Effect of antipsychotic medications on plasma lipids

Lipids in Schizophrenia

• Individuals with schizophrenia are at increased risk for cardiovascular disease due to higher morbidity and mortality rates.
• Dyslipidemia (imbalance of lipids in the blood) is a known risk factor for cardiovascular disease, and antipsychotic medications can contribute to this.
• Antipsychotic medications have varying effects on lipid profiles.
  • First-generation antipsychotics (FGAs) like phenothiazines are often associated with increased triglycerides and LDL cholesterol, but decreased HDL cholesterol.
    • The magnitude of these effects is not fully understood.
    • Haloperidol, another FGA, seems to have minimal impact on lipid profiles.
  • Second-generation antipsychotics (SGAs) have more varied results.
    • While cholesterol levels can rise, triglycerides are often a more pronounced target of these effects, usually linked to obesity and diabetes.

Monitoring Lipid Levels

• All patients starting new antipsychotic medications should have their lipid levels measured at baseline and three months later.
• Lipid levels should be measured annually, or every three months for the first year of treatment in the case of clozapine and olanzapine.
• While changes in cholesterol levels are typically not substantial over short periods, triglyceride levels can dramatically increase.

Specific Antipsychotic Effects

• Clozapine and olanzapine are associated with a greater propensity to increase lipids.
• Quetiapine and risperidone have a moderate propensity to impact lipid levels.
• Aripiprazole, lurasidone, and ziprasidone generally seem to have minimal adverse effects on blood lipids, and in some cases, may even modestly improve lipid profiles previously affected by antipsychotics.
• Cariprazine and brexpiprazole demonstrate relatively limited impact on plasma lipids.
• Iloperidone was noted to cause weight gain but not a significant impact on cholesterol or triglycerides.
• Lumatetperone showed no significant effects on plasma cholesterol or triglycerides in the short term compared to placebo.

Olanzapine and Lipid Effects

• Olanzapine has been shown to increase triglyceride levels by 40% in the short term (12 weeks), and this effect can continue for up to a year.
• Up to two-thirds of olanzapine-treated patients experience raised triglycerides and nearly 10% develop severe hypertriglyceridemia.
• Weight gain associated with olanzapine is often accompanied by increased cholesterol and triglycerides.
• However, severe hypertriglyceridemia can occur independently of weight gain in some cases.
• One study found that olanzapine patients had four times more increase in serum triglycerides compared to risperidone patients.

Hyperlipidemia and Antipsychotic Medications

• Patients taking antipsychotic medications, particularly clozapine and risperidone, have a higher likelihood of developing hyperlipidemia compared to those not taking such medications.
• Clozapine, in particular, can lead to a doubling or more of triglyceride levels and cholesterol levels within five years.

Management of Hyperlipidemia

• Patients with raised cholesterol might benefit from dietary advice and lifestyle changes along with statins to help manage their condition.
  • Statin efficacy in this patient group is observed but interactions are possible.
  • Risk tables and guidelines for managing high cholesterol can be found in the British National Formulary (BNF).
  • Evidence supports treatment even for patients with significantly elevated cholesterol.
• Treatment for elevated triglycerides includes reducing saturated fats in the diet, consuming fish oil, and/or using fibrates.
  • However there is no clear proof of reduced mortality with these treatments.
• Patients with triglycerides as the primary issue should be screened for IGT (impaired glucose tolerance) and diabetes.

Switching Medications for Hyperlipidemia

• When moderate to severe hyperlipidemia is apparent during antipsychotic treatment, a switch to a different antipsychotic medication is necessary.
  • Clozapine-induced hypertriglyceridemia is considered a more manageable problem for patients using the medication for treatment-resistant illness than for other indications.
• Switching to risperidone may reverse some effects that arise from other antipsychotic medications, but more data are required.
• Aripiprazole and other D2 partial agonists are often preferred treatments for individuals with prior antipsychotic-induced dyslipidaemia (if not in the UK where other options like lumateperone and ziprasidone are available).
• Adjuvant aripiprazole with clozapine or olanzapine may have positive effects on plasma cholesterol and triglycerides.
• Metformin use alongside antipsychotic medications may improve total cholesterol and triglyceride levels.

This quiz explores the relationship between lipid levels and schizophrenia, focusing on the cardiovascular risks associated with antipsychotic medications. It examines how different generations of antipsychotics affect lipid profiles, particularly concerning dyslipidemia and other metabolic factors. Understanding these interactions is crucial for managing the health of individuals with schizophrenia.