News and Events
1999 Wyeth-Ayerst American Psychiatric Association Resident Reporter
ATUL MEHRA, M.D.
Reboxetine—the First Selective Noradrenaline Reuptake Inhibitor
These were three abstracts that were presented on reboxetine, which is a new type of antidepressant that is now presently available in North America.
The first abstract was by H.J. Moler in the Department of Psychiatry at Ludwig Maximilians University in Munich, Germany, and was entitled, “Reboxetine, the First Selective Noradrenaline Reuptake Inhibitor, is More Effective at Improving Social Functioning than Fluoxetine.” In this study two double-blind parallel groups, randomized, multi-center studies were conducted in 549 patients with major depression. They compared Reboxetine 8-10 mg per day with fluoxetine 24 mg per day or placebo for approximately 8 weeks. In total, 513 patients completed the social adaptation self-evaluation scale or the SASS. The normal range of the SASS is between 35-52. The treatment efficacy was assessed using the observer rated Hamilton Depression rating scale as well.
The results of the study revealed that the reboxetine treatment led to more patients achieving a normal SASS total score at last assessment than did the fluoxetine, treatment bracket, 49 versus 44% greater than or equal to 35 po0ints. Among the overall population, improvements in the SASS total scores from baseline to last assessment in the placebo control study were 10.3 for reboxetine, 7.6 for fluoxetine, and 3.4 for placebo. Among patients in remission at the last assessment, improvement in SASS total score was greatest with reboxetine of 16.2 compared with fluoxetine 9.7 and placebo 5.2. The reboxetine treatment led to improved individual SASS item scores for active social behavior and self-perception. The conclusion of the study was that reboxetine is more effective than fluoxetine in improving social functioning in depressed patients and produces a better quality of remission.
The second reboxetine study was titled, “Reboxetine is as Effective and Well-Tolerated as Fluoxetine in Major Depression.” This study was carried ou7t by Jay Massana in the Department of Psychiatry Hospital, Clinic One, Provincial de Barcelona, in Barcelona, Spain. During this study, the efficacy and tolerability of reboxetine and fluoxetine were compared.
Two double-blind parallel groups, randomized multi-center studies were performed on 549 patients with major depression comparing reboxetine 8-10 mg per day [205 patients] with fluoxetine 20-40 mg per day [216 patients] for 8 weeks. The results revealed reboxetine was as effective as fluoxetine in both studies with reductions in the mean HAMD total scores being 19.2 for reboxetine and 16.8 for fluoxetine. Reboxetine was also as well tolerated as fluoxetine in both studies with similar overall adverse event rates with 67% being reported for reboxetine and 65% for fluoxetine. In the reboxetine group, there was a significantly higher risk of developing dry mouth, constipation, hypotension, paraesthesia, urinary urgency and retention, and flushing. Conversely, there was a significantly higher reported rate of side effects for nausea, diarrhea and somnolence in the fluoxetine group.
The conclusion of this study was that reboxetine was as effective and well tolerated as fluoxetine in the treatment of major depression in the general population. There was also some suggestion that reboxetine may be more effective than fluoxetine in severe depression, however, their definition of severe depression was not indicated in the abstract.
The final study was entitled, “Reboxetine is Effective in Preventing Relapse and Recurrence in Major Depressive Disorder.” This was done by M. Versiani at the Institute of Psychiatry at Federal University, Rio, Brazil. In the presentation the investigators looked at adult and elderly patients with major depressive disorder responding to 6 weeks of reboxetine treatment with the average adult dosage being 6-8 mg per day and the average elderly dosage being 4-6 mg per day. They were enrolled in one placebo control study [N=283], or one of two open studies [N=209, N=160] for 12 months. The efficacy was assessed using the HAMD and CGI-global improvement scale.
The results of the studies revealed that in the placebo control study, relapse and recurrence rates were 22% and 56% in the reboxetine and placebo groups respectively. The relapse rates of 14.8% and less than 1% were reported in the open studies. In patients who entered long term treatment, remission rates at last assessment were between 73%-78% in the three studies. At baseline mean, HAMD total scores were 24-29.2 points compared with 6.8-8.4 points at last assessment. The majority of adverse advance occurred in the first four weeks of treatment and were mild to moderate in severity. The conclusions of the study revealed that reboxetine was more effective than placebo in preventing the relapse and recurrence of depression during 12 month continuation therapy. Reboxetine treatment was also shown to be effective in sustaining remission in the long term treatment of depression. The patients who received long term reboxetine treatment showed sustained improvement in mean HAMD score total throughout the duration of the study and reboxetine was well tolerated during long term [12 month] treatment.
The results of these three studies suggests that the novel selective noradrenaline reuptake inhibitor or SNRI, is a newer drug that may be useful in the treatment of major depression. It has been shown to be as effective and as tolerable as fluoxetine of the SSRI class. It would be interesting however to compare its effectiveness against venlafaxne which has duel serotonergic and noradrenaline activity. Further studies as well, in the future, may reveal a subset of patients with major depression who may selectively respond to this medication better than the other antidepressants presently available on the market.
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