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Treatment of Psychotic Depression

TO THE EDITOR: A number of case reports have suggested that clozapine, with its broad pharmacological activity, may be useful in the treatment of psychotic depression. Parsa et al. (1) found clozapine to be useful and well tolerated in a patient with Parkinson's disease for whom the use of a standard neuroleptic had been problematic. Likewise, Dassa et al. (2) found that clozapine was effective in treating psychotic depression in a 40-year-old patient for whom conventional treatments, including ECT, had been ineffective. Olanzapine shows many of the pharmacological properties of clozapine but has a better side effect profile (3). We present a case that suggests that, like clozapine, olanzapine monotherapy may be an effective treatment for psychotic depression.

Mr. A was a white, 59-year-old man whose approximately 6-year history of depression (characterized by despondency, fatigue, anhedonia, crying bouts, and anorexia) followed the death of his mother; he had never sought treatment. Approximately 2 months before seeking consultation, he began to experience increasingly severe paranoid delusions that he was being monitored by video cameras in his home, that his food was being tampered with, that he was being followed, and that his life might be in danger. His baseline scores on the 21-item Hamilton depression scale and the Brief Psychiatric Rating Scale (BPRS) were 33 and 73, respectively.

Results of routine laboratory analyses revealed no abnormality, and the medical history was unremarkable. Various treatment options were reviewed, and olanzapine was suggested for treatment of the prominent psychotic symptoms because of its favorable side effect profile. The plan was to initiate olanzapine treatment and subsequently add an antidepressant as needed. Mr. A had been reluctant to take medication but consented to start a regimen of olanzapine, 5 mg/day. There was no significant change in the depressive or psychotic symptoms after 1 week, so the dose was increased to 10 mg/day. The drug was well tolerated, with only mild dizziness and nausea noted at the higher dose. Orthostatic blood pressure was within normal limits. Four weeks later, Mr. A began to question if he was really being monitored by other people or whether it was all in his mind. He was less motorically retarded and more verbal and reported feeling better. By week 6, his Hamilton depression scale score had dropped to 13, and his BPRS score fell to 38. Beck Depression Inventory scores fell approximately 34% during this period. His family confirmed substantial improvement in Mr. A's activity level, mood, and paranoia.

There are several possible explanations for the efficacy of olanzapine monotherapy in this patient. Olanzapine's pharmacological properties include antagonism of dopamine (D₁–D₄) receptors, as well as serotonin (5-HT₂), muscarinic, -1, and histamine receptors (3). It is conceivable that olanzapine, with its moderate 5-HT₂ antagonism and broad dopamine antagonism, has both primary antidepressant effects and antipsychotic effects.

On the other hand, the marked improvement in depression may have been largely secondary to the improvement in psychotic symptoms. As the paranoia gradually subsided, the patient became less anxious and more hopeful and generally felt better. In contrast to the rater's assessment, the patient felt that "thinking" had benefited more than mood but endorsed improvement in both areas. It is conceivable that continued benefits will result with longer treatment. Given its broad pharmacological activity and relatively benign side effect profile (4), olanzapine appears to warrant further research in the treatment of psychotic depression.

REFERENCES

1. Parsa MA, Ramirez LF, Loula EC, Meltzer HY: Effect of clozapine on psychotic depression and parkinsonism (letter). J Clin Psychopharmacol 1991; 11:330–331[Medline]
2. Dassa D, Kaladjian A, Azorin JM, Giudicelli S: Clozapine in the treatment of psychotic refractory depression. Br J Psychiatry 1993; 163:822–824[Abstract/Free Full Text]
3. Moore NA, Tye NC, Axton MS, Risius FC: The behavioral pharmacology of olanzapine, a novel "atypical" antipsychotic agent. J Pharmacol Exp Ther 1992; 262:545–551[Abstract/Free Full Text]
4. Baldwin DS, Montgomery SA: First clinical experience with olanzapine (LY 170053): results of an open-label safety and dose-ranging study in patients with schizophrenia. Int Clin Psychopharmacol 1995; 10:239–244[Medline]

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