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This review provides a summary of the most recent evidence of the adverse effects profiles of each of the currently available antipsychotic medications.
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This article reviews the relative propensity for certain antipsychotics to induce weight gain, diabetes, hyperlipidemia (HLP), cardiac side effects, sudden death, sexual side effects, and osteoporosis.
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Readers will learn about appropriate clinical approaches to recognizing, monitoring and mitigating adverse effects.
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Guidelines for appropriate
Detecting and Managing Adverse Effects of Antipsychotic Medications: Current State of Play
Section snippets
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
Mortality in Schizophrenia
It is well known that individuals with schizophrenia have a greater risk of early mortality compared with the general population, with a reduced life expectancy of 10 to 25 years.129 A systematic review of international studies found a median standard mortality ratio of 2.58 for schizophrenia, meaning that persons with the illness have between a 2-fold to 3-fold increase in death compared with age-matched controls.130 This mortality gap for schizophrenia has been increasing since the 1970s,
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
Mechanisms
APDs have been associated with all phases of sexual dysfunction, such as decreased sexual desire, sexual arousal, anorgasmia, and delayed or retrograde ejaculation.194, 195 Dopamine exerts a positive influence on libido, whereas serotonin has negative effects. PRL can decrease testosterone, which is an important hormone for healthy libido in both men and women. As D2 antagonists, APDs can, therefore, decrease libido. Norepinephrine, acetylcholine, and dopamine facilitate sexual arousal, whereas
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.
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