Atypical antipsychotics, also known as second-generation antipsychotics (SGAs), are a class of medications used to manage symptoms for a range of psychiatric disorders, including schizophrenia, bipolar disorder, and severe depression [1.7.1, 1.7.3]. They are often preferred over older, typical antipsychotics because they generally have a lower risk of causing extrapyramidal symptoms (EPS), which are drug-induced movement disorders [1.6.3]. However, they are associated with a different set of significant adverse effects.
Understanding the Most Common Side Effects
Atypical antipsychotics are strongly associated with a cluster of metabolic side effects [1.3.1]. While it is difficult to single out one "most common" side effect across all drugs in this diverse class, weight gain is among the most frequently cited and distressing for patients [1.3.4]. Many atypical antipsychotics can interfere with the body's natural satiety signals, making individuals feel hungrier and leading them to eat more [1.2.6].
Beyond weight gain, a constellation of metabolic issues, often termed metabolic syndrome, is a primary concern. This syndrome includes [1.3.4, 1.3.7]:
- Significant Weight Gain: Some medications, like clozapine and olanzapine, are associated with the highest potential for weight gain, which can exceed 10 kg in the first year of treatment [1.2.3, 1.3.5].
- Dyslipidemia: This refers to an unhealthy level of lipids (fats) in the blood, such as high cholesterol and triglycerides [1.2.3]. Olanzapine and clozapine are also linked to a greater risk of increased cholesterol and triglyceride levels [1.2.6].
- Hyperglycemia (High Blood Sugar): These medications can impair glucose metabolism and increase the risk of developing type 2 diabetes. This can occur even without significant weight gain [1.3.2, 1.2.6].
- Hypertension (High Blood Pressure): An increase in blood pressure is another component of metabolic syndrome that can be influenced by these drugs [1.3.7].
Other Prevalent Side Effects
Besides metabolic changes, patients may experience a variety of other side effects, which vary in intensity depending on the specific medication:
- Sedation and Drowsiness: Many atypical agents cause sedation due to their antihistamine activity. Quetiapine, olanzapine, and clozapine are known to be particularly sedating [1.2.1, 1.2.6].
- Anticholinergic Effects: These include dry mouth, blurred vision, constipation, and urinary retention. Clozapine, olanzapine, and quetiapine are powerful anti-muscarinic agents that can cause these effects [1.2.1, 1.6.7].
- Orthostatic Hypotension: This is a drop in blood pressure when standing up, which can cause dizziness and falls. It's caused by the blockade of alpha-adrenergic receptors and is common with drugs like clozapine and quetiapine [1.2.7, 1.5.4].
- Hyperprolactinemia: Some atypical antipsychotics, most notably risperidone and paliperidone, can increase levels of the hormone prolactin. This can lead to sexual dysfunction, menstrual irregularities, and breast enlargement or discharge [1.2.3, 1.5.2].
Comparison of Side Effect Risks
Atypical antipsychotics are not a homogenous class; their side effect profiles differ significantly. Clinicians must weigh these differences when selecting a medication for an individual patient [1.2.3].
| Side Effect Category | High Risk | Moderate Risk | Low Risk |
|---|---|---|---|
| Weight Gain | Clozapine, Olanzapine [1.3.5] | Quetiapine, Risperidone, Paliperidone [1.3.5] | Ziprasidone, Aripiprazole, Lurasidone [1.3.5] |
| Extrapyramidal Symptoms (EPS) | Risperidone (at higher doses) [1.2.6] | Olanzapine [1.2.3] | Quetiapine, Clozapine [1.6.4] |
| Prolactin Elevation | Risperidone, Paliperidone [1.5.2] | Olanzapine [1.2.3] | Aripiprazole, Quetiapine, Clozapine [1.5.2, 1.2.3] |
| Sedation | Clozapine, Quetiapine, Olanzapine [1.2.1] | Risperidone [1.2.3] | Aripiprazole [1.2.6] |
Managing Side Effects
Effective management of side effects is crucial for treatment adherence and overall health. Strategies include:
- Lifestyle Interventions: For metabolic side effects, diet and exercise programs are the first line of defense [1.5.1]. This includes focusing on a nourishing diet, staying active, planning meals, and being mindful of portion sizes [1.5.3].
- Medication Adjustments: A healthcare provider may lower the dose, switch to an antipsychotic with a lower metabolic risk, or prescribe the dose to be taken at night to manage sedation [1.5.1].
- Concomitant Medications: In some cases, other medications may be prescribed to manage side effects. For example, metformin is sometimes used off-label to help with weight gain and insulin resistance [1.5.2]. For movement disorders, anticholinergic agents like benztropine might be used [1.5.2].
- Regular Monitoring: Patients taking atypical antipsychotics require regular monitoring of their weight, waist circumference, blood pressure, fasting glucose, and lipid profile to detect metabolic changes early [1.3.7, 1.5.6]. The Abnormal Involuntary Movement Scale (AIMS) test is used to monitor for movement disorders [1.7.1].
Conclusion
While atypical antipsychotics are effective treatments for several serious mental health conditions, they carry a significant risk of side effects, most notably a cluster of metabolic changes including weight gain, dyslipidemia, and hyperglycemia. These medications are a heterogeneous group, and the risk for any specific side effect varies considerably from one drug to another. The lower risk of movement disorders compared to typical antipsychotics is a major advantage, but this is balanced by the higher risk of metabolic syndrome [1.6.1, 1.6.3]. Close collaboration between the patient and healthcare provider, involving regular monitoring and proactive management strategies, is essential to balance the therapeutic benefits of these medications against their potential adverse effects.
For more information, a valuable resource is the National Institute of Mental Health (NIMH): https://www.nimh.nih.gov/health/topics/mental-health-medications.
