Twenty-Four Week, Randomized, Double-Blind, Placebo-Controlled Trial of Metformin for Antipsychotic-Induced Weight Gain in Patients with First-Episode Psychosis: A Pilot Study

Abstract

Excessive weight gain and cardiometabolic dysfunction are common and clinically relevant side effects of antipsychotic medications. In this pilot study, we aimed to establish the feasibility of using metformin and its effectiveness in managing antipsychotic-induced weight gain in patients with first-episode psychosis (FEP) on follow-up with the Singapore Early Psychosis Intervention Programme in a 24-week, randomized, double-blind, placebo-controlled trial, to ascertain the effects of metformin discontinuation on body weight and evaluate the safety and tolerability of metformin. Participants between the ages of 16 and 40 with FEP assessed as clinically stable and who had gained ≥5% of their pre-drug weight after initiation of the antipsychotic treatment were recruited from outpatient clinics between April 2015 and April 2018. Seventeen participants met all the inclusion criteria and were randomized to receive metformin (n = 8) or the placebo (n = 9) at Week 0, with follow up assessments at Weeks 3, 6, 12, 24, and 36. Metformin was generally well-tolerated. Participants in the metformin arm were able to control their weight better than participants receiving the placebo, an effect that did not persist after discontinuation. Our results support the use of metformin as a safe and tolerable weight control measure in a typical outpatient sample of young people with FEP.

The potential effect of metformin on cognitive and other symptom dimensions in patients with schizophrenia and antipsychotic-induced weight gain: a systematic review, meta-analysis, and meta-regression

“…Four studies ( 66–69 ) included patients diagnosed with bipolar disorder and other psychiatric disorders (DSM-IV), however in a negligible percentage: as an example, Agarwal et al 2 patients out of 30; Baptista et al 4 patients out of 80. In 5 trials ( 66 , 70–73 ) only overweight/obese patients were included, and 6 trials reported diabetes or prediabetes among the exclusion criteria ( 66 , 69 , 70 , 72 , 74 , 75 ). All studies, except Mondal et al ( 64 ), reported any other chronic disease (such as thyroid, liver or renal dysfunction, cardiovascular disease) and pregnancy among the exclusion criteria.…”

“…Clozapine, olanzapine, aripiprazole, and risperidone were the most used antipsychotics. In 3 trials the concomitant use of mood stabilizers, benzodiazepines and antidepressants was permitted ( 65 , 69 , 75 ). Lifestyle intervention involving diet and physical exercise was provided in 6 trials ( 65 , 66 , 68 , 72 , 76 , 77 ).…”

Should antidiabetic medicines be considered to reduce cardiometabolic risk in patients with serious mental illness?

“…Most prevention trials clarified their exclusion of people with diabetes, whereas trials to mitigate antipsychotic‐induced weight gain often included such patients. Trials aimed at reversing weight gain typically recruited patients who experienced weight gain of at least 10% bodyweight, although results from a recent pilot RCT conducted in Singapore that included 17 participants suggest that there may be benefits following first episode psychosis for patients with weight gain as low as 5% bodyweight 32 …”

“…Trials aimed at reversing weight gain typically recruited patients who experienced weight gain of at least 10% bodyweight, although results from a recent pilot RCT conducted in Singapore that included 17 participants suggest that there may be benefits following first episode psychosis for patients with weight gain as low as 5% bodyweight. 32 A caveat for interpreting meta-analysis results is that many do not provide subgroup analyses for those without (and with) diabetes at baseline. Indeed, ten of 17 meta-analyses did not provide baseline descriptions of diabetes status (Supporting Information, supplementary material 1).…”

“…Trials aimed at reversing weight gain typically recruited patients who experienced weight gain of at least 10% bodyweight, although results from a recent pilot RCT conducted in Singapore that included 17 participants suggest that there may be benefits following first episode psychosis for patients with weight gain as low as 5% bodyweight. 32 …”