluoxetine versus TCAs: endpoint score

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 follow‐up <6 weeks Show forest plot	12	541	Std. Mean Difference (IV, Random, 95% CI)	0.18 [‐0.15, 0.50]

1.1 Fluoxetine vs Amiptriptyline	6	290	Std. Mean Difference (IV, Random, 95% CI)	0.39 [‐0.25, 1.02]
1.2 Fluoxetine vs Clomipramine	2	124	Std. Mean Difference (IV, Random, 95% CI)	‐0.00 [‐0.36, 0.35]
1.3 Fluoxetine vs Desipramine	1	26	Std. Mean Difference (IV, Random, 95% CI)	0.05 [‐0.72, 0.82]
1.4 Fluoxetine vs Imipramine	2	60	Std. Mean Difference (IV, Random, 95% CI)	‐0.04 [‐1.31, 1.22]
1.5 Fluoxetine vs Trimipramine	1	41	Std. Mean Difference (IV, Random, 95% CI)	0.38 [‐0.24, 1.00]
2 follow‐up 6‐16 weeks Show forest plot	36	2727	Std. Mean Difference (IV, Random, 95% CI)	0.04 [‐0.06, 0.14]

2.1 Fluoxetine vs Amiptriptyline	13	733	Std. Mean Difference (IV, Random, 95% CI)	0.07 [‐0.07, 0.22]
2.2 Fluoxetine vs Clomipramine	3	248	Std. Mean Difference (IV, Random, 95% CI)	‐0.15 [‐0.40, 0.10]
2.3 Fluoxetine vs Desipramine	3	121	Std. Mean Difference (IV, Random, 95% CI)	0.33 [‐0.47, 1.12]
2.4 Fluoxetine vs Dothiepin/dosulepin	4	266	Std. Mean Difference (IV, Random, 95% CI)	0.16 [‐0.27, 0.59]
2.5 Fluoxetine vs Imipramine	10	1003	Std. Mean Difference (IV, Random, 95% CI)	‐0.01 [‐0.21, 0.19]
2.6 Fluoxetine vs Lofepramine	1	183	Std. Mean Difference (IV, Random, 95% CI)	0.13 [‐0.16, 0.42]
2.7 Fluoxetine vs Nortriptyline	1	154	Std. Mean Difference (IV, Random, 95% CI)	‐0.12 [‐0.44, 0.20]
2.8 Fluoxetine vs Trimipramine	1	19	Std. Mean Difference (IV, Random, 95% CI)	0.47 [‐0.44, 1.39]
3 follow‐up >16 weeks Show forest plot	1	97	Std. Mean Difference (IV, Random, 95% CI)	‐0.86 [‐1.27, ‐0.44]

3.1 Fluoxetine vs Nortriptyline	1	97	Std. Mean Difference (IV, Random, 95% CI)	‐0.86 [‐1.27, ‐0.44]

Comparison 9. Subgroup analysis for fluoxetine versus TCAs: endpoint score

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Comparison 10. Subgroup analysis for fluoxetine versus TCAs: failure to complete ‐ total

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 follow‐up <6 weeks Show forest plot	11	663	Odds Ratio (M‐H, Random, 95% CI)	0.70 [0.47, 1.05]

1.1 Fluoxetine vs Amitriptyline	6	309	Odds Ratio (M‐H, Random, 95% CI)	0.57 [0.29, 1.13]
1.2 Fluoxetine vs Doxepine	1	51	Odds Ratio (M‐H, Random, 95% CI)	1.25 [0.29, 5.31]
1.3 Fluoxetine vs Imipramine	3	98	Odds Ratio (M‐H, Random, 95% CI)	0.56 [0.10, 3.13]
1.4 Fluoxetine vs Nortriptyline	1	205	Odds Ratio (M‐H, Random, 95% CI)	0.77 [0.44, 1.35]
2 follow‐up 6‐16 weeks Show forest plot	36	3450	Odds Ratio (M‐H, Random, 95% CI)	0.79 [0.63, 0.98]

2.1 Fluoxetine vs Amitriptyline	12	780	Odds Ratio (M‐H, Random, 95% CI)	0.63 [0.44, 0.90]
2.2 Fluoxetine vs Clomipramine	2	263	Odds Ratio (M‐H, Random, 95% CI)	0.65 [0.38, 1.14]
2.3 Fluoxetine vs Desipramine	2	104	Odds Ratio (M‐H, Random, 95% CI)	0.44 [0.16, 1.24]
2.4 Fluoxetine vs Dothiepin/dosulepin	5	478	Odds Ratio (M‐H, Random, 95% CI)	1.57 [0.92, 2.69]
2.5 Fluoxetine vs Doxepine	3	272	Odds Ratio (M‐H, Random, 95% CI)	0.78 [0.44, 1.40]
2.6 Fluoxetine vs Imipramine	9	1127	Odds Ratio (M‐H, Random, 95% CI)	0.81 [0.51, 1.27]
2.7 Fluoxetine vs Lofepramine	1	183	Odds Ratio (M‐H, Random, 95% CI)	0.50 [0.24, 1.04]
2.8 Fluoxetine vs Nortriptyline	2	243	Odds Ratio (M‐H, Random, 95% CI)	0.82 [0.17, 3.93]

Comparison 10. Subgroup analysis for fluoxetine versus TCAs: failure to complete ‐ total

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Comparison 11. Subgroup analysis for fluoxetine versus TCAs: failure to complete ‐ inefficacy

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 follow‐up <6 weeks Show forest plot	5	401	Odds Ratio (M‐H, Random, 95% CI)	0.49 [0.16, 1.50]

1.1 Fluoxetine vs Amitriptyline	2	105	Odds Ratio (M‐H, Random, 95% CI)	0.38 [0.07, 2.09]
1.2 Fluoxetine vs Doxepine	1	51	Odds Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
1.3 Fluoxetine vs Imipramine	1	40	Odds Ratio (M‐H, Random, 95% CI)	3.15 [0.12, 82.16]
1.4 Fluoxetine vs Nortriptyiline	1	205	Odds Ratio (M‐H, Random, 95% CI)	0.38 [0.07, 2.03]
2 follow‐up 6‐16 weeks Show forest plot	28	2510	Odds Ratio (M‐H, Random, 95% CI)	1.38 [1.02, 1.87]

2.1 Fluoxetine vs Amitriptyline	11	730	Odds Ratio (M‐H, Random, 95% CI)	1.11 [0.50, 2.47]
2.2 Fluoxetine vs Clomipramine	1	120	Odds Ratio (M‐H, Random, 95% CI)	7.37 [0.37, 145.75]
2.3 Fluoxetine vs Desipramine	2	104	Odds Ratio (M‐H, Random, 95% CI)	1.03 [0.20, 5.35]
2.4 Fluoxetine vs Dothiepin/dosulepin	3	271	Odds Ratio (M‐H, Random, 95% CI)	1.34 [0.49, 3.66]
2.5 Fluoxetine vs Doxepine	2	232	Odds Ratio (M‐H, Random, 95% CI)	1.72 [0.60, 4.92]
2.6 Fluoxetine vs Imipramine	9	1053	Odds Ratio (M‐H, Random, 95% CI)	1.40 [0.96, 2.04]

Comparison 11. Subgroup analysis for fluoxetine versus TCAs: failure to complete ‐ inefficacy

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Comparison 12. Subgroup analysis for fluoxetine versus TCAs: failure to complete ‐ side effects

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 follow‐up <6 weeks Show forest plot	7	554	Odds Ratio (M‐H, Random, 95% CI)	0.81 [0.46, 1.43]

1.1 Fluoxetine vs Amitriptyline	4	258	Odds Ratio (M‐H, Random, 95% CI)	0.62 [0.21, 1.82]
1.2 Fluoxetine vs Doxepine	1	51	Odds Ratio (M‐H, Random, 95% CI)	3.13 [0.30, 32.31]
1.3 Fluoxetine vs Imipramine	1	40	Odds Ratio (M‐H, Random, 95% CI)	0.63 [0.09, 4.24]
1.4 Fluoxetine vs Nortriptyline	1	205	Odds Ratio (M‐H, Random, 95% CI)	0.86 [0.42, 1.77]
2 follow‐up 6‐16 weeks Show forest plot	33	3093	Odds Ratio (M‐H, Random, 95% CI)	0.51 [0.36, 0.72]

2.1 Fluoxetine vs Amitriptyline	12	780	Odds Ratio (M‐H, Random, 95% CI)	0.33 [0.18, 0.61]
2.2 Fluoxetine vs Clomipramine	2	263	Odds Ratio (M‐H, Random, 95% CI)	0.30 [0.12, 0.79]
2.3 Fluoxetine vs Desipramine	2	104	Odds Ratio (M‐H, Random, 95% CI)	0.27 [0.04, 1.68]
2.4 Fluoxetine vs Dothiepin/dosulepin	5	478	Odds Ratio (M‐H, Random, 95% CI)	2.05 [0.59, 7.16]
2.5 Fluoxetine vs Doxepine	2	232	Odds Ratio (M‐H, Random, 95% CI)	0.73 [0.42, 1.28]
2.6 Fluoxetine vs Imipramine	9	1053	Odds Ratio (M‐H, Random, 95% CI)	0.47 [0.25, 0.87]
2.7 Fluoxetine vs Lofepramine	1	183	Odds Ratio (M‐H, Random, 95% CI)	0.16 [0.02, 1.38]

Comparison 12. Subgroup analysis for fluoxetine versus TCAs: failure to complete ‐ side effects

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Comparison 13. Subgroup analysis for fluoxetine versus heterocyclics: endpoint score

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 follow‐up <6 weeks Show forest plot	2		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Maprotiline	2	181	Std. Mean Difference (IV, Random, 95% CI)	0.06 [‐0.34, 0.46]
2 follow‐up 6‐16 weeks Show forest plot	6		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only

2.1 Fluoxetine vs Maprotiline	3	252	Std. Mean Difference (IV, Random, 95% CI)	0.05 [‐0.20, 0.30]
2.2 Fluoxetine vs Mianserin	3	128	Std. Mean Difference (IV, Random, 95% CI)	0.43 [‐0.38, 1.23]

Comparison 13. Subgroup analysis for fluoxetine versus heterocyclics: endpoint score

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Comparison 14. Subgroup analysis for fluoxetine versus heterocyclics: failure to complete ‐ total

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 follow‐up <6 weeks Show forest plot	2		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Maprotiline	2	188	Odds Ratio (M‐H, Random, 95% CI)	1.54 [0.63, 3.75]
2 follow‐up 6‐16 weeks Show forest plot	4		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Fluoxetine vs Maprotiline	2	163	Odds Ratio (M‐H, Random, 95% CI)	2.06 [0.75, 5.63]
2.2 Fluoxetine vs Mianserin	2	93	Odds Ratio (M‐H, Random, 95% CI)	0.63 [0.18, 2.25]

Comparison 14. Subgroup analysis for fluoxetine versus heterocyclics: failure to complete ‐ total

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Comparison 15. Subgroup analysis for fluoxetine versus heterocyclics: failure to complete ‐ inefficacy

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 follow‐up <6 weeks Show forest plot	1		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Maprotiline	1	46	Odds Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2 follow‐up 6‐16 weeks Show forest plot	3		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Fluoxetine vs Maprotiline	2	163	Odds Ratio (M‐H, Random, 95% CI)	2.54 [0.33, 19.19]
2.2 Fluoxetine vs Mianserin	1	53	Odds Ratio (M‐H, Random, 95% CI)	2.27 [0.38, 13.63]

Comparison 15. Subgroup analysis for fluoxetine versus heterocyclics: failure to complete ‐ inefficacy

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Comparison 16. Subgroup analysis for fluoxetine versus heterocyclics: failure to complete ‐ side effects

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 follow‐up <6 weeks Show forest plot	1		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Maprotiline	1	46	Odds Ratio (M‐H, Random, 95% CI)	0.41 [0.07, 2.49]
2 follow‐up 6‐16 weeks Show forest plot	3		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Fluoxetine vs Maprotiline	2	163	Odds Ratio (M‐H, Random, 95% CI)	0.69 [0.11, 4.38]
2.2 Fluoxetine vs Mianserin	1	53	Odds Ratio (M‐H, Random, 95% CI)	1.05 [0.23, 4.70]

Comparison 16. Subgroup analysis for fluoxetine versus heterocyclics: failure to complete ‐ side effects

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Comparison 17. Subgroup analysis for fluoxetine versus other SSRIs: failure to respond

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 follow‐up <6 weeks Show forest plot	1		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Citalopram	1	59	Odds Ratio (M‐H, Random, 95% CI)	0.60 [0.20, 1.79]
2 follow‐up 6‐16 weeks Show forest plot	15		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Fluoxetine vs Fluvoxamine	1	177	Odds Ratio (M‐H, Random, 95% CI)	0.95 [0.52, 1.74]
2.2 Fluoxetine vs Paroxetine	9	1574	Odds Ratio (M‐H, Random, 95% CI)	1.23 [0.93, 1.65]
2.3 Fluoxetine vs Sertraline	5	950	Odds Ratio (M‐H, Random, 95% CI)	1.31 [1.00, 1.71]
2.4 Fluoxetine vs Escitalopram	1	240	Odds Ratio (M‐H, Random, 95% CI)	1.02 [0.56, 1.85]
3 follow‐up >16 weeks Show forest plot	1		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

3.1 Fluoxetine vs Sertraline	1	238	Odds Ratio (M‐H, Random, 95% CI)	1.67 [0.97, 2.85]

Comparison 17. Subgroup analysis for fluoxetine versus other SSRIs: failure to respond

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Comparison 18. Subgroup analysis for fluoxetine versus other SSRIs: endpoint score

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 follow‐up <6 weeks Show forest plot	1		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Citalopram	1	51	Std. Mean Difference (IV, Random, 95% CI)	0.07 [‐0.48, 0.61]
2 follow‐up >16 weeks Show forest plot	2		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only

2.1 Fluoxetine vs Paroxetine	1	242	Std. Mean Difference (IV, Random, 95% CI)	0.24 [‐0.01, 0.49]
2.2 Fluoxetine vs Sertraline	1	168	Std. Mean Difference (IV, Random, 95% CI)	0.22 [‐0.08, 0.53]
3 follow‐up 6‐16 weeks Show forest plot	18		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only

3.1 Fluoxetine vs Citalopram	2	610	Std. Mean Difference (IV, Random, 95% CI)	0.05 [‐0.10, 0.21]
3.2 Fluoxetine vs Paroxetine	10	1819	Std. Mean Difference (IV, Random, 95% CI)	‐0.03 [‐0.31, 0.24]
3.3 Fluoxetine vs Sertraline	6	992	Std. Mean Difference (IV, Random, 95% CI)	0.06 [‐0.06, 0.19]
3.4 Fluoxetine vs Escitalopram	1	231	Std. Mean Difference (IV, Random, 95% CI)	0.07 [‐0.19, 0.33]

Comparison 18. Subgroup analysis for fluoxetine versus other SSRIs: endpoint score

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Comparison 19. Subgroup analysis for fluoxetine versus other SSRIs: failure to complete ‐ total

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 follow‐up <6 weeks Show forest plot	1		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Citalopram	1	59	Odds Ratio (M‐H, Random, 95% CI)	0.96 [0.22, 4.27]
2 follow‐up 6‐16 weeks Show forest plot	21		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Fluoxetine vs Citalopram	2	673	Odds Ratio (M‐H, Random, 95% CI)	0.87 [0.59, 1.27]
2.2 Fluoxetine vs Fluvoxamine	2	284	Odds Ratio (M‐H, Random, 95% CI)	0.71 [0.36, 1.37]
2.3 Fluoxetine vs Paroxetine	9	1606	Odds Ratio (M‐H, Random, 95% CI)	1.00 [0.81, 1.25]
2.4 Fluoxetine vs Sertraline	7	1111	Odds Ratio (M‐H, Random, 95% CI)	1.12 [0.85, 1.48]
2.5 Fluoxetine vs Escitalopram	2	578	Odds Ratio (M‐H, Random, 95% CI)	1.53 [1.00, 2.37]
3 follow‐up >16 weeks Show forest plot	3		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

3.1 Fluoxetine vs Paroxetine	1	242	Odds Ratio (M‐H, Random, 95% CI)	0.89 [0.53, 1.49]
3.2 Fluoxetine vs Sertraline	2	480	Odds Ratio (M‐H, Random, 95% CI)	1.33 [0.84, 2.09]

Comparison 19. Subgroup analysis for fluoxetine versus other SSRIs: failure to complete ‐ total

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Comparison 20. Subgroup analysis for fluoxetine versus other SSRIs: failure to complete ‐ inefficacy

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 follow‐up <6 weeks Show forest plot	1		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Citalopram	1	59	Odds Ratio (M‐H, Random, 95% CI)	0.47 [0.04, 5.43]
2 follow‐up >16 weeks Show forest plot	1		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Fluoxetine vs Sertraline	1	238	Odds Ratio (M‐H, Random, 95% CI)	0.98 [0.47, 2.07]
3 follow‐up 6‐16 weeks Show forest plot	11		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

3.1 Fluoxetine vs Citalopram	2	673	Odds Ratio (M‐H, Random, 95% CI)	0.90 [0.49, 1.65]
3.2 Fluoxetine vs Paroxetine	4	1005	Odds Ratio (M‐H, Random, 95% CI)	0.75 [0.41, 1.39]
3.3 Fluoxetine vs Sertraline	4	818	Odds Ratio (M‐H, Random, 95% CI)	1.18 [0.61, 2.29]
3.4 Fluoxetine vs Escitalopram	2	578	Odds Ratio (M‐H, Random, 95% CI)	1.74 [0.46, 6.53]

Comparison 20. Subgroup analysis for fluoxetine versus other SSRIs: failure to complete ‐ inefficacy

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Comparison 21. Subgroup analysis for fluoxetine versus other SSRIs: failure to complete ‐ side effects

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 follow‐up <6 weeks Show forest plot	1		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Citalopram	1	59	Odds Ratio (M‐H, Random, 95% CI)	1.5 [0.23, 9.70]
2 follow‐up 6‐16 weeks Show forest plot	20		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Fluoxetine vs Citalopram	2	673	Odds Ratio (M‐H, Random, 95% CI)	0.57 [0.29, 1.12]
2.2 Fluoxetine vs Fluvoxamine	1	100	Odds Ratio (M‐H, Random, 95% CI)	1.04 [0.14, 7.71]
2.3 Fluoxetine vs Paroxetine	9	1509	Odds Ratio (M‐H, Random, 95% CI)	0.85 [0.62, 1.16]
2.4 Fluoxetine vs Sertraline	7	1111	Odds Ratio (M‐H, Random, 95% CI)	1.21 [0.85, 1.71]
2.5 Fluoxetina vs Escitalopram	2	578	Odds Ratio (M‐H, Random, 95% CI)	1.17 [0.64, 2.12]
3 follow‐up >16 weeks Show forest plot	2		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

3.1 Fluoxetine vs Sertraline	2	480	Odds Ratio (M‐H, Random, 95% CI)	1.41 [0.72, 2.76]

Comparison 21. Subgroup analysis for fluoxetine versus other SSRIs: failure to complete ‐ side effects

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Comparison 22. Subgroup analysis for fluoxetine versus MAOIs or newer ADs: failure to respond

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 follow‐up <6 weeks Show forest plot	1		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Moclobemide	1	70	Odds Ratio (M‐H, Random, 95% CI)	1.01 [0.39, 2.60]
2 follow‐up 6‐16 weeks Show forest plot	15		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Fluoxetine vs Agomelatine	1	515	Odds Ratio (M‐H, Random, 95% CI)	1.44 [0.99, 2.09]
2.2 Fluoxetine vs Mirtazapine	4	600	Odds Ratio (M‐H, Random, 95% CI)	1.46 [1.04, 2.04]
2.3 Fluoxetine vs Moclobemide	6	651	Odds Ratio (M‐H, Random, 95% CI)	1.31 [0.90, 1.89]
2.4 Fluoxetine vs Phenelzine	1	40	Odds Ratio (M‐H, Random, 95% CI)	1.42 [0.27, 7.34]
2.5 Fluoxetine vs Reboxetine	3	721	Odds Ratio (M‐H, Random, 95% CI)	0.77 [0.55, 1.10]

Comparison 22. Subgroup analysis for fluoxetine versus MAOIs or newer ADs: failure to respond

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Comparison 23. Subgroup analysis for fluoxetine versus MAOIs or newer ADs: endpoint score

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 follow‐up <6 weeks Show forest plot	1		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Moclobemide	1	53	Std. Mean Difference (IV, Random, 95% CI)	‐0.12 [‐0.66, 0.42]
2 follow‐up 6‐16 weeks Show forest plot	12		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only

2.1 Fluoxetine vs Agomelatine	3	1213	Std. Mean Difference (IV, Random, 95% CI)	0.02 [‐0.18, 0.23]
2.2 Fluoxetine vs Mirtazapine	1	31	Std. Mean Difference (IV, Random, 95% CI)	0.57 [‐0.15, 1.29]
2.3 Fluoxetine vs Moclobemide	5	487	Std. Mean Difference (IV, Random, 95% CI)	0.16 [‐0.02, 0.33]
2.4 Fluoxetine vs Phenelzine	1	40	Std. Mean Difference (IV, Random, 95% CI)	‐0.05 [‐0.67, 0.57]
2.5 Fluoxetine vs Reboxetine	2	205	Std. Mean Difference (IV, Random, 95% CI)	0.04 [‐0.31, 0.40]

Comparison 23. Subgroup analysis for fluoxetine versus MAOIs or newer ADs: endpoint score

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Comparison 24. Subgroup analysis for fluoxetine versus MAOIs or newer ADs: failure to complete ‐ total

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 follow‐up <6 weeks Show forest plot	1		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Moclobemide	1	70	Odds Ratio (M‐H, Random, 95% CI)	0.92 [0.31, 2.76]
2 follow‐up 6‐16 weeks Show forest plot	15		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Fluoxetina vs Agomelatine	2	785	Odds Ratio (M‐H, Random, 95% CI)	1.22 [0.59, 2.49]
2.2 Fluoxetine vs Mirtazapine	3	301	Odds Ratio (M‐H, Random, 95% CI)	0.92 [0.51, 1.68]
2.3 Fluoxetine vs Moclobemide	6	651	Odds Ratio (M‐H, Random, 95% CI)	1.02 [0.68, 1.53]
2.4 Fluoxetine vs Reboxetine	4	764	Odds Ratio (M‐H, Random, 95% CI)	0.60 [0.44, 0.83]

Comparison 24. Subgroup analysis for fluoxetine versus MAOIs or newer ADs: failure to complete ‐ total

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Comparison 25. Subgroup analysis for fluoxetine versus MAOIs or newer ADs: failure to complete ‐ inefficacy

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 follow‐up <6 weeks Show forest plot	1		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Moclobemide	1	70	Odds Ratio (M‐H, Random, 95% CI)	1.06 [0.20, 5.68]
2 follow‐up 6‐16 weeks Show forest plot	15		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Fluoxetine vs Agomelatine	2	785	Odds Ratio (M‐H, Random, 95% CI)	1.08 [0.41, 2.88]
2.2 Fluoxetine vs Mirtazapine	4	600	Odds Ratio (M‐H, Random, 95% CI)	1.45 [0.71, 2.96]
2.3 Fluoxetine vs Moclobemide	5	609	Odds Ratio (M‐H, Random, 95% CI)	0.61 [0.23, 1.65]
2.4 Fluoxetine vs Phenelzine	1	40	Odds Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2.5 Fluoxetine vs Reboxetine	3	464	Odds Ratio (M‐H, Random, 95% CI)	0.92 [0.47, 1.77]

Comparison 25. Subgroup analysis for fluoxetine versus MAOIs or newer ADs: failure to complete ‐ inefficacy

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Comparison 26. Subgroup analysis for fluoxetine versus MAOIs or newer ADs: failure to complete ‐ side effects

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 follow‐up <6 weeks Show forest plot	1		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Fluoxetine vs Moclobemide	1	70	Odds Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
2 follow‐up 6‐16 weeks Show forest plot	15		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Fluoxetine vs Agomelatine	2	785	Odds Ratio (M‐H, Random, 95% CI)	1.50 [0.73, 3.08]
2.2 Fluoxetine vs Mirtazapine	4	600	Odds Ratio (M‐H, Random, 95% CI)	0.95 [0.54, 1.66]
2.3 Fluoxetine vs Moclobemide	6	651	Odds Ratio (M‐H, Random, 95% CI)	1.04 [0.54, 2.01]
2.4 Fluoxetine vs Phenelzine	1	40	Odds Ratio (M‐H, Random, 95% CI)	0.32 [0.01, 8.26]
2.5 Fluoxetine vs Reboxetine	2	211	Odds Ratio (M‐H, Random, 95% CI)	0.40 [0.10, 1.61]

Comparison 26. Subgroup analysis for fluoxetine versus MAOIs or newer ADs: failure to complete ‐ side effects

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