Sertraline studies/trials

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. 

Sertraline. To our knowledge, no controlled studies of sertraline in subjects with autistic disorder or other PDDs have been published, although a number of open-label reports have appeared. In a 28-day trial of sertraline (at doses of 25 to 150 mg daily) in nine adults with mental retardation (five of whom had autistic disorder), significant decreases in aggression and... 

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. 

Results from two large multicenter trials evaluating SRIs for the treatment of dysthymia were similar to those found above (M. Steiner, personal communication, December 1995 Halbreich et ah, in press). In a study evaluating the efficacy of sertraline versus that of IMl and placebo for the treatment of dysthymia, women were again found more likely to respond to sertraline than to either IMI or placebo. Similarly, dysthymic women treated with paroxetine were more likely to respond using a definition of 50% decrease in the HRS-D. In this latter case, 54% of women treated with paroxetine responded compared with 21% of women treated with placebo, whereas 30% of men in either treatment cell responded (M. Steiner, personal communication, December 1995). 

A number of SSRIs and SNRIs were tested for their effects on cognitive function in repeated-dose studies in healthy, non-depressed volunteers. Studies with SSRIs before 1999 have been reviewed by Lane and O Hanlon (1999) and some more recent reports deal with nefazodone. paroxetine and sertraline (Furlan et al., 2001 Schmitt et al., 2001 van Laar et al.. 2002). However, considering the populations studied in these trials (non-depressed subjects), the duration of drug administration (1 2 weeks) and the mostly low drug doses used, the relevance of these studies for a clinical situation may be questioned. 

With regard to its effects on cognitive performance in the target population, the SSRI sertraline appears to be the most thoroughly studied newer antidepressant. Lane and O Hanlon (1999) listed three controlled clinical studies with fluoxetine and three with sertraline however, all three trials with fluoxetine and one of the trials with sertraline were not sufficiently powered to demonstrate reliable differences between treatments. One of the two adequately powered studies, a comparison between nortriptyline and sertraline in elderly depressed patients (Bondareff et al., 2000 see Box 7.3), supports the notion that antidepressants with anticholinergic action (such as nortriptyline) are similarly... 

A larger set of placebo-controlled studies show conclusively that imipramine is also effective for the treatment of panic disorders. Other agents shown to be effective in panic disorders include the SSRIs paroxetine, sertraline, fluvoxamine, fluoxetine and citalopram. Generally, initial treatment of moderate to severe panic disorders may require the initiation of a short course of benzodiazepines e.g. clonazepam (0.5 1 mg twice daily), and an SSRI. The patient will obtain immediate relief from panic attacks with the benzodiazepine whereas the SSRI may take 1 6 weeks to become effective. Once a patient is relieved of initial panic attacks, clonazepam should be tapered and discontinued over several weeks and SSRI therapy continued thereafter. There are no pharmacological treatments available for specific phobias, however controlled trials have shown efficacy for several agents, e.g. phenelzine, moclobemide. clonazepam, alprazolam, fluvoxamine. sertraline and paroxetine in the treatment of social phobia (Roy-Byrne and Cowlev, 2002). 

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). 

The meta-analysis of all studies comparing clomipramine or SRIs with placebo for the treatment of OCD found that the active drug produced a better result in every trial. We then calculated the effect size and the statistical significance for clomipramine alone and fluvoxamine alone. Their results showed a highly significant effect for both drugs (Table 13-10 and Table 13-11). There were also several studies with sertraline, fluoxetine, and paroxetine that demonstrated similar results (219, 220, 221, 222. 223,. 224, 225 and 226). 

Since the study by Emsiie and colleagues, there has also been a positive, double-blind, placebo-controlled study with paroxetine (120), and sertraline has also shown promise in an open-label trial in adolescents with major depression (121). 

Both fluvoxamine and sertraline are approved for the treatment of OCD in children and adolescents. Fluvoxamine was proven effective in a 10-week, double-blind, placebo-controlled trial in patients 8 to 17 years of age with OCD ( 149). Dosages in this study were adjusted to a total daily fluvoxamine dose of approximately 100 mg per day over the first 2 weeks using a balanced, twice-daily dosing schedule. After that, the dose was adjusted within a range of 50 to 200 mg per day based on clinical assessment of efficacy and tolerability. Fluvoxamine was superior to placebo on the Children s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) at weeks 1 to 6 and week 10. However, the effect was mainly in the 8- to 11-year-old versus the 12- to 17-year-old age group. The significance of this age difference is not known. 

Bipolar patients with so-called breakthrough major depressive episodes, despite adequate treatment, were placed in a randomized doubleblind 10-week study and treated with bupropion, sertraline, or venlafaxine augmentation (Post et al., 2001). Switches to hypomania or mania occurred in 14% of the patients. Those who responded positively to the treatment were continued for 1 year in a blinded maintenance trial, and 33% switched into hypomania or mania. In a second phase of their antidepressant augmentation studies, 18.2% switched into hypomania or... 

The ability of SSRIs to cause delayed ejaculation has been used in controlled trials of men with premature ejaculation (61,62). Of the SSRIs, paroxetine and sertraline produced the most benefit in terms of increase in time to ejaculation, but fluvoxamine did not differ from placebo. Clomipramine was more effective than the SSRIs but caused most adverse effects. From a practical point of view many patients might prefer to take medication for sexual dysfunction when needed rather than on a regular daily basis, and it would be of interest to study the beneficial effects of SSRIs on premature ejaculation when used in this way. 

Sertraline In a small open study, five patients with bulimia nervosa binged less after being prescribed sertraline (Sloan et al. 2004). In a randomised, placebo-controlled trial of sertraline 100 mg daily for 12 weeks, the patients treated with sertraline had a statistically significant reduction in the number of binge eating crises and purging compared with those who received placebo (Milano et al. 2004). No patients withdrew from the trial because of side effects. 

Antidepressants of the serotonin reuptake inhibitor type (SSRI) have been found effective in ameliorating the symptoms of PMS in over 20 randomised placebo-controlled clinical trials. Therefore, these drugs are currently considered the treatment of choice (Pearlstein 2002). Sertraline and fluoxetine have been the most widely studied. Their beneficial effects appear fairly quickly, suggesting that their pharmacological mode of action in PMS differs from that underlying their antidepressant action which takes longer to become manifest. A possible explanation for this difference is that SSRI act directly on brain neuroendocrine activity. 

The bulk of literature examining antidepressant use in AD is made up of case reports and uncontrolled studies. Most of these report a favorable response to antidepressants, but several placebo-controlled trials have demonstrated mixed results. Of the antidepressants studied, citalopram, sertraline, clomipramine, and moclobe-mide (a monoamine oxidase inhibitor not marketed in the U.S.) were considered efficacious in at least one study but fluoxetine and imipramine were no better than placebo. It should be noted that citalopram and sertraline have both been studied in other placebo-controlled trials in this population with no difference over placebo. ... 

SAD can present in children of preschool to elementary school age. If the disorder is not treated, it can persist into adulthood and increase the risk of depression and substance abuse. CBT and social skills training are effective nonpharmacological therapies in children. Pharmacological evidence is limited to case studies or open-label trials. SSRIs are considered first-line therapy because of tolerability and effectiveness. Fluoxetine, fluvoxamine, sertraline, and paroxetine were effective in children with SAD. Headache, nausea, drowsiness, insomnia, jitteriness, and stomach aches were reported in children receiving SSRIs. 

Compared with other classes of antidepressants, SRIs have a more favorable side-effect profile and better efficacy data. A review of randomized, controlled trials with SRIs for the treatment of PMDD reported that the agents were well tolerated and effective in treating physical as well as behavioral symptoms with either intermittent or continuous dosing. Citalopram, fluoxetine, paroxetine, sertraline, and venlafaxine all have been effective in PMDD placebo-controlled trials (60% to 90% efficacy rates with almost complete relief of symptoms). For fluvoxamine, there are mixed results because one controlled study reported that it had similar efficacy to placebo treatment in PMDD. Although antidepressants usually take... 

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