Update on weight-gain caused by antipsychotics: a systematic review and meta-analysis

ABSTRACT

Introduction: Antipsychotic-induced weight-gain (AIWG) is a very important, yet often neglected side-effect in the treatment with first and second generation antipsychotics. AIWG can increase the risk of developing metabolic syndrome, diabetes and cardiovascular disease. Meta-analyzes mostly concentrate on AIWG in schizophrenic and bipolar patients, even though antipsychotics are prescribed off-label across many other diagnostic groups (e.g. anxiety disorders, depression, autistic disorder).

Areas covered: Pub Med and Web of Science were systematically searched for RCTs reporting on AIWG with a sample size of ≥ 100 published between 2014 and 2019. All diagnoses and ages were included.

Expert opinion: Inclusion criteria were fulfilled by 27 RCTs. All antipsychotics led to significantly more weight-gain (p < .001) and most antipsychotics led to a significantly higher risk for a clinically relevant weight-gain of ≥7% compared to placebo (RR = 2.04). The results support previous findings that weight-gain occurs quickly. To efficaciously and efficiently tackle the problem of AIWG in clinical practice and trials, people at high risk need to be identified by predictive tools enabling the clinician to offer tailored adjunctive therapies (medication and/or lifestyle interventions). Most importantly, weight and metabolic monitoring ought to be consequently implemented in clinical routine in the treatment of any patient with any diagnosis when antipsychotics are prescribed.

KEYWORDS:

• Aripiprazole
• asenapine
• brexpiprazole
• cariprazine
• lurasidone
• number needed to harm
• olanzapine
• quetiapine extended release
• risperidone
• transdiagnostically

Article highlights

• The overall results of the meta-analysis was that compared to placebo, antipsychotics led to significantly more weight-gain (mean difference=0.86 [CI: 0.65;1.07], p < .001) and to a significantly higher risk of gaining ≥7% of the baseline weight (RR=2.04 [1.54; 2.71]], p < .001) after 3 to 12 weeks of treatment. NNH was 34 and very heterogeneous across studies.

• Most weight-gain was caused by olanzapine followed by asenapine, risperidone, aripiprazole, quetiapine XR, brexpiprazole, cariprazine and lurasidone. Thus, also relatively new compounds like cariprazine and brexpiprazole resulted in significantly more weight-gain compared to placebo. Only aripiprazole, lurasidone and quetiapine XR did not lead to a clinical significant weight-gain of ≥7%.

• All patients, regardless of their diagnosis or age, treated with any antipsychotic need to be routinely monitored on weight and metabolic parameters to timely detect relevant changes.

• More research to better understand the underlying mechanisms of AIWG (e.g. genetics) is urgently needed.

• In the future, predictive tools to identify patients at high risk for AIWG should be implemented in clinical routine and research to offer tailored therapies, consisting of adjunctive medication or psychoeducative programs, aiming at preventing or ameliorating AIWG.

Acknowledgments

Editing of language was assisted by Thelma Coutts.

Declaration of interest

R Musil has received research support from Lundbeck and Speaker Honoraria from Otsuka and Lundbeck. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have received manuscript or speaker’s fees from Astellas, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, Elsevier Japan, Janssen Pharmaceuticals, Kyowa Yakuhin, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Novartis, Otsuka Pharmaceutical, Shionogi, Tsumura, Wiley Japan, and Yoshitomi Yakuhin, and research grants from Eisai, Mochida Pharmaceutical, and Meiji Seika Pharma. All other peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not Funded.