Sir: Several studies showed the usefulness of aripiprazole augmentation of antidepressant treatment in refractory depression.1–4 Berman et al.4 suggest that the effective dose for many (depressed) patients is lower than those recommended for schizophrenia and bipolar disorder and that the true efficacious dose for some depressed patients may have been even lower. In most cases, however, aripiprazole was started at 5 to 10 mg/day and increased to 10 to 30 mg/day.1–3 A smaller dose may be useful to prevent side effects and thereby reduce the likelihood of patient dropout. There is, to my knowledge, no report describing small doses of aripiprazole augmentation and maintenance in the treatment of depressed patients.
I report 3 cases of refractory depression responding to 3 mg/day of aripiprazole that were maintained in remission with the same dose. This study was approved by the Oita University Faculty of Medicine ethics committee, and written informed consent was obtained from the 3 patients.
Case 1
Ms. A, a 61-year-old woman, had DSM-IV major depressive disorder of 2 years' duration. Just before the start of aripiprazole augmentation in 2006, she was receiving 150 mg/day of fluvoxamine for 2 months, and her Hamilton Rating Scale for Depression (HAM-D)5 score was 19. Twelve days after aripiprazole 3 mg/day was added to her fluvoxamine regimen, her HAM-D score improved to 6. After 5 months of remission, she complained of insomnia, and aripiprazole was discontinued whereas fluvoxamine was continued. Within 2 weeks, she experienced relapse of depression, and aripiprazole was resumed. Two weeks later, her condition improved, and subsequently her depression was in remission for 5 months.
Case 2
Mr. B, a 46-year-old man, had DSM-IV major depressive disorder of 7 years' duration. Just before the start of aripiprazole augmentation in 2006, he had been receiving the combination of 150 mg/day of amoxapine, 100 mg/day of sertra-line, 50 mg/day of trazodone, and 30 mg/day of mianserin for 7 weeks, and his HAM-D score was 14. Two weeks after 3 mg/day of aripiprazole was added to this regimen, his HAM-D score improved to 5. After 6 months of remission, he was restored to his position as a junior high school teacher. During another 6 months on treatment with this regimen, he gradually adjusted to his job.
Case 3
Ms. C, a 27-year-old woman, had DSM-IV major depressive disorder of 3 years' duration. Just before the start of aripiprazole augmentation in 2006, she had been receiving the combination of 40 mg/day of paroxetine, 100 mg/day of maprotiline, and 800 mg/day of lithium for 4 weeks, and her HAM-D score was 21. One week after 3 mg/day of aripiprazole was added to this regimen, her HAM-D score dramatically improved to 0. Thereafter, lithium and paroxetine were discontinued without relapse. After 5 months of remission, she began to work as a clerk. During another 5 months, she gradually adjusted to her job while undergoing treatment with 100 mg/day of maprotiline and 3 mg/day of aripiprazole.
These patients responded very well to 3 mg/day of aripiprazole augmentation, and the effects were maintained for several months without increasing the aripiprazole dosage. Particularly in case 1, aripiprazole withdrawal induced relapse and resumption led to a return of remission. Although placebo effects cannot be ruled out completely, these findings suggest that small doses of aripiprazole addition may be useful for some patients with refractory depression. Further controlled trials are required to draw a definite conclusion.
Acknowledgments
Dr. Terao reports no financial affiliation or other relationship relevant to the subject of this letter.
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