Strategies to prevent fatal arrhythmias in patients taking antipsychotics
Concern has grown about the cardiac effects of antipsychotics as more is learned about rare but deadly torsade de pointes. Which patients require an ECG before you prescribe an antipsychotic? And which agents require the greatest caution?
Table 2
Relative risk of QTc interval prolongation with common antipsychotic agents
| Risk level | Agent |
|---|---|
| ECG required or strongly recommended before prescribing (most commonly associated with QTc interval prolongation and torsade de pointes) | Thioridazine Mesoridazine Droperidol Pimozide Haloperidol in large doses IV (commonly ≥ 100 mg/d) |
| Mild to moderate risk of QTc interval prolongation (~20 msec) when prescribed alone or with a metabolic inhibitor | Quetiapine Ziprasidone Chlorpromazine |
| Little or no risk of QTc interval prolongation (~20 msec) when prescribed alone or with a metabolic inhibitor | Haloperidol (oral) Olanzapine Risperidone Clozapine |
Recommendations
Taking a careful history is key to cardiovascular assessment before prescribing an antipsychotic. An ECG is indicated for patients with:
- Personal or family history of syncope or sudden death;
- Personal history of angina pectoris, myocardial infarction, congestive heart failure, cardiac arrhythmias, hypokalemia, hypomagnesemia, or significant cardiac risk factors.
The relative cardiovascular risks associated with antipsychotic agents are shown in Table 2.
An ECG also is required or strongly recommended before prescribing the antipsychotic drugs most commonly associated with QT prolongation and torsade de pointes—droperidol, haloperidol in large doses IV (commonly 100 mg/d), mesoridazine, pimozide, and thioridazine.
The FDA has strengthened the warning labels required for these agents, adding “black box” warnings about the risks of prolonged QTc intervals, torsade de pointes, and sudden death for droperidol, mesoridazine, and thioridazine. Thioridazine, for example, is indicated only for patients with schizophrenia who fail to show an acceptable response to other antipsychotic drugs. Its use is contraindicated in patients who take:
- fluvoxamine, propranolol, and pindolol;
- any drug that inhibits the cytochrome P-450 2D6 isoenzyme (e.g., fluoxetine, paroxetine);
- agents known to prolong the QTc interval.
Use of thioridazine also is contraindicated in patients known to have reduced levels of the cytochrome P450 2D6 isozyme, as well as in patients with congenital LQTS or a history of cardiac arrhythmias. Psychiatrists are advised to read the warnings and prescribing information in the labeling of all antipsychotics for potential cardiovascular side effects.
When the psychiatrist receives a report of suspected QTc interval prolongation on a patient’s ECG, the following steps are recommended:
- Obtain another ECG.
- Assess serum potassium, magnesium, calcium, and thyroid hormone levels.
In patients with confirmed QTc interval prolongation, any complaint of palpitations, presyncope, or syncope are grounds for urgent referral to a cardiologist.
Related resources
- European Society of Cardiology guidelines: www.escardio.org/scinfo/Guidelines/Haverkamp.pdf
- Sudden Arrhythmia Death Syndromes Foundation (SADSF): www.sads.org (800) 786-7723.
- Drugs that prolong the QT interval and/or induce torsade de pointes. Georgetown Center for Education and Research Therapeutics: www.torsades.org
