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Meta-Analysis
. 2018 Mar 26;3(3):CD000206.
doi: 10.1002/14651858.CD000206.pub4.

Calcium channel blockers for antipsychotic-induced tardive dyskinesia

Adib Essali  1 , Karla Soares-Weiser, Hanna Bergman, Clive E Adams
Affiliations
Meta-Analysis

Calcium channel blockers for antipsychotic-induced tardive dyskinesia

Adib Essali et al. Cochrane Database Syst Rev. .

Abstract

Background: Schizophrenia and related disorders affect a sizable proportion of any population. Antipsychotic medications are the primary treatment for these disorders. Antipsychotic medications are associated with a variety of adverse effects including tardive dyskinesia. Dyskinesia is a disfiguring movement disorder of the orofacial region that can be tardive (having a slow or belated onset). Tardive dyskinesia is difficult to treat, despite experimentation with several treatments. Calcium channel blockers (diltiazem, nifedipine, nimodipine, verapamil, flunarizine) have been among these experimental treatments.

Objectives: To determine the effects of calcium channel blocker drugs (diltiazem, nifedipine, nimodipine, verapamil) for treatment of neuroleptic-induced tardive dyskinesia in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses.

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

Selection criteria: We selected randomised controlled trials comparing calcium channel blockers with placebo, no intervention or any other intervention for people with both tardive dyskinesia and schizophrenia or serious mental illness who remained on their antipsychotic medication.

Data collection and analysis: We independently extracted data and estimated risk ratios of dichotomous data or mean differences (MD) of continuous data, with 95% confidence intervals (CI). We assumed that people who left the trials early had no improvement. We also created a 'Summary of findings' table using GRADE.

Main results: Previous versions of this review included no trials. From the 2015 search, we identified three cross-over trials that could be included. The 2017 search found no new studies relevant to this review. The included trials randomised 47 inpatients with chronic mental illnesses in the USA and China. Trials were published in the 1990s and were of short duration (six to 10 weeks). Overall, the risk of bias was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, studies were not clearly blinded, and attrition and outcome data were not fully reported. Findings were sparse, no study reported on the primary outcome 'no clinically important improvement in tardive dyskinesia symptoms,' but two small studies (37 participants) found no difference on the tardive dyskinesia symptoms scale Abnormal Involuntary Movement Scale (AIMS) scores between diltiazem or flunarizine and placebo after three to four weeks' treatment (MD -0.71, 95% CI -2.68 to 1.26, very low quality evidence). Only one study randomising 20 participants reported on adverse events, and reported that there were no adverse events with flunarizine or with placebo (very low quality evidence). One study with 18 participants reported no events of deterioration in mental state with diltiazem or with placebo (very low quality evidence). No studies reported on acceptability of treatment or on social confidence, social inclusion, social networks or personalised quality of life outcomes designated important to patients.

Authors' conclusions: Available evidence from randomised controlled trials is extremely limited and very low quality, conclusions cannot be drawn. The effects of calcium channel blockers for antipsychotic-induced tardive dyskinesia are unknown. Their use is experimental and should only be given in the context of well-designed randomised trials.

PubMed Disclaimer

Conflict of interest statement

AE: none known.

KSW is the Deputy Editor‐in‐Chief for Cochrane and Cochrane Innovations. When the NHIR HTA programme grant was awarded that included to update this review, Karla 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 is a private company that performs systematic reviews of literature. HB works for Cochrane Response, an evidence consultancy linked to Cochrane that take commissions from healthcare guideline developers and policy makers.

CEA: none known.

Figures

1
1
Calcium channel blockers.
2
2
Message from one of the participants of the public and patient involvement consultation of service user perspectives on tardive dyskinesia research.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
5
5
Study flow diagram (2015 and 2017 update search results only).
1.1
1.1. Analysis
Comparison 1 Calcium channel blockers versus placebo, Outcome 1 Tardive dyskinesia: AIMS endpoint score (low = better).
1.2
1.2. Analysis
Comparison 1 Calcium channel blockers versus placebo, Outcome 2 Adverse effects: any adverse effects (short term).
1.3
1.3. Analysis
Comparison 1 Calcium channel blockers versus placebo, Outcome 3 Mental state: deterioration (short‐term).
1.4
1.4. Analysis
Comparison 1 Calcium channel blockers versus placebo, Outcome 4 Cognitive state: mean endpoint score (DRS, low = better, short term).
See this image and copyright information in PMC

Update of

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