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Message from one of the participants of the Public and patient involvement consultation of service user perspectives on tardive dyskinesia research.
Figures and Tables -
Figure 1

Message from one of the participants of the Public and patient involvement consultation of service user perspectives on tardive dyskinesia research.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 2

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

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figures and Tables -
Figure 3

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

Study flow diagram for 2015 and 2017 searching
Figures and Tables -
Figure 4

Study flow diagram for 2015 and 2017 searching

Comparison 1 NORADRENERGIC DRUGS vs PLACEBO, Outcome 1 Tardive dyskinesia: 1. No clinically important improvement ‐ short term.
Figures and Tables -
Analysis 1.1

Comparison 1 NORADRENERGIC DRUGS vs PLACEBO, Outcome 1 Tardive dyskinesia: 1. No clinically important improvement ‐ short term.

Comparison 1 NORADRENERGIC DRUGS vs PLACEBO, Outcome 2 Tardive dyskinesia: 2. Not any improvement.
Figures and Tables -
Analysis 1.2

Comparison 1 NORADRENERGIC DRUGS vs PLACEBO, Outcome 2 Tardive dyskinesia: 2. Not any improvement.

Comparison 1 NORADRENERGIC DRUGS vs PLACEBO, Outcome 3 Tardive dyskinesia: 3. Deterioration ‐ short term.
Figures and Tables -
Analysis 1.3

Comparison 1 NORADRENERGIC DRUGS vs PLACEBO, Outcome 3 Tardive dyskinesia: 3. Deterioration ‐ short term.

Comparison 1 NORADRENERGIC DRUGS vs PLACEBO, Outcome 4 Acceptability of treatment: Leaving the study early ‐ medium term.
Figures and Tables -
Analysis 1.4

Comparison 1 NORADRENERGIC DRUGS vs PLACEBO, Outcome 4 Acceptability of treatment: Leaving the study early ‐ medium term.

Comparison 1 NORADRENERGIC DRUGS vs PLACEBO, Outcome 5 Quality of life: No improvement ‐ medium term.
Figures and Tables -
Analysis 1.5

Comparison 1 NORADRENERGIC DRUGS vs PLACEBO, Outcome 5 Quality of life: No improvement ‐ medium term.

Comparison 2 NORADRENERGIC DRUGS vs DOPAMINERGIC DRUGS, Outcome 1 Tardive dyskinesia: 1. No clinically important improvement ‐ short term.
Figures and Tables -
Analysis 2.1

Comparison 2 NORADRENERGIC DRUGS vs DOPAMINERGIC DRUGS, Outcome 1 Tardive dyskinesia: 1. No clinically important improvement ‐ short term.

Comparison 2 NORADRENERGIC DRUGS vs DOPAMINERGIC DRUGS, Outcome 2 Tardive dyskinesia: 2. Not any improvement ‐ short term.
Figures and Tables -
Analysis 2.2

Comparison 2 NORADRENERGIC DRUGS vs DOPAMINERGIC DRUGS, Outcome 2 Tardive dyskinesia: 2. Not any improvement ‐ short term.

Comparison 2 NORADRENERGIC DRUGS vs DOPAMINERGIC DRUGS, Outcome 3 Tardive dyskinesia: 3. Deterioration ‐ short term.
Figures and Tables -
Analysis 2.3

Comparison 2 NORADRENERGIC DRUGS vs DOPAMINERGIC DRUGS, Outcome 3 Tardive dyskinesia: 3. Deterioration ‐ short term.

Comparison 3 DOPAMINERGIC DRUGS vs PLACEBO, Outcome 1 Tardive dyskinesia: 1. No clinically important improvement.
Figures and Tables -
Analysis 3.1

Comparison 3 DOPAMINERGIC DRUGS vs PLACEBO, Outcome 1 Tardive dyskinesia: 1. No clinically important improvement.

Comparison 3 DOPAMINERGIC DRUGS vs PLACEBO, Outcome 2 Tardive dyskinesia: 2. Not any improvement.
Figures and Tables -
Analysis 3.2

Comparison 3 DOPAMINERGIC DRUGS vs PLACEBO, Outcome 2 Tardive dyskinesia: 2. Not any improvement.

Comparison 3 DOPAMINERGIC DRUGS vs PLACEBO, Outcome 3 Tardive dyskinesia: 3. Deterioration.
Figures and Tables -
Analysis 3.3

Comparison 3 DOPAMINERGIC DRUGS vs PLACEBO, Outcome 3 Tardive dyskinesia: 3. Deterioration.

Comparison 3 DOPAMINERGIC DRUGS vs PLACEBO, Outcome 4 Mental state: Deterioration ‐ medium term.
Figures and Tables -
Analysis 3.4

Comparison 3 DOPAMINERGIC DRUGS vs PLACEBO, Outcome 4 Mental state: Deterioration ‐ medium term.

Comparison 3 DOPAMINERGIC DRUGS vs PLACEBO, Outcome 5 Acceptability of treatment: Leaving the study early.
Figures and Tables -
Analysis 3.5

Comparison 3 DOPAMINERGIC DRUGS vs PLACEBO, Outcome 5 Acceptability of treatment: Leaving the study early.

Comparison 4 DOPAMINERGIC DRUGS vs OTHER DRUGS, Outcome 1 Tardive dyskinesia: 1. No clinically important improvement ‐ medium term.
Figures and Tables -
Analysis 4.1

Comparison 4 DOPAMINERGIC DRUGS vs OTHER DRUGS, Outcome 1 Tardive dyskinesia: 1. No clinically important improvement ‐ medium term.

Comparison 4 DOPAMINERGIC DRUGS vs OTHER DRUGS, Outcome 2 Tardive dyskinesia: 2. Not any improvement ‐ medium term.
Figures and Tables -
Analysis 4.2

Comparison 4 DOPAMINERGIC DRUGS vs OTHER DRUGS, Outcome 2 Tardive dyskinesia: 2. Not any improvement ‐ medium term.

Comparison 4 DOPAMINERGIC DRUGS vs OTHER DRUGS, Outcome 3 Tardive dyskinesia: 3. Deterioration ‐ medium term.
Figures and Tables -
Analysis 4.3

Comparison 4 DOPAMINERGIC DRUGS vs OTHER DRUGS, Outcome 3 Tardive dyskinesia: 3. Deterioration ‐ medium term.

Comparison 4 DOPAMINERGIC DRUGS vs OTHER DRUGS, Outcome 4 Acceptability of treatment: Leaving the study early ‐ medium term.
Figures and Tables -
Analysis 4.4

Comparison 4 DOPAMINERGIC DRUGS vs OTHER DRUGS, Outcome 4 Acceptability of treatment: Leaving the study early ‐ medium term.

Table 2. Suggestions for design of future studies

Methods

Allocation: randomised, with sequence generation and concealment of allocation clearly described.
Blindness: double, tested.
Duration: 12 months beyond end of intervention at least.
Raters: independent.

Participants

People with antipsychotic‐induced tardive dyskinesia.*
Age: any.
Sex: both.
History: any.
N = 300.**

Interventions

1. Non‐antipsychotic catecholaminergic compound. N = 150.
2. Placebo: N = 150.

Outcomes

Tardive dyskinesia: any clinically important improvement in TD, any improvement, deterioration.***
Adverse effects: no clinically significant extrapyramidal adverse effects ‐ any time period***, use of any antiparkinsonism drugs, other important adverse events.
Leaving the study early.
Service outcomes: admitted, number of admissions, length of hospitalisation, contacts with psychiatric services.
Compliance with drugs.
Economic evaluations: cost‐effectiveness, cost‐benefit.
General state: relapse, frequency and intensity of minor and major exacerbations.
Social confidence, social inclusion, social networks, or personalised quality of life: binary measure
Distress among relatives: binary measure.
Burden on family: binary measure.

Notes

* This could be diagnosed by clinical decision. If funds were permitting all participants could be screened using operational criteria, otherwise a random sample should suffice.

** Size of study with sufficient power to highlight about a 10% difference between groups for primary outcome.
*** Primary outcome. The same applies to the measure of primary outcome as for diagnosis. Not everyone may need to have operational criteria applied if clinical impression is proved to be accurate.

Figures and Tables -
Table 2. Suggestions for design of future studies
Summary of findings for the main comparison. NORADRENERGIC DRUGS compared to PLACEBO for antipsychotic‐induced tardive dyskinesia

NORADRENERGIC DRUGS compared to PLACEBO for antipsychotic‐induced tardive dyskinesia

Patient or population: patients with antipsychotic‐induced tardive dyskinesia
Settings: inpatients in Austria and the USA
Intervention: NORADRENERGIC DRUGS (alpha‐methyldopa, celiprolol)
Comparison: PLACEBO

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

PLACEBO

NORADRENERGIC DRUGS

Tardive dyskinesia: No clinically important improvement

follow‐up: 2 weeks

1000 per 1000

330 per 1000
(140 to 800)

RR 0.33
(0.14 to 0.80)

20
(1 study)

⊕⊕⊝⊝
low1,2

The included study evaluated alpha‐methyldopa.

Tardive dyskinesia: deterioration

follow‐up: 2 weeks

100 per 1000

33 per 1000
(2 to 732)

RR 0.33
(0.02 to 7.32)

20
(1 study)

⊕⊝⊝⊝
very low1,3

The included study evaluated alpha‐methyldopa.

Adverse events ‐ not reported

See comment

See comment

Not estimable

0
(0)

See comment

We found no studies rating this outcome.

Mental state ‐ not reported

See comment

See comment

Not estimable

0
(0)

See comment

We found no studies rating this outcome.

Acceptability of treatment: Leaving the study early

follow‐up: 13 weeks

0 per 1000

0 per 1000
(0 to 0)

RR 5.28
(0.27 to 102.58)

35
(1 study)

⊕⊝⊝⊝
very low1,3

The included study evaluated celiprolol.

No improvement in quality of life

follow‐up: 13 weeks

944 per 1000

822 per 1000
(642 to 1000)

RR 0.87
(0.68 to 1.12)

35
(1 study)

⊕⊝⊝⊝
very low1,3

The included study evaluated celiprolol.

*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; RR: Risk 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 Downgraded one step for risk of bias: unclear whether randomisation procedure and allocation concealment were carried out adequately, blinding of outcome assessors was not described.
2 Downgraded one step for imprecision: few events and small sample size.
3 Downgraded two steps for imprecision: few events, small sample size and wide CI that includes both no effect and appreciable benefit for intervention group.
4 Downgraded one level for indirectness: leaving the study early can give an indication, but is not a direct measurement, of treatment acceptability.

Figures and Tables -
Summary of findings for the main comparison. NORADRENERGIC DRUGS compared to PLACEBO for antipsychotic‐induced tardive dyskinesia
Summary of findings 2. NORADRENERGIC DRUGS compared to DOPAMINERGIC DRUGS for antipsychotic‐induced tardive dyskinesia

NORADRENERGIC DRUGS compared to DOPAMINERGIC DRUGS for antipsychotic‐induced tardive dyskinesia

Patient or population: patients with antipsychotic‐induced tardive dyskinesia
Setting: inpatients in the USA
Intervention: NORADRENERGIC DRUGS (alpha‐methyldopa)
Comparison: DOPAMINERGIC DRUGS (reserpine)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with DOPAMINERGIC DRUGS

Risk with NORADRENERGIC DRUGS

Tardive dyskinesia: No clinically important improvement

follow‐up: 2 weeks

Study population

RR 0.60
(0.19 to 1.86)

20
(1 study)

⊕⊝⊝⊝
very low1,2

500 per 1,000

300 per 1,000
(95 to 930)

Tardive dyskinesia: Deterioration

follow‐up: 2 weeks

Study population

not estimable

20
(1 study)

⊕⊝⊝⊝
very low1,3

Among the 20 participants no events were reported.

0 per 1,000

0 per 1,000
(0 to 0)

Adverse events

‐ not reported

See comment

See comment

not estimable

0
(0)

See comment

We found no studies reporting on this outcome.

Mental state

‐ not reported

See comment

See comment

not estimable

0
(0)

See comment

We found no studies reporting on this outcome.

Acceptability of treatment: Leaving the study early

See comment

See comment

not estimable

0
(0)

See comment

We found no studies reporting on this outcome.

Social confidence, social inclusion, social networks, or personalised quality of life ‐ not reported

See comment

See comment

not estimable

0
(0)

See comment

We found no studies reporting on this outcome.

*The risk in the intervention group (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; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

1 Downgraded one step for risk of bias: unclear whether randomisation procedure and allocation concealment were carried out adequately.
2 Downgraded two steps for imprecision: few events, very small sample size, and wide CI that includes both appreciable benefit and appreciable harm for intervention group as well as no effect.
3 Downgraded two steps for imprecision: no events were reported, effect estimate cannot be calculated.

Figures and Tables -
Summary of findings 2. NORADRENERGIC DRUGS compared to DOPAMINERGIC DRUGS for antipsychotic‐induced tardive dyskinesia
Summary of findings 3. DOPAMINERGIC DRUGS compared to PLACEBO for antipsychotic‐induced tardive dyskinesia

DOPAMINERGIC DRUGS compared to PLACEBO for antipsychotic‐induced tardive dyskinesia

Patient or population: patients with antipsychotic‐induced tardive dyskinesia
Settings: inpatients in the UK and the USA
Intervention: DOPAMINERGIC DRUGS (carbidopa/levodopa, oxypertine, reserpine)
Comparison: PLACEBO

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

PLACEBO

DOPAMINERGIC DRUGS

Tardive dyskinesia: No clinically important improvement

follow‐up: 2 weeks

1000 per 1000

520 per 1000
(290 to 960)

RR 0.52
(0.29 to 0.96)

20
(1 study)

⊕⊕⊝⊝
low1,2

The included study evaluated reserpine.

Tardive dyskinesia: Deterioration

follow‐up: 2‐6 weeks

167 per 1000

197 per 1000
(58 to 665)

RR 1.18
(0.35 to 3.99)

37
(2 studies)

⊕⊝⊝⊝
very low1,3

The included studies evaluated reserpine and carbidopa/levodopa.

Adverse events ‐ not reported

See comment

See comment

Not estimable

0
(0)

See comment

We found no studies rating this outcome.

General mental state: Deterioration

follow‐up: 24 weeks

45 per 1000

100 per 1000
(10 to 1000)

RR 2.2
(0.22 to 22.45)

42
(1 study)

⊕⊝⊝⊝
very low3,4

The included study evaluated oxypertine.

Acceptability of treatment: Leaving the study early

follow‐up: 2‐24 weeks

111 per 1000

143 per 1000
(72 to 282)

RR 1.29
(0.65 to 2.54)

163
(6 studies)

⊕⊝⊝⊝
very low3,5,6,7

Only two studies (59 participants) evaluating carbidopa/levodopa and oxypertine reported any events for this outcome. 4 studies evaluating amantadine, bromocriptine, and tiapride reported no events and consequently no estimates could be made for these 3 compounds.

Social confidence, social inclusion, social networks, or personalised quality of life ‐ not reported

See comment

See comment

Not estimable

0
(0)

See comment

This outcome was designated to be of importance, especially to patients. We found no studies rating this outcome.

*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; RR: Risk 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 Downgraded one step for risk of bias: unclear whether randomisation procedure and allocation concealment were carried out adequately, blinding of outcome assessors was not described.
2 Downgraded one step for imprecision: few events and small sample size.
3 Downgraded two steps for imprecision: few events, small sample size and wide CI that includes both no effect and appreciable benefit for intervention group.
4 Downgraded one step for risk of bias: unclear whether randomisation procedure and allocation concealment were carried out adequately, attrition was high (45%).
5 Downgraded one step for risk of bias: unclear whether randomisation procedure and allocation concealment were carried out adequately, attrition was high (45%) or unbalanced between groups (25% vs. 0%).
6 Downgraded one step for inconsistency: statistical heterogeneity was high (I² = 58%).
7 Downgraded one step for indirectness: leaving the study early can give an indication, but is not a direct measurement, of treatment acceptability.

Figures and Tables -
Summary of findings 3. DOPAMINERGIC DRUGS compared to PLACEBO for antipsychotic‐induced tardive dyskinesia
Summary of findings 4. DOPAMINERGIC DRUGS compared to OTHER DRUGS for antipsychotic‐induced tardive dyskinesia

DOPAMINERGIC DRUGS compared to OTHER DRUGS for antipsychotic‐induced tardive dyskinesia

Patient or population: patients with antipsychotic‐induced tardive dyskinesia
Setting: inpatients in the USA
Intervention: DOPAMINERGIC DRUGS (tetrabenazine)
Comparison: OTHER DRUGS (haloperidol)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with OTHER DRUGS

Risk with DOPAMINERGIC DRUGS

Tardive dyskinesia: No clinically important improvement

follow‐up: 18 weeks

Study population

RR 0.93
(0.45 to 1.95)

13
(1 study)

⊕⊝⊝⊝
very low1,2

714 per 1000

664 per 1000
(321 to 1000)

Tardive dyskinesia: Deterioration

follow‐up: 18 weeks

Study population

RR 1.17
(0.09 to 14.92)

13
(1 study)

⊕⊝⊝⊝
very low1,2

143 per 1000

167 per 1000
(13 to 1,000)

Adverse events

‐ not reported

See comment

See comment

not estimable

0
(0)

See comment

We found no studies reporting on this outcome.

Mental state

‐ not reported

See comment

See comment

not estimable

0
(0)

See comment

We found no studies reporting on this outcome.

Acceptability of treatment: Leaving the study early

follow‐up: 18 weeks

Study population

RR 0.23
(0.01 to 4.00)

13
(1 study)

⊕⊝⊝⊝
very low1,2

286 per 1000

66 per 1000
(3 to 1,000)

Social confidence, social inclusion, social networks, or personalised quality of life ‐ not reported

See comment

See comment

not estimable

0
(0)

See comment

We found no studies reporting on this outcome.

*The risk in the intervention group (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; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

1 Downgraded one step for risk of bias: unclear whether randomisation procedure and allocation concealment were carried out adequately.
2 Downgraded two steps for imprecision: few events, very small sample size, and wide CI that includes both appreciable benefit and appreciable harm for intervention group as well as no effect.

Figures and Tables -
Summary of findings 4. DOPAMINERGIC DRUGS compared to OTHER DRUGS for antipsychotic‐induced tardive dyskinesia
Table 1. Other reviews in the series

Interventions

Reference

Anticholinergic medication

Soares‐Weiser 1997

Benzodiazepines

Bhoopathi 2006

Calcium channel blockers

Essali 2011

Cholinergic medication

Tammenmaa 2002

Gamma‐aminobutyric acid agonists

Alabed 2011

Miscellaneous treatments

Soares‐Weiser 2003

Neuroleptic reduction and/or cessation and neuroleptics

Soares‐Weiser 2006

Non‐neuroleptic catecholaminergic drugs

This review

Vitamin E

Soares‐Weiser 2011

Figures and Tables -
Table 1. Other reviews in the series
Comparison 1. NORADRENERGIC DRUGS vs PLACEBO

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Tardive dyskinesia: 1. No clinically important improvement ‐ short term Show forest plot

1

20

Risk Ratio (IV, Fixed, 95% CI)

0.33 [0.14, 0.80]

1.1 Alpha‐methyldopa

1

20

Risk Ratio (IV, Fixed, 95% CI)

0.33 [0.14, 0.80]

2 Tardive dyskinesia: 2. Not any improvement Show forest plot

2

55

Risk Ratio (IV, Fixed, 95% CI)

0.91 [0.65, 1.27]

2.1 Alpha‐methyldopa ‐ short term

1

20

Risk Ratio (IV, Fixed, 95% CI)

0.33 [0.02, 7.32]

2.2 Celiprolol ‐ medium term

1

35

Risk Ratio (IV, Fixed, 95% CI)

0.92 [0.66, 1.28]

3 Tardive dyskinesia: 3. Deterioration ‐ short term Show forest plot

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.02, 7.32]

3.1 Alpha‐methyldopa

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.02, 7.32]

4 Acceptability of treatment: Leaving the study early ‐ medium term Show forest plot

1

35

Risk Ratio (M‐H, Fixed, 95% CI)

5.28 [0.27, 102.58]

4.1 Celiprolol

1

35

Risk Ratio (M‐H, Fixed, 95% CI)

5.28 [0.27, 102.58]

5 Quality of life: No improvement ‐ medium term Show forest plot

1

35

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.68, 1.12]

5.1 Celiprolol

1

35

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.68, 1.12]

Figures and Tables -
Comparison 1. NORADRENERGIC DRUGS vs PLACEBO
Comparison 2. NORADRENERGIC DRUGS vs DOPAMINERGIC DRUGS

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Tardive dyskinesia: 1. No clinically important improvement ‐ short term Show forest plot

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.6 [0.19, 1.86]

1.1 Alpha‐methyldopa versus Reserpine

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.6 [0.19, 1.86]

2 Tardive dyskinesia: 2. Not any improvement ‐ short term Show forest plot

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2.1 Alpha‐methyldopa versus Reserpine

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3 Tardive dyskinesia: 3. Deterioration ‐ short term Show forest plot

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.1 Alpha‐methyldopa versus Reserpine

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

Figures and Tables -
Comparison 2. NORADRENERGIC DRUGS vs DOPAMINERGIC DRUGS
Comparison 3. DOPAMINERGIC DRUGS vs PLACEBO

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Tardive dyskinesia: 1. No clinically important improvement Show forest plot

1

20

Risk Ratio (IV, Fixed, 95% CI)

0.52 [0.29, 0.96]

1.1 Reserpine ‐ short term

1

20

Risk Ratio (IV, Fixed, 95% CI)

0.52 [0.29, 0.96]

2 Tardive dyskinesia: 2. Not any improvement Show forest plot

3

57

Risk Ratio (M‐H, Fixed, 95% CI)

0.60 [0.35, 1.03]

2.1 Reserpine ‐ short term

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.02, 7.32]

2.2 L‐DOPA ‐ short term

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.35, 1.27]

2.3 Carbidopa/levodopa ‐ medium term

1

17

Risk Ratio (M‐H, Fixed, 95% CI)

0.59 [0.26, 1.36]

3 Tardive dyskinesia: 3. Deterioration Show forest plot

2

37

Risk Ratio (M‐H, Fixed, 95% CI)

1.18 [0.35, 3.99]

3.1 Reserpine ‐ short term

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.02, 7.32]

3.2 Carbidopa/levodopa ‐ medium term

1

17

Risk Ratio (M‐H, Fixed, 95% CI)

1.78 [0.44, 7.25]

4 Mental state: Deterioration ‐ medium term Show forest plot

1

Risk Ratio (IV, Fixed, 95% CI)

Subtotals only

4.1 Oxypertine

1

42

Risk Ratio (IV, Fixed, 95% CI)

2.2 [0.22, 22.45]

5 Acceptability of treatment: Leaving the study early Show forest plot

6

163

Risk Ratio (M‐H, Fixed, 95% CI)

1.29 [0.65, 2.54]

5.1 Amantadine ‐ short term

1

22

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

5.2 Bromocriptine ‐ short term

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

5.3 Tiapride ‐ short term

1

12

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

5.4 Tiapride ‐ medium term

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

5.5 Oxypertine ‐ medium term

1

42

Risk Ratio (M‐H, Fixed, 95% CI)

1.73 [0.83, 3.58]

5.6 Carbidopa/levodopa ‐ medium term

1

17

Risk Ratio (M‐H, Fixed, 95% CI)

0.18 [0.01, 3.27]

Figures and Tables -
Comparison 3. DOPAMINERGIC DRUGS vs PLACEBO
Comparison 4. DOPAMINERGIC DRUGS vs OTHER DRUGS

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Tardive dyskinesia: 1. No clinically important improvement ‐ medium term Show forest plot

1

13

Risk Ratio (IV, Fixed, 95% CI)

0.93 [0.45, 1.95]

1.1 Tetrabenazine vs Haloperidol

1

13

Risk Ratio (IV, Fixed, 95% CI)

0.93 [0.45, 1.95]

2 Tardive dyskinesia: 2. Not any improvement ‐ medium term Show forest plot

1

13

Risk Ratio (IV, Fixed, 95% CI)

0.39 [0.05, 2.83]

2.1 Tetrabenazine vs Haloperidol

1

13

Risk Ratio (IV, Fixed, 95% CI)

0.39 [0.05, 2.83]

3 Tardive dyskinesia: 3. Deterioration ‐ medium term Show forest plot

1

13

Risk Ratio (IV, Fixed, 95% CI)

1.17 [0.09, 14.92]

3.1 Tetrabenazine vs Haloperidol

1

13

Risk Ratio (IV, Fixed, 95% CI)

1.17 [0.09, 14.92]

4 Acceptability of treatment: Leaving the study early ‐ medium term Show forest plot

1

13

Risk Ratio (IV, Fixed, 95% CI)

0.23 [0.01, 4.00]

4.1 Tetrabenazine vs Haloperidol

1

13

Risk Ratio (IV, Fixed, 95% CI)

0.23 [0.01, 4.00]

Figures and Tables -
Comparison 4. DOPAMINERGIC DRUGS vs OTHER DRUGS