Placebo-controlled studies advantages

Treatment of GAD can be undertaken using a number of pharmacological agents. Benzodiazepines have been found to be superior to placebo in several studies and all benzodiazepines appear to be equally effective. However, side effects include sedation, psvchomotor impairment, amnesia and tolerance (Chapter 1). Recent clinical data indicate that SSRIs and SNRIs are effective in the treatment of acute GAD symptoms. Venlafaxine, paroxetine and imipramine have been shown to be effective antianxiety medications in placebo-controlled studies. Case studies also indicate the usefulness of clomipramine, nefazodone, mirtazapine, fluoxetine and fluvoxamine in GAD. Buspirone, a 5-HTla receptor partial agonist, has been shown to be effective in several placebo-controlled, double-blind trials (Roy-Byme and Cowley, 2002). Buspirone has a later onset of action than both benzodiazepines and SSRIs but with the advantage of being non-addictive and non-sedating. 

It is important to distinguish between acute (e.g., 1 day) and longer term treatment with a BZD. Most of the literature addressing this issue consists of anecdotal reports, retrospective chart reviews, and uncontrolled studies in small patient samples, plus a small number of controlled trials for short-term acute BZD therapy. To our knowledge, at least 12 studies (including more than 450 patients) have evaluated the efficacy of adjunctive BZDs in nonresponsive schizophrenics (Table 5-23). Two of three open studies showed positive results, as did two controlled, single-blind studies ( 343, 344, 345, 346 and 347). In seven double-blind, crossover studies (six with placebo controls), the results are more contradictory, in that five showed no advantage to an adjunctive BZD, and one of the two positive studies had a small sample size (188, 189, 348, 349, 350 and 351). 

The approval of mirtazapine in the United States was based on six double-blind, placebo- and amitriptyline-controlled studies in which it was found to be superior to placebo and comparable with amitriptyline in terms of antidepressant efficacy (173,174). In a double-blind, crossover study, 63% of patients who failed to respond to 6 weeks of double-blind treatment with amitriptyline responded to mirtazapine (175). In two studies, mirtazapine was found to be efficacious in the treatment of patients hospitalized for major depression. In the first study, the antidepressant efficacy of mirtazapine was comparable with that of amitriptyline and superior to placebo (176). In the other study, the antidepressant efficacy was superior to that of fluoxetine (118). There are advantages and disadvantages to mirtazapine, including the following ... 

There is a need for more comparisons with short to medium half-life BZDs for the treatment of insomnia to show that zolpidem has any advantages over the BZDs. One placebo-controlled, randomized polysomnographic study of 24 patients with chronic insomnia found that zolpidem (10 mg) was comparable with triazolam (0.5 mg) and superior to placebo in enhancing sleep efficacy. Further, rebound insomnia occurred during the posttreatment, 3-day withdrawal phase in the triazolam group, but not in the zolpidem or the placebo groups (149). 

Typically, patients with confirmed CVST are treated with intravenous heparin even in the presence of intracerebral hemorrhage. Although there is only one placebo-controlled, double-blind study showing a significant advantage of intravenous dose-adjusted unfractionated heparin therapy in patients with CVST (Einhaupl et al. 1991), heparin as the first-line treatment is recommended because of its efficacy, safety and feasibility (Ameri and Bousser 1992 Bousser 1999). Only in rare cases may fibrinolytic therapy or thrombectomy be considered as alternative treatment options. 

Some in vitro studies have demonstrated that azithromycin is active against chloroquine-sensitive and -resistant strains of Plasmodium falciparum [285]. A trial using daily azithromycin at a dose of 250 mg as a malaria prophylaxis in volunteers has shown azithromycin to be protective against P. falciparum challenge [286,287]. A randomized, placebo-controlled, double-blind study of malaria prophylaxis compared two regimens of azithromycin versus daily doxycycline for a period of 10 weeks in western Kenya [287]. Both regimens with daily azithromycin and doxycycline provided effective prophylaxis of falciparum malaria in this trial. A potential advantage of azithromycin over doxycycline for malaria prophylaxis is... 

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