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Rationale for combining sulfamethoxazole and trimethoprim with fluoxetine" [36]. Sulfamethoxazole was recommended for the treatment of fluoxetine-induced flu-like symptoms because the decreased side effects and increased effectiveness of these drugs over other treatments. Fluoxetine is often recommended by physicians and in the media as a treatment option for depression. Although there have never been direct clinical studies to support the use of this drug for depression, there is evidence that fluoxetine safe and effective for the treatment of depression; many psychiatrists prescribe fluoxetine for depression. The U.S. General Accounting Office reports in a January 2001 report that approximately 3.8 percent of adults aged 12 or older take the antidepressant drugs fluoxetine, paroxetine, or sertraline. About 30 percent of these fluoxetine users use the drug to treat depression [37]. The number of fluoxetine users is rising, and the FDA considers risk of serotonin syndrome during treatment with fluoxetine "very low". A total of 7,879 reports adverse events associated with the treatment fluoxetine were filed with the FDA during 1990 in cases involving approximately 1,000 patients [38]. Of these, 561 developed a serotonin syndrome. Only five cases of serious reactions were reported to the FDA [39]. A meta-analysis published in 1995 indicated that, of 469 patients treated with fluoxetine for depression, 1.4 percent developed serotonin syndrome (serotonin syndrome) during treatment [40]. There is no evidence that fluoxetine treatment has increased the risk of stroke or death in patients with depression. It has been shown that is not related to cardiovascular risk factors, but a causal relation has not been established. Fluoxetine increased the risk of stroke when compared to placebo, but there was no risk in studies with other antidepressants [41]. Fluoxetine has not been associated with increased risk of death in persons aged 65 years through 79 who have a history of heart disease or stroke and are not on hormone replacement therapy. No case of death and stroke in persons not taking hormone replacement therapy (e.g. on estrogen therapy) occurred in the Fluoxetine Intervention for Depression (FITD) trial. In addition, studies conducted both placebo and treatment groups in the FITD trial had no increase in mortality or stroke women with heart failure, congestive failure (CHF), and heart associated with hormone replacement therapy [42, 43], so fluoxetine should be safe for persons taking hormone replacement therapy [44]. It is recommended that in patients taking fluoxetine who are hospitalized, should be added to routine maintenance therapy for at least 1 week before discharge (e.g. the fluoxetine dose should not be increased more than 4-fold) in patients who are being actively evaluated for suicide prevention [45]. A recent trial of 2 months duration involving a placebo control and fluoxetine (45 mg/day) showed that added to standard antidepressants resulted in fewer nonfatal suicidal acts over 24 weeks, but this effect was not significant when compared to fluoxetine alone [46]. This suggests that fluoxetine addition may be safe for patients who previously experienced symptoms of suicidal behavior, but more research is needed to determine if fluoxetine added standard antidepressants is a treatment option for the prevention of suicide in patients clinical trials [11]. The recommended strategy for managing fluoxetine-treated patients with depression is to begin a dose of fluoxetine that corresponds to the patient's therapeutic dose [47]. should then be tapered gradually and may more aggressively with time if the patient requires more than indicated therapeutic dose. Fluoxetine has a short half life. study in women with major depression aged 55 years (aged +/- 10 years) who were already receiving an antidepressant showed that fluoxetine (45 mg/day) continued therapy in such patients could have a shorter duration (less than one day) fluoxetine monotherapy at 3 months. However, additional evidence was required to conclude whether continuing fluoxetine monotherapy at such a short duration is safe [48]. Therefore, in general, the duration of treatment with fluoxetine in individuals depression should be limited to 1–2 weeks. A trial was conducted in healthy volunteers to determine the effects of prolonged fluoxetine (2 weeks) treatment in women aged 55 with major depression who were also receiving other agents. The trial examined relapse rates within 3 months of long-term fluoxetine therapy, as compared with short-term fluoxetine therapy [49]. After 8 weeks of fluoxetine (45 mg/day) therapy with no additional antidepressant exposure, the relapse rate of depression symptoms was 42%, whereas after 6 months of fluoxetine (45 mg)



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