Which psychiatric medications cause a rise in triglycerides?

From the Guidelines

Psychiatric medications such as antipsychotics, particularly clozapine and olanzapine, can cause a significant rise in triglycerides. According to the Endocrine Society's guidelines on the diagnosis and management of hypertriglyceridemia 1, certain medications, including antipsychotics, can contribute to elevated triglyceride levels. The guidelines highlight that hypertriglyceridemia may be a marker for cardiovascular disease rather than a causal factor, but it is essential to manage it to reduce cardiovascular risk.

Some key points to consider:

• Atypical antipsychotics like clozapine and olanzapine are associated with significant increases in triglyceride levels 1.
• Other psychiatric medications, such as valproic acid, mirtazapine, and certain selective serotonin reuptake inhibitors (SSRIs), may also cause modest increases in triglycerides.
• The mechanisms by which these medications affect triglyceride levels include weight gain, altered glucose metabolism, and direct effects on lipid metabolism.
• Regular lipid panel monitoring is crucial when starting these medications, with baseline testing before initiation and follow-up testing at 3 months and then annually.

It is essential to note that patients with pre-existing hyperlipidemia, obesity, diabetes, or metabolic syndrome are at higher risk for medication-induced triglyceride elevations and may require more frequent monitoring or consideration of alternative medications with better metabolic profiles. Healthcare providers should carefully weigh the benefits and risks of these medications and consider alternative options with more favorable metabolic profiles to minimize the risk of triglyceride elevations and associated cardiovascular risks.

From the FDA Drug Label

Dyslipidemia: Undesirable alterations in lipids have been observed with olanzapine use. Clinical monitoring, including baseline and periodic follow-up lipid evaluations in patients using olanzapine, is recommended [see Patient Counseling Information (17)] Clinically significant, and sometimes very high (>500 mg/dL), elevations in triglyceride levels have been observed with olanzapine use.

Table 4: Changes in Fasting Lipids Values from Adult Olanzapine Monotherapy Studies: Laboratory Analyte Category Change (at least once) from Baseline Treatment Arm N Patients N Patients Fasting Triglycerides Increase by ≥50 mg/dL Olanzapine 745 39.6% 487 61.4% Normal to High (<150 mg/dL to ≥200 mg/dL) Olanzapine 457 9.2% 293 32.4% Borderline to High (≥150 mg/dL and <200 mg/dL to ≥200 mg/dL) Olanzapine 135 39.3% 75 70.7%

• Olanzapine causes a rise in triglycerides, with clinically significant elevations observed in some patients.
• The proportion of patients with triglyceride increases of ≥50 mg/dL was 39.6% in short-term studies and 61.4% in long-term studies.
• Ziprasidone may also cause changes in lipid levels, but the overall effect on triglycerides is less clear, with some studies showing decreases and others showing increases.
• In long-term studies, the mean change from baseline in random triglycerides for ziprasidone 20 to 40 mg BID was +26.3 mg/dL 2.

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From the Research

Psychiatric Medications and Triglyceride Levels

The relationship between psychiatric medications and triglyceride levels has been studied in various research papers. The following medications have been found to cause a rise in triglycerides:

• Olanzapine: Studies have shown that olanzapine increases weight and serum triglyceride levels 4, 5, 6.
• Clozapine: Research has found that clozapine is associated with increases in serum triglyceride levels 5, 7, 8.
• Quetiapine: Although not directly studied in the provided evidence, other reports have shown increases in triglyceride levels with quetiapine 7.

Comparison of Medications

Some studies have compared the effects of different psychiatric medications on triglyceride levels:

• A study found that switching from clozapine to risperidone decreased serum triglyceride levels in four patients 7.
• Another study found that olanzapine, but not risperidone, increased triglyceride levels in a postprandial test 6.
• A prospective observational study found that increases in triglyceride levels were associated with clinical response to clozapine treatment 8.

Key Findings

Key findings from the studies include:

• Olanzapine and clozapine have been found to increase triglyceride levels in multiple studies.
• The increase in triglyceride levels with olanzapine may be related to weight gain 4.
• The metabolic effects of olanzapine and clozapine may be revealed in postprandial tests of lipid metabolism 6.
• Increases in triglyceride levels have been found to be associated with clinical response to clozapine treatment 8.