Adjunctive Versus Monotherapeutic Treatment for Schizophrenia: Addressing Antipsychotic Side Effects
To The Editor: In the article by Joo-Cheol Shim, M.D., Ph.D., et al., published in the September 2007 issue of the Journal, aripiprazole was added to haloperidol to evaluate the beneficial effects on haloperidol-induced hyperprolactinemia. The authors pointed out that switching is “not always possible in clinical practice, especially if the patient has responded well to the antipsychotic that produced the hyperprolactinemia” ( 1 , p. 1404). The addition of aripiprazole significantly decreased prolactin levels and improved negative symptoms, sleep, and extrapyramidal side effects. The authors attributed these effects to aripiprazole’s unique mechanism(s) of action (2) . We do not take issue with the scientific merit of this study but are concerned with the clinical implications, specifically the apparent promotion and justification of the adjunctive use of aripiprazole.
Well-controlled clinical studies have not supported the use of antipsychotic polypharmacy, and this practice has been associated with increased adverse effects (3 , 4) , premature death (5) , and unnecessary economic demands (6) . Good clinical practice argues for the fewest medications possible and, in the case of treatment with antipsychotics, advocates for the adjunctive use of antipsychotics as a last resort (7) . As a class, the newer antipsychotics have afforded us advantages in decreasing extrapyramidal symptoms, lowering prolactin levels, and reducing the risk of tardive dyskinesia (2 , 7 , 8) . Furthermore, contrary to what is stated in the article by Dr. Joo-Cheol Shim et al., switching antipsychotic drugs, including a switch from haloperidol to aripiprazole, has previously been shown to be safe and effective (9) .
1. Shim J-C, Shin JG, Kelly DL, Jung DU, Seo YS, Liu KH, Shon JH, Conley RR: Adjunctive treatment with a dopamine partial agonist, aripiprazole, for antipsychotic-induced hyperprolactinemia: a placebo-controlled trial. Am J Psychiatry 2007; 164:1404–1410Google Scholar
2. Mamo D, Graff A, Mizrahi R, Shammi CM, Romeyer F, Kapur S: Differential effects of aripiprazole on D (2) , 5-HT (2) , and 5-HT (1A) receptor occupancy in patients with schizophrenia: a triple tracer PET study. Am J Psychiatry 2007; 164:1411–1417 Google Scholar
3. Honer WG, Thornton AE, Chen EY, Chan RC, Wong JO, Bergmann A, Falkai P, Pomarol-Clotet E, McKenna PJ, Stip E, Williams R, MacEwan GW, Wasan K, Procyshyn R: Clozapine alone versus clozapine and risperidone with refractory schizophrenia. N Engl J Med 2006; 354:472–482Google Scholar
4. Duggal HS: Aripiprazole-olanzapine combination for treatment of schizophrenia. Can J Psychiatry 2004; 49:151Google Scholar
5. Waddington JL, Youssef HA, Kinsella A: Mortality in schizophrenia: antipsychotic polypharmacy and absence of adjunctive anticholinergics over the course of a 10-year prospective study. Br J Psychiatry 1998; 173:325–329Google Scholar
6. Stahl SM, Grady MM: High-cost use of second-generation antipsychotics under California’s Medicaid program. Psychiatr Serv 2006; 57:127–129Google Scholar
7. Stahl SM: Focus on antipsychotic polypharmacy: evidence-based prescribing or prescribing-based evidence? Int J Neuropsychopharmacol 2004; 7:113–116Google Scholar
8. Remington G, Saha A, Chong SA, Shammi C: Augmenting strategies in clozapine-resistant schizophrenia. CNS Drugs 2006; 20:171Google Scholar
9. Kasper S, Lerman MN, McQuade RD, Saha A, Carson WH, Ali M, Archibald D, Ingenito G, Marcus R, Pigott T: Efficacy and safety of aripiprazole vs haloperidol for long-term maintenance treatment following acute relapse of schizophrenia. Int J Neuropsychopharmacol 2003; 6:325–337Google Scholar
