Second‐generation antipsychotics for major depressive disorder and dysthymia

Katja Komossa; Anna M Depping; Andrea Gaudchau; Werner Kissling; Stefan Leucht

doi:10.1002/14651858.CD008121.pub2

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Figure 1

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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Figure 2

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Analysis 1.1

Comparison 1 Amisulpride versus antidepressants for major depression ‐ all data short‐term, Outcome 1 No clinically important response to treatment (as defined by original study).

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Analysis 1.2

Comparison 1 Amisulpride versus antidepressants for major depression ‐ all data short‐term, Outcome 2 Global state: no clinically important change ‐ CGI.

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Analysis 1.3

Comparison 1 Amisulpride versus antidepressants for major depression ‐ all data short‐term, Outcome 3 Mental state: 1a. Depressive symptoms ‐ no clinically important change ‐ MADRS.

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Analysis 1.4

Comparison 1 Amisulpride versus antidepressants for major depression ‐ all data short‐term, Outcome 4 Mental state: 1b. Depressive symptoms ‐ no clinically important change ‐ HAM‐D.

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Analysis 1.5

Comparison 1 Amisulpride versus antidepressants for major depression ‐ all data short‐term, Outcome 5 Mental state: 1c. Depressive symptoms ‐ MADRS score at endpoint.

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Analysis 1.6

Comparison 1 Amisulpride versus antidepressants for major depression ‐ all data short‐term, Outcome 6 Mental state: 1d. Depressive symptoms ‐ HAM‐D score at endpoint.

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Analysis 1.7

Comparison 1 Amisulpride versus antidepressants for major depression ‐ all data short‐term, Outcome 7 Leaving the study early.

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Analysis 1.8

Comparison 1 Amisulpride versus antidepressants for major depression ‐ all data short‐term, Outcome 8 Adverse effects: 1. At least one adverse effect.

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Analysis 2.1

Comparison 2 Aripiprazole added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 1 No clinically important response (as defined by original study).

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Analysis 2.2

Comparison 2 Aripiprazole added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 2 Global state: no clinically important change ‐ CGI.

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Analysis 2.3

Comparison 2 Aripiprazole added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 3 Remission ‐ number of people without remission ‐ as defined by the original study.

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Analysis 2.4

Comparison 2 Aripiprazole added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 4 Mental state: 1a. Depressive symptoms ‐ MADRS score at endpoint.

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Analysis 2.5

Comparison 2 Aripiprazole added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 5 Leaving the study early.

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Analysis 2.6

Comparison 2 Aripiprazole added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 6 Adverse effects: 1. At least one adverse effect.

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Analysis 2.7

Comparison 2 Aripiprazole added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 7 Adverse effects: 2. Death.

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Analysis 2.8

Comparison 2 Aripiprazole added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 8 Adverse effects: 3a. Extrapyramidal effects.

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Analysis 2.9

Comparison 2 Aripiprazole added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 9 Adverse effects: 4a. Significant weight gain.

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Analysis 2.10

Comparison 2 Aripiprazole added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 10 Adverse effects: 4b. Weight ‐ change from baseline in kg.

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Analysis 2.11

Comparison 2 Aripiprazole added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 11 Adverse effects: 5. Sedation.

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Analysis 3.1

Comparison 3 Olanzapine versus placebo for psychotic depression ‐ all data short‐term, Outcome 1 No clinically important response to treatment (as defined by original study).

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Analysis 3.2

Comparison 3 Olanzapine versus placebo for psychotic depression ‐ all data short‐term, Outcome 2 Remission ‐ number of participants without remission ‐ as defined by the original study.

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Analysis 3.3

Comparison 3 Olanzapine versus placebo for psychotic depression ‐ all data short‐term, Outcome 3 Mental state: 1. Depressive symptoms ‐ HAM‐D score at endpoint.

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Analysis 3.4

Comparison 3 Olanzapine versus placebo for psychotic depression ‐ all data short‐term, Outcome 4 Mental state: 2. Anxiety symptoms ‐ HAM‐A score at endpoint.

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Analysis 3.5

Comparison 3 Olanzapine versus placebo for psychotic depression ‐ all data short‐term, Outcome 5 Leaving the study early.

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Analysis 3.6

Comparison 3 Olanzapine versus placebo for psychotic depression ‐ all data short‐term, Outcome 6 Adverse effects: 1. At least one adverse effect.

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Analysis 3.7

Comparison 3 Olanzapine versus placebo for psychotic depression ‐ all data short‐term, Outcome 7 Adverse effects: 2. Prolactin increase ‐ number of participants with significant increase ‐ as defined by the original study.

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Analysis 3.8

Comparison 3 Olanzapine versus placebo for psychotic depression ‐ all data short‐term, Outcome 8 Adverse effects: 3a. Significant weight gain ‐ spontaneously reported.

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Analysis 3.9

Comparison 3 Olanzapine versus placebo for psychotic depression ‐ all data short‐term, Outcome 9 Adverse effects: 3b. Weight ‐ change from baseline in kg.

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Analysis 3.10

Comparison 3 Olanzapine versus placebo for psychotic depression ‐ all data short‐term, Outcome 10 Adverse effects: 4. Sedation.

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Analysis 4.1

Comparison 4 Olanzapine versus antidepressants for major depression ‐ all data short‐term, Outcome 1 No clinically important response to treatment (as defined by original study).

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Analysis 4.2

Comparison 4 Olanzapine versus antidepressants for major depression ‐ all data short‐term, Outcome 2 Remission ‐ number of participants without remission ‐ as defined by the original study.

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Analysis 4.3

Comparison 4 Olanzapine versus antidepressants for major depression ‐ all data short‐term, Outcome 3 Mental state: 1a. Depressive symptoms ‐ no clinically important change ‐ at least 50% MADRS reduction.

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Analysis 4.4

Comparison 4 Olanzapine versus antidepressants for major depression ‐ all data short‐term, Outcome 4 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint.

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Analysis 4.5

Comparison 4 Olanzapine versus antidepressants for major depression ‐ all data short‐term, Outcome 5 Mental state: 1c. Depressive symptoms ‐ HAM‐D score at endpoint.

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Analysis 4.6

Comparison 4 Olanzapine versus antidepressants for major depression ‐ all data short‐term, Outcome 6 Mental state: 2. Anxiety symptoms ‐ HAM‐A score at endpoint.

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Analysis 4.7

Comparison 4 Olanzapine versus antidepressants for major depression ‐ all data short‐term, Outcome 7 Leaving the study early.

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Analysis 4.8

Comparison 4 Olanzapine versus antidepressants for major depression ‐ all data short‐term, Outcome 8 Adverse effects: 1. At least one adverse effect.

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Analysis 4.9

Comparison 4 Olanzapine versus antidepressants for major depression ‐ all data short‐term, Outcome 9 Adverse effects: 2. Death ‐ natural cause.

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Analysis 4.10

Comparison 4 Olanzapine versus antidepressants for major depression ‐ all data short‐term, Outcome 10 Adverse effects: 3. Extrapyramidal effects ‐ tremor.

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Analysis 4.11

Comparison 4 Olanzapine versus antidepressants for major depression ‐ all data short‐term, Outcome 11 Adverse effects: 4. Prolactin ‐ change from baseline in ng/ml.

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Analysis 4.12

Comparison 4 Olanzapine versus antidepressants for major depression ‐ all data short‐term, Outcome 12 Adverse effects: 5a. Significant weight gain.

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Analysis 4.13

Comparison 4 Olanzapine versus antidepressants for major depression ‐ all data short‐term, Outcome 13 Adverse effects: 5b. Weight ‐ change from baseline in kg.

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Analysis 4.14

Comparison 4 Olanzapine versus antidepressants for major depression ‐ all data short‐term, Outcome 14 Adverse effects: 6. Sedation.

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Analysis 5.1

Comparison 5 Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 1 No clinically important response ‐ as defined by original study.

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Analysis 5.2

Comparison 5 Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 2 Remission ‐ number of people without remission ‐ as defined by the original study.

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Analysis 5.3

Comparison 5 Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 3 Mental state: 1a. No clinically important change ‐ at least 50% MADRS total score reduction.

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Analysis 5.4

Comparison 5 Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 4 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint.

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Analysis 5.5

Comparison 5 Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 5 Mental state: 1c. Depressive symptoms ‐ HAM‐D score at endpoint.

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Analysis 5.6

Comparison 5 Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 6 Mental state: 2. Anxiety symptoms ‐ HAM‐A score at endpoint.

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Analysis 5.7

Comparison 5 Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 7 Leaving the study early.

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Analysis 5.8

Comparison 5 Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 8 Adverse effects: 1. At least one adverse effect.

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Analysis 5.9

Comparison 5 Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 9 Adverse effects: 2. Death.

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Analysis 5.10

Comparison 5 Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 10 Adverse effects: 3. Extrapyramidal effects ‐ tremor.

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Analysis 5.11

Comparison 5 Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 11 Adverse effects: 4. Prolactin ‐ change from baseline in ng/ml.

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Analysis 5.12

Comparison 5 Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 12 Adverse effects: 5a. Significant weight gain.

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Analysis 5.13

Comparison 5 Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 13 Adverse effects: 5b. Weight ‐ change from baseline in kg.

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Analysis 5.14

Comparison 5 Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 14 Adverse effects: 6. Sedation.

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Analysis 6.1

Comparison 6 Quetiapine versus placebo for major depression, Outcome 1 Non‐response to treatment ‐ as defined by the original study.

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Analysis 6.2

Comparison 6 Quetiapine versus placebo for major depression, Outcome 2 Global state: no clinically important change ‐ CGI.

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Analysis 6.3

Comparison 6 Quetiapine versus placebo for major depression, Outcome 3 Remission ‐ number of participants without remission ‐ as defined by the original study.

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Analysis 6.4

Comparison 6 Quetiapine versus placebo for major depression, Outcome 4 Relapse.

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Analysis 6.5

Comparison 6 Quetiapine versus placebo for major depression, Outcome 5 Mental state: 1a. Depressive symptoms ‐ no clinically important change‐ MADRS.

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Analysis 6.6

Comparison 6 Quetiapine versus placebo for major depression, Outcome 6 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint.

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Analysis 6.7

Comparison 6 Quetiapine versus placebo for major depression, Outcome 7 Mental state: 1c. Depressive symptoms ‐ HAM‐D score at endpoint.

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Analysis 6.8

Comparison 6 Quetiapine versus placebo for major depression, Outcome 8 Mental state: 2. Anxiety symptoms ‐ HAM‐A score at endpoint.

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Analysis 6.9

Comparison 6 Quetiapine versus placebo for major depression, Outcome 9 Leaving the study early ‐ due to adverse events.

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Analysis 6.10

Comparison 6 Quetiapine versus placebo for major depression, Outcome 10 Adverse effects: 1. Death ‐ suicidal thoughts ‐ MADRS item 10 of at least 4.

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Analysis 6.11

Comparison 6 Quetiapine versus placebo for major depression, Outcome 11 Adverse effects: 2. Extrapyramidal effects ‐ general EPS.

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Analysis 6.12

Comparison 6 Quetiapine versus placebo for major depression, Outcome 12 Adverse effects: 3. Prolactin ‐ change from baseline in ng/ml.

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Analysis 6.13

Comparison 6 Quetiapine versus placebo for major depression, Outcome 13 Adverse effects: 4a. Significant weight gain.

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Analysis 6.14

Comparison 6 Quetiapine versus placebo for major depression, Outcome 14 Adverse effects: 4b. Weight ‐ change from baseline in kg.

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Analysis 6.15

Comparison 6 Quetiapine versus placebo for major depression, Outcome 15 Adverse effects: 5. Sedation.

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Analysis 7.1

Comparison 7 Quetiapine versus antidepressants for major depression ‐ all data short‐term, Outcome 1 No clinically important response to treatment (as defined by original study).

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Analysis 7.2

Comparison 7 Quetiapine versus antidepressants for major depression ‐ all data short‐term, Outcome 2 Global state: no clinically important change ‐ CGI.

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Analysis 7.3

Comparison 7 Quetiapine versus antidepressants for major depression ‐ all data short‐term, Outcome 3 Remission ‐ number of participants without remission.

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Analysis 7.4

Comparison 7 Quetiapine versus antidepressants for major depression ‐ all data short‐term, Outcome 4 Mental state: 1a. No clinically important change‐ MADRS.

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Analysis 7.5

Comparison 7 Quetiapine versus antidepressants for major depression ‐ all data short‐term, Outcome 5 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint.

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Analysis 7.6

Comparison 7 Quetiapine versus antidepressants for major depression ‐ all data short‐term, Outcome 6 Mental state: 1c. Depressive symptoms ‐ HAM‐D score at endpoint.

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Analysis 7.7

Comparison 7 Quetiapine versus antidepressants for major depression ‐ all data short‐term, Outcome 7 Mental state: 2. Anxiety symptoms ‐ HAM‐A score at endpoint.

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Analysis 7.8

Comparison 7 Quetiapine versus antidepressants for major depression ‐ all data short‐term, Outcome 8 Leaving the study early ‐ due to adverse events.

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Analysis 7.9

Comparison 7 Quetiapine versus antidepressants for major depression ‐ all data short‐term, Outcome 9 Adverse effects: 1. Extrapyramidal effects ‐ general EPS.

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Analysis 7.10

Comparison 7 Quetiapine versus antidepressants for major depression ‐ all data short‐term, Outcome 10 Adverse effects: 2. Prolactin ‐ change from baseline in ng/ml.

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Analysis 7.11

Comparison 7 Quetiapine versus antidepressants for major depression ‐ all data short‐term, Outcome 11 Adverse effects: 3a. Significant weight gain ‐ ≥7% from baseline.

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Analysis 7.12

Comparison 7 Quetiapine versus antidepressants for major depression ‐ all data short‐term, Outcome 12 Adverse effects: 3b. Weight ‐ change from baseline in ng/ml.

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Analysis 7.13

Comparison 7 Quetiapine versus antidepressants for major depression ‐ all data short‐term, Outcome 13 Adverse effects: 4. Sedation.

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Analysis 8.1

Comparison 8 Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 1 No clinically important response (as defined by original study).

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Analysis 8.2

Comparison 8 Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 2 Global state: no clinically important change ‐ CGI.

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Analysis 8.3

Comparison 8 Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 3 Remission ‐ number of people without remission ‐ as defined by the original study.

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Analysis 8.4

Comparison 8 Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 4 Mental state: 1a. Depressive symptoms ‐ no clinically important change ‐ MADRS.

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Analysis 8.5

Comparison 8 Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 5 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint.

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Analysis 8.6

Comparison 8 Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 6 Mental state: 1c. Depressive symptoms ‐ no clinically important change ‐ HAM‐D.

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Analysis 8.7

Comparison 8 Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 7 Mental state: 1d. Depressive symptoms ‐ HAM‐D score at endpoint.

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Analysis 8.8

Comparison 8 Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 8 Mental state: 2a. Anxiety symptoms ‐ no clinically important change ‐ HAM‐A.

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Analysis 8.9

Comparison 8 Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 9 Mental state: 2b. Anxiety symptoms ‐ HAM‐A score at endpoint.

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Analysis 8.10

Comparison 8 Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 10 Leaving the study early.

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Analysis 8.11

Comparison 8 Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 11 Adverse effects: 1. Extrapyramidal symptoms.

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Analysis 8.12

Comparison 8 Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 12 Adverse effects: 2. Prolactin ‐ change from baseline in ng/ml.

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Analysis 8.13

Comparison 8 Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 13 Adverse effects: 3a. Significant weight gain.

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Analysis 8.14

Comparison 8 Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 14 Adverse effects: 3b. Weight ‐ change from baseline in kg.

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Analysis 8.15

Comparison 8 Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 15 Adverse effects: 4. Sedation.

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Analysis 9.1

Comparison 9 Risperidone added to antidepressants versus placebo added to antidepressants for major depression, Outcome 1 No clinically important response (as defined by original study).

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Analysis 9.2

Comparison 9 Risperidone added to antidepressants versus placebo added to antidepressants for major depression, Outcome 2 Remission ‐ number of participants without remission ‐ as defined by the original study.

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Analysis 9.3

Comparison 9 Risperidone added to antidepressants versus placebo added to antidepressants for major depression, Outcome 3 Relapse (as defined by the original study).

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Analysis 9.4

Comparison 9 Risperidone added to antidepressants versus placebo added to antidepressants for major depression, Outcome 4 Mental state: 1a. Depressive symptoms ‐ MADRS score at endpoint.

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Analysis 9.5

Comparison 9 Risperidone added to antidepressants versus placebo added to antidepressants for major depression, Outcome 5 Mental state: 1b. Depressive symptoms ‐ no clinically important change ‐ HAM‐D.

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Analysis 9.6

Comparison 9 Risperidone added to antidepressants versus placebo added to antidepressants for major depression, Outcome 6 Mental state: 1c. Depressive symptoms ‐ HAM‐D score at endpoint.

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Analysis 9.7

Comparison 9 Risperidone added to antidepressants versus placebo added to antidepressants for major depression, Outcome 7 Leaving the study early.

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Analysis 9.8

Comparison 9 Risperidone added to antidepressants versus placebo added to antidepressants for major depression, Outcome 8 Adverse effects: 1. At least one adverse effect.

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Analysis 9.9

Comparison 9 Risperidone added to antidepressants versus placebo added to antidepressants for major depression, Outcome 9 Adverse effects: 2a. Extrapyramidal effects ‐ tremor.

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Analysis 9.10

Comparison 9 Risperidone added to antidepressants versus placebo added to antidepressants for major depression, Outcome 10 Adverse effects: 3a. Prolactin increase ‐ associated effects.

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Analysis 9.11

Comparison 9 Risperidone added to antidepressants versus placebo added to antidepressants for major depression, Outcome 11 Adverse effects: 3b. Prolactin ‐ change from baseline in ng/ml ‐ endpoint.

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Analysis 9.12

Comparison 9 Risperidone added to antidepressants versus placebo added to antidepressants for major depression, Outcome 12 Adverse effects: 4a. Significant weight gain.

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Analysis 9.13

Comparison 9 Risperidone added to antidepressants versus placebo added to antidepressants for major depression, Outcome 13 Adverse effects: 4b. Weight ‐ change from baseline in kg.

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Analysis 9.14

Comparison 9 Risperidone added to antidepressants versus placebo added to antidepressants for major depression, Outcome 14 Adverse effects: 5. Sedation.

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Analysis 10.1

Comparison 10 Amisulpride versus placebo for dysthymia, Outcome 1 No clinically important response (as defined by original study).

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Analysis 10.2

Comparison 10 Amisulpride versus placebo for dysthymia, Outcome 2 Global state: no clinically important change ‐ CGI.

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Analysis 10.3

Comparison 10 Amisulpride versus placebo for dysthymia, Outcome 3 Mental state: 1a. Depressive symptoms ‐ no clinically important change‐ MADRS < 7.

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Analysis 10.4

Comparison 10 Amisulpride versus placebo for dysthymia, Outcome 4 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint.

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Analysis 10.5

Comparison 10 Amisulpride versus placebo for dysthymia, Outcome 5 Mental state: 1c. Depressive symptoms ‐ HAM‐D score at endpoint.

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Analysis 10.6

Comparison 10 Amisulpride versus placebo for dysthymia, Outcome 6 Leaving the study early.

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Analysis 10.7

Comparison 10 Amisulpride versus placebo for dysthymia, Outcome 7 Adverse effects: 1. At least one adverse effect.

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Analysis 10.8

Comparison 10 Amisulpride versus placebo for dysthymia, Outcome 8 Adverse effects: 2. Extrapyramidal effects.

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Analysis 10.9

Comparison 10 Amisulpride versus placebo for dysthymia, Outcome 9 Adverse effects: 3. Prolactin associated effects.

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Analysis 10.10

Comparison 10 Amisulpride versus placebo for dysthymia, Outcome 10 Adverse effects: 4. Significant weight gain ‐ spontaneously reported.

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Analysis 11.1

Comparison 11 Amisulpride versus antidepressants for dysthymia, Outcome 1 No clinically important response ‐ as defined by original study.

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Analysis 11.2

Comparison 11 Amisulpride versus antidepressants for dysthymia, Outcome 2 Global state: no clinically important change ‐ CGI.

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Analysis 11.3

Comparison 11 Amisulpride versus antidepressants for dysthymia, Outcome 3 Service use ‐ number of patients rehospitalised.

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Analysis 11.4

Comparison 11 Amisulpride versus antidepressants for dysthymia, Outcome 4 Mental state: 1a. Depressive symptoms ‐ MADRS ‐ score at endpoint.

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Analysis 11.5

Comparison 11 Amisulpride versus antidepressants for dysthymia, Outcome 5 Mental state: 1b. No clinically important change ‐ at least 50% HAM‐D reduction.

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Analysis 11.6

Comparison 11 Amisulpride versus antidepressants for dysthymia, Outcome 6 Mental state: 1c. No clinically important change ‐ at least 25% HAM‐D reduction.

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Analysis 11.7

Comparison 11 Amisulpride versus antidepressants for dysthymia, Outcome 7 Mental state: 1d. Depressive symptoms ‐ HAM‐D score at endpoint.

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Analysis 11.8

Comparison 11 Amisulpride versus antidepressants for dysthymia, Outcome 8 Mental state: 2. Anxiety symptoms‐ HAM‐A score at endpoint.

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Analysis 11.9

Comparison 11 Amisulpride versus antidepressants for dysthymia, Outcome 9 Leaving the study early.

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Analysis 11.10

Comparison 11 Amisulpride versus antidepressants for dysthymia, Outcome 10 Adverse effects: 1. At least one adverse effect.

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Analysis 11.11

Comparison 11 Amisulpride versus antidepressants for dysthymia, Outcome 11 Adverse effects: 2.Death ‐ suicide attempt.

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Analysis 11.12

Comparison 11 Amisulpride versus antidepressants for dysthymia, Outcome 12 Adverse effects: 3. Extrapyramidal effects.

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Analysis 11.13

Comparison 11 Amisulpride versus antidepressants for dysthymia, Outcome 13 Adverse effects: 4. Significant weight gain.

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Analysis 11.14

Comparison 11 Amisulpride versus antidepressants for dysthymia, Outcome 14 Adverse effects: 5. Prolactin associated effects ‐ amenorrhoea.

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Analysis 11.15

Comparison 11 Amisulpride versus antidepressants for dysthymia, Outcome 15 Adverse effects: 6. Sedation.

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Analysis 12.1

Comparison 12 Sensitivity analysis ‐ imputed statistics excluded ‐ 3. Quetiapine versus placebo for major depression, Outcome 1 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint.

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Analysis 12.2

Comparison 12 Sensitivity analysis ‐ imputed statistics excluded ‐ 3. Quetiapine versus placebo for major depression, Outcome 2 Mental state: 1c. Depressive symptoms ‐ HAM‐D score at endpoint.

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Analysis 12.3

Comparison 12 Sensitivity analysis ‐ imputed statistics excluded ‐ 3. Quetiapine versus placebo for major depression, Outcome 3 Mental state: 2. Anxiety symptoms ‐ HAM‐A score at endpoint.

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Analysis 13.1

Comparison 13 Sensitivity analysis ‐ imputed statistics excluded ‐ 4. Amisulpride versus antidepressants for dysthymia, Outcome 1 Mental state: 1a. Depressive symptoms ‐ MADRS ‐ score at endpoint.

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Analysis 14.1

Comparison 14 Sensitivity analysis ‐ imputed statistics excluded ‐ 6. Olanzapine versus antidepressants for major depression ‐ all data short‐term, Outcome 1 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint.

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Analysis 14.2

Comparison 14 Sensitivity analysis ‐ imputed statistics excluded ‐ 6. Olanzapine versus antidepressants for major depression ‐ all data short‐term, Outcome 2 Mental state: 2. Anxiety symptoms ‐ HAM‐A score at endpoint.

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Analysis 14.3

Comparison 14 Sensitivity analysis ‐ imputed statistics excluded ‐ 6. Olanzapine versus antidepressants for major depression ‐ all data short‐term, Outcome 3 Adverse effects: 4. Prolactin ‐ change from baseline in ng/ml.

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Analysis 15.1

Comparison 15 Sensitivity analysis ‐ imputed statistics excluded ‐ 9. Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 1 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint.

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Analysis 15.2

Comparison 15 Sensitivity analysis ‐ imputed statistics excluded ‐ 9. Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 2 Mental state: 2. Anxiety symptoms ‐ HAM‐A score at endpoint.

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Analysis 15.3

Comparison 15 Sensitivity analysis ‐ imputed statistics excluded ‐ 9. Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 3 Adverse effects: 4. Prolactin ‐ change from baseline in ng/ml.

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Analysis 16.1

Comparison 16 Sensitivity analysis ‐ imputed statistics excluded ‐ 10. Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 1 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint.

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Analysis 16.2

Comparison 16 Sensitivity analysis ‐ imputed statistics excluded ‐ 10. Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 2 Mental state: 1d. Depressive symptoms‐ HAM‐D score at endpoint.

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Analysis 16.3

Comparison 16 Sensitivity analysis ‐ imputed statistics excluded ‐ 10. Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 3 Mental state: 2b. Anxiety symptoms ‐ HAM‐A score at endpoint.

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Analysis 16.4

Comparison 16 Sensitivity analysis ‐ imputed statistics excluded ‐ 10. Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term, Outcome 4 Adverse effects: 3b. Weight ‐ change from baseline in kg.

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Analysis 17.1

Comparison 17 Sensitivity analysis ‐ imputed statistics excluded ‐ 11. Risperidone added to antidepressants versus placebo added to antidepressants for major depression, Outcome 1 Mental state: 1c. Depressive symptoms ‐ HAM‐D score at endpoint.

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Comparison 1. Amisulpride versus antidepressants for major depression ‐ all data short‐term

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 No clinically important response to treatment (as defined by original study) Show forest plot	1	277	Odds Ratio (M‐H, Random, 95% CI)	1.55 [0.87, 2.76]

2 Global state: no clinically important change ‐ CGI Show forest plot	1	277	Odds Ratio (M‐H, Random, 95% CI)	1.17 [0.63, 2.17]

3 Mental state: 1a. Depressive symptoms ‐ no clinically important change ‐ MADRS Show forest plot	1	277	Odds Ratio (M‐H, Random, 95% CI)	1.20 [0.67, 2.15]

4 Mental state: 1b. Depressive symptoms ‐ no clinically important change ‐ HAM‐D Show forest plot	1	277	Odds Ratio (M‐H, Random, 95% CI)	1.55 [0.87, 2.76]

5 Mental state: 1c. Depressive symptoms ‐ MADRS score at endpoint Show forest plot	1	272	Mean Difference (IV, Random, 95% CI)	1.20 [‐0.78, 3.18]

6 Mental state: 1d. Depressive symptoms ‐ HAM‐D score at endpoint Show forest plot	1	272	Mean Difference (IV, Random, 95% CI)	0.90 [‐0.69, 2.49]

7 Leaving the study early Show forest plot	1		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

7.1 due to any reason	1	277	Odds Ratio (M‐H, Random, 95% CI)	1.14 [0.57, 2.26]
7.2 due to adverse events	1	277	Odds Ratio (M‐H, Random, 95% CI)	0.83 [0.25, 2.80]
7.3 due to inefficacy	1	277	Odds Ratio (M‐H, Random, 95% CI)	1.01 [0.29, 3.56]
8 Adverse effects: 1. At least one adverse effect Show forest plot	1	277	Odds Ratio (M‐H, Random, 95% CI)	0.67 [0.40, 1.12]

Comparison 1. Amisulpride versus antidepressants for major depression ‐ all data short‐term

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Comparison 2. Aripiprazole added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 No clinically important response (as defined by original study) Show forest plot	3	1092	Odds Ratio (M‐H, Random, 95% CI)	0.48 [0.37, 0.63]

2 Global state: no clinically important change ‐ CGI Show forest plot	1	362	Odds Ratio (M‐H, Random, 95% CI)	0.51 [0.34, 0.78]

3 Remission ‐ number of people without remission ‐ as defined by the original study Show forest plot	3	1092	Odds Ratio (M‐H, Random, 95% CI)	0.48 [0.36, 0.64]

4 Mental state: 1a. Depressive symptoms ‐ MADRS score at endpoint Show forest plot	3	1077	Mean Difference (IV, Random, 95% CI)	‐3.04 [‐4.09, 0.00]

5 Leaving the study early Show forest plot	3		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

5.1 due to any reason	3	1092	Odds Ratio (M‐H, Random, 95% CI)	1.21 [0.86, 1.71]
5.2 due to adverse events	3	1092	Odds Ratio (M‐H, Random, 95% CI)	2.59 [1.18, 5.71]
5.3 due to inefficacy	3	1092	Odds Ratio (M‐H, Random, 95% CI)	0.98 [0.36, 2.66]
6 Adverse effects: 1. At least one adverse effect Show forest plot	2	743	Odds Ratio (M‐H, Random, 95% CI)	2.53 [1.81, 3.52]

7 Adverse effects: 2. Death Show forest plot	3		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

7.1 due to natural causes	2	711	Odds Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.2 due to suicide	1	349	Odds Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.3 suicide attempt	1	362	Odds Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
7.4 suicidal ideation	2	711	Odds Ratio (M‐H, Random, 95% CI)	0.24 [0.03, 2.23]
8 Adverse effects: 3a. Extrapyramidal effects Show forest plot	3		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

8.1 EPS in general	1	362	Odds Ratio (M‐H, Random, 95% CI)	3.53 [1.95, 6.41]
8.2 akathisia	3	1092	Odds Ratio (M‐H, Random, 95% CI)	6.77 [4.22, 10.84]
8.3 tremor	1	381	Odds Ratio (M‐H, Random, 95% CI)	2.48 [0.86, 7.18]
9 Adverse effects: 4a. Significant weight gain Show forest plot	3	1092	Odds Ratio (M‐H, Random, 95% CI)	5.93 [2.15, 16.36]

10 Adverse effects: 4b. Weight ‐ change from baseline in kg Show forest plot	3	1087	Mean Difference (IV, Random, 95% CI)	1.07 [0.30, 1.84]

11 Adverse effects: 5. Sedation Show forest plot	2	711	Odds Ratio (M‐H, Random, 95% CI)	3.42 [0.66, 17.81]

Comparison 2. Aripiprazole added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term

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Comparison 3. Olanzapine versus placebo for psychotic depression ‐ all data short‐term

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 No clinically important response to treatment (as defined by original study) Show forest plot	2	201	Odds Ratio (M‐H, Random, 95% CI)	0.84 [0.46, 1.54]

2 Remission ‐ number of participants without remission ‐ as defined by the original study Show forest plot	2	200	Odds Ratio (M‐H, Fixed, 95% CI)	0.84 [0.35, 2.05]

3 Mental state: 1. Depressive symptoms ‐ HAM‐D score at endpoint Show forest plot	2	184	Mean Difference (IV, Random, 95% CI)	‐2.86 [‐6.19, 0.47]

4 Mental state: 2. Anxiety symptoms ‐ HAM‐A score at endpoint Show forest plot	2	184	Mean Difference (IV, Random, 95% CI)	‐1.38 [‐3.46, 0.69]

5 Leaving the study early Show forest plot	2		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

5.1 due to any reason	2	201	Odds Ratio (M‐H, Random, 95% CI)	0.87 [0.50, 1.52]
5.2 due to adverse events	2	201	Odds Ratio (M‐H, Random, 95% CI)	1.67 [0.30, 9.34]
5.3 due to inefficacy	2	201	Odds Ratio (M‐H, Random, 95% CI)	0.39 [0.18, 0.86]
6 Adverse effects: 1. At least one adverse effect Show forest plot	1	201	Odds Ratio (M‐H, Random, 95% CI)	0.89 [0.45, 1.79]

7 Adverse effects: 2. Prolactin increase ‐ number of participants with significant increase ‐ as defined by the original study Show forest plot	1	201	Odds Ratio (M‐H, Random, 95% CI)	6.59 [2.41, 17.97]

8 Adverse effects: 3a. Significant weight gain ‐ spontaneously reported Show forest plot	1	201	Odds Ratio (M‐H, Random, 95% CI)	5.99 [1.29, 27.76]

9 Adverse effects: 3b. Weight ‐ change from baseline in kg Show forest plot	1	201	Mean Difference (IV, Random, 95% CI)	3.4 [1.40, 5.40]

10 Adverse effects: 4. Sedation Show forest plot	1	201	Odds Ratio (M‐H, Random, 95% CI)	4.40 [1.57, 12.31]

Comparison 3. Olanzapine versus placebo for psychotic depression ‐ all data short‐term

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Comparison 4. Olanzapine versus antidepressants for major depression ‐ all data short‐term

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 No clinically important response to treatment (as defined by original study) Show forest plot	5	749	Odds Ratio (M‐H, Random, 95% CI)	1.59 [0.98, 2.58]

2 Remission ‐ number of participants without remission ‐ as defined by the original study Show forest plot	4	766	Odds Ratio (M‐H, Random, 95% CI)	1.35 [0.89, 2.03]

3 Mental state: 1a. Depressive symptoms ‐ no clinically important change ‐ at least 50% MADRS reduction Show forest plot	2	302	Odds Ratio (M‐H, Fixed, 95% CI)	1.18 [0.69, 2.00]

4 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint Show forest plot	5	747	Mean Difference (IV, Random, 95% CI)	0.56 [‐1.15, 2.27]

5 Mental state: 1c. Depressive symptoms ‐ HAM‐D score at endpoint Show forest plot	1	13	Mean Difference (IV, Random, 95% CI)	‐2.10 [‐11.18, 6.98]

6 Mental state: 2. Anxiety symptoms ‐ HAM‐A score at endpoint Show forest plot	4	734	Mean Difference (IV, Random, 95% CI)	0.39 [‐0.63, 1.42]

7 Leaving the study early Show forest plot	4		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

7.1 due to any reason	4	748	Odds Ratio (M‐H, Random, 95% CI)	1.12 [0.80, 1.57]
7.2 due to adverse events	3	735	Odds Ratio (M‐H, Random, 95% CI)	3.03 [1.55, 5.91]
7.3 due to inefficacy	3	735	Odds Ratio (M‐H, Random, 95% CI)	1.03 [0.57, 1.88]
8 Adverse effects: 1. At least one adverse effect Show forest plot	1	283	Odds Ratio (M‐H, Random, 95% CI)	1.10 [0.57, 2.14]

9 Adverse effects: 2. Death ‐ natural cause Show forest plot	2	355	Odds Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]

10 Adverse effects: 3. Extrapyramidal effects ‐ tremor Show forest plot	2	516	Odds Ratio (M‐H, Random, 95% CI)	1.05 [0.49, 2.23]

11 Adverse effects: 4. Prolactin ‐ change from baseline in ng/ml Show forest plot	2	584	Mean Difference (IV, Random, 95% CI)	4.46 [2.17, 6.75]

12 Adverse effects: 5a. Significant weight gain Show forest plot	2	434	Odds Ratio (M‐H, Random, 95% CI)	4.58 [1.84, 11.37]

12.1 ≥ 10% weight gain from baseline	1	283	Odds Ratio (M‐H, Random, 95% CI)	13.09 [0.73, 234.67]
12.2 spontaneously reported	1	151	Odds Ratio (M‐H, Random, 95% CI)	4.07 [1.56, 10.63]
13 Adverse effects: 5b. Weight ‐ change from baseline in kg Show forest plot	2	296	Mean Difference (IV, Random, 95% CI)	4.07 [2.71, 5.44]

14 Adverse effects: 6. Sedation Show forest plot	1	151	Odds Ratio (M‐H, Random, 95% CI)	2.53 [0.92, 6.94]

Comparison 4. Olanzapine versus antidepressants for major depression ‐ all data short‐term

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Comparison 5. Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 No clinically important response ‐ as defined by original study Show forest plot	5	808	Odds Ratio (M‐H, Random, 95% CI)	0.70 [0.48, 1.02]

2 Remission ‐ number of people without remission ‐ as defined by the original study Show forest plot	4	793	Odds Ratio (M‐H, Random, 95% CI)	0.60 [0.39, 0.92]

3 Mental state: 1a. No clinically important change ‐ at least 50% MADRS total score reduction Show forest plot	4	793	Odds Ratio (M‐H, Random, 95% CI)	0.73 [0.51, 1.04]

4 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint Show forest plot	5	808	Mean Difference (IV, Random, 95% CI)	‐2.84 [‐5.48, ‐0.20]

5 Mental state: 1c. Depressive symptoms ‐ HAM‐D score at endpoint Show forest plot	1	15	Mean Difference (IV, Random, 95% CI)	‐7.90 [‐16.63, 0.83]

6 Mental state: 2. Anxiety symptoms ‐ HAM‐A score at endpoint Show forest plot	4	793	Mean Difference (IV, Random, 95% CI)	‐1.44 [‐2.81, ‐0.06]

7 Leaving the study early Show forest plot	4		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

7.1 due to any reason	4	807	Odds Ratio (M‐H, Random, 95% CI)	1.22 [0.82, 1.83]
7.2 due to adverse events	3	792	Odds Ratio (M‐H, Random, 95% CI)	3.51 [1.58, 7.80]
7.3 due to inefficacy	3	792	Odds Ratio (M‐H, Random, 95% CI)	0.58 [0.28, 1.21]
8 Adverse effects: 1. At least one adverse effect Show forest plot	1	217	Odds Ratio (M‐H, Random, 95% CI)	1.30 [0.58, 2.93]

9 Adverse effects: 2. Death Show forest plot	2	575	Odds Ratio (M‐H, Random, 95% CI)	0.38 [0.02, 9.47]

10 Adverse effects: 3. Extrapyramidal effects ‐ tremor Show forest plot	1	302	Odds Ratio (M‐H, Random, 95% CI)	1.21 [0.53, 2.75]

11 Adverse effects: 4. Prolactin ‐ change from baseline in ng/ml Show forest plot	2	518	Mean Difference (IV, Random, 95% CI)	4.19 [‐0.18, 8.56]

12 Adverse effects: 5a. Significant weight gain Show forest plot	3	792	Odds Ratio (M‐H, Random, 95% CI)	4.77 [1.82, 12.50]

12.1 ≥ 10% weight gain from baseline	1	217	Odds Ratio (M‐H, Random, 95% CI)	12.14 [0.70, 208.95]
12.2 spontaneously reported	2	575	Odds Ratio (M‐H, Random, 95% CI)	4.22 [1.29, 13.77]
13 Adverse effects: 5b. Weight ‐ change from baseline in kg Show forest plot	2	519	Mean Difference (IV, Random, 95% CI)	4.58 [4.06, 5.09]

14 Adverse effects: 6. Sedation Show forest plot	2	575	Odds Ratio (M‐H, Random, 95% CI)	3.53 [1.64, 7.60]

Comparison 5. Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term

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Comparison 6. Quetiapine versus placebo for major depression

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Non‐response to treatment ‐ as defined by the original study Show forest plot	3	1342	Odds Ratio (M‐H, Random, 95% CI)	0.52 [0.41, 0.66]

2 Global state: no clinically important change ‐ CGI Show forest plot	3	1342	Odds Ratio (M‐H, Random, 95% CI)	0.56 [0.44, 0.71]

3 Remission ‐ number of participants without remission ‐ as defined by the original study Show forest plot	3	1337	Odds Ratio (M‐H, Fixed, 95% CI)	0.65 [0.49, 0.86]

4 Relapse Show forest plot	1	776	Odds Ratio (M‐H, Fixed, 95% CI)	0.34 [0.24, 0.48]

5 Mental state: 1a. Depressive symptoms ‐ no clinically important change‐ MADRS Show forest plot	3	1342	Odds Ratio (M‐H, Random, 95% CI)	0.52 [0.41, 0.66]

6 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint Show forest plot	4	2069	Mean Difference (IV, Random, 95% CI)	‐2.59 [‐3.50, ‐1.69]

6.1 short‐term	3	1298	Mean Difference (IV, Random, 95% CI)	‐3.36 [‐4.62, ‐2.10]
6.2 long‐term	1	771	Mean Difference (IV, Random, 95% CI)	‐1.88 [‐1.00, ‐0.76]
7 Mental state: 1c. Depressive symptoms ‐ HAM‐D score at endpoint Show forest plot	3	1298	Mean Difference (IV, Random, 95% CI)	‐2.52 [‐3.66, ‐1.37]

8 Mental state: 2. Anxiety symptoms ‐ HAM‐A score at endpoint Show forest plot	4	2069	Mean Difference (IV, Random, 95% CI)	‐1.40 [‐1.97, ‐0.84]

8.1 short‐term	3	1298	Mean Difference (IV, Random, 95% CI)	‐1.42 [‐2.20, ‐0.64]
8.2 long‐term	1	771	Mean Difference (IV, Random, 95% CI)	‐1.38 [‐2.20, ‐0.56]
9 Leaving the study early ‐ due to adverse events Show forest plot	4	2118	Odds Ratio (M‐H, Random, 95% CI)	2.33 [1.37, 3.98]

9.1 short‐term	3	1342	Odds Ratio (M‐H, Random, 95% CI)	3.03 [1.91, 4.80]
9.2 long‐term	1	776	Odds Ratio (M‐H, Random, 95% CI)	1.25 [0.68, 2.28]
10 Adverse effects: 1. Death ‐ suicidal thoughts ‐ MADRS item 10 of at least 4 Show forest plot	1	723	Odds Ratio (M‐H, Random, 95% CI)	0.48 [0.18, 1.27]

11 Adverse effects: 2. Extrapyramidal effects ‐ general EPS Show forest plot	4	2118	Odds Ratio (M‐H, Random, 95% CI)	1.74 [1.01, 3.02]

11.1 short‐term	3	1342	Odds Ratio (M‐H, Random, 95% CI)	1.84 [0.94, 3.60]
11.2 long‐term	1	776	Odds Ratio (M‐H, Random, 95% CI)	1.56 [0.60, 4.08]
12 Adverse effects: 3. Prolactin ‐ change from baseline in ng/ml Show forest plot	1	309	Mean Difference (IV, Random, 95% CI)	0.76 [‐0.19, 1.71]

13 Adverse effects: 4a. Significant weight gain Show forest plot	4		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

13.1 ≥7% weight gain from baseline ‐ short‐term	4	2118	Odds Ratio (M‐H, Random, 95% CI)	2.12 [1.13, 3.99]
13.2 spontaneously reported	1	776	Odds Ratio (M‐H, Random, 95% CI)	6.80 [2.84, 16.28]
14 Adverse effects: 4b. Weight ‐ change from baseline in kg Show forest plot	4	2027	Mean Difference (IV, Random, 95% CI)	0.65 [0.11, 1.18]

14.1 short‐term	3	1306	Mean Difference (IV, Random, 95% CI)	0.60 [‐0.09, 1.29]
14.2 long‐term	1	721	Mean Difference (IV, Random, 95% CI)	0.8 [0.13, 1.47]
15 Adverse effects: 5. Sedation Show forest plot	4	2118	Odds Ratio (M‐H, Random, 95% CI)	5.76 [2.32, 14.32]

15.1 short‐term	3	1342	Odds Ratio (M‐H, Random, 95% CI)	4.94 [1.97, 12.36]
15.2 long‐term	1	776	Odds Ratio (M‐H, Random, 95% CI)	31.74 [1.89, 532.38]

Comparison 6. Quetiapine versus placebo for major depression

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Comparison 7. Quetiapine versus antidepressants for major depression ‐ all data short‐term

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 No clinically important response to treatment (as defined by original study) Show forest plot	1	303	Odds Ratio (M‐H, Random, 95% CI)	0.94 [0.60, 1.47]

2 Global state: no clinically important change ‐ CGI Show forest plot	1	303	Odds Ratio (M‐H, Random, 95% CI)	0.94 [0.60, 1.47]

3 Remission ‐ number of participants without remission Show forest plot	1	303	Odds Ratio (M‐H, Random, 95% CI)	1.08 [0.66, 1.77]

4 Mental state: 1a. No clinically important change‐ MADRS Show forest plot	1	303	Odds Ratio (M‐H, Random, 95% CI)	0.72 [0.46, 1.13]

5 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint Show forest plot	1	288	Mean Difference (IV, Random, 95% CI)	‐0.41 [‐2.65, 1.83]

6 Mental state: 1c. Depressive symptoms ‐ HAM‐D score at endpoint Show forest plot	1	288	Mean Difference (IV, Random, 95% CI)	‐1.20 [‐2.99, 0.59]

7 Mental state: 2. Anxiety symptoms ‐ HAM‐A score at endpoint Show forest plot	1	288	Mean Difference (IV, Random, 95% CI)	0.26 [‐1.39, 1.91]

8 Leaving the study early ‐ due to adverse events Show forest plot	1	303	Odds Ratio (M‐H, Random, 95% CI)	16.82 [3.93, 72.02]

9 Adverse effects: 1. Extrapyramidal effects ‐ general EPS Show forest plot	1	303	Odds Ratio (M‐H, Random, 95% CI)	0.64 [0.26, 1.62]

10 Adverse effects: 2. Prolactin ‐ change from baseline in ng/ml Show forest plot	1	301	Mean Difference (IV, Random, 95% CI)	0.07 [‐1.21, 1.35]

11 Adverse effects: 3a. Significant weight gain ‐ ≥7% from baseline Show forest plot	1	303	Odds Ratio (M‐H, Random, 95% CI)	4.05 [0.45, 36.70]

12 Adverse effects: 3b. Weight ‐ change from baseline in ng/ml Show forest plot	1	301	Mean Difference (IV, Random, 95% CI)	1.65 [1.13, 2.17]

13 Adverse effects: 4. Sedation Show forest plot	1	303	Odds Ratio (M‐H, Random, 95% CI)	3.27 [1.89, 5.63]

Comparison 7. Quetiapine versus antidepressants for major depression ‐ all data short‐term

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Comparison 8. Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 No clinically important response (as defined by original study) Show forest plot	3	995	Odds Ratio (M‐H, Random, 95% CI)	0.66 [0.51, 0.87]

2 Global state: no clinically important change ‐ CGI Show forest plot	2	937	Odds Ratio (M‐H, Random, 95% CI)	0.64 [0.49, 0.84]

3 Remission ‐ number of people without remission ‐ as defined by the original study Show forest plot	3	847	Odds Ratio (M‐H, Random, 95% CI)	0.52 [0.38, 0.71]

4 Mental state: 1a. Depressive symptoms ‐ no clinically important change ‐ MADRS Show forest plot	2	937	Odds Ratio (M‐H, Random, 95% CI)	0.68 [0.52, 0.90]

5 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint Show forest plot	2	919	Mean Difference (IV, Random, 95% CI)	‐2.67 [‐4.00, ‐1.34]

6 Mental state: 1c. Depressive symptoms ‐ no clinically important change ‐ HAM‐D Show forest plot	1	58	Odds Ratio (M‐H, Random, 95% CI)	0.41 [0.14, 1.22]

7 Mental state: 1d. Depressive symptoms ‐ HAM‐D score at endpoint Show forest plot	3	977	Mean Difference (IV, Random, 95% CI)	‐2.67 [‐3.79, ‐1.55]

8 Mental state: 2a. Anxiety symptoms ‐ no clinically important change ‐ HAM‐A Show forest plot	1	58	Odds Ratio (M‐H, Random, 95% CI)	0.23 [0.08, 0.70]

9 Mental state: 2b. Anxiety symptoms ‐ HAM‐A score at endpoint Show forest plot	3	977	Mean Difference (IV, Random, 95% CI)	‐2.62 [‐4.69, ‐0.55]

10 Leaving the study early Show forest plot	3		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

10.1 due to any reason	1	58	Odds Ratio (M‐H, Random, 95% CI)	0.75 [0.26, 2.14]
10.2 due to adverse events	3	995	Odds Ratio (M‐H, Random, 95% CI)	5.59 [1.47, 21.26]
10.3 due to inefficacy	1	58	Odds Ratio (M‐H, Random, 95% CI)	0.04 [0.00, 0.66]
11 Adverse effects: 1. Extrapyramidal symptoms Show forest plot	1	446	Odds Ratio (M‐H, Fixed, 95% CI)	1.95 [0.71, 5.32]

12 Adverse effects: 2. Prolactin ‐ change from baseline in ng/ml Show forest plot	1	491	Mean Difference (IV, Random, 95% CI)	‐0.33 [‐1.00, 2.34]

13 Adverse effects: 3a. Significant weight gain Show forest plot	3		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

13.1 ≥ 7% weight gain from baseline	3	995	Odds Ratio (M‐H, Random, 95% CI)	3.06 [1.22, 7.68]
13.2 Increase in body weight from baseline to week 8	1	58	Odds Ratio (M‐H, Random, 95% CI)	3.39 [1.01, 11.41]
13.3 spontaneously reported	1	446	Odds Ratio (M‐H, Random, 95% CI)	6.17 [0.79, 47.90]
14 Adverse effects: 3b. Weight ‐ change from baseline in kg Show forest plot	3	959	Mean Difference (IV, Random, 95% CI)	1.11 [0.56, 1.66]

15 Adverse effects: 4. Sedation Show forest plot	3	995	Odds Ratio (M‐H, Random, 95% CI)	8.79 [4.90, 15.77]

Comparison 8. Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term

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Comparison 9. Risperidone added to antidepressants versus placebo added to antidepressants for major depression

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 No clinically important response (as defined by original study) Show forest plot	2	371	Odds Ratio (M‐H, Random, 95% CI)	0.57 [0.36, 0.89]

2 Remission ‐ number of participants without remission ‐ as defined by the original study Show forest plot	2	371	Odds Ratio (M‐H, Fixed, 95% CI)	0.39 [0.22, 0.69]

3 Relapse (as defined by the original study) Show forest plot	1	243	Odds Ratio (M‐H, Random, 95% CI)	0.95 [0.57, 1.57]

4 Mental state: 1a. Depressive symptoms ‐ MADRS score at endpoint Show forest plot	2	264	Mean Difference (IV, Random, 95% CI)	‐1.85 [‐9.17, 5.47]

4.1 short‐term	1	23	Mean Difference (IV, Random, 95% CI)	‐7.11 [‐16.50, 2.28]
4.2 medium‐term	1	241	Mean Difference (IV, Random, 95% CI)	0.80 [‐2.21, 3.81]
5 Mental state: 1b. Depressive symptoms ‐ no clinically important change ‐ HAM‐D Show forest plot	2	371	Odds Ratio (M‐H, Random, 95% CI)	0.60 [0.38, 0.95]

6 Mental state: 1c. Depressive symptoms ‐ HAM‐D score at endpoint Show forest plot	2	509	Mean Difference (IV, Random, 95% CI)	‐1.69 [‐4.13, 0.74]

6.1 short‐term	1	268	Mean Difference (IV, Random, 95% CI)	‐2.80 [‐4.14, ‐1.46]
6.2 medium‐term	1	241	Mean Difference (IV, Random, 95% CI)	‐0.30 [‐2.43, 1.83]
7 Leaving the study early Show forest plot	4		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

7.1 due to any reason	4	637	Odds Ratio (M‐H, Random, 95% CI)	1.04 [0.59, 1.83]
7.2 due to adverse events	2	517	Odds Ratio (M‐H, Random, 95% CI)	2.11 [0.79, 5.68]
7.3 due to inefficacy	2	517	Odds Ratio (M‐H, Random, 95% CI)	0.95 [0.59, 1.51]
8 Adverse effects: 1. At least one adverse effect Show forest plot	2	371	Odds Ratio (M‐H, Random, 95% CI)	0.75 [0.48, 1.16]

9 Adverse effects: 2a. Extrapyramidal effects ‐ tremor Show forest plot	2		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

9.1 EPS general ‐ medium‐term	1	243	Odds Ratio (M‐H, Random, 95% CI)	1.98 [0.36, 11.04]
9.2 akathisia ‐ short‐term	1	274	Odds Ratio (M‐H, Random, 95% CI)	2.85 [0.12, 70.59]
9.3 dystonia ‐ short‐term	1	274	Odds Ratio (M‐H, Random, 95% CI)	0.31 [0.01, 7.73]
9.4 tremor ‐ short‐term	1	274	Odds Ratio (M‐H, Random, 95% CI)	0.94 [0.06, 15.23]
9.5 use of antiparkinson medication ‐ short‐term	1	274	Odds Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
10 Adverse effects: 3a. Prolactin increase ‐ associated effects Show forest plot	1	243	Odds Ratio (M‐H, Random, 95% CI)	7.0 [0.36, 136.98]

11 Adverse effects: 3b. Prolactin ‐ change from baseline in ng/ml ‐ endpoint Show forest plot	2	256	Mean Difference (IV, Random, 95% CI)	29.42 [19.49, 39.34]

11.1 short‐term	1	15	Mean Difference (IV, Random, 95% CI)	40.42 [‐2.67, 83.51]
11.2 medium‐term	1	241	Mean Difference (IV, Random, 95% CI)	28.8 [18.60, 39.00]
12 Adverse effects: 4a. Significant weight gain Show forest plot	3		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

12.1 ≥ 7% weight gain from baseline	2	340	Odds Ratio (M‐H, Random, 95% CI)	3.32 [0.99, 11.12]
12.2 spontaneously reported	2	371	Odds Ratio (M‐H, Random, 95% CI)	2.12 [0.55, 8.16]
13 Adverse effects: 4b. Weight ‐ change from baseline in kg Show forest plot	4	633	Mean Difference (IV, Random, 95% CI)	‐0.09 [‐2.22, 2.04]

13.1 short‐term	3	392	Mean Difference (IV, Random, 95% CI)	‐2.77 [‐8.03, 2.49]
13.2 medium‐term	1	241	Mean Difference (IV, Random, 95% CI)	1.80 [0.95, 2.65]
14 Adverse effects: 5. Sedation Show forest plot	4	637	Odds Ratio (M‐H, Random, 95% CI)	1.10 [0.31, 3.99]

14.1 short‐term	3	394	Odds Ratio (M‐H, Random, 95% CI)	1.21 [0.17, 8.46]
14.2 medium‐term	1	243	Odds Ratio (M‐H, Random, 95% CI)	0.73 [0.16, 3.31]

Comparison 9. Risperidone added to antidepressants versus placebo added to antidepressants for major depression

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Comparison 10. Amisulpride versus placebo for dysthymia

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 No clinically important response (as defined by original study) Show forest plot	2	322	Odds Ratio (M‐H, Random, 95% CI)	0.29 [0.18, 0.46]

2 Global state: no clinically important change ‐ CGI Show forest plot	2	322	Odds Ratio (M‐H, Random, 95% CI)	0.29 [0.18, 0.46]

3 Mental state: 1a. Depressive symptoms ‐ no clinically important change‐ MADRS < 7 Show forest plot	1	212	Odds Ratio (M‐H, Random, 95% CI)	0.28 [0.15, 0.51]

4 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint Show forest plot	2	284	Mean Difference (IV, Random, 95% CI)	‐4.90 [‐6.67, ‐3.12]

5 Mental state: 1c. Depressive symptoms ‐ HAM‐D score at endpoint Show forest plot	1	39	Mean Difference (IV, Random, 95% CI)	‐7.20 [‐10.08, ‐4.32]

6 Leaving the study early Show forest plot	3		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

6.1 due to any reason	3	361	Odds Ratio (M‐H, Random, 95% CI)	0.65 [0.38, 1.11]
6.2 due to adverse events	3	361	Odds Ratio (M‐H, Random, 95% CI)	3.85 [0.96, 15.39]
6.3 due to inefficacy	3	361	Odds Ratio (M‐H, Random, 95% CI)	0.40 [0.20, 0.83]
7 Adverse effects: 1. At least one adverse effect Show forest plot	3	361	Odds Ratio (M‐H, Random, 95% CI)	1.39 [0.71, 2.73]

7.1 short‐term	1	39	Odds Ratio (M‐H, Random, 95% CI)	4.58 [0.81, 25.80]
7.2 medium‐term	2	322	Odds Ratio (M‐H, Random, 95% CI)	1.20 [0.67, 2.15]
8 Adverse effects: 2. Extrapyramidal effects Show forest plot	2	149	Odds Ratio (M‐H, Random, 95% CI)	3.58 [0.74, 17.40]

8.1 tremor	1	39	Odds Ratio (M‐H, Random, 95% CI)	5.27 [0.24, 117.26]
8.2 EPS in general	1	110	Odds Ratio (M‐H, Random, 95% CI)	3.13 [0.50, 19.63]
9 Adverse effects: 3. Prolactin associated effects Show forest plot	2		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

9.1 galactorrhoea	1	212	Odds Ratio (M‐H, Random, 95% CI)	11.99 [0.65, 219.71]
9.2 menstrual disorder	1	212	Odds Ratio (M‐H, Random, 95% CI)	10.14 [1.26, 81.50]
9.3 general	1	84	Odds Ratio (M‐H, Random, 95% CI)	8.65 [1.01, 73.75]
10 Adverse effects: 4. Significant weight gain ‐ spontaneously reported Show forest plot	1	212	Odds Ratio (M‐H, Random, 95% CI)	6.55 [0.77, 55.38]

Comparison 10. Amisulpride versus placebo for dysthymia

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Comparison 11. Amisulpride versus antidepressants for dysthymia

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 No clinically important response ‐ as defined by original study Show forest plot	4	957	Odds Ratio (M‐H, Random, 95% CI)	0.61 [0.38, 0.99]

1.1 short‐term	1	313	Odds Ratio (M‐H, Random, 95% CI)	0.61 [0.35, 1.07]
1.2 medium‐term	3	644	Odds Ratio (M‐H, Random, 95% CI)	0.60 [0.30, 1.19]
2 Global state: no clinically important change ‐ CGI Show forest plot	4	957	Odds Ratio (M‐H, Random, 95% CI)	0.52 [0.32, 0.86]

2.1 short‐term	1	313	Odds Ratio (M‐H, Random, 95% CI)	0.50 [0.28, 0.90]
2.2 medium‐term	3	644	Odds Ratio (M‐H, Random, 95% CI)	0.52 [0.26, 1.06]
3 Service use ‐ number of patients rehospitalised Show forest plot	2	528	Odds Ratio (M‐H, Random, 95% CI)	5.91 [0.73, 48.09]

4 Mental state: 1a. Depressive symptoms ‐ MADRS ‐ score at endpoint Show forest plot	4	902	Mean Difference (IV, Random, 95% CI)	‐1.28 [‐2.75, 0.18]

4.1 short‐term	1	306	Mean Difference (IV, Random, 95% CI)	‐1.10 [‐2.84, 0.64]
4.2 medium‐term	3	596	Mean Difference (IV, Random, 95% CI)	‐1.60 [‐3.97, 0.78]
5 Mental state: 1b. No clinically important change ‐ at least 50% HAM‐D reduction Show forest plot	1	313	Odds Ratio (M‐H, Random, 95% CI)	0.61 [0.35, 1.07]

6 Mental state: 1c. No clinically important change ‐ at least 25% HAM‐D reduction Show forest plot	1	313	Odds Ratio (M‐H, Random, 95% CI)	0.20 [0.09, 0.41]

7 Mental state: 1d. Depressive symptoms ‐ HAM‐D score at endpoint Show forest plot	1	306	Mean Difference (IV, Random, 95% CI)	‐0.90 [‐2.24, 0.44]

8 Mental state: 2. Anxiety symptoms‐ HAM‐A score at endpoint Show forest plot	3	824	Mean Difference (IV, Random, 95% CI)	‐0.98 [‐2.33, 0.38]

8.1 short‐term	1	306	Mean Difference (IV, Random, 95% CI)	‐0.90 [‐2.25, 0.45]
8.2 medium‐term	2	518	Mean Difference (IV, Random, 95% CI)	‐1.04 [‐3.69, 1.60]
9 Leaving the study early Show forest plot	4		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

9.1 due to any reason	4	957	Odds Ratio (M‐H, Random, 95% CI)	0.74 [0.55, 1.00]
9.2 due to adverse events	4	957	Odds Ratio (M‐H, Random, 95% CI)	1.17 [0.74, 1.86]
9.3 due to inefficacy	3	644	Odds Ratio (M‐H, Random, 95% CI)	0.93 [0.30, 2.83]
10 Adverse effects: 1. At least one adverse effect Show forest plot	4	957	Odds Ratio (M‐H, Random, 95% CI)	0.95 [0.73, 1.25]

10.1 short‐term	1	313	Odds Ratio (M‐H, Random, 95% CI)	0.89 [0.57, 1.39]
10.2 medium‐term	3	644	Odds Ratio (M‐H, Random, 95% CI)	0.96 [0.63, 1.46]
11 Adverse effects: 2.Death ‐ suicide attempt Show forest plot	1	253	Odds Ratio (M‐H, Random, 95% CI)	0.17 [0.01, 4.30]

12 Adverse effects: 3. Extrapyramidal effects Show forest plot	3		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

12.1 tremor	1	253	Odds Ratio (M‐H, Random, 95% CI)	0.05 [0.00, 0.82]
12.2 EPS in general	3	644	Odds Ratio (M‐H, Random, 95% CI)	0.68 [0.09, 4.86]
13 Adverse effects: 4. Significant weight gain Show forest plot	2		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only

13.1 ≥ 5% weight gain from baseline	2	534	Odds Ratio (M‐H, Random, 95% CI)	2.23 [1.21, 4.13]
13.2 spontaneously reported	1	253	Odds Ratio (M‐H, Random, 95% CI)	1.29 [0.65, 2.57]
14 Adverse effects: 5. Prolactin associated effects ‐ amenorrhoea Show forest plot	2	236	Odds Ratio (M‐H, Random, 95% CI)	7.07 [1.60, 31.29]

15 Adverse effects: 6. Sedation Show forest plot	2	531	Odds Ratio (M‐H, Random, 95% CI)	0.70 [0.08, 6.42]

Comparison 11. Amisulpride versus antidepressants for dysthymia

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Comparison 12. Sensitivity analysis ‐ imputed statistics excluded ‐ 3. Quetiapine versus placebo for major depression

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint Show forest plot	2	1070	Mean Difference (IV, Random, 95% CI)	‐2.18 [‐3.35, ‐1.00]

1.1 short‐term	1	299	Mean Difference (IV, Random, 95% CI)	‐3.39 [‐5.95, ‐0.83]
1.2 long‐term	1	771	Mean Difference (IV, Random, 95% CI)	‐1.88 [‐1.00, ‐0.76]
2 Mental state: 1c. Depressive symptoms ‐ HAM‐D score at endpoint Show forest plot	1	299	Mean Difference (IV, Random, 95% CI)	‐2.40 [‐5.79, 0.99]

3 Mental state: 2. Anxiety symptoms ‐ HAM‐A score at endpoint Show forest plot	2	1070	Mean Difference (IV, Random, 95% CI)	‐1.39 [‐2.11, ‐0.68]

3.1 short‐term	1	299	Mean Difference (IV, Random, 95% CI)	‐1.44 [‐2.88, ‐0.00]
3.2 long‐term	1	771	Mean Difference (IV, Random, 95% CI)	‐1.38 [‐2.20, ‐0.56]

Comparison 12. Sensitivity analysis ‐ imputed statistics excluded ‐ 3. Quetiapine versus placebo for major depression

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Comparison 13. Sensitivity analysis ‐ imputed statistics excluded ‐ 4. Amisulpride versus antidepressants for dysthymia

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mental state: 1a. Depressive symptoms ‐ MADRS ‐ score at endpoint Show forest plot	3	824	Mean Difference (IV, Random, 95% CI)	‐0.89 [‐2.01, 0.23]

1.1 short‐term	1	306	Mean Difference (IV, Random, 95% CI)	‐1.10 [‐2.84, 0.64]
1.2 medium‐term	2	518	Mean Difference (IV, Random, 95% CI)	‐0.74 [‐2.20, 0.73]

Comparison 13. Sensitivity analysis ‐ imputed statistics excluded ‐ 4. Amisulpride versus antidepressants for dysthymia

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Comparison 14. Sensitivity analysis ‐ imputed statistics excluded ‐ 6. Olanzapine versus antidepressants for major depression ‐ all data short‐term

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint Show forest plot	2	302	Mean Difference (IV, Random, 95% CI)	0.38 [‐1.86, 2.62]

2 Mental state: 2. Anxiety symptoms ‐ HAM‐A score at endpoint Show forest plot	2	302	Mean Difference (IV, Random, 95% CI)	0.78 [‐0.77, 2.34]

3 Adverse effects: 4. Prolactin ‐ change from baseline in ng/ml Show forest plot	1	301	Mean Difference (IV, Random, 95% CI)	4.1 [1.35, 6.85]

Comparison 14. Sensitivity analysis ‐ imputed statistics excluded ‐ 6. Olanzapine versus antidepressants for major depression ‐ all data short‐term

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Comparison 15. Sensitivity analysis ‐ imputed statistics excluded ‐ 9. Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint Show forest plot	2	303	Mean Difference (IV, Random, 95% CI)	‐3.50 [‐7.62, 0.61]

2 Mental state: 2. Anxiety symptoms ‐ HAM‐A score at endpoint Show forest plot	2	303	Mean Difference (IV, Random, 95% CI)	‐1.27 [‐4.41, 1.86]

3 Adverse effects: 4. Prolactin ‐ change from baseline in ng/ml Show forest plot	1	301	Mean Difference (IV, Random, 95% CI)	2.5 [0.41, 4.59]

Comparison 15. Sensitivity analysis ‐ imputed statistics excluded ‐ 9. Olanzapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term

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Comparison 16. Sensitivity analysis ‐ imputed statistics excluded ‐ 10. Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mental state: 1b. Depressive symptoms ‐ MADRS score at endpoint Show forest plot	1	432	Mean Difference (IV, Random, 95% CI)	‐2.46 [‐4.33, ‐0.59]

2 Mental state: 1d. Depressive symptoms‐ HAM‐D score at endpoint Show forest plot	1	432	Mean Difference (IV, Random, 95% CI)	‐2.28 [‐3.97, ‐0.59]

3 Mental state: 2b. Anxiety symptoms ‐ HAM‐A score at endpoint Show forest plot	1	432	Mean Difference (IV, Random, 95% CI)	‐1.30 [‐2.72, 0.12]

4 Adverse effects: 3b. Weight ‐ change from baseline in kg Show forest plot	1	491	Mean Difference (IV, Random, 95% CI)	0.95 [0.49, 1.41]

Comparison 16. Sensitivity analysis ‐ imputed statistics excluded ‐ 10. Quetiapine added to antidepressants versus placebo added to antidepressants for major depression ‐ all data short‐term

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Comparison 17. Sensitivity analysis ‐ imputed statistics excluded ‐ 11. Risperidone added to antidepressants versus placebo added to antidepressants for major depression

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mental state: 1c. Depressive symptoms ‐ HAM‐D score at endpoint Show forest plot	1	241	Mean Difference (IV, Random, 95% CI)	‐0.30 [‐2.43, 1.83]

Comparison 17. Sensitivity analysis ‐ imputed statistics excluded ‐ 11. Risperidone added to antidepressants versus placebo added to antidepressants for major depression

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