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Meta-Analysis
. 2018 Jan 18;1(1):CD000458.
doi: 10.1002/14651858.CD000458.pub3.

Non-antipsychotic catecholaminergic drugs for antipsychotic-induced tardive dyskinesia

Hany G El-Sayeh  1 , John Rathbone, Karla Soares-Weiser, Hanna Bergman
Affiliations
Meta-Analysis

Non-antipsychotic catecholaminergic drugs for antipsychotic-induced tardive dyskinesia

Hany G El-Sayeh et al. Cochrane Database Syst Rev. .

Abstract

Background: Tardive dyskinesia (TD) is a disabling movement disorder associated with the prolonged use of antipsychotic medication. Several strategies have been examined in the treatment of TD. Currently, however, there is no clear evidence of the effectiveness of these drugs in TD and they have been associated with many side effects. One particular strategy would be to use pharmaceutical agents which are known to influence the catecholaminergic system at various junctures.

Objectives: 1. To determine the effects of any of the following drugs for antipsychotic-induced TD in people with schizophrenia or other chronic mental illnesses.i. Drugs which influence the noradrenergic system.ii. Dopamine receptor agonists.iii. Dopamine receptor antagonists.iv. Dopamine-depletor drugs.v. Drugs that increase the production or release of dopamine.2. To examine whether any improvement occurred with short periods of intervention (less than 6 weeks) and, if this did occur, whether this effect was maintained at longer periods of follow-up.3. To examine if there was a differential effect for the various compounds.4. To examine whether the use of non-antipsychotic catecholaminergic drugs are most effective in those with more recent onset TD (less than five years).

Search methods: We retrieved 712 references from searching the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017). We also inspected references of all identified studies for further trials and contacted authors of trials for additional information.

Selection criteria: We selected studies if they were randomised controlled trials focusing on people with schizophrenia or other chronic mental illnesses and antipsychotic-induced tardive dyskinesia. We compared the use of catecholaminergic interventions versus placebo, no intervention, or any other intervention for the treatment of antipsychotic-induced tardive dyskinesia.

Data collection and analysis: We independently extracted data from these trials and we estimated risk ratios (RRs) with 95% confidence intervals (CIs). We assumed that people who left the studies early had no improvement.

Main results: There are 10 included trials (N = 261) published between 1973 and 2010; eight are new from the 2015 and 2017 update searches. Forty-eight studies are excluded. Participants were mostly chronically mentally ill inpatients in their 50s, and studies were primarily of short (2 to 6 weeks) duration. The overall risk of bias in these studies was unclear, mainly due to poor reporting of allocation concealment and generation of the sequence. Studies were also not clearly blinded and we are unsure if data are incomplete or selectively reported, or if other biases were operating.One small, three-arm trial found that both alpha-methyldopa (N = 20; RR 0.33, 95% CI 0.14 to 0.80; low-quality evidence) and reserpine (N = 20; RR 0.52 95% CI 0.29 to 0.96; low-quality evidence) may lead to a clinically important improvement in tardive dyskinesia symptoms compared with placebo after 2 weeks' treatment, but found no evidence of a difference between alpha-methyldopa and reserpine (N = 20; RR 0.60, 95% CI 0.19 to 1.86; very low quality evidence). Another small trial compared tetrabenazine and haloperidol after 18 weeks' treatment and found no evidence of a difference on clinically important improvement in tardive dyskinesia symptoms (N = 13; RR 0.93, 95% CI 0.45 to 1.95; very low quality evidence). No study reported on adverse events.For remaining outcomes there was no evidence of a difference between any of the interventions: alpha-methyldopa versus placebo for deterioration of tardive dyskinesia symptoms (1 RCT; N = 20; RR 0.33, 95% CI 0.02 to 7.32; very low quality evidence), celiprolol versus placebo for leaving the study early (1 RCT; N = 35; RR 5.28, 95% CI 0.27 to 102.58; very low quality evidence) and quality of life (1 RCT; N = 35; RR 0.87, 95% CI 0.68 to 1.12; very low quality evidence), alpha-methyldopa versus reserpine for deterioration of tardive dyskinesia symptoms (1 RCT; N = 20; not estimable, no reported events; very low quality evidence), reserpine or carbidopa/levodopa versus placebo for deterioration of tardive dyskinesia symptoms (2 RCTs; N = 37; RR 1.18, 95% CI 0.35 to 3.99; very low quality evidence), oxypertine versus placebo for deterioration of mental state (1 RCT; N = 42; RR 2.20, 95% CI 0.22 to 22.45; very low quality evidence), dopaminergic drugs (amantadine, bromocriptine, tiapride, oxypertine, carbidopa/levodopa) versus placebo for leaving the study early (6 RCTs; N = 163; RR 1.29, 95% CI 0.65 to 2.54; very low quality evidence), and tetrabenazine versus haloperidol for deterioration of tardive dyskinesia symptoms (1 RCT; N = 13; RR 1.17, 95% CI 0.09 to 14.92) and leaving the study early (1 RCT; N = 13; RR 0.23, 95% CI 0.01 to 4.00).

Authors' conclusions: Although there has been a large amount of research in this area, many studies were excluded due to inherent problems in the nature of their cross-over designs. Usually data are not reported before the cross-over and the nature of TD and its likely response to treatments make it imprudent to use this data. The review provides little usable information for service users or providers and more well-designed and well-reported studies are indicated.

PubMed Disclaimer

Conflict of interest statement

None known.

KSW is the Deputy Editor‐in‐Chief for Cochrane and Cochrane Innovations. When the NHIR HTA programme grant relevant to this review update was awarded, KSW was the Managing Director of Enhance Reviews Ltd.

HB worked for Enhance Reviews Ltd. during preparation of this review and was paid for her contribution to this review. Enhance Reviews Ltd. was a private company that performs systematic reviews of literature. HB works for Cochrane Response, an evidence consultancy that takes commissions from healthcare guideline developers and policy makers.

Figures

1
1
Message from one of the participants of the Public and patient involvement consultation of service user perspectives on tardive dyskinesia research.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Study flow diagram for 2015 and 2017 searching
1.1
1.1. Analysis
Comparison 1 NORADRENERGIC DRUGS vs PLACEBO, Outcome 1 Tardive dyskinesia: 1. No clinically important improvement ‐ short term.
1.2
1.2. Analysis
Comparison 1 NORADRENERGIC DRUGS vs PLACEBO, Outcome 2 Tardive dyskinesia: 2. Not any improvement.
1.3
1.3. Analysis
Comparison 1 NORADRENERGIC DRUGS vs PLACEBO, Outcome 3 Tardive dyskinesia: 3. Deterioration ‐ short term.
1.4
1.4. Analysis
Comparison 1 NORADRENERGIC DRUGS vs PLACEBO, Outcome 4 Acceptability of treatment: Leaving the study early ‐ medium term.
1.5
1.5. Analysis
Comparison 1 NORADRENERGIC DRUGS vs PLACEBO, Outcome 5 Quality of life: No improvement ‐ medium term.
2.1
2.1. Analysis
Comparison 2 NORADRENERGIC DRUGS vs DOPAMINERGIC DRUGS, Outcome 1 Tardive dyskinesia: 1. No clinically important improvement ‐ short term.
2.2
2.2. Analysis
Comparison 2 NORADRENERGIC DRUGS vs DOPAMINERGIC DRUGS, Outcome 2 Tardive dyskinesia: 2. Not any improvement ‐ short term.
2.3
2.3. Analysis
Comparison 2 NORADRENERGIC DRUGS vs DOPAMINERGIC DRUGS, Outcome 3 Tardive dyskinesia: 3. Deterioration ‐ short term.
3.1
3.1. Analysis
Comparison 3 DOPAMINERGIC DRUGS vs PLACEBO, Outcome 1 Tardive dyskinesia: 1. No clinically important improvement.
3.2
3.2. Analysis
Comparison 3 DOPAMINERGIC DRUGS vs PLACEBO, Outcome 2 Tardive dyskinesia: 2. Not any improvement.
3.3
3.3. Analysis
Comparison 3 DOPAMINERGIC DRUGS vs PLACEBO, Outcome 3 Tardive dyskinesia: 3. Deterioration.
3.4
3.4. Analysis
Comparison 3 DOPAMINERGIC DRUGS vs PLACEBO, Outcome 4 Mental state: Deterioration ‐ medium term.
3.5
3.5. Analysis
Comparison 3 DOPAMINERGIC DRUGS vs PLACEBO, Outcome 5 Acceptability of treatment: Leaving the study early.
4.1
4.1. Analysis
Comparison 4 DOPAMINERGIC DRUGS vs OTHER DRUGS, Outcome 1 Tardive dyskinesia: 1. No clinically important improvement ‐ medium term.
4.2
4.2. Analysis
Comparison 4 DOPAMINERGIC DRUGS vs OTHER DRUGS, Outcome 2 Tardive dyskinesia: 2. Not any improvement ‐ medium term.
4.3
4.3. Analysis
Comparison 4 DOPAMINERGIC DRUGS vs OTHER DRUGS, Outcome 3 Tardive dyskinesia: 3. Deterioration ‐ medium term.
4.4
4.4. Analysis
Comparison 4 DOPAMINERGIC DRUGS vs OTHER DRUGS, Outcome 4 Acceptability of treatment: Leaving the study early ‐ medium term.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Bateman 1979 {published data only}
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NCT00310661 2006 {published data only}
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NCT00845000 2009 {published data only}
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O'Suilleabhain 2003 {published data only}
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References to other published versions of this review

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