The effects of fluoxetine on the polysomnogram of depressed outpatients: a pilot study.

The effects of fluoxetine (FLU) and its active metabolite, norfluoxetine (NFLU), on the polysomnogram (PSG) of nine depressed outpatients (eight with major depression; one with bipolar II, depressed phase disorder) were investigated by contrasting PSG values prior to treatment and during administration of FLU. The PSG changes were correlated with daily dose, cumulative dosage, single serum concentrations, and the total area under the serum concentration curve (AUC) of both FLU and NFLU. Fluoxetine clearly increased both stage 1 sleep time and rapid-eye-movement (REM) latency and decreased both percent REM and REM density. With a few exceptions, the cumulative dosage of FLU and the AUC of FLU and NFLU were better predictors of the changes in awake and movement time in the PSG than single-sample concentrations of FLU and NFLU taken at the time of PSG assessment.

Reduced REM latency predicts response to tricyclic medication in depressed outpatients.

Forty-two outpatients with major depressive disorder entered a double-blind, randomized trial of either desipramine or amitriptyline for a minimum of 6 weeks. Pretreatment polysomnographic and clinical measures were used to predict response. Response was defined as a 17-item Hamilton Rating Scale for Depression score less than or equal to 9 at the end of treatment. There was a 61.1% response rate for patients treated with amitriptyline and a 66.7% response rate for patients treated with desipramine. Reduced REM latency (2-night mean less than or equal to 65.0 min) predicted a positive response to these tricyclic antidepressants. REM latency did not differentiate between desipramine or amitriptyline responders. More patients with reduced REM latency (80%) responded to treatment compared with patients with nonreduced REM latency (50%). The 80% response rate in reduced REM latency depressed patients confirms our previous findings in a mixed inpatient and outpatient sample. Contrary to our hypothesis, in this sample, endogenous depression was not associated with a good response to tricyclic medication.

Fluoxetine versus trazodone in the treatment of outpatients with major depression.

Fluoxetine and trazodone were compared in a double-blind, randomized, parallel, 6-week trial in 43 outpatients with major depression after a 1-week single-blind placebo period. Thirty-five patients completed at least 3 weeks of active medication, while 25 patients completed all 6 weeks. Response rates, whether defined by end-of-treatment Hamilton Rating Scale for Depression (HAM-D) score less than 10 or by a 50% reduction in HAM-D scores, were equivalent for the two medications. For fluoxetine, HAM-D scores were significantly lower at Weeks 1 and 2 compared with those of trazodone. Trazodone improved sleep significantly more than fluoxetine. Fluoxetine was associated more frequently with weight loss (p = .002) and less frequently with dizziness (p = .04) than trazodone.

Determination of the antidepressant fluoxetine and its metabolite norfluoxetine in serum by reversed-phase HPLC with ultraviolet detection.

A procedure has been developed for measuring fluoxetine and its desmethyl metabolite, norfluoxetine, in serum by reversed-phase high-performance liquid chromatography (HPLC), with ultraviolet detection at 226 nm. Fluoxetine and norfluoxetine are isolated from serum by liquid-liquid extraction. They are then separated by HPLC and quantified, with reduced haloperidol as the internal standard. Fluoxetine, norfluoxetine, and the reduced haloperidol are separated from all interfering peaks in about 15 min. The standard curve is linear (r = 1.000) for both fluoxetine and norfluoxetine concentrations over the range of 25 to 800 micrograms/L. Between-run CVs for 60 and 200 micrograms/L controls (n = 8) were 6.8 and 4.1% for fluoxetine, and 8.8 and 6.2% for norfluoxetine, respectively. In a study of 24 patients with depression who were being treated with 20-60 mg of fluoxetine per day, fluoxetine and norfluoxetine concentrations in serum, measured during the last three weeks of treatment, were 47-469 micrograms/L and 52-446 micrograms/L, respectively.