Detecting and Managing Adverse Effects of Antipsychotic Medications: Current State of Play

Key points

Weight gain

Relative to the general population, treatment-naïve patients with schizophrenia and bipolar disorder have a higher prevalence of obesity and being overweight.2, 3 Nonetheless, controlled clinical trials have consistently demonstrated greater degrees of weight gain during treatment with APDs compared with placebo, although individual differences in relative weight gain exist between medications. Weight gain and obesity are concerning due to an associated decrease in medication adherence and an

Diabetes

Patients with schizophrenia and bipolar disorder have a 2 to 3 times greater risk of diabetes and obesity than the general population, with an estimated prevalence of 10% to 15%.54, 55 Although the observation that diabetes is overrepresented among those with schizophrenia dates back to before the introduction and widespread use of APDs,56, 57 subsequent research clearly indicates a strong association between treatment with APDs and insulin resistance, glucose dysregulation, and the development

Hyperlipidemia

In addition to weight gain and glucose dysregulation, SGAs have been shown to cause HLP. HLP encompasses triglycerides and cholesterol, which is composed of low-density lipoproteins (LDLs), commonly known as “bad cholesterol,” and high-density lipoproteins (HDLs), commonly known as “good cholesterol.” That APDs can lead to HLP is of clinical significance due to the long-term consequences on overall cardiovascular health in individuals taking this class of medications, particularly those with

Cardiac adverse effects

In 2001, evidence from a large, controlled, epidemiologic study underscored concerns about the proarrhythmic effects of FGAs, including sudden cardiac death (SCD).⁹⁰ Between 2004 and 2006, case reports of drug-induced torsades de pointes (TdP) involving RIS, QTP, and ZIP were published,91, 92, 93 followed in 2009 by epidemiologic data establishing an association between SGAs and increased risk for SCD.⁹⁴

Hyperprolactinemia

Drug-induced hPRL is a side effect commonly associated with FGAs, occurring in up to 70% of patients receiving APDs overall.¹⁶⁶ Estrogen’s effects on prolactin (PRL) gene expression regulate PRL synthesis. Elevated PRL levels associated with APDs are greater in women than in men. In 1 study, the prevalence of hPRL was more common in premenopausal women taking FGAs (48%–93%) compared with men (42%–47%).¹⁶⁷ Another study found a similar prevalence range of hPRL for women (42%–93%); however, the

Osteoporosis

Like many chronic diseases, osteoporosis is more prevalent among people with schizophrenia than the general population.²¹¹ Stubbs and colleagues²¹² performed a meta-analysis of 19 cross-sectional studies examining bone mineral density (BMD) in patients with schizophrenia and found that 51.7% of patients had low bone mass, 40.0% had osteopenia, and 13.2% had osteoporosis. The prevalence of low bone mass was twice that of age-matched and gender-matched controls (OR = 1.9), whereas osteoporosis

Summary

This article provides an extensive review of many of the nonextrapyramidal side effects of APDs. Given a multitude of APD options, clinicians must weigh the relative risks and benefits of medications with collaborative decision making with patients to optimize recovery. Patients should be informed of potential adverse effects, with each visit representing an opportunity to review both positive and negative experiences associated with APD treatment. Optimal care requires that clinicians be adept

Acknowledgments

The authors wish to thank Alissa Myer, Christine Canilao, Thien Nguyen, and Zachary Erickson for article preparation assistance.