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sion or bipolar disorder have a 1.2 to 1.5 increased likelihood adolescents (<18 years old) identified the same hierarchy for of being obese (BMI ≥30) (44,69,70,81,82). Clinical research risk of weight gain for this vulnerable population (109). Among has suggested that up to 68% of treatment-seeking bipolar the conventional AP, so-called low-potency agents, such as disorder patients are overweight or obese (83). One study chlorpromazine and thioridazine, have a higher risk than found an obesity rate (BMI ≥30) of 57.8% among those with high-potency drugs, such as haloperidol (110-112). No agent, however, should be considered as truly weight-neutral, as the In patients with SMI, as in the general population, obe- proportion of individuals experiencing ≥7% weight gain is sity is associated with lifestyle factors (e.g., lack of exercise, greater with any atypical AP than with placebo (92), and all poor diet), but also with illness-related (negative, disorgan- AP have been found to cause significant weight gain in AP-ized and depressive symptoms) and treatment-related fac- naïve or first-episode patients (113-115). Even amisulpride, tors, including weight liability of certain psychotropic ziprasidone and low-dose haloperidol demonstrated notable agents. Adverse effects, such as sedation, should also be weight gain of 9.7 kg, 4.8 kg and 6.3 kg respectively at endpoint considered as potential contributors to weight gain in addi- in a 12-month trial of AP in first-episode patients (102). Equal-tion to, still not fully elucidated, medication induced effects ly, antidepressants (AD) such as paroxetine (116), and mood on appetite and food intake (45,73,50,85-87). stabilizers, such as lithium and valproate (117-119), have been associated with weight gain (Table 3).
The high interindividual variability in medication-induced weight gain suggests that genetic factors influence the risk to Weight gain during acute and maintenance treatment of gain weight (50,122). Studies of genetic predictors of weight patients with schizophrenia is a well established side effect of gain under AP therapy have mainly but not exclusively (131) antipsychotics (AP), affecting between 15 and 72% of patients focused on HTR2C (132-135) and LEPR (135,136) gene (26,50,77,88-98). There is growing evidence for similar effects polymorphisms. Although the results are promising, the role in patients with bipolar disorder (65,83,99). There is a hierar- of genetic factors in predicting this severe side effect remains chy for risk of weight gain with AP that has been confirmed in an option for the future. different studies and meta-analyses (88,92,100-106). Weight gain is greatest with clozapine and olanzapine (107,108), while quetiapine and risperidone have an intermediate risk. Metabolic syndrome Aripiprazole, asenapine, amisulpride and ziprasidone have little effect on weight. A recent systematic review of random- Obesity is also associated with the metabolic syndrome ized, placebo controlled trials of novel AP in children and (MetS), a clustering of abnormalities that confers a 5-6-fold Table 3 Weight gain liability of psychotropic agents used in SMI (see 45,63-65,87,95,99,104,120,121-130)
Drug class
Weight loss
Relatively weight neutral
Weight gain
Aripiprazole (in pre-treated individuals)

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