Clinical twisters: Updating antipsychotic choice

March 20, 2006

A 58-year-old man, G.C., is hospitalized with an acute myocardialinfarction (MI). His physician has prescribed metoprolol, ramipril,warfarin, and atorvastatin (Lipitor, Pfizer), but is debatingwhether to continue G.C.'s bedtime chlorpromazine 400 mg, whichhe's taken for 20 years for schizophrenia, or switch to a newermedication. G.C. is showing signs of tardive dyskinesia (TD). Hisrecent records show normal fasting blood glucose levels. His BMI is22. He is a smoker. His physician asks your opinion aboutantipsychotic therapy. What do you recommend?

A 58-year-old man, G.C., is hospitalized with an acute myocardial infarction (MI). His physician has prescribed metoprolol, ramipril, warfarin, and atorvastatin (Lipitor, Pfizer), but is debating whether to continue G.C.'s bedtime chlorpromazine 400 mg, which he's taken for 20 years for schizophrenia, or switch to a newer medication. G.C. is showing signs of tardive dyskinesia (TD). His recent records show normal fasting blood glucose levels. His BMI is 22. He is a smoker. His physician asks your opinion about antipsychotic therapy. What do you recommend?

Discuss the use of alternative agents such as second-generation antipsychotics that have a lesser association with EPS and are effective against both positive and negative symptoms of schizophrenia. Recommend oral olanzapine (Zyprexa, Lilly) 10 mg at bedtime as blood glucose and BMI are within normal limits. Chlorpromazine should be tapered at one- or two-week intervals after olanzapine initiation. Monitor for withdrawal TD, weight gain, hyperglycemia, sedation, and cardiac side effects, including QT prolongation. Smoking cessation should be addressed as cigarettes can decrease the effectiveness of antipsychotics as well as increase cardiovascular complications.

Side effects like chlorpromazine-induced TD are associated with medication noncompliance, drug cessation, or long-term use. Guidelines recommend atypical neuroleptics. Suggested is olanzapine, which has proven efficacy for treatment-responsive or resistant symptoms and relapse prevention. It has a high risk of endocrine side effects; however, these can be minimized by aggressive management.

Quetiapine (Seroquel, AstraZeneca) is effective and aids any post-MI depression, but it has moderate risk of orthostatic/reflex tachycardia. It should be avoided due to potential fall risk because G.C. is taking new antihypertensives and also warfarin.

Aripiprazole (Abilify, Bristol-Myers Squibb) is very effective for positive symptoms; however, efficacy in negative symptoms is less clear. Transient insomnia and agitation that can occur during the first weeks of therapy could jeopardize early cardiac rehabilitation.

Use Risperdal IM (risperidone, Janssen) if noncompliance issues present themselves to optimize mental health and aid cardiac rehabilitation. Otherwise, avoid risperidone as limited data show it has a small increase in stroke risk in the elderly.

Avoid ziprasidone (Geodon, Pfizer) post-MI due to possible QTc prolongation. Clozapine should be reserved for treatment resistance.

Kristine E. Keplar, Pharm.D.
Clinical Pharmacist
St. Anthony's Memorial Hospital
Effingham, Ill.