To The Editor: We agree with Drs. Hazra, Mamo, and Remington that antipsychotic monotherapy is the standard of care for treating schizophrenia. Polypharmacy should only be considered as a last resort because of the potential for adverse effects and economic burden. When metabolic or extrapyramidal side effects or clinical consequences of hyperprolactinemia develop during antipsychotic treatment, strategies to eliminate or reduce these side effects should involve lowering the dose or switching to other agents.
For many chronic patients with multiple relapses, however, lowering the dose and switching treatments are not always effective and not always feasible in clinical practice. In our study, subjects with hyperprolactinemia, stabilized on high-dose haloperidol, were chronic with a history of multiple relapses. We recognize that some studies have demonstrated equivalent efficacy of aripiprazole and haloperidol in the treatment of schizophrenia symptoms (1) and that switching to aripiprazole from haloperidol has been found to be safe and effective (2); however, other studies have shown worsening of psychotic symptoms after switching to aripiprazole in some patients who were chronic and appeared only partially responsive to previous antipsychotics (3, 4).
There is a growing need to consider new and different treatment strategies, whether they are adjunctive or monotherapeutic, for schizophrenia symptoms that continue to be resistant or only partially responsive to treatment. Recently, some studies have reported that the combination of aripiprazole with other antipsychotics improved refractory schizophrenia symptoms (5, 6).
Our study was not intended to encourage or advocate the blanket use of antipsychotic polypharmacy, and unless empirical evidence suggests that there are beneficial effects of polypharmacy for schizophrenia, the smallest number of medications possible should be used to treat our patients with this illness. While we share the concerns expressed by Drs. Hazra, Mamo, and Remington, we also feel that clinicians should not underestimate the importance and significance of addressing and treating antipsychotic side effects such as the clinical consequences of hyperprolactinemia.
1.Kane JM, Crandall DT, Marcus RN, Eudicone J, Pikalov A 3rd, Carson WH, Swyzen W: Symptomatic remission in schizophrenia patients treated with aripiprazole or haloperidol for up to 52 weeks. Schizophr Res 2007; 95:143–150
2.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; 6:325–337
3.McCue RE, Waheed R, Urcuyo L, Orendain G, Joseph MD, Charles R, Hasan SM: Comparative effectiveness of second-generation antipsychotics and haloperidol in acute schizophrenia. Br J Psychiatry 2006; 189:433–440
4.Glick ID, Duggal V, Hodulik C: Aripiprazole as a dopamine partial agonist: positive and negative effects. J Clin Psychopharmacol 2006; 26:101–103
5.Henderson DC, Kunkel L, Nguyen DD, Borba CP, Daley TB, Louie PM, Freudenreich O, Cather C, Evins AE, Goff DC: An exploratory open-label trial of aripiprazole as an adjuvant to clozapine therapy in chronic schizophrenia. Acta Psychiatr Scand 2006; 113:142–147
6.Clarke LA, Lindenmayer JP, Kaushik S: Clozapine augmentation with aripiprazole for negative symptoms. J Clin Psychiatry 2006; 67:675–676
The authors’ disclosures accompany the original article.
This letter (doi: 10.1176/appi.ajp.2007.07111738r) was accepted for publication in November 2007.