Antipsychotic dose reduction compared to dose continuation for people with schizophrenia

Abstract

Background Antipsychotic drugs are the mainstay treatment for schizophrenia, yet they are associated with diverse and potentially dose‐related side effects which can reduce quality of life. For this reason, the lowest possible doses of antipsychotics are generally recommended, but higher doses are often used in clinical practice. It is still unclear if and how antipsychotic doses could be reduced safely in order to minimise the adverse‐effect burden without increasing the risk of relapse. Objectives To assess the efficacy and safety of reducing antipsychotic dose compared to continuing the current dose for people with schizophrenia. Search methods We conducted a systematic search on 10 February 2021 at the Cochrane Schizophrenia Group's Study‐Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PubMed, ClinicalTrials.gov, ISRCTN, and WHO ICTRP. We also inspected the reference lists of included studies and previous reviews. Selection criteria We included randomised controlled trials (RCTs) comparing any dose reduction against continuation in people with schizophrenia or related disorders who were stabilised on their current antipsychotic treatment. Data collection and analysis At least two review authors independently screened relevant records for inclusion, extracted data from eligible studies, and assessed the risk of bias using RoB 2. We contacted study authors for missing data and additional information. Our primary outcomes were clinically important change in quality of life, rehospitalisations and dropouts due to adverse effects; key secondary outcomes were clinically important change in functioning, relapse, dropouts for any reason, and at least one adverse effect. We also examined scales measuring symptoms, quality of life, and functioning as well as a comprehensive list of specific adverse effects. We pooled outcomes at the endpoint preferably closest to one year. We evaluated the certainty of the evidence using the GRADE approach. Main results We included 25 RCTs, of which 22 studies provided data with 2635 participants (average age 38.4 years old). The median study sample size was 60 participants (ranging from 18 to 466 participants) and length was 37 weeks (ranging from 12 weeks to 2 years). There were variations in the dose reduction strategies in terms of speed of reduction (i.e. gradual in about half of the studies (within 2 to 16 weeks) and abrupt in the other half), and in terms of degree of reduction (i.e. median planned reduction of 66% of the dose up to complete withdrawal in three studies). We assessed risk of bias across outcomes predominantly as some concerns or high risk. No study reported data on the number of participants with a clinically important change in quality of life or functioning, and only eight studies reported continuous data on scales measuring quali...

Restarting smoking after discharge from clozapine inpatient initiation: Elevated rehospitalization rates smoking & clozapine rehospitalization

“…4 Individuals with schizophrenia and their clinicians can choose an antipsychotic based on not only the tolerability profile but also the formulation. 3 Unanswered is the place in therapy of antipsychotic transdermal delivery systems as an alternative to both orally administered antipsychotic medication and their long-acting injectable formulations. 4 All-cause discontinuation (ACD) is an important acceptability outcome in double-blind, randomized, placebo-controlled trials for schizophrenia drugs and can serve as a proxy measure for overall effectiveness.…”

“…2 For other antipsychotics, meta-analyses of randomized controlled trials have demonstrated that dose reduction increases the risk of relapse. 3,4 However, no study, to our knowledge, has examined the effect of clozapine dose reduction on relapse.…”

Changing vistas of psychosis and antipsychotic drug dosing toward personalized management of antipsychotics in clinical practice.

“…Most studies examining low-dose treatment were performed in chronic patients, or nonselected patients, who were often treated with antipsychotics for many years (Rodolico et al, 2022). Of the 25 studies selected by Rodolico et al in their recent Cochrane review of dose-reduction studies, all but one were either in chronic patients (nine studies) or in patients whose course characteristics were not specified (15 studies).…”

“…The abrupt dose-reduction schemes and the rather long-term treatment with antipsychotics of most patients included in the review probably add to the likelihood of rebound psychoses. Nevertheless, the figures on relapse rates are reassuring: “Dose reduction in comparison to continuation may increase the risk of rehospitalization based on data from eight studies with estimable effect sizes; however, the 95% confidence interval included the possibility of no difference, amounting to very low certainty evidence.” Similarly, in data from 20 studies, dose reduction increased the risk of relapse twofold, but this was limited to low-certainty evidence too (Rodolico et al, 2022).…”

Dose-tapering trajectories in patients with remitted psychosis undergoing guided antipsychotic reduction to reach minimum effective dose

“…Even though a meta-analysis suggested that the risk of relapse in patients undergoing dose reduction is twofold of their maintenance counterparts, neurocognitive functioning in the former is significantly improved after dose reduction [23]. A recent systematic review reported similar findings and called for more attention to this approach concerning its potential to improve patients’ quality of life and global functioning [24].…”