Olanzapine has greater potential for causing weight gain than risperidone or quetiapine and may increase the risk of excessive weight gain and hyperlipidemia in patients who are not on a well-controlled diet. Quetiapine causes some significant orthostatic hypotension, no significant QT prolongation, and some weight gain. Risperidone is metabolized by the CYP2D6 isoenzyme and can cause orthostatic hypotension, some weight gain, and slight QT prolongation; it—like other atypical antipsychotics—is not known to alter thrombocyte function or thrombus formation.
The recently approved antipsychotic aripiprazole causes some orthostatic hypotension, no significant QT prolongation, and slight weight gain. It is metabolized by CYP3A4 and 2D6 and does not inhibit those enzymes. It is highly bound to albumin and does not interfere with warfarin.19
Selecting a mood stabilizer
Bipolar disorder presents numerous dilemmas when treating the post-MI patient. The three agents approved for treating bipolar mania—lithium, divalproex, and olanzapine—all require close therapeutic monitoring.
Lithium, olanzapine, and divalproex are the standard first-choice therapies for patients with acute mania, whereas olanzapine and divalproex are known to be more effective than lithium in patients with mixed states.1 Using the HALT framework, none of these mood stabilizers directly aggravates hypertension. However, lithium can cause significant electrolyte aberrations, and its combination with ACE inhibitors could increase the risk of sudden death from arrhythmia.20
Divalproex is known to elevate liver enzymes, and its combination with lipid-lowering agents carries the risk of significant liver injury.12 Divalproex also is known to result in some thrombocytopenia and could increase patients’ risk for bleeding complications when combined with clopidogrel, aspirin, warfarin, or niacin.
Divalproex has a black-box warning of increased risk of hemorrhagic pancreatitis. Patients who take divalproex with other agents known to affect platelet and clotting function should be watched closely.
Olanzapine, as discussed above, carries a risk of weight gain and requires careful dietary control in post-MI patients. Alternate atypical antipsychotics may need to be considered as mood-stabilizing therapy if the risk/benefit ratio of electrolyte imbalance (lithium), liver enzyme elevation and thrombocytopenia (divalproex), or weight gain (olanzapine) is not favorable.
Related resources
- American College of Cardiology www.acc.org
- Physicians’ Desk Reference (56th ed). Montvale, NJ: Medical Economics, 2002.
Drug brand names
- Aripiprazole • Abilify
- Atorvastatin • Lipitor
- Bupropion • Wellbutrin
- Clopidogrel bisulfate • Plavix
- Divalproex • Depakote
- Fluoxetine • Prozac
- Fluvastatin • Lescol
- Lisinopril • Prinivil
- Lovastatin • Mevacor
- Metoprolol • Toprol-XL
- Mirtazapine • Remeron
- Niacin • Niaspan
- Paroxetine • Paxil
- Pravastatin • Pravachol
- Olanzapine • Zyprexa
- Ramipril • Altace
- Sertraline • Zoloft
- Simvastatin • Zocor
- Venlafaxine • Effexor-XR
- Warfarin • Coumadin
- Ziprasidone • Geodon
Disclosure
Dr. Dewan receives grant/research support from Eli Lilly and Co. and is a speaker for Eli Lilly and Co. and Janssen Pharmaceutica.
Dr. Suresh and Dr. Blomkalns report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Acknowledgment
The authors wish to acknowledge the assistance of W. Andrew Jenkins, BS, medical student, University of Cincinnati College of Medicine, in preparing this manuscript for publication.