Correspondence
Schizophrenia
N Engl J Med 1994; 331:275-276July 28, 1994
- Article
To the Editor:
Carpenter and Buchanan provide a succinct yet comprehensive overview of schizophrenia (March 10 issue)1. Their article presents a fairly clear discussion of the diagnosis, course, and outcome; epidemiology and causes; and pathophysiology of this troubling illness. But their thoroughly referenced review does not mention the newly approved drug risperidone and fails to note any potential benefits associated with a strong treatment alliance.
Risperidone has been shown to be an effective antipsychotic agent, improving both the positive and negative symptoms of schizophrenia yet having less potential for producing extrapyramidal symptoms at therapeutic doses2-5. This benzisoxazole derivative acts as a potent antagonist of both dopamine (D2) and serotonin (5-hydroxytryptamine2) receptors3 and also binds with a lower affinity to α1-adrenergic and H1-histaminergic receptors. Unlike clozapine, risperidone has little affinity for cholinergic receptors2. Evaluated in many patients, this medication has been compared with other antipsychotic agents and placebo in numerous double-blind studies. Research indicates that it is well tolerated, has a rapid onset of action, and is associated with a diminished risk of extrapyramidal side effects2-5. It has also been reported to decrease existing tardive dyskinetic movements4. Clinical data indicate that the optimal dose is 4 to 8 mg.
The action of risperidone resembles that of clozapine but without clozapine's potentially fatal side effect, agranulocytosis. Common side effects of risperidone are dizziness, extrapyramidal symptoms, fatigue, dry mouth, nausea, somnolence, and an increase in the prolactin level, which is common with neuroleptic agents. Given the existing positive data on risperidone, it has been strongly recommended as a first-line agent in treating schizophrenia2-4. The price of risperidone is comparable to that of clozapine, but because routine laboratory testing is not required with risperidone, its overall cost is lower5.
Although new medications such as risperidone offer new hope, the relation between the health care provider and the patient also affects the course of schizophrenia. One of the most common problems in treating people with schizophrenia is noncompliance, which affects both outpatients and inpatients. An attempt to understand the patient's intrapsychic difficulties may help treaters develop a strong therapeutic alliance, which has been documented to increase compliance with drug treatment, as well as to provide a personal relationship that serves, in essence, as another treatment mode6.
6 ReferencesRobert A. Mosqueda, M.D.
Joyce E. Davidson, M.D.
Menninger Clinic, Topeka, KS 66601-08291
Carpenter WT Jr ,Buchanan RW . Schizophrenia. N Engl J Med 1994;330:681-690
Full Text | Web of Science | Medline2
Chouinard G ,Arnott W . Clinical review of risperidone. Can J Psychiatry 1993;38:Suppl 3:S89-S95
Web of Science | Medline3
Remington GJ . Clinical considerations in the use of risperidone. Can J Psychiatry 1993;38:Suppl 3:S96-S100
Web of Science | Medline4
Chouinard G ,Jones B ,Remington G , et al. A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. J Clin Psychopharmacol 1993;13:25-40[Erratum, J Clin Psychopharmacol 1993;13:149.]
CrossRef | Web of Science | Medline5
Gelenberg AJ . Risperidone. Biological Therapies in Psychiatry Newsletter. December 1993;16:45, 47-45, 486
Gabbrd GO. Psychodynamic psychiatry in clinical practice: the DSM-IV edition. Washington, D.C.: American Psychiatric Press, 1994.
Author/Editor Response
The authors reply:
To the Editor: Drs. Mosqueda and Davidson note our failure to mention risperidone and the potential benefits of a strong therapeutic alliance. We agree that a strong therapeutic alliance is important and consider this implicit in our discussion of psychosocial treatment.
Drs. Mosqueda and Davidson pay greater attention to risperidone, one of the drugs we had in mind when we stated that “neuroleptic drugs that are relatively free of extrapyramidal side effects will probably soon be available.” Our concern with their discussion of risperidone is that they have moved beyond the scientific evidence in their extensive comparison of risperidone with clozapine and in their statements that “the action of risperidone resembles that of clozapine” and that it offers “new hope.”
We discussed clozapine as the only antipsychotic drug with proved superior efficacy in patients with treatment-resistant schizophrenia and noted its lack of extrapyramidal side effects. What we currently know about risperidone is that it is an effective antipsychotic drug with a relative absence of extrapyramidal side effects at the recommended low dose1. This combination of features provides a substantial advantage over many other antipsychotic medications, but the relation between risperidone and extrapyramidal side effects is dose-linear, and the advantage will depend on maintaining the recommended low dose even with an inadequate therapeutic response. Risperidone has not been demonstrated to exhibit differential efficacy for either positive or negative symptoms, nor has the Food and Drug Administration confirmed the claim that the efficacy of risperidone is superior to that of other antipsychotic drugs. All antipsychotic drugs are effective for the reduction of general negative symptoms, but effective treatment has not yet been established for the chronic deficit or avolitional component of the disease2. The risperidone studies, to which Drs. Mosqueda and Davidson refer, only provide a basis for a hypothesis of differential efficacy. This hypothesis has not yet been tested in either a general population of patients with schizophrenia or a predefined group of patients with a poor response to neuroleptic treatment, nor has any direct comparison of risperidone and clozapine in the latter group been reported. It will be very good news indeed if risperidone proves to have superior therapeutic effects, but it will be news.
Finally, the authors note that risperidone has been observed to decrease existing tardive dyskinetic movements. This effect is presented as an advantage of risperidone, but it is quite troublesome, since all drugs that cause tardive dyskinesia have also been shown to suppress dyskinetic movements.
2 ReferencesWilliam T. Carpenter, Jr., M.D.
Robert W. Buchanan, M.D.
University of Maryland School of Medicine, Baltimore, MD 212281
Chouinard G ,Jones B ,Remington G , et al. A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. J Clin Psychopharmacol 1993;13:25-40[Erratum, J Clin Psychopharmacol 1993;13:149.]
CrossRef | Web of Science | Medline2
Breier A ,Buchanan RW ,Kirkpatrick B , et al. Effects of clozapine on positive and negative symptoms in outpatients with schizophrenia. Am J Psychiatry 1994;151:20-26
Web of Science | Medline
