Is there a relationship between baseline and treatment-associated changes in [3H]-IMI platelet binding and clinical response in major depression?

A peripheral model for the central 5-HT neuron is the characterization of platelet imipramine binding. We studied an outpatient major depressive cohort who fulfilled Research Diagnostic Criteria for agitation. After a 1-week placebo lead-in, subjects were blindly randomized to either imipramine (IMI) or fluoxetine (FLU) during an 8-week, double-blind study period. Thirty-three subjects (15 IMI, 18 FLU) provided both baseline and endpoint samples for the platelet [3H]-IMI assay. Depression efficacy was comparable across the two treatments, whereas FLU was significantly more effective in reducing secondary anxiolysis (p = .023). Discontinuations due to an adverse event were significantly more frequent with IMI than FLU (p < .01). Baseline affinity (KD) was mildly predictive of change in the HAMD (r = -.22; p = .07). Whereas baseline to endpoint density (Bmax) changes (delta) were similar for IMI (183 +/- 329 fmol/mg) and FLU (196 +/- 402 fmol/mg), a statistically significant treatment difference in delta KD emerged (IMI -0.005 +/- 0.010 pmol/ml versus FLU 0.008 +/- 0.013 at p = 004). Moreover, the changes in KD and HAMD17 trended to a positive correlation among only the FLU-treated subjects (4 = 0.406, p = .095). The clinical effects of 5-HT-based selective antidepressant may be reflected by dynamic changes in the platelet 5-HT uptake apparatus. These data suggest that the baseline confirmational status of the [3H]-IMI:5-HT transporter may reflect a "capacity" for a treatment response.

Is baseline agitation a relative contraindication for a selective serotonin reuptake inhibitor: a comparative trial of fluoxetine versus imipramine.

A common presentation for major depression includes psychomotor agitation. However, this subtype has been the infrequent subject of controlled investigation during depression trials. Yet, the subcategorization of agitated depression has historically been associated with the belief that older, sedating compounds have a superior risk:benefit profile. In the 8-week, double-blind, randomized, parallel trial, 124 subjects with Research Diagnostic Criteria-compatible agitated depression were randomized to either imipramine (IMI) or fluoxetine (FLU). Both compounds proved to be similarly effective as measured by change in HAM-D17, HAM-D17 response, and HAM-D17 remission rates. Similar comparability was seen in secondary measures of agitation, anxiety, suicidality, and global impressions. However, of note, a statistically significant difference in early discontinuations because of intolerable adverse events emerged. Whereas 43.5% of IMI subjects discontinued early, only 9.7% of FLU subjects (p < 0.001) did. Significantly more central nervous system events characterized the IMI than the FLU subgroup (IMI, 24.2%, vs. FLU, 6.5%; p = 0.006). In conclusion, among subjects with major depression, subtype agitated, the risk:benefit profile favored FLU over IMI. This was driven by the superior tolerance of FLU. No evidence emerged in support of the clinical hypothesis that a "sedating" agent is the treatment of choice for this group. The results are important when striving to maximize compliance with pharmacotherapy in order to minimize recidivism and associated psychological and economic morbidity.

Treatment of comorbid generalized anxiety in a recently detoxified alcoholic population with a selective serotonergic drug (buspirone).

Recent literature has addressed a common dyad: alcoholism and anxiety. Both disorders have been interdigitated with the brain amine serotonin. We investigated 51 dually diagnosed patients (generalized anxiety/alcohol abuse:dependence) in a randomized, double-blind, placebo-controlled trial of the serotonin partial agonist buspirone. Buspirone was superior to placebo as an anxiolytic, was well tolerated, and was associated with both a reduction in the number of days desiring alcohol and an overall clinical global improvement.

An open label trial of alprazolam in comorbid irritable bowel syndrome and generalized anxiety disorder.

BACKGROUND: The irritable bowel syndrome (IBS) is very prevalent and psychiatric comorbidity runs high. A significant proportion of generalized anxiety disorder (GAD) patients manifest concurrent IBS. METHOD: We conducted a 14-week, open-label trial of the triazolobenzodiazepine alprazolam in 32 patients with comorbid generalized anxiety and IBS. At the end of a 2-week placebo run-in, eligible subjects received 6 weeks of active drug therapy. RESULTS: Ninety-four percent of subjects (N = 25) had a full or partial anxiolytic response at the 6th treatment week (p less than .001). Eighty-nine percent (N = 24) experienced a concomitant reduction in IBS severity. For the majority, these dual benefits were still evident at the conclusion of a 4-week drug taper (p = .05) and achieved a trend (p = .07) at a 4-week postdrug discontinuation visit. CONCLUSION: Alprazolam was safe, effective, and well tolerated during the acute treatment of comorbid GAD and IBS; only a limited posttreatment rebound was observed.