Letters to the Editor
D2 Antagonist Augmentation in Patients With a Partial Response to Atypical Antipsychotics
Dear Editor:
Atypical antipsychotic medications have become the first-line treatment for schizophrenia (1) because of their broader efficacy and lower risk of extrapyramidal symptoms (EPS) and tardive dyskinesia (TD) (2). Clozapine is indicated in treatment-resistant schizophrenia (3); however, for patients who cannot tolerate clozapine therapy or who reveal only partial response to it (4), targeted treatment strategies tailored to the variable expression of schizophrenia in each patient are in order (5). Coprescribing typical, atypical, and depot antipsychotic agents may be considered (6).
We report 4 cases of individuals who met DSM-IV criteria for schizophrenia that only partially responded to monotherapy. For 12 weeks, a classic antipsychotic agent was added to ongoing atypical drug therapy on an open-label basis. Results were assessed with the Clinical Global Impression (CGI) scale.
Case Report 1
A woman aged 29 years, who had been diagnosed at age 16 years with unspecified schizophrenia, had a baseline CGI score of 6. Olanzapine was initiated at 20 mg daily, and anxiety and troubling ideas of reference ameliorated (CGI score, 5). After 6 weeks, zuclopenthixol was added and titrated to 60 mg daily. The patient’s ideas of reference disappeared and anxiety diminished (CGI score, 4).
Case Report 2
A man aged 23 years, who had been diagnosed at age 17 years with severe disorganized schizophrenia (CGI score, 7), had disorganized speech and behaviour that did not respond to typical antipsychotics. Olanzapine 20 mg daily yielded only a minor improvement. Clozapine 250 mg daily was initiated, and the patient showed remarkable improvement (CGI score, 5). Three months later, clotiapine 80 mg daily was added, and further progress was noted (CGI score, 4).
Case Report 3
A woman aged 40 years, with severe paranoid schizophrenia onset at age 24 years, was socially isolated following her last psychotic episode (CGI score, 7). Olanzapine 20 mg daily diminished her paranoid ideation (CGI score, 5). Three months later, her treatment regimen was augmented with haloperidol 15 mg daily. Her functioning further improved, and paranoid ideation ceased (CGI score, 4).
Case Report 4
A man aged 52 years had chronic, unremitting, paranoid schizophrenia beginning at age 24 years. He was hospitalized following severe paranoid delusions (CGI score, 7).Treatment with olanzapine 20 mg daily yielded mild improvement (CGI score, 6). Six weeks later, perphenazine was added and titrated to 16 mg daily. His paranoid delusions gradually lost their disabling nature and improvement was noted (CGI score, 5).
Discussion
Medical management of treatment- refractory psychosis patients poses a difficult challenge. Although widespread use of atypical antipsychotic agents has improved patient outcomes, some patients still do not respond to treatment. The Texas Medication Algorithm Project (7) suggested a combination of typical and atypical medications for partial responders. The rationale lies in their different mechanisms of action: dopamine and postsynaptic 5-HT2A blockade. Combined therapy has been described in case reports, but randomized trials are lacking (8–9)
In our 4 chronic schizophrenia patients, combined typical and atypical anti- psychotic therapy led to marked improvement. We chose adjuvant classic antipsychotic agents according to each individual patient’s prior side effect profile.
Though remission was not achieved, the polypharmacy reduced side effects and enabled their discharge to day care. This treatment alternative provides an additional option in the ongoing struggle to treat patients with refractory schizophrenia.
References
1. Lalonde P. Evaluating antipsychotic medications: predictors of clinical effectiveness. Report of an expert review panel on efficacy and effectiveness. Can J Psychiatry 2003;48(Suppl 1):3S–12S.
2. Tandon R, Jibson MD. Efficacy of newer generation antipsychotics in the treatment of schizophrenia. Psychoneuroendocrinology 2003;28(Suppl 1):9–26.
3. Taylor DM, Young C, Paton C. Prior antipsychotic prescribing in patients currently receiving clozapine: a case note review. J Clin Psychiatry 2003;64(1):30–4.
4. Beasley CM, Tollefson G, Tran P, Satterlee W, Sanger T, Hamilton S. Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial. Neuropsychopharmacology 1996;14:111–23.
5. Kapur S, Remington G. Dopamine D(2) receptors and their role in atypical antipsychotic action: still necessary and may even be sufficient. Biol Psychiatry 2001;50:873–83.
6. Jaffe AB, Levine J. Antipsychotic medication coprescribing in a large state hospital system. Pharmacoepidemiol Drug Saf 2003;12:41–8.
7. Miller AL, Chiles JA, Chiles JK, Crismon ML, Rush J, Shon SP. The Texas Medication Algorithm Project (TMAP) schizophrenia algorithms. J Clin Psychiatry 1999;60:10:649–57.
8. Gupta S, Sonnenberg SJ, Frank B. Olanzapine augmentation of clozapine. Ann Clin Psychiatry 1998;10:113–5.
9. McCarthy RH, Terkelsen KG. Risperidone augmentation of clozapine. Pharmacopsychiatry 1995;28(2):61–3.
Doron Mazeh, MD
Bat Yam, Israel
Yuval Melamed, MD
Netanya, Israel
Abraham Weizman, MD
Tel Aviv, Israel
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