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Meta-Analysis
. 2018 Feb 6;2(2):CD000459.
doi: 10.1002/14651858.CD000459.pub3.

Antipsychotic reduction and/or cessation and antipsychotics as specific treatments for tardive dyskinesia

Hanna Bergman  1 , John Rathbone, Vivek Agarwal, Karla Soares-Weiser
Affiliations
Meta-Analysis

Antipsychotic reduction and/or cessation and antipsychotics as specific treatments for tardive dyskinesia

Hanna Bergman et al. Cochrane Database Syst Rev. .

Abstract

Background: Since the 1950s antipsychotic medication has been extensively used to treat people with chronic mental illnesses such as schizophrenia. These drugs, however, have also been associated with a wide range of adverse effects, including movement disorders such as tardive dyskinesia (TD) - a problem often seen as repetitive involuntary movements around the mouth and face. Various strategies have been examined to reduce a person's cumulative exposure to antipsychotics. These strategies include dose reduction, intermittent dosing strategies such as drug holidays, and antipsychotic cessation.

Objectives: To determine whether a reduction or cessation of antipsychotic drugs is associated with a reduction in TD for people with schizophrenia (or other chronic mental illnesses) who have existing TD. Our secondary objective was to determine whether the use of specific antipsychotics for similar groups of people could be a treatment for TD that was already established.

Search methods: We updated previous searches of Cochrane Schizophrenia's study-based Register of Trials including the registers of clinical trials (16 July 2015 and 26 April 2017). We searched references of all identified studies for further trial citations. We also contacted authors of trials for additional information.

Selection criteria: We included reports if they assessed people with schizophrenia or other chronic mental illnesses who had established antipsychotic-induced TD, and had been randomly allocated to (a) antipsychotic maintenance versus antipsychotic cessation (placebo or no intervention), (b) antipsychotic maintenance versus antipsychotic reduction (including intermittent strategies), (c) specific antipsychotics for the treatment of TD versus placebo or no intervention, and (d) specific antipsychotics versus other antipsychotics or versus any other drugs for the treatment of TD.

Data collection and analysis: We independently extracted data from these trials and estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assumed that people who dropped out had no improvement.

Main results: We included 13 RCTs with 711 participants; eight of these studies were newly included in this 2017 update. One trial is ongoing.There was low-quality evidence of a clear difference on no clinically important improvement in TD favouring switch to risperidone compared with antipsychotic cessation (with placebo) (1 RCT, 42 people, RR 0.45 CI 0.23 to 0.89, low-quality evidence). Because evidence was of very low quality for antipsychotic dose reduction versus antipsychotic maintenance (2 RCTs, 17 people, RR 0.42 95% CI 0.17 to 1.04, very low-quality evidence), and for switch to a new antipsychotic versus switch to another new antipsychotic (5 comparisons, 5 RCTs, 140 people, no meta-analysis, effects for all comparisons equivocal), we are uncertain about these effects. There was low-quality evidence of a significant difference on extrapyramidal symptoms: use of antiparkinsonism medication favouring switch to quetiapine compared with switch to haloperidol (1 RCT, 45 people, RR 0.45 CI 0.21 to 0.96, low-quality evidence). There was no evidence of a difference for switch to risperidone or haloperidol compared with antipsychotic cessation (with placebo) (RR 1 RCT, 48 people, RR 2.08 95% CI 0.74 to 5.86, low-quality evidence) and switch to risperidone compared with switch to haloperidol (RR 1 RCT, 37 people, RR 0.68 95% CI 0.34 to 1.35, very low-quality evidence).Trials also reported on secondary outcomes such as other TD symptom outcomes, other adverse events outcomes, mental state, and leaving the study early, but the quality of the evidence for all these outcomes was very low due mainly to small sample sizes, very wide 95% CIs, and risk of bias. No trials reported on social confidence, social inclusion, social networks, or personalised quality of life, outcomes that we designated as being important to patients.

Authors' conclusions: Limited data from small studies using antipsychotic reduction or specific antipsychotic drugs as treatments for TD did not provide any convincing evidence of the value of these approaches. There is a need for larger trials of a longer duration to fully investigate this area.

PubMed Disclaimer

Conflict of interest statement

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 that takes commissions from healthcare guideline developers and policy makers.

JR is not aware of any conflicts of interest for this review.

VA has declared no known conflicts of interest for this review.

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.

One of the earlier reviewers (JJM) is a member of the following advisory boards: Janssen‐Cilag Australia, Eli Lilly Australia, Lundbeck Australia. In addition, JJM has been a co‐investigator on studies of neuroleptic medications produced by the following companies: Astra Zeneca (ICI), Janssen‐Cilag, Eli Lilly, Sandoz, and Pfizer. The same companies have provided travel and accommodation expenses for JJM to attend relevant investigator meetings and scientific symposia. No funds have been paid directly to JJM. Payments related to participation in drug trials and board attendance has been paid to a Government‐audited trust account to support schizophrenia research.

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 searches for this review
1.1
1.1. Analysis
Comparison 1 Reduced overall dose of antipsychotic vs antipsychotic maintenance, Outcome 1 Tardive dyskinesia: no clinically important improvement (long term).
1.2
1.2. Analysis
Comparison 1 Reduced overall dose of antipsychotic vs antipsychotic maintenance, Outcome 2 Tardive dyskinesia: no improvement (long term).
1.3
1.3. Analysis
Comparison 1 Reduced overall dose of antipsychotic vs antipsychotic maintenance, Outcome 3 Tardive dyskinesia: deterioration (long term).
1.4
1.4. Analysis
Comparison 1 Reduced overall dose of antipsychotic vs antipsychotic maintenance, Outcome 4 General mental state: relapse (long term).
1.5
1.5. Analysis
Comparison 1 Reduced overall dose of antipsychotic vs antipsychotic maintenance, Outcome 5 Acceptability of the treatment: leaving the study early (long term).
2.1
2.1. Analysis
Comparison 2 Switch to specific antipsychotic vs antipsychotic cessation, Outcome 1 Tardive dyskinesia: no clinically important improvement (medium term).
2.2
2.2. Analysis
Comparison 2 Switch to specific antipsychotic vs antipsychotic cessation, Outcome 2 Tardive dyskinesia: average endpoint score (AIMS, high = poor) (medium term).
2.3
2.3. Analysis
Comparison 2 Switch to specific antipsychotic vs antipsychotic cessation, Outcome 3 General mental state: average endpoint score (BPRS, high = poor) (medium term).
2.4
2.4. Analysis
Comparison 2 Switch to specific antipsychotic vs antipsychotic cessation, Outcome 4 Acceptability of the treatment: leaving the study early (medium term).
2.5
2.5. Analysis
Comparison 2 Switch to specific antipsychotic vs antipsychotic cessation, Outcome 5 Adverse effects: use of antiparkinsonism drugs (medium term).
2.6
2.6. Analysis
Comparison 2 Switch to specific antipsychotic vs antipsychotic cessation, Outcome 6 Adverse effects: parkinsonism ‐ average endpoint score (ESRS) (medium term).
2.7
2.7. Analysis
Comparison 2 Switch to specific antipsychotic vs antipsychotic cessation, Outcome 7 Adverse effects: dystonia ‐ average endpoint score (ESRS) (medium term).
3.1
3.1. Analysis
Comparison 3 Switch to a specific antipsychotic vs switch to a different antipsychotic, Outcome 1 Tardive dyskinesia: no clinically important improvement.
3.2
3.2. Analysis
Comparison 3 Switch to a specific antipsychotic vs switch to a different antipsychotic, Outcome 2 Tardive dyskinesia: not any improvement (short term).
3.3
3.3. Analysis
Comparison 3 Switch to a specific antipsychotic vs switch to a different antipsychotic, Outcome 3 Tardive dyskinesia: deterioration (short term).
3.4
3.4. Analysis
Comparison 3 Switch to a specific antipsychotic vs switch to a different antipsychotic, Outcome 4 Tardive dyskinesia: average endpoint score (various scales).
3.5
3.5. Analysis
Comparison 3 Switch to a specific antipsychotic vs switch to a different antipsychotic, Outcome 5 Tardive dyskinesia: average change score (AIMS, low = better) (medium term).
3.6
3.6. Analysis
Comparison 3 Switch to a specific antipsychotic vs switch to a different antipsychotic, Outcome 6 General mental state: deterioration.
3.7
3.7. Analysis
Comparison 3 Switch to a specific antipsychotic vs switch to a different antipsychotic, Outcome 7 General mental state: average endpoint score (PANSS‐general psychopathology, low = better) (long term).
3.8
3.8. Analysis
Comparison 3 Switch to a specific antipsychotic vs switch to a different antipsychotic, Outcome 8 General mental state: average change score (BPRS, low = better) (medium term).
3.9
3.9. Analysis
Comparison 3 Switch to a specific antipsychotic vs switch to a different antipsychotic, Outcome 9 Acceptability of the treatment: leaving the study early (short term).
3.10
3.10. Analysis
Comparison 3 Switch to a specific antipsychotic vs switch to a different antipsychotic, Outcome 10 Acceptability of the treatment: leaving the study early (medium term).
3.11
3.11. Analysis
Comparison 3 Switch to a specific antipsychotic vs switch to a different antipsychotic, Outcome 11 Acceptability of the treatment: leaving the study early (long term).
3.12
3.12. Analysis
Comparison 3 Switch to a specific antipsychotic vs switch to a different antipsychotic, Outcome 12 Adverse events: extrapyramidal symptoms (need of antiparkinsonism drugs).
3.13
3.13. Analysis
Comparison 3 Switch to a specific antipsychotic vs switch to a different antipsychotic, Outcome 13 Adverse effects: parkinsonism (SHRS) ‐ average endpoint scores (short term).
3.14
3.14. Analysis
Comparison 3 Switch to a specific antipsychotic vs switch to a different antipsychotic, Outcome 14 Adverse effects: parkinsonism (SAS, ESRS, low = better) ‐ average change score (medium term).
3.15
3.15. Analysis
Comparison 3 Switch to a specific antipsychotic vs switch to a different antipsychotic, Outcome 15 Adverse effects: dyskinesia (ESRS, low = better) ‐ average change score (medium term).
3.16
3.16. Analysis
Comparison 3 Switch to a specific antipsychotic vs switch to a different antipsychotic, Outcome 16 Adverse effects: akathisia (BAS, ESRS, low = better) ‐ average change scores (medium term).
3.17
3.17. Analysis
Comparison 3 Switch to a specific antipsychotic vs switch to a different antipsychotic, Outcome 17 Adverse effects: dystonia (ESRS, low = better) ‐ average change score (medium term).
3.18
3.18. Analysis
Comparison 3 Switch to a specific antipsychotic vs switch to a different antipsychotic, Outcome 18 Adverse effects: general adverse events (UKU, low = better) ‐ average change score (medium term).
3.19
3.19. Analysis
Comparison 3 Switch to a specific antipsychotic vs switch to a different antipsychotic, Outcome 19 General global state: average change score (CGI) (medium term).
4.1
4.1. Analysis
Comparison 4 Specific antipsychotic vs other drugs, Outcome 1 Tardive dyskinesias: no clinically important improvement (medium term).
4.2
4.2. Analysis
Comparison 4 Specific antipsychotic vs other drugs, Outcome 2 Tardive dyskinesia: no improvement (medium term).
4.3
4.3. Analysis
Comparison 4 Specific antipsychotic vs other drugs, Outcome 3 Tardive dyskinesia: deterioration (medium term).
4.4
4.4. Analysis
Comparison 4 Specific antipsychotic vs other drugs, Outcome 4 Acceptability of the treatment: leaving the study early (medium term).
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References to other published versions of this review

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