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.

Weight gain is a long-recognized side-effect of antipsychotic (AP) drugs and a major health concern in the treatment of psychosis. The strength of the causal relationship between AP drug exposure and weight gain can only be gauged by a drugs trial conducted on AP-naive patients.

We conducted a review of the literature regarding the amount of weight gain induced by APs in AP-naive patients and carried out a meta-analysis of mean weight gains.

We found 11 primary studies reporting the effects of APs on body weight or body mass index (BMI) in AP-naive patients. The mean body weight and BMI gains in AP-naive patients were highly significant from the first weeks of treatment. When we limited the analysis to studies conducted on patients hospitalized and without any adjunctive treatment potentially affecting weight, the resultant sample showed less heterogeneity and confirmed the final picture of weight gain at around 3.8 kg and 1.2 points BMI.

Weight gain associated with AP therapy in AP-naive patients occurs rapidly in the first few weeks and continues during the following months. Clinicians should be aware of the high probability of causing weight gain in AP-naive patients and should strictly monitor such patients.

Spontaneous movement disorders (SMDs), such as spontaneous dyskinesia and parkinsonism, have been described in patients with schizophrenia who have never been treated with antipsychotic medication. Their presence has been documented extensively in chronic schizophrenia but not at the time of illness onset.

We performed a systematic review of studies investigating spontaneous abnormal movements elicited on clinical examination in antipsychotic-naive patients with first-episode psychosis.

We identified a total of 13 studies. Findings suggest a spontaneous dyskinesia median rate of 9% and a spontaneous parkinsonism median rate of 17%. Information on akathisia and dystonia was limited. The presence of SMDs may be associated with negative symptoms and cognitive dysfunction.

These findings support the notion that spontaneous abnormal movements are part of a neurodysfunction intrinsic to the pathogenesis of schizophrenia. Future studies should further investigate the role of basal ganglia and extrapyramidal pathways in the pathophysiology of psychosis, with particular attention to treatment implications.