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

Review question

To determine whether stopping or reducing antipsychotic drugs helps in the reduction of tardive dyskinesia for people with schizophrenia. To examine whether specific antipsychotic drugs could be a treatment for tardive dyskinesia.

Background

People with schizophrenia often hear voices and see things (hallucinations) and have strange beliefs (delusions). The main treatment for schizophrenia is antipsychotic drugs. However, these drugs can have debilitating side effects. Tardive dyskinesia is an involuntary movement that causes the face, mouth, tongue, and jaw to convulse, spasm, and grimace. It is caused by long-term use or high doses of antipsychotic drugs, is difficult to treat, and can be incurable. Various strategies have been proposed to reduce a person’s exposure to antipsychotic drugs. These include lowering the dose of medication, intermittent ‘drug holidays’, and stopping taking antipsychotic medication altogether.

Study characteristics

The review includes 13 trials with a total of 711 people with schizophrenia and other psychiatric diagnoses.

Key results

Due to the poor quality, small size, and limited data from the 13 studies, there is limited evidence. It is not known if strategies such as dose reduction, ‘drug holidays’, and stopping medication are helpful in the treatment of tardive dyskinesia. There is limited evidence on specific antipsychotic drugs in the treatment of tardive dyskinesia.

Quality of the evidence

Evidence is poor, small scale, and of short duration. There is a need for larger trials of a longer duration in order to fully investigate this area.

This plain language summary was adapted by the review authors from a summary originally written by Ben Gray, Senior Peer Researcher, McPin Foundation (http://mcpin.org/).

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.

Read the full 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 strategy: 

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.

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