Schizophrenia is a debilitating and often life-long disorder that ranks among the 20 top causes of disability according to the Global Burden of Disease Study [
1]. Antipsychotic drugs are the mainstay of the treatment of schizophrenia. They are proven to be effective for the acute phase [
2] and for recurrence prophylaxis [
3], and many individuals take antipsychotics for years, or even lifetime [
4,
5]. However, antipsychotics cause important side effects, most importantly extrapyramidal motor disorders, increase in prolactin and metabolic side effects [
6]. Metabolic side effects comprise weight gain, disturbances in cholesterol and triglyceride metabolism (dyslipidaemia) and dysregulation of glucose homeostasis (insulin resistance extending in diabetes) [
7]. Obesity, dyslipidaemia and insulin resistance are key components of the metabolic syndrome [
8‐
13] and are associated with important somatic diseases such as cardiovascular disorders, stroke and diabetes [
14]. Thereby, metabolic side effects of antipsychotics are likely to contribute to the on average 14.5 years reduced life-span of individuals with schizophrenia [
15]. Moreover, weight gain is an important subjective factor reducing the quality of life among persons with schizophrenia [
16]. As a consequence, metabolic side effects are also linked to drug non-adherence [
17], resulting in poor treatment outcomes and psychotic relapses. The decision of clinicians and individuals with schizophrenia which antipsychotic compound to use is often based on the profile of side effects because antipsychotic substances do not differ much in efficacy, but enormously in side effects [
6]. Therefore, it is a field of big interest and ongoing research.
Recently Pillinger et al. [
18] conducted a network meta-analysis focussing on the comparative effects of 18 antipsychotics on metabolic function during short-term treatment of patients with schizophrenia. The median treatment duration of the included trials was 6 weeks (IQR 6–8). However, it can be assumed that the metabolic side effects have not peaked after few weeks of treatment yet, and data of longer treatment duration could differ. Up to date, it is unknown how antipsychotic compounds differ in extent and time pattern of causing metabolic side effects in medium- to long-term use. Pérez-Iglesias et al. [
19] observed changes in weight and lipids especially during the course of the first year (in a cohort of first episode patients treated with haloperidol, olanzapine and risperidone for up to 3 years). Millen et al. [
20] showed in a pooled analysis of 86 clinical trials including adults treated with the oral or depot formulations of olanzapine that weight increases most rapidly in the first 3 months of treatment, and then the increase slows down but continues, tending to reach a plateau after 6–12 months. De Hert et al. [
7] assumed that the greatest amount of weight gain associated with antipsychotic therapy in previously drug-naive individuals with schizophrenia occurs on a scale of few months. Thus, analysing the metabolic parameters after several months of treatment in an expected nearly “steady-state” can deliver important information on how antipsychotics differ in the medium- to long-term treatment. To date, evidence is still fragmentary, and there is no comprehensive comparison of this kind.