Fluoxetine, clinical trials

In a recent open clinical trial, patients receiving venlafaxine XR or fluoxetine for six weeks without sleep improvement were randomly assigned to either mirtazapine (7.5 mg) or zolpidem (10 mg). Although both groups improved in terms of their sleep, the patients with either fluoxetine or venlafaxine had a more rapid... 

SSRI structurally related to fluoxetine with a shorter half-life, was reported to be an effective and generally well-tolerated treatment for men with moderate-to-severe PE in clinical trial [13,14],... 

Emslie, G.J., Heiligenstein, J.H., Hoog, S.L., Judge, R., Brown E.B., and Nilsson, M. (2000) Fluoxetine for acute treatment of depression in children and adolescents a placebo controlled randomized clinical trial. Presented at the 39th Annual Meeting of the American College of Neuropsychopharmacology, San Juan, Puerto Rico. 

Another open trial of fluoxetine was reported by Van Ameringen et al. (1993). In this study, 16 subjects with a primary diagnosis of social phobia were entered into a 12-week clinical trial. Treatment started at a dose of 20 mg/day and was increased every 4 weeks, according to clinical response and side effects, to a maximum daily dose of 60 mg. Of the 16 subjects, 10 were considered responders, 3 were nonresponders, and 3 dropped out of the trial as a result of adverse effects related to the medication. The response rate of the different subtypes of social phobia was not reported in this study. 

There have been five double-blind studies comparing the antidepressant efficacy of different SSRIs versus different TCAs in patients with HDRS scores of 25 or more (122, 123,124, 125 and 126). Three of these studies permitted inclusion of both inpatients and outpatients ( 122, 123 and 124), whereas the other two were solely done in outpatients (125, 126). Three were placebo-controlled (1.23, 125,126). In these three studies, the SSRI (i.e., fluvoxamine, paroxetine, or sertraline) was either superior to both the f CA and placebo or was comparable with the TCA and superior to placebo. In the other two studies, the SSRI was not different from the TCA and there was no placebo control. There have also been four studies and one metaanalysis of European clinical trials which found no difference in antidepressant efficacy between several different SSRIs and several different tertiary amine TCAs in patients hospitalized for major depression ( 127,128, 129,130 and 131). Finally, there have been two relatively small studies showing that fluoxetine and fluvoxamine both had antidepressant efficacy superior to placebo in patients with melancholia ( 132, 133). Another larger study failed to find a difference between paroxetine and amitriptyline in treating such patients ( 134). 

Most efficacy trials with reboxetine have so far only been published in review articles ( 178). Most of these articles did not have peer review and do not contain the full details concerning methodology or results. This fact limits the ability to accurately determine its relative efficacy and tolerability. In short-term (4 to 8 weeks), placebo-controlled clinical trials, reboxetine produced a response (defined as at least a 50% reduction in severity scores) in 56% to 74% of patients. These results were statistically superior to placebo in most studies. Reboxetine was also found to be as effective as imipramine and desipramine in four double-blind, randomized, active-controlled (but not placebo-controlled) studies involving more than 800 outpatients or inpatients with major depression. Reboxetine produced equivalent antidepressant response rates compared with fluoxetine in two clinical trials, one of which was also placebo-controlled. However, reboxetine was reported to have improved social motivation and behavior more than fluoxetine as assessed by the newly developed Social Adaptation Self-Evaluation Scale. In all of the studies, reboxetine had a similar time (i.e., 2 to 3 weeks) to onset of the antidepressant efficacy as do other antidepressants. 

The dearth of information on the metabolism of bupropion may initially seem surprising however, this drug is one of the oldest of the newer antidepressants, having entered clinical trials in the mid-1970 s and having been approved before fluoxetine ( 308, 314, 315). Ironically, its marketing was delayed after its approval because of the risk of seizures, which, in turn, is almost undoubtedly a consequence of its complicated pharmacokinetics ( 163). 

Gwirtsman HE, Guze BH, Vager J, et al. Fluoxetine treatment of anorexia nervosa an open clinical trial. J Clin Psychiatry 1990 51 378-382. 

St. John s wort (Hypericum perforatum) is a perennial wildflower indigenous to Europe, North Africa, and western Asia (Fig. 1) and has been used for medicinal purposes for over two millennia. As far back as the early 16th century, St. John s wort was used primarily to treat anxiety, depression, and sleep disorders. In the late 20th and early 21st century, St. John s wort has been recommended for the treatment of mild to moderate depression (7). In support of its use for the treatment of mild to moderate depression, a number of clinical trials have demonstrated that St. John s wort has comparable efficacy to the tricyclic antidepressants (i.e., imipramine) and selective serotonin reuptake inhibitors (e.g., fluoxetine and paroxetine) (8-13). 

Altamura, A. C., De Novalis, F., Guercetti, G. et al. Fluoxetine compared with amitriptyline in elderly depression a controlled clinical trial. Int. ]. Clin. Pharmacol. Res. 9 (1989) 391-396. 

Pedrinola F, Sztejnsznajd C, Lima N, Halpem A, Medeiros-Neto G. The addition of dexfenfluramine to fluoxetine in the treatment of obesity a randomized clinical trial. Obes Res 1996 4 549-554. 

An unpublished document obtained during discovery in product liability suits against the drug company disclosed that Eli Lilly, the manufacturer of fluoxetine (Prozac), had evaluated the comparative rates of suicide attempts on fluoxetine, amitriptyline, and placebo (the documents are available from http //www.breggin.com). The data were generated during controlled clinical trials conducted for the FDA approval process for Prozac for depression. On the basis of the company s data for controlled clinical trials, patients taking fluoxetine were 12 times more... 

Healy et al. (2006) described nine cases in England, Scotland, Australia, and the United States as illustrations of antidepressant-induced violence. Two paroxetine, three sertraline, and one fluoxetine case resulted in homicide. One paroxetine case resulted in assault, one venlafaxine case resulted in attempted murder, and one fluoxetine case resulted in assault and robbery. Some were associated with maniclike symptoms. They also evaluated clinical trial data (see subsequent discussion). 

A controlled clinical trial found that fluoxetine caused a 6% rate of mania in depressed children and youngsters age 7-17 (Emslie et al., 1997). The reactions were severe enough to cause the children to be dropped out of the trials. By contrast, none of the depressed youngsters... 

In defense of their company and their drug, these authors then explained, The subjects who received fluoxetine in Phase I clinical trial have not described any change in mood nor have observers noted any change in affect. This claim is not supported by the facts as disclosed... 

Muijen, M., Roy, D., Silverstone, T., Mehmet, A., 6c Christie, M. (1988). A comparative clinical trial of fluoxetine, mianserin and placebo in depressed outpatients. Acta Psy-chiatrica Scandinavica 78, 384-390. 

In a meta-analysis based on 9087 patients in 87 different randomized clinical trials fluoxetine was more effective than placebo from the first week of therapy (2). In bulimia nervosa, fluoxetine was as effective as other agents. It was as effective as clomipramine in the treatment of obsessive-compulsive disorder. 

In a meta-analysis based on 9087 patients in 87 different randomized clinical trials with fluoxetine there was no increased risk of suicide (2). 

In a post-marketing surveillance study there were some cases in which fluoxetine alone appeared to have precipitated hepatitis, which remitted when treatment was withdrawn (27). Fluoxetine can cause mild increases in liver enzymes, with a rate in clinical trials of about 0.5%. Rarely this can progress to hepatitis. 

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