Reversibility of Antipsychotic-Induced Weight Gain: A Systematic Review and Meta-Analysis

Abstract

Background and AimsWeight gain is a major adverse effect of antipsychotic medication, negatively affecting physical and mental well-being. The objective of this study was to explore if dose reduction, discontinuation, switch to a partial agonist, or switch from polypharmacy to monotherapy will lead to weight loss.MethodsControlled and uncontrolled studies reporting the effects of discontinuation, dose reduction, switch to a partial agonist, or switch from polypharmacy to monotherapy on weight were included. Primary outcome was difference in weight compared to maintenance groups based on controlled studies. Secondary outcome was change in weight from initiation of one of the included interventions until follow-up in a pre-post analysis.ResultsWe identified 40 randomized controlled trials and 15 uncontrolled studies including 12,279 individuals. The effect of the interventions, i.e. dose reduction, drug discontinuation, or switch to a partial agonis, reduced the weight with 1.5 kg (95% CI −2.03 to −0.98; P < 0.001) compared to maintenance treatment. The weight change from pre to post was a reduction of 1.13 kg (95% CI −1.36 to −0.90; P < 0.001).ConclusionWe found a significant but small reduction in weight, suggesting that antipsychotic-induced weight gain can be reversed to some degree. Only a few studies were designed to address the question as primary outcome, which limits the generalizability of our findings.

Predicting antipsychotic-induced weight gain in first episode psychosis – A field-wide systematic review and meta-analysis of non-genetic prognostic factors

“…However, for most assessments, average weight differences between higher and lower doses did not differ to a clinically significant extent, although studies were of short duration [59]. A separate review highlighting dose reduction as ineffective in significantly reversing AIWG supports the hypothesis of AIWG being somewhat dose-independent [60], although the absence of linear relationships may mean dose reductions are more effective within certain ranges. Taken together, additional research is required to confirm whether antipsychotic dosing meaningfully impacts AIWG prognosis.…”

Effects of Combined Therapy of Olanzapine and Samidorphan on Safety and Metabolic Parameters in Schizophrenia Patients: A Meta-Analysis

“…Some researchers believe that OLZ treatment should be coupled with real-time monitoring and must be switched swiftly to other antipsychotics in case of intense adverse events. [6][7][8] Various perspectives propose co-administering metformin, topiramate, and reboxetine to reduce weight gain is also a viable option. 9,10 The new application of SAM appears to provide an additional therapeutic approach.…”

Antipsychotic‐induced weight gain: Is the weight over? New guidelines needed

“…12,13 Moreover, it is well known that long-term maintenance of weight loss following lifestyle interventions is challenging. 14,15 Depressive and negative symptoms may negatively impact the implementation of lifestyle interventions. Furthermore, participants of clinical trials are potentially better able to stay motivated and to follow structured lifestyle programs than patients in clinical practice depending on the severity of illness.…”

“…However, studies demonstrated variable efficacy of lifestyle interventions 12,13 . Moreover, it is well known that long‐term maintenance of weight loss following lifestyle interventions is challenging 14,15 . Depressive and negative symptoms may negatively impact the implementation of lifestyle interventions.…”

“…Hence, the usability of switching antipsychotics seems to be limited. Dose reduction of antipsychotics is also not an appropriate intervention, as a meta‐analysis showed no significant effect of dose reduction as treatment for AiWG and dose reduction could also cause a risk of relapse 15 . Considering the variable efficacy of lifestyle interventions and the limited impact of switching antipsychotics, additional management strategies are necessary to clinically significantly reduce AiWG.…”