Which psychotropic medications increase triglyceride levels?

Psychiatric Medications That Increase Triglycerides

Atypical antipsychotics are the primary psychiatric medications that increase triglyceride levels, with clozapine and olanzapine having the highest risk, followed by quetiapine and risperidone, while aripiprazole and ziprasidone have lower risk. 1

Atypical Antipsychotics and Triglyceride Elevation

• Clozapine is strongly associated with elevated triglycerides, with studies showing increases of up to 71 mg/dL (54%) in treated patients 2
• Olanzapine causes significant increases in triglycerides, with FDA data showing increases of 20.8 mg/dL compared to decreases of 10.7 mg/dL in placebo groups 3
• The triglyceride elevation with olanzapine is dose-dependent, with 39.6% of patients experiencing increases of at least 50 mg/dL during short-term treatment 3
• Long-term olanzapine treatment results in even higher rates of hypertriglyceridemia, with 61.4% of patients showing increases of at least 50 mg/dL 3
• Risperidone has a lower risk of increasing triglycerides compared to clozapine and olanzapine 1, 4
• Quetiapine has been associated with triglyceride elevations, though to a lesser extent than clozapine and olanzapine 5
• Aripiprazole and ziprasidone have minimal effects on triglyceride levels compared to other atypical antipsychotics 1

Severity and Mechanisms

• The triglyceride elevation with atypical antipsychotics is often clinically significant, with over one-third of patients experiencing meaningful increases 5
• Triglyceride elevations are strongly associated with weight gain induced by these medications 6
• The relationship between antipsychotic serum concentration and triglyceride levels is dose-dependent for clozapine 7
• For olanzapine, the ratio of the parent compound to its metabolite N-desmethylolanzapine correlates with triglyceride elevation 7
• The risk of hypertriglyceridemia with antipsychotics persists even after adjusting for other risk factors like diet, waist circumference, physical activity, smoking, and alcohol consumption 8

Other Psychiatric Medications Affecting Triglycerides

• Valproic acid can cause weight gain that may contribute to elevated triglycerides 1
• Carbamazepine has been associated with weight gain that may indirectly affect lipid profiles 1
• Lithium can cause weight gain that may indirectly increase triglyceride levels 1
• Most SSRIs are generally weight-neutral or may cause initial weight loss, having minimal direct effects on triglycerides 1
• Mirtazapine is associated with weight gain that could indirectly affect triglycerides 1

Clinical Implications and Monitoring

• Regular monitoring of triglyceride levels is recommended for patients on atypical antipsychotics, particularly clozapine and olanzapine 5
• Severe hypertriglyceridemia (≥500 mg/dL) increases the risk of acute pancreatitis 9
• Very severe hypertriglyceridemia (≥2,000 mg/dL) poses an immediate risk for pancreatitis 10
• When possible, consider antipsychotics with lower metabolic risk (aripiprazole, ziprasidone) in patients with pre-existing dyslipidemia or metabolic syndrome 1
• For patients requiring clozapine or olanzapine, more frequent monitoring of lipid profiles is warranted 5

Management Considerations

• For medication-induced hypertriglyceridemia, consider alternative agents when clinically appropriate 10
• Nonpharmacological management of high triglycerides includes weight loss, reduction in alcohol consumption, smoking cessation, and increased physical activity 9
• Pharmacological options for managing antipsychotic-induced hypertriglyceridemia include fibrates, niacin, and omega-3 fatty acids when lifestyle modifications are insufficient 9
• Statin plus fibrate combination therapy is generally not recommended as it has not been shown to improve cardiovascular outcomes 9
• Similarly, statin plus niacin combination therapy is not recommended due to lack of cardiovascular benefit and potential increased risk of stroke 9