Metabolic disturbances associated with antipsychotic drug treatment in patients with schizophrenia: State-of-the-art and future perspectives

Abstract

Metabolic disturbances and obesity are major cardiovascular risk factors in patients with schizophrenia, resulting in a higher mortality rate and shorter life expectancy compared with those in the general population. Although schizophrenia and metabolic disturbances may share certain genetic or pathobiological risks, antipsychotics, particularly those of second generation, may further increase the risk of weight gain and metabolic disturbances in patients with schizophrenia. This review included articles on weight gain and metabolic disturbances related to antipsychotics and their mechanisms, monitoring guidelines, and interventions. Nearly all antipsychotics are associated with weight gain, but the degree of the weight gain varies considerably. Although certain neurotransmitter receptor-binding affinities and hormones are correlated with weight gain and specific metabolic abnormalities, the precise mechanisms underlying antipsychotic-induced weight gain and metabolic disturbances remain unclear. Emerging evidence indicates the role of genetic polymorphisms associated with antipsychotic-induced weight gain and antipsychotic-induced metabolic disturbances. Although many guidelines for screening and monitoring antipsychotic-induced metabolic disturbances have been developed, they are not routinely implemented in clinical care. Numerous studies have also investigated strategies for managing antipsychotic-induced metabolic disturbances. Thus, patients and their caregivers must be educated and motivated to pursue a healthier life through smoking cessation and dietary and physical activity programs. If lifestyle intervention fails, switching to another antipsychotic drug with a lower metabolic risk or adding adjunctive medication to mitigate weight gain should be considered. Antipsychotic medications are essential for schizophrenia treatment, hence clinicians should monitor and manage the resulting weight gain and metabolic disturbances.

Mental and Body Health: The Association between Psychological Factors, Overweight, and Blood Pressure in Young Adults

“…On the one hand, obesity-related stigmatization may result in high mental distress [ 20 , 21 , 22 ]; on the other hand, inappropriate eating behaviors (e.g., emotional eating) may lead to obesity in individuals with poor mental health and maladaptive coping strategies [ 23 ]. Moreover, the effect of antipsychotic medication for the treatment of psychiatric disorders (e.g., schizophrenia [ 24 ]) is a risk factor for severe weight gain. If associated with severe adiposity, both conditions can generate cardiovascular damage.…”

Functional characterization of six SLCO1B1 (OATP1B1) variants observed in Finnish individuals with a psychotic disorder

“…While to date, according to The University of Washington Drug Interaction Database (DIDB) 41 , no central nervous system agents have been identified as OATP1B1 substrates, many other drugs can be prescribed to these patients to treat their somatic diseases. Among these are often statins to treat dyslipidemias which are associated with antipsychotic medications 9 . The association between statin-use and muscle symptoms has been thoroughly investigated.…”

Crosstalk between Schizophrenia and Metabolic Syndrome: The Role of Oxytocinergic Dysfunction

“…Several hormones are also thought to be involved in the management of satiety, feeding, and glucose metabolism, and they have been implicated in the mechanism of antipsychotics-related metabolic disturbances. For example, dysregulations of insulin, cortisol, glucagon, glucagon-like peptide 1, cholecystokinin, adiponectin, ghrelin, leptin, orexin, prolactin, and oxytocin have been observed during treatment with antipsychotics among persons with schizophrenia [69,70]. Although it is still debatable whether this is a compensatory mechanism for insulin resistance or a direct consequence of β-cell stimulation by antipsychotics [66], increased basal insulin secretion at high concentrations was observed in persons with schizophrenia after receiving antipsychotics [71].…”