Pattern analysis method for assessing successful weight reduction.

Researchers reporting on clinical weight loss programmes have been challenged to provide information about long-term follow-up. To evaluate long-term weight reduction, a methodology was developed for analysis of longitudinal data. Under this method, a pattern of interest is defined a priori, and the proportions of patients attaining the pattern are compared between treatments. The methodology permits objective summarization and statistical analysis of the data. Applications of the method and corresponding results demonstrate its utility for assessing the treatment effect on weight reduction and systolic blood pressure. To show that the method may be further generalized, suggestions for alternative types of patterns are presented.

Fluoxetine, placebo, and tricyclic antidepressants in major depression with and without anxious features.

BACKGROUND: The presence or absence of anxiety has traditionally determined choice of an antidepressant ("activating" or "sedating"); however, there is little scientific support for the construct. We conducted a meta-analysis to determine whether comorbid anxiety affected efficacy or predisposed patients to specific adverse events. METHOD: Data were evaluated from 19 randomized, double-blind clinical trials comparing fluoxetine with placebo or a tricyclic antidepressant (TCA) or both in 3,183 patients with major depression (Cochran-Mantel-Haenszel, Mantel-Haenszel incidence difference, analysis of variance, and Pearson's chi-square methods). On the basis of the anxiety/somatization factor within the 21-item Hamilton Rating Scale for Depression (HAM-D21), patients were characterized as anxious (score > or = 7) or nonanxious (score < 7). RESULTS: Fluoxetine was significantly (p < or = .05) more effective than placebo in treating both anxious and nonanxious major depression (mean improvement in HAM-D21 total score, 11.0 versus 8.1 and 8.1 versus 5.5, respectively). Fluoxetine was also statistically significantly more effective than placebo in reducing the HAM-D21 anxiety/somatization factor score (anxious, all patients). The efficacy of fluoxetine and TCAs was comparable (all measures, all groups). Discontinuations for adverse events were statistically significantly higher with fluoxetine than placebo (anxious, 15.2% versus 3.8%; nonanxious, 13.2% versus 6.7%) and with TCAs than fluoxetine (anxious, 28.9% versus 15.5%; nonanxious, 34.1% versus 19.0%). Among events suggestive of "activation" or "sedation," incidence rates ranged from 0.0% to 32.9%; discontinuation rates were low (0.0% to 4.1%), except for somnolence with TCAs (9.4% to 13.2%). CONCLUSION: Anxiety in major depression does not appear to affect response to an antidepressant. Therefore, antidepressant selection should be determined by an agent's overall risk:benefit ratio, not the presence or absence of anxiety.

How long to onset of antidepressant action: a meta-analysis of patients treated with fluoxetine or placebo.

The onset of action of antidepressant medications is commonly believed to require three or more weeks based on clinical observation and corollary receptor-based hypotheses. However, this is not congruent with early published observations with the tricyclic antidepressants and has been recently challenged. Time to response has implications for treatment compliance, dose adjustment, patient well-being, and the associated economic costs of depression. Weekly improvement on the 21-item Hamilton Depression Rating Scale (HAMD21) from baseline and time to response for fluoxetine- and placebo-treated patients were compared. Data from six double-blind clinical trials of 6-7 weeks' duration, in which 1447 patients with DSM-III-R major depression had been randomly allocated to fluoxetine (n = 962) or placebo (n = 485), were pooled. Analysis of variance was used to evaluate HAMD21 improvement and the Kaplan-Meier estimate was used to evaluate time to response (> or = 50% improvement in HAMD21). Improvement in HAMD21 was statistically significantly greater for fluoxetine than placebo beginning at Week 1 and continuing throughout all weeks of therapy. However, Week 1 and 2 results varied among the individual studies. HAMD factors of cognition and psychomotor status revealed the most rapid changes for fluoxetine-treated compared with placebo-treated patients. The probability of achieving a clinical response, defined as a HAMD21 score reduction from baseline of at least 50%, was similar for both fluoxetine (0.043) and placebo (0.049) at the end of Week 1. However, by Week 2 and thereafter the probability of a response was greater for fluoxetine than placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Fluoxetine compared with imipramine in the treatment of inpatient depression. A multicenter trial.

Fluoxetine and imipramine were compared in a six-week, double-blind, randomized trial in 118 men and women, ages 18 to 70 years, hospitalized for major depressive disorder. Treatment groups were comparable at baseline. Median maintenance doses were: fluoxetine, 80 mg/day; imipramine, 200 mg/day. Efficacy with fluoxetine and imipramine was comparable: none of the between-treatment differences was statistically significant. Mean +/- standard deviation baseline HAMD21 total scores and change (last-visit-carried-forward analysis), respectively, were fluoxetine, 28.0 +/- 5.3 and -8.5 +/- 9.9; imipramine, 27.0 +/- 5.8 and -11.9 +/- 9.0. Response and remission rates, respectively, were fluoxetine, 54.5 and 21.2%; imipramine, 60.0 and 34.3%. Discontinuations for adverse events were comparable (fluoxetine, 21.4%; imipramine, 22.6%). Common treatment-emergent events with fluoxetine were dry mouth (28.6%), constipation (17.9%), and somnolence (17.9%); those with imipramine were dry mouth (58.1%), constipation (32.3%), and headache (22.6%). Fluoxetine was as effective as imipramine in this population of inpatients.

Analysis of the Hamilton Depression Rating Scale factors from a double-blind, placebo-controlled trial of fluoxetine in geriatric major depression.

Major depression during later life represents a clinical challenge. Conventional antidepressant pharmacotherapy is relatively less well tolerated in geriatric patients compared with younger patients. Despite the striking impairments associated with this disorder, clinical investigations into the relative risk-benefit ratio of various depression treatment strategies have been limited. In this multicentre, placebo-controlled, double-blind trial with fluoxetine, 671 major depressed (DSM-III-R-compatible) outpatients aged 60 years or older were evaluated. The 21-item Hamilton Depression Rating Scale (HAMD21) response (p = 0.014) and remission (p = 0.008) criteria favoured fluoxetine over placebo. Analysis of the treatment effect on change in the HAMD21 factors (anxiety/somatization, cognitive disturbance, psychomotor retardation, and sleep disturbance) revealed advantages for fluoxetine within the cognitive disturbance and psychomotor retardation factors. Overall, the rate of discontinuation for an adverse event between fluoxetine (11.6%) and placebo (8.6%) was not statistically significant. Baseline HAMD21 factor scores were not predictive of adverse events leading to premature treatment discontinuation. Fluoxetine, 20 mg/day, is a well-tolerated and effective treatment option in the management of geriatric major depression.