High-dose fluoxetine in the treatment of depressed patients not responsive to a standard dose of fluoxetine
In a four-week, open label study of major depression, 15 patients who had failed to respond to a trial of fluoxetine 20 mg/day of 8–12 weeks duration were then treated with fluoxetine 40 mg/day for one week and then, if tolerated, with either 60 or 80 mg/day. The mean HAM-D-17 and CGIS scores of these 15 patients decreased significantly at the end of 4 weeks on a higher dosage of fluoxetine (60 or 80 mg/day) with respect to the beginning of the four-week study. No significant side-effects were noted.
- [Show abstract] [Hide abstract] ABSTRACT: Purpose The serotonin system is undoubtedly involved in the pathogenesis of major depressive disorder (MDD). More specifically the serotonin transporter (SERT) serves as a major target for antidepressant drugs. There are conflicting results about SERT availability in depressed patients versus healthy controls. We aimed to measure SERT availability and study the effects of age, gender and season of scanning in MDD patients in comparison to healthy controls. Methods We included 49 depressed outpatients (mean±SD 42.3 ± 8.3 years) with a Hamilton depression rating scale score above 18, who were drug-naive or drug-free for ≥4 weeks, and 49 healthy controls matched for age (±2 years) and sex. Subjects were scanned with single photon emission computed tomography (SPECT) using [123I]β-CIT. SERT availability was expressed as specific to nonspecific binding ratios (BPND) in the midbrain and diencephalon with cerebellar binding as a reference. Results In crude comparisons between patients and controls, we found no significant differences in midbrain or diencephalon SERT availability. In subgroup analyses, depressed males had numerically lower midbrain SERT availability than controls, whereas among women SERT availability was not different (significant diagnosis×gender interaction; p = 0.048). In the diencephalon we found a comparable diagnosis×gender interaction (p = 0.002) and an additional smoking×gender (p = 0.036) interaction. In the midbrain the season of scanning showed a significant main effect (p = 0.018) with higher SERT availability in winter. Conclusion Differences in SERT availability in the midbrain and diencephalon in MDD patients compared with healthy subjects are affected by gender. The season of scanning is a covariate in the midbrain. The diagnosis×gender and gender×smoking interactions in SERT availability should be considered in future studies of the pathogenesis of MDD.0Comments 53Citations
- [Show abstract] [Hide abstract] ABSTRACT: Selective serotonin re-uptake inhibitors are often combined with tricyclic antidepressants (TCA) in the aim of optimalizing pharmacotherapy of the psychiatric patient. However, the real clinical benefit is still not well documented, but it is known, that fluoxetine and fluvoxamine interact with TCAs by increasing their plasma levels. Several reports describe the manifestation of severe adverse effects during such combination therapies. Case studies with citalopram correlate with in vitro investigations, in that citalopram is less likely to interact with TCAs at the pharmacokinetic level. Clinical studies are needed to evaluate the risk and benefit of a combination of other SSRIs such as paroxetine and sertraline, which are also potent inhibitors of cytochrome P-4502D6, an isozyme implicated in the metabolism of TCAs.0Comments 21Citations
- [Show abstract] [Hide abstract] ABSTRACT: An open-label, randomized study was conducted in 60 patients with dysthymia to determine whether the addition of bentazepam to fluoxetine speeded the onset of antidepressant effects. The patients, 46 women and 14 men aged 19 to 73 years (mean, 42 years), were assigned to receive 20 mg of fluoxetine only (n = 29) or 20 mg of fluoxetine plus 50 mg of bentazepam (n = 31) each morning for 4 weeks. At baseline and at the end of weeks 1, 2, and 4 the patients completed the Hamilton Anxiety and Depression Rating Scales and the State-Trait Anxiety Inventory. Patient scores on these three scales were significantly reduced in both treatment groups; significant reductions in scores were observed during the first week of treatment in patients receiving fluoxetine plus bentazepam, but not until the second week of treatment in the patients receiving fluoxetine alone. Side effects were reported by 10 patients in each group; treatment was discontinued in two patients in the fluoxetine group because of restlessness and headache. No rebound or withdrawal symptoms were reported when the patients were withdrawn from bentazepam during the 3-month follow-up period. It is concluded that the addition of bentazepam to fluoxetine accelerated the onset of action of fluoxetine.0Comments 5Citations