Key messages
– Reducing the number of antipsychotics may be associated with more participants leaving the study early, especially due to inefficacy.
- The low number of studies and participants do not allow us to make strong conclusions.
Introduction
Schizophrenia is a severe mental disorder. People with the illness struggle to differentiate between their own thoughts, beliefs and ideas versus reality. For example, they may be hearing voices in their head but it feels like someone is really talking to them. It is mainly treated with medications called antipsychotics. Often people with schizophrenia are offered treatment with more than one antipsychotic in order to achieve an effective treatment. Use of antipsychotics is connected with side effects, and the different antipsychotics could interact, making side effects worse.
What did we want to find out?
We wanted to find out if reducing the number of antipsychotics was better than keeping the same number of antipsychotics to improve:
– quality of life
– number of people readmitted to hospital
– number of people leaving the study early because of side effects
– a person's daily functioning
– relapse
– number of people leaving the study early for any reason
– number of people with at least one side effect.
What did we do?
We searched for studies that examined reducing the number of antipsychotics compared with keeping the same number of antipsychotics in people with schizophrenia.
We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We found five studies that involved 319 participants with schizophrenia. The studies lasted between three months and one year. They were conducted in Canada, Japan, Finland and two in the USA, and were all sponsored by public institutions.
We found that reducing the number of antipsychotics may increase the number of participants leaving the study early, especially because the treatment did not work as well.
We found no differences in terms of readmission to hospital, leaving the study early due to side effects, functioning and number of participants with at least one side effect, but we are very uncertain about the results.
We found no data about quality of life and relapses.
What are the limitations of the evidence?
We are not confident in the evidence because it is possible that the people in the studies were aware of which treatment they were getting. Not all of the studies provided data about everything that we were interested in. In addition, there were not enough studies to be certain about the results of our outcomes, and studies were small.
How up to date is this evidence?
The evidence is up to date to February 2021.
This review summarises the latest evidence on polypharmacy continuation compared with polypharmacy reduction. Our results show that polypharmacy continuation might be associated with a lower number of participants leaving the study early, especially due to inefficacy. However, the evidence is of low and very low certainty and the data analyses based on few study only, so that it is not possible to draw strong conclusions based on the results of the present review.
Further high-quality RCTs are needed to investigate this important topic.
In clinical practice, different antipsychotics can be combined in the treatment of people with schizophrenia (polypharmacy). This strategy can aim at increasing efficacy, but might also increase the adverse effects due to drug–drug interactions. Reducing polypharmacy by withdrawing one or more antipsychotics may reduce this problem, but must be done carefully, in order to maintain efficacy.
To examine the effects and safety of reducing antipsychotic polypharmacy compared to maintaining people with schizophrenia on the same number of antipsychotics.
On 10 February 2021, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, CINAHL, ClinicalTrials.Gov, Embase, ISRCTN, MEDLINE, PsycINFO, PubMed and WHO ICTRP.
We included randomised controlled trials (RCTs) that compared reduction in the number of antipsychotics to continuation of the current number of antipsychotics. We included adults with schizophrenia or related disorders who were receiving more than one antipsychotic and were stabilised on their current treatment.
Two review authors independently screened all the identified references for inclusion, and all the full papers. We contacted study authors if we needed any further information. Two review authors independently extracted the data, assessed the risk of bias using RoB 2 and the certainty of the evidence using the GRADE approach. The primary outcomes were: quality of life assessed as number of participants with clinically important change in quality of life; service use assessed as number of participants readmitted to hospital and adverse effects assessed with number of participants leaving the study early due to adverse effects.
We included five RCTs with 319 participants. Study duration ranged from three months to one year. All studies compared polypharmacy continuation with two antipsychotics to polypharmacy reduction to one antipsychotic.
We assessed the risk of bias of results as being of some concern or at high risk of bias.
A lower number of participants left the study early due to any reason in the polypharmacy continuation group (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.29 to 0.68; I2 = 0%; 5 RCTs, n = 319; low-certainty evidence), and a lower number of participants left the study early due to inefficacy (RR 0.21, 95% CI 0.07 to 0.65; I2 = 0%; 3 RCTs, n = 201).
Polypharmacy continuation resulted in more severe negative symptoms (MD 3.30, 95% CI 1.51 to 5.09; 1 RCT, n = 35).
There was no clear difference between polypharmacy reduction and polypharmacy continuation on readmission to hospital, leaving the study early due to adverse effects, functioning, global state, general mental state and positive symptoms, number of participants with at least one adverse effect, weight gain and other specific adverse effects, mortality and cognition.
We assessed the certainty of the evidence as very low or low across measured outcomes.
No studies reported quality of life, days in hospital, relapse, depressive symptoms, behaviour and satisfaction with care.
Due to lack of data, it was not possible to perform some planned sensitivity analyses, including one controlling for increasing the dose of the remaining antipsychotic. As a result, we do not know if the observed results might be influenced by adjustment of dose of remaining antipsychotic compound.