Previous meta-analyses have shown that almost all antipsychotics are associated with weight gain. However, mean weight gain is not informative about clinically relevant weight gain or weight loss.

To provide further insight into the more severe body weight changes associated with antipsychotic use, we assessed the proportion of patients with clinically relevant weight gain (CRWG) and clinically relevant weight loss (CRWL), defined as ≥7% weight gain and ≥7% weight loss.

We searched PubMed, Embase and PsycInfo for randomised controlled trials of antipsychotics that reported CRWG and CRWL in study populations aged 15 years or older. We conducted meta-analyses stratified by antipsychotic and study duration using a random-effects model. We performed meta-regression analyses to assess antipsychotic-naive status and psychiatric diagnosis as modifiers for CRWG. PROSPERO: CRD42020204734.

We included 202 articles (201 studies). Almost all included antipsychotics were associated with CRWG. For CRWL, available data were too limited to draw firm conclusions. For some antipsychotics, CRWG was more pronounced in individuals who were antipsychotic-naive than in individuals switching to another antipsychotic. Moreover, a longer duration of antipsychotic use was associated with more CRWG, but not CRWL. For some antipsychotics, CRWG was higher in people diagnosed with schizophrenia, but this was inconsistent.

Switching antipsychotic medication is associated with both weight gain and weight loss, but the level of CRWG is higher than CRWL in antipsychotic-switch studies. CRWG was more pronounced in antipsychotic-naive patients, highlighting their vulnerability to weight gain. The impact of diagnosis on CRWG remains inconclusive.