Almost All Antipsychotics Result in Weight Gain: A Meta-Analysis

Abstract

IntroductionAntipsychotics (AP) induce weight gain. However, reviews and meta-analyses generally are restricted to second generation antipsychotics (SGA) and do not stratify for duration of AP use. It is hypothesised that patients gain more weight if duration of AP use is longer.MethodA meta-analysis was conducted of clinical trials of AP that reported weight change. Outcome measures were body weight change, change in BMI and clinically relevant weight change (7% weight gain or loss). Duration of AP-use was stratified as follows: ≤6 weeks, 6–16 weeks, 16–38 weeks and >38 weeks. Forest plots stratified by AP as well as by duration of use were generated and results were summarised in figures.Results307 articles met inclusion criteria. The majority were AP switch studies. Almost all AP showed a degree of weight gain after prolonged use, except for amisulpride, aripiprazole and ziprasidone, for which prolonged exposure resulted in negligible weight change. The level of weight gain per AP varied from discrete to severe. Contrary to expectations, switch of AP did not result in weight loss for amisulpride, aripiprazole or ziprasidone. In AP-naive patients, weight gain was much more pronounced for all AP.ConclusionGiven prolonged exposure, virtually all AP are associated with weight gain. The rational of switching AP to achieve weight reduction may be overrated. In AP-naive patients, weight gain is more pronounced.

Altered reward anticipation: Potential explanation for weight gain in schizophrenia?

“…As shown in a recent meta-analysis (Bak et al, 2014), the life expectancy of patients with severe mental illness is lower than that of the general population (Chang et al, 2011). Patients with schizophrenia have 2-3 times higher standard mortality ratio for all causes of death (Laursen et al, 2012).…”

“…A recent meta-analysis showed that all antipsychotic drugs are associated with weight gain (Bak et al, 2014). Moreover, antipsychotic medication is not only related to weight gain in schizophrenia but also in other severe mental disorders (Bak et al, 2014;Parsons et al, 2009;Rummel-Kluge et al, 2010).…”

“…However, histaminergic action cannot fully explain the subsequently increased weight gain: As a recent meta-analysis pointed out, all antipsychotic drugs result in weight gain (Bak et al, 2014). While the antihistaminergic properties might explain why some drugs result in faster or greater weight gain, they do not explain the mechanism common to almost all antipsychotics.…”

“…They typically concentrate on i) dysregulation of neuroendocrinological circuits (e.g., hormonal regulation by the hypothalamus; Sharma et al, 2014); ii) dysregulation of peripheral hormones (e.g., leptin and ghrelin) implicated in weight homeostasis and in regulation of glucose (De Hert et al, 2009;Mitchell et al, 2013;Sentissi et al, 2008); and iii) the effect of antipsychotic medication on weight (Bak et al, 2014;Deng et al, 2010;Sharma et al, 2014). All of these factors are important.…”

The Effects of Modafinil in People with a Diagnosis of Schizophrenia

“…Furthermore, through a reduction in appetite modafinil has been found to reduce food intake in healthy people [25] [26] and may counteract the weight gain caused by anti-psychotics [27] which increase appetite [28]. However, modafinil is not without risks when used with people with a diagnosis of schizophrenia, there have been reported cases of increased positive symptoms [29].…”