Can melatonin prevent or improve metabolic side effects during antipsychotic treatments?

In the last two decades, second-generation antipsychotics (SGAs) were more frequently used than typical antipsychotics for treating both psychotic and nonpsychotic psychiatric disorders in both children and adolescents, because of their lower risk of adverse neurological effects, that is, extrapyramidal symptoms. Recent studies have pointed out their effect on weight gain and increased visceral adiposity as they induce metabolic syndrome. Patients receiving SGAs often need to be treated with other substances to counteract metabolic side effects. In this paper, we point out the possible protective effect of add-on melatonin treatment in preventing, mitigating, or even reversing SGAs metabolic effects, improving quality of life and providing safer long-term treatments in pediatric patients. Melatonin is an endogenous indolamine secreted during darkness by the pineal gland; it plays a key role in regulating the circadian rhythm, generated by the suprachiasmatic nuclei (SCN) of the hypothalamus, and has many other biological functions, including chronobiotic, antioxidant and neuroprotective properties, anti-inflammatory and free radical scavenging effects, and diminishing oxidative injury and fat distribution. It has been hypothesized that SGAs cause adverse metabolic effects that may be restored by nightly administration of melatonin because of its influence on autonomic and hormonal outputs. Interestingly, atypical anti-psychotics (AAPs) can cause several sleep disorders, and circadian misalignment can influence hormones involved in the metabolic regulation, such as insulin, leptin, and ghrelin; furthermore, a relationship between obesity and sleep curtailment has been demonstrated, as well as sleep deprivation in rats has been associated with hyperphagia. Metabolic effects of melatonin, both central and peripheral, direct and indirect, target most metabolic disorders reported during and after SGA treatment in children, adolescents, and adults. Further systematic studies on psychiatric patients are needed to explore the effect of add-on melatonin on metabolic side effects of SGAs, independent of energy intake, diet, and exercise.