Antipsychotic polypharmacy reduction versus polypharmacy continuation for people with schizophrenia

Abstract

Background 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. Objectives To examine the effects and safety of reducing antipsychotic polypharmacy compared to maintaining people with schizophrenia on the same number of antipsychotics. Search methods 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. Selection criteria 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. Data collection and analysis 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. Main results 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; I 2 = 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; I 2 = 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, globa...

Association of Antipsychotic Polypharmacy and Two-Year All-Cause Mortality: A Population-Based Cohort Study of 33,221 Italian Continuous Users

“…Conversely, our analysis highlights the critical need for a more cautious interpretation of APP benefits. While the results of Buhagiar et al [29], Kadra et al [61] and Bighelli et al [62] contribute to the complex discourse on antipsychotic treatments, our findings emphasize the necessity of a more rigorous evaluation before endorsing APP as simply an equivalent treatment modality compared to APM, suggesting that its potential risks may outweigh the perceived benefits in many cases. This stance is not only informed by our analysis of mortality risks but also by a broader consideration of patient safety and treatment efficacy [48][49][50][51][52][53][54][55][56].…”

“…Bighelli et al (2022) in their meta-analysis compared antipsychotic polypharmacy (APP) reduction to persistence in schizophrenia, focusing on outcomes like hospitalization, side effects, and, notably, mortality. The results showed no significant differences between the two approaches [62]. Furthermore, the study observed that persistence with APP might be associated with a lower rate of participant discontinuation due to inefficacy, emphasizing the critical need for personalized treatment plans and further investigation into the complex effects of APP.…”

A lifetime of mental health treatments for people with schizophrenia: update and narrative review

“…In the future the use of genetics beyond drug metabolism, but rather polygenic risk scores or epigenetic methylation analyses may prove fruitful for response prediction [55]. Regardless, many psychiatrists will move as the next step to the concept of polypharmacy and adding a second antipsychotic with perhaps a different receptor profile [56]. While some believe polypharmacy leads to reduced longevity overall, there is no evidence for that [57].…”

Relationships Between Adherence to Guideline Recommendations for Pharmacological Therapy Among Clinicians and Psychotic Symptoms in Patients With Schizophrenia

“…Polypharmacy, the concurrent use of multiple medications, is common and a complex issue in the treatment of schizophrenia ( Kishimoto et al, 2013 ; Bighelli et al, 2022 ). Polypharmacy in schizophrenia is often based on clinical experience rather than evidence-based practice.…”