eTable 4. Detection and treatment of metabolic adverse events (modified from [1]).

Intervention	Recommendation	Evidence (selected) [95% confidence interval]
►Step 1 Detection and classification (7% rule), check whether dose reduction, a switch to another preparation, or discontinuation is feasible. These strategies must be balanced against the danger of worsening symptoms or relapse.	52, 53, 54 (all CCP)	Detection according to the 7% rule: – A position paper of the European Psychiatric Association (EPA), the European Association for the Study of Diabetes (EASD), and the European Society of Cardiology (ESC) recommends intervention if >7% of weight is gained in the first 6 weeks after initiation of antipsychotic treatment, relative to baseline (e40) Particularly close monitoring of antipsychotics that are known to sometimes lead to significant weight gain (network meta-analysis [33]): – zotepine, olanzapine, sertindole, iloperidone, quetiapine, clozapine, paliperidone, risperidone, asenapine Meta-analysis on switch from olanzapine to aripiprazole/quetiapine: – weight loss of −1.94 kg [−3.90; 0.08] (e41)
►Step 2 In the event of >7% weight gain, offer psychotherapeutic and psychosocial interventions (nutritional counseling, psychoeducation, exercise programs) to prevent weight gain or achieve weight loss.	55 (A)	Psychosocial intervention/psychotherapy vs. standard treatment (meta-analysis) (e42): – weight loss of −2.56 kg [−3.20; −1.92] Nutritional program vs. control (meta-analysis) (e43): – weight loss in general g = −0.39 [−0.56; −0.21] – weight loss when program was offered at the beginning of antipsychotic treatment g = –0.61 [−1.02; –0.18]
►Step 3 In the event of pronounced weight gain, and after step 2 has taken place, offer off-label metformin (first choice) or topiramate (second choice). Look out for potential interactions and worsening of adverse events due to combination treatments, as well as substance-specific characteristics (e.g., metformin → metabolic acidosis, topiramate → dyscognitive effects)	56 (A)	Metformin versus placebo (meta-analyses) – weight loss: −3.27 kg [−4.66; −1.89] (e44) – weight loss: −3.17 kg [−4.44; −1.90] (e45) – clozapine subgroup: −3.12 kg [−4.88; −1.37] (e46) Topiramate versus placebo (meta-analyses) – weight loss: −2.83 kg [−4.62; −1.03] (e47) –  weight loss: −2.75 kg [−4.03; −1.47] (e48)