Therapy on Weight
A dual-purpose study involving 284 patients with major depression was done to assess the effects of extended selective serotonin reuptake inhibitor (SSRI) treatment on weight and to examine whether different drugs have differential effects. These patients were comparable at baseline for age, sex and body mass index. They were randomly assigned to double-blind treatment with fluoxetine (n=92), sertraline (Zoloft, n=96) or paroxetine (Paxil, n=96). Data were analyzed from 44 fluoxetine patients, 44 sertraline patients and 48 paroxetine patients who completed 26 to 32 weeks of treatment.
Paroxetine-treated patients had a significant weight gain from baseline to endpoint; fluoxetine-treated patients had a modest but nonsignificant decrease in weight; and patients treated with sertraline had a modest but nonsignificant weight increase. These findings indicate that extended treatment with an SSRI (fluoxetine, sertraline or paroxetine) is associated with different risks for weight gain.Breastfeeding During
SSRI levels in infants exposed through breastfeeding are reported to be generally low. To assess the safety of breastfeeding during sertraline therapy, Yale University investigators measured whole blood 5-HT in 10 nursing mothers, before and after treatment with sertraline at a maximum dose of 200 mg/day for nine to 12 weeks. Mean age of the infants at the time of initial exposure was 2114.7 weeks (range two weeks to 12 months).
Marked declines in platelet 5-HT were observed in the mothers after sertraline, but little or no change was seen in infant 5-HT levels. Infant plasma sertraline and desmethylsertraline levels were less than 2.5 ng/mL and less than 5 ng/mL, respectively. The investigators aptly concluded that these findings suggest that women can safely breastfeed an infant while undergoing sertraline treatment but warn that, given the small sample size in their study, cautious interpretation of their findings is warranted.Reboxetine for Hospitalized Depressed Patients
Reboxetine(Drug information on reboxetine) is a selective noradrenaline reuptake inhibitor that has been marketed for depression in the United Kingdom this past year and is currently in phase III clinical evaluation in the United States. It has negligible affinity for muscarinic, adrenergic and histaminergic receptors. It has been shown to be equieffective with desipramine (Norpramine) and imipramine(Drug information on imipramine) (Tofranil) in the treatment of mixed populations of patients with mild to severe major depressive disorder.
Reboxetine is an antidepressant that reputedly significantly improves social interaction as indicated by the Social Adaptation Self-evaluation Scale. Its usual therapeutic dose is 4 mg twice daily. The Reboxetine Brazil and Canadian Study Group reported the results of a trial in which reboxetine's efficacy and tolerability (6 mg/day titrated to 10 mg/day over three days) was compared with placebo in a double-blind, six-week study of 52 hospitalized patients. The mean HAM-D-21 total score at baseline was greater than 35 in both groups, indicating severe depression.
After six weeks, 74% of the reboxetine-treated patients and 20% of patients taking placebo had a 50% or more reduction in total HAM-D score (P<0.001). Response to reboxetine was reported as early as day 10. There also were significant improvements noted on the Zung Depression Scale.
Side effects were mild and transient; the most common were dry mouth (57% reboxetine versus 21% placebo) and insomnia (25% reboxetine versus 0% placebo). Prophylactic Reboxetine for Recurrent Major Depression
The International Reboxetine Study Group reported on a study in which reboxetine was shown to be more effective than placebo in preventing relapse in patients with recurrent depression and to be well-tolerated in long-term treatment.
This placebo-controlled, double-blind, parallel-group, 46-week study was conducted to assess the long-term tolerability and efficacy of reboxetine 8 mg/day in 283 depressed patients who had a 50% reduction in HAM-D score following an initial six-week treatment. They were then enrolled in a long-term (46-week) placebo-controlled study.
The relapse rate was much lower in reboxetine-treated patients than in placebo-treated patients (22% versus 56%, P<0.001). Reboxetine-treated patients in remission (HAM-D score less than 10) at randomization were less likely to relapse (16% versus 48%, P<0.001). At the end of the first and second six-month periods, a higher proportion of reboxetine-treated patients were relapse-free. In addition, the frequency of newly reported adverse events was similar for reboxetine (28%) and placebo (22.8%). The majority of adverse events were mild, and the most common were constipation (8% reboxetine, 4% placebo) and insomnia (5% reboxetine and 5% placebo). These results indicate that long-term reboxetine treatment is well-tolerated and more effective than placebo in preventing relapse in patients with recurrent depression.Mirtazapine: The First Million Patients
Mirtazapine(Drug information on mirtazapine) (Remeron) has been available in the Netherlands since 1994 and marketed in the United States since 1996, providing both pre- and post-marketing data and literature reports of sufficient quantity for a meta-analysis. The meta-analysis was conducted by Davis and Giakas from the department of psychiatry at the University of Illinois Chicago using the Hedges-Olkin and the Mantel-Haenszel methods to quantify efficacy.
This review substantiated that mirtazapine is superior to placebo, comparable to tricyclic antidepressants (TCAs) and at least as effective as fluoxetine for the treatment of major depression. In addition, mirtazapine is substantially safer than the TCAs, does not cause significant overdose toxicity and has a favorable side-effect profile.
In a direct comparison with fluoxetine, mirtazapine did not produce nausea or related gastrointestinal side effects, which are adverse events common to the SSRIs. Post-marketing studies showed mirtazapine to be useful for treating patients intolerant of the SSRIs and verified that it does not produce sexual side effects.
Davis and Giakas also reviewed epidemiologic data on such rare side effects as agranulocytosis. The few reported cases of agranulocytosis associated with mirtazapine usually occurred in patients receiving other drugs known for or suspected of causing agranulocytosis. It is important to note that this research and the report on its findings were not supported by the manufacturer of mirtazapine.