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1 Clinical Professor Department of Psychiatry and Behavioral Sciences
University of Washington Veterans Affairs Puget Sound Health Care System
American Lake Division (A-116-R) Tacoma, Washington 98493 fax 253/589-4177
Andre.Tapp{at}med.va.gov
2 Clinical Assistant Professor Department of Psychiatry and Behavioral
Sciences University of Washington
3 Clinical Assistant Professor Department of Psychiatry and Behavioral
Sciences University of Washington
4 Clinical Psychologist Seattle Institute of Biomedical and Clinical
Research Seattle, Washington
5 Professor Department of Psychiatry and Behavioral Sciences University of
Washington
Published Online, September 6, 2005. www.theannals.com, DOI 10.1345/aph.1E429
Methods. A retrospective records review was conducted at the Veterans Affairs Puget Sound Health Care System. Records were identified for patients who had their primary atypical antipsychotic augmented with a conventional antipsychotic and had clinical assessments before and after augmentation. These psychiatric ratings included the Positive and Negative Symptom Scale (PANSS) and the Extrapyramidal Symptom Scale (ESRS).
Results. Of 1794 patients prescribed an antipsychotic medication, 715 were prescribed an atypical antipsychotic and 93 of those were prescribed more than one antipsychotic. Shortly after the above survey was completed, 11 patients (1 female, mean age 45.64 y) were identified who had been administered the PANSS and the ESRS shortly before the augmentation and after an average of 6 weeks (range 5-8, mean 6) on the combination. Eight patients had a diagnosis of paranoid schizophrenia, 2 of schizoaffective disorder, and 1 of psychosis not otherwise specified.
The PANSS total score at baseline (mean ± SD 85.5 ± 13.7) was not significantly different at endpoint (78.8 ± 16.6), using paired-samples t-test (t = 1.86; df = 10; p = 0.09). Further analyses found no significant differences on the Positive or Negative subscale of the PANSS; however, the General Psychopathology subscale showed an 11% improvement, but was still not statistically significant (t = 2.02; df = 10; p = 0.07). Ratings of extrapyramidal symptoms (EPS) on the ESRS were not statistically different between baseline and endpoint. However, the patients' subjective reports of EPS on the ESRS increased a clinically significant 22% (Table 1).
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Discussion. The results of this retrospective review raise questions about the practice of prescribing multiple antipsychotics, particularly augmenting an atypical with a conventional agent. In our sample, only 4 of 11 patients experienced a clinically relevant change (identified as a 20% improvement). Objective measures are important to help to identify patients who benefit with the combination and those who do not. This information is crucial in determining which patients should continue combination antipsychotic therapy.
Although this report has many limitations, it does raise concern about the use of antipsychotic polypharmacy. Augmentation with a typical antipsychotic may reduce refractory positive symptoms, but it may also minimize the advantages associated with atypical antipsychotics. At worst, prescribing multiple antipsychotics may expose patients to risks such as EPS and tardive dyskinesia from conventional antipsychotics, weight gain and metabolic disturbances from novel antipsychotics, while significantly increasing the cost of treatment and yielding minimal or no improvement in symptoms. Clearly, controlled studies are needed to identify the clinical profile of augmentation responders, examine the long-term risk/benefit ratio, and provide evidence-based guidelines for when and for whom an antipsychotic combination should be prescribed.
Footnotes
This information was presented as a poster at the American College of Neuropsychopharmacology, Las Croabas, Puerto Rico, in 2000, and at the Eleventh Biennial Winter Workshop on Schizophrenia, Davos, Switzerland, 2000.
We thank Jamie Erdmann BA, Laurie Maus BA, Lori Secrest OTR/L, and Dance Smith PharmD.
References
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