Fluoxetine studies/trials

Michelson D, Pollack M, Lydiard RB, Tamura R, Tepner R, Tollefson G (1999) Continuing treatment of panic disorder after acute response randomised, placebo-controlled trial with fiuoxetine. The Fluoxetine Panic Disorder Study Group. Br J Psychiatry 174 213-218... 

A multicenter trial comparing more appropriate doses of imipramine (75 mg twice daily, N = 167) and St. John s wort extract (250 mg twice daily standardized to 0.2% hypericin, N = 157) showed no difference in efficacy after 6 weeks of treatment. However, St. John s wort seemed to reduce anxiety symptoms more often than imipramine and was better tolerated (Woelk, 2000). A study including 240 participants compared St. John s wort with fluoxetine in mild to moderate depression and also concluded that efficacy of both treatments was comparable (Schrader, 2000). These results have been replicated in a smaller trial us-... 

A potential limitation of most of the controlled studies discussed above relates to the numerous exclusion criteria used for patient selection. For example, in order to find homogenous samples, major depression, bipolar disorder, Tourette s disorder, psychosis (clomipramine, fluvoxamine and fluoxetine trials), primary psychiatric disorder other than OCD (clomipramine and sertraline trials), and attention deficit/hyperactivity disorder (ADHD), autism, or other developmental disorders (clomipramine and fluoxetine trials) were excluded. Thus it remains unknown how well these controlled studies will generalize to more naturalistic clinical populations that are highly comorbid and where exclusion criteria are not applied. 

Fluoxetine Bulimia Netvosa Collabotative Study Group (1992) Fluoxetine in the tteatment of bulimia netvosa a multicentet, placebo-controlled, double-blind trial. Arch Gen Psychiatry 49 139-147. 

Another study by the same group assessed the use of fluoxetine (Prozac) (20 mg) in a 7-week open trial in 10 adolescents with the commonly occurring triad of SUD, CD, and major depression (Riggs et ah, 1997). Seven of the eight subjects had significant improvement in mood p < 0.001), and the majority reported that the fluoxetine (Prozac) assisted in their substance rehabilitation. The medication was well tolerated and no interactions between fluoxetine (Prozac) and any substances of abuse were reported. There were no positive drug tests for the duration for the study. 

Of the SSRIs, fluoxetine has been studied most extensively. Birmaher et al. (1994) and Fairbanks et al. (1997) both found significant improvement in various anxiety disorder symptoms in typically developing children. Fluoxetine was also found to be effective in the treatment of selective mutism (Black and Udhe, 1994 Dummit et ah, 1996). Fluoxetine has also been studied in individuals with MR and autistic disorder. In an open trial. Cook et al (1992) found that fluoxetine was associated with significant improvement in the Clinical Global Impression (CGI) severity ratings in 15 of 23 individuals (65%) with autistic disorder and in 10 of 16 individuals (62%) with MR. All of the SSRIs appear to have similar properties and have been approved for panic disorder, phobias, OCD, and anxiety disorder. Sertraline has been approved for treatment of PTSD, and paroxetine, for social phobia. 

In the Zito et al. study (2000), antidepressants were the second most commonly prescribed psychotropic medication. There are a total of 10 studies or case reports in the literature examining antidepressant use in preschool children (Table 49.4). None of the 10 studies are randomized, double-blind, or placebo-controlled trials. The ten uncontrolled studies looked at a total of 37 preschool children. Six of the studies looked at a total of 29 preschoolers with autism or childhood schizophrenia (Campbell et ah, 1971a Petti and Campbell, 1975 Holttum et ah, 1994 Sanchez et ah, 1996 DeLong et ah, 1998 Hollander et ah, 2000). While these six studies are difficult to compare, given the small sample sizes and the different treatment medications, these open-label studies suggest that clomipramine, venlafaxine, and fluoxetine may be helpful to reduce some psychiatric symptoms found in autistic... 

In another study, B. Black et al. [1992] reported an open trial of fluoxetine in 14 subjects, all with a primary diagnosis of social phobia, generalized subtype. Ten of the subjects were treated with only fluoxetine. Four subjects... 

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. 

Fluoxetine has been the subject of four reports in the treatment of social phobia. However, no double-blind, control studies have been reported. Preliminary results suggest that fluoxetine is effective in social phobia. Doses ranged from 10 to 100 mg/day. The onset of symptom resolution was variable among subjects. A justifiable approach to treatment with fluoxetine would be to implement an approach similar to that in the treatment of depression. One would start with a dose of 10-20 mg/day and titrate slowly upward over a period of several weeks. A duration of at least 6 weeks would be recommended as a minimum trial of this agent, with 12 weeks perhaps affording a better opportunity to assess the full measure of improvement. 

Fluoxetine. Fluoxetine has been proven to be effective for OCD in open studies as well as in a few controlled trials. In the Lilly European OCD study (Montgomery et al. 1993b), 217 patients with OCD were treated with fixed... 

Tollefson et al. (1994] reported an American multicenter investigation of fixed-dose fluoxetine in the treatment of OCD. Three hundred fifty-five outpatients participated in two randomized, double-blind, parallel, 13-week trials, receiving fluoxetine or placebo. Fluoxetine (20 mg, 40 mg, and 60 mg] was significantly superior to placebo on the Y-BOCS total score and other efficacy measures. However, a trend was noted suggesting greater efficacy of the 60 mg/day dose. The authors reported few side effects, and most patients (79.2%] completed the study. Similarly to CMl, fluoxetine led to a significant reduction in OCD severity, regarding both obsessions and compulsions. 

The olanzapine-fluoxetine combination is currently the only medication approved by the FDA specifically for the treatment of depression in patients with bipolar disorder. This indication was based on data from a double-bhnd, randomized study in which the combination was superior to both olanzapine monotherapy and placebo (Tohen et al. 2003). Treatment-emergent mania or hypomania did not occur more frequently in the olanzapine-fluoxetine combination group than in the placebo group during the acute trial. 

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