Timing of clinical improvement and symptom resolution in the treatment of major depressive disorder.

The goal of the present work is to assess for the relationship between the timing of clinical improvement and the resolution of depressive symptoms in Major Depressive Disorder (MDD). 182 MDD outpatients (40.5+/-9.7 years; 53.8% female) who responded following an 8-week, 20 mg, open trial of fluoxetine were included in the analysis. The symptoms questionnaire (SQ) and Beck hopelessness scale (BHS) were also administered to 83 and 153 of these patients, respectively. Onset of clinical improvement was defined as a 30% decrease in 17-item Hamilton depression scale (HDRS-17) scores. Controlling for baseline symptom severity, we then assessed for the relationship between the timing of clinical improvement and depressive symptom at endpoint. Earlier clinical improvement in responders predicted lower HDRS-17, BHS, SQ-depression, SQ-anxiety, but not SQ-somatic symptom or SQ-anger/hostility scores at week 8. This was true regardless of whether improvement was defined as a continuous measure (30% decrease in symptom severity), as a dichotomous measure (clinical response occurring in the first two weeks of treatment). In conclusion, earlier clinical improvement with fluoxetine treatment is predictive of greater symptom resolution at endpoint. Further studies exploring the impact of various treatment modalities and placebo on the timing of clinical improvement and symptom resolution in MDD are warranted.

Serum prolactin levels among outpatients with major depressive disorder during the acute phase of treatment with fluoxetine.

OBJECTIVE: To determine changes in serum prolactin levels in outpatients with DSM-IV-diagnosed major depressive disorder (MDD) following a 12-week open-label trial of fluoxetine. METHOD: 87 outpatients enrolled in the trial had serum prolactin levels determined at baseline and during their final visit (week 12 or discontinuation visit). In addition, serum testosterone levels were measured in 44 of the 46 men during these 2 visits. Hyperprolactinemia was defined as a serum prolactin level greater than 16.5 ng/mL or 18.9 ng/mL for men and women, respectively. The study was conducted from September 1997 to March 2002. RESULTS: Of 80 patients with normal prolactin levels at baseline, 10 (12.5%) developed hyper-prolactinemia following fluoxetine treatment. Specifically, 2 (4.5%) of 44 men and 8 (22.2%) of 36 women with normal prolactin levels at baseline developed hyperprolactinemia following treatment with fluoxetine (p = .0174 for between-gender difference). In addition, there was a significant increase in mean +/- SD serum prolactin levels following treatment with fluoxetine in all patients with normal baseline prolactin levels (6.4 +/- 3.4 to 10.0 +/- 7.0 ng/mL, p = .002). There were no significant changes from baseline in testosterone levels in men following fluoxetine treatment (448.4 +/- 139.6 to 439.5 +/- 142.1 ng/dL, p > .05; normal above 245 ng/dL), while none of the 44 men developed low testosterone levels following fluoxetine treatment. CONCLUSION: 4.5% of men and 22.2% of women with MDD developed new onset hyper-prolactinemia following fluoxetine treatment.

Somatic symptoms as predictors of time to onset of response to fluoxetine in major depressive disorder.

OBJECTIVE: In the present study we assessed the relationship between somatic symptoms and the time to onset of clinical response to fluoxetine in patients with major depressive disorder (MDD). METHOD: 87 outpatients (mean age = 41.4 +/- 10.2 years; 59.8% women) with DSM-III-R MDD who had sustained acute response to fluoxetine completed the Symptom Questionnaire (SQ) at baseline. Onset of response was defined as a 30% decrease in the total score for the 17-item Hamilton Rating Scale for Depression that led to a 50% decrease by week 8. With the use of 2 separate multiple regressions, controlling for the severity of depression at baseline, we then assessed the relationship between the number of somatic symptoms as assessed by the SQ subscale for somatic symptoms (SQ-SS) and both the time to onset of clinical response and the time to clinical response. The study was conducted between November 1992 and January 1999. RESULTS: A greater number of somatic symptoms at baseline predicted a greater amount of time to onset of clinical response to fluoxetine (p =.0233). The relationship between SQ-SS scores and time to response was not found to be statistically significant (p >.05). CONCLUSION: Somatic symptoms of depression were found to be associated with a delayed onset of antidepressant response to fluoxetine in MDD.