S2. ANTIPSYCHOTICS RESULT IN WEIGHT GAIN BUT THE SEVERITY OF WEIGHT GAIN DIFFERS BETWEEN ANTIPSYCHOTICS
Authors: Bak Maarten , Drukker Marjan , Campforts Bea , Cortenraad Shauna , Vandenberk Emma , Viechtbauer Wolfgang 
Published: May 2020

Abstract

Background
Antipsychotic (AP) medication is associated with metabolic dysregulation, increasing the risk for weight gain. Previously, we showed that all antipsychotics are related with body weight gain and there was a time effect, the longer the AP was taken the more the weight gain was (Bak, Fransen, Janssen, van Os, & Drukker, 2014). This study included data from 1999–2013. The aim of this study is to up-date the previous study on weight gain by extending the search from 1960 – July 2019. So, older studies of before 2000 were in included as well as studies on AP’s after 2014. The differences in weight change between the various AP’s were calculated.

Methods
A systematic search was performed using the databases PubMed and EMBASE. Eligible RCTs were identified and no restriction was made regarding diagnosis or publication date. Statistical analysis was based on a random effects model from which forest plots were generated. Effect sizes were reported as the standardized mean difference (SMD) with 95% confidence intervals (CI). Results were presented stratified by four exposure categories, namely &lt; 6 weeks, 6–16 weeks, 16–38 weeks, and ≥ 38 weeks. Furthermore, that results are divided in AP naive patients (patients who had no AP previously) and patient in whom AP were switched from at least one other AP. Patients &gt;17 years of age were excluded and all diagnostic categories were included.

Results
In total 3488 papers were found. Following PRSIMA guidelines in total 472 papers were eligible for inclusion.
Preliminary results. For the longer term 16–38 & &gt;38 wks all AP-naive patients showed an increase in weight of &gt; 5 kg, except for aripiprazole (&lt; 6wks, 0.46kg; 6-16wks, 2.04kg; 16-38wks, 4.5kg; &gt;38 wks, 3.31kg), paliperidone (&lt; 6wks, 1.24kg; 6-16wks, 1.69kg; 16-38wks, -0.3kg; &gt;38wks 0.2kg), quetiapine (&lt; 6wks, 2.51kg; 6-16wks, 2.69kg; 16-38wks, 3.02kg; &gt;38wks 6.14kg) and ziprasidone (&lt; 6wks, 0.06kg; 6-16wks, 0.32kg; 16-38wks, 0.51kg; &gt;38wks 2.18kg). The result of the switch studies shows that clozapine and olanzapine result in most weight gain after switch. Other AP result in modest weight gain to weight loss over the various time periods: amisulpride (range -0.76 and 1.40), aripriprazole (range -0.81 and 0.81), asenapine (-0.99 – 1.14), haloperidol (0.49 – 1.31) and ziprasidone (-1.18 – -0.38).
During SIRS final results will be presented.

Discussion
The number of studies in AP naif patients is limited. Most RCT’s discuses medication evaluation after switch into a new compound. Here, metabolic changes may interact with evaluation of changes in weight. However, switching an AP because after severe weight gain needs to be considered with caution as it does not result in considerable weight loss. The AP-naive show that all AP lead to weight gain. Given only patient older than 17years were included, this might explain the limited number of available studies. However, younger age seems to be associated were an increased risk of weight gain.

Reference
Bak, M., Fransen, A., Janssen, J., van Os, J., & Drukker, M. (2014). Almost all antipsychotics result in weight gain: a meta-analysis. PLoS One, 9(4), e94112. doi:10.1371/journal.pone.0094112