Weight gain and metabolic disturbances are common side effects during psychopharmacological
treatment with specific antipsychotics and antidepressants. The antipsychotics clozapine and
olanzapine, and antidepressants tricyclics and mirtazapine have a high risk of inducing weight gain.
Recently discovered pathophysiological mechanisms include antihistaminergic effects, activation of
hypothalamic adenosine monophosphate-activated protein kinase (AMPK), modulation of hormonal signaling of ghrelin
and leptin, changes in the production of cytokines such as tumor necrosis factor-alpha (TNF)-alpha and adipokines such as
adiponektin, and the impact of genes, in particular the melanocortin 4 receptor (MC4R), serotonin 2C receptor (HTR2C),
leptin, neuropeptide Y (NPY) and cannabinoid receptor 1 (CNR1) genes.
Metabolic changes associated with weight gain include disturbances of glucose and lipid metabolism. Clozapine and
olanzapine may, in addition to mechanisms resulting from weight gain, impair glucose metabolism by blockade of the
muscarinic M3 receptor (M3R). Antidepressants associated with weight gain appear to have fewer unfavourable effects on
glucose and lipid metabolism than the second-generation antipsychotics clozapine and olanzapine.
To assess the risk of weight gain and its consequences for the patient’s health, assessing body weight changes and
metabolic monitoring in the first week of treatment as well as in long-term treatment is recommended.