Cardiometabolic effects of psychotropic medications

Abstract

Background Many psychiatric disorders including schizophrenia, bipolar disorder and major depression convey an excess burden of cardiovascular morbidity and mortality. The medications used to treat these conditions may further adversely affect cardiovascular risk and exacerbate health disparities for vulnerable populations. There is a clinical need to appreciate the cardiometabolic adverse effects of psychotropic medications. Methods This paper reviews the most relevant cardiometabolic effects of psychotropic medications, organized around the components of metabolic syndrome. When known, the molecular and physiological mechanisms underlying any adverse cardiometabolic effects are detailed. Results Many commonly used psychotropic medications, particularly antipsychotics, mood stabilizers and some antidepressants, have been independently associated with cardiometabolic risk factors such as insulin resistance, obesity and dyslipidemia. Stimulants, antidepressants that inhibit reuptake of norepinephrine, some antipsychotics and valproic acid derivatives may also increase blood pressure. Conclusion Understanding, assessing and subsequently managing cardiometabolic complications of psychotropic medications are important to mitigate the excess cardiovascular morbidity and mortality in the clinical populations prescribed psychotropic medications. There is considerable variability in risk between medications and individuals. Timely management of iatrogenic cardiometabolic effects is critical.

Keywords: adverse effects; anticonvulsants; antidepressive agents; antipsychotics; diabetes mellitus; dyslipidemias; lithium; metabolic syndrome; psychotropic drugs; weight gain.

Figure 1.. Variability in observed weight gain.

This figure illustrates the considerable individual variability in weight changes that can be seen with antipsychotic treatment. This data is from a Correll CU et al. study of 135 antipsychotic-naïve children and adolescents treated with risperidone for three months. The mean weight gain in this study was 5.3 kg [19]. Antipsychotic-naïve individuals gain more weight than those with prior treatment.

Figure 2.. Weight gain for antipsychotics used in the CATIE study.

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study randomly assigned 1,493 patients with schizophrenia to flexibly dosed olanzapine (7.5–30 mg/day), quetiapine (200–800 mg/day), risperidone (1.5–6.0 mg/day), perphenazine (8–32 mg/day), and, introduced in the latter portion of the study, ziprasidone (40–60 mg/day). The greatest weight gain was observed with olanzapine, followed by quetiapine and risperidone [20].

Figure 3.. Propensity for weight gain for selected psychotropic medications.

Medications and those who take them exhibit considerable variability in liability for weight gain. Aripiprazole, as an exemplar for this, shows variable propensity for weight gain across studies. The figure approximates risk across a variety of commonly prescribed psychiatric medications associated with weight gain. Relative position should not be used to infer clear differences between agents, particularly for agents from different classes where head-to-head data is less common.

Figure 4.. Summary of psychotropic medications associated with cardiometabolic iatrogenic effects.

This figure summarizes the medications or medication classes, where appropriate, associated with the cardiometabolic adverse effects that served as the focus of this review: weight gain dyslipidemia, insulin resistance or frank type 2 diabetes mellitus, and hypertension.