Paroxetine design

Antidepressants Desipramine, imipramine, sertraline, fluoxetine, paroxetine, venlafaxine, bupropion, nefazodone, mirtazapine, gepirone, amineptine Mixed findings suggest that better designed studies may find a niche for some of these drugs. Amineptine was effective for withdrawal symptoms. 

A prospective, randomized, placebo-controlled trial of paroxetine in adults with chronic post-traumatic stress disorder (PTSD) was recently conducted (Marshall etal., 2007). The subjects were New Yorkers, predominantly female (67%) and Hispanic (65.4%). Seventy subjects entered the study and after a one week placebo lead-in, 52 subjects were randomized to placebo or paroxetine for ten weeks. The subjects were treated with a flexible dosage design (mean dosage, 40.4 mg/day). Dropout rates were 32% for paroxetine and 51.9% for placebo. There were no differences in rates of adverse effects between treatment arms. Paroxetine was superior to placebo in ameliorating the primary symptoms of PTSD (56% vs. 22.2%). 

In general, the SSRIs have a more tolerable side effect profile than the tricyclic antidepressants with their anticholinergic effects. Review of the rate that subjects in the controlled studies discontinued a SSRI because of adverse effects provides some perspective on how well tolerated the medications are, although the specifics may vary according to dosage and design (e.g., forced titration) and are not directly comparable. The rate of discontinuation was reported to be 12% (4/48) for fluoxetine (Emslie et ah, 1997), 9.7% for paroxetine (Keller et ah, 2001), 13% (12/92) for sertraline (March et ah, 1998), and 33% (19/57) (Riddle et ah, 2001) and 7.9% (5/63) for fluvoxamine (Walkup et ah, 2001). 

A higher percentage of patients would be expected to relapse in the crossover design for two reasons. First, a significant portion of the patients in the crossover study had, in fact, responded specifically to the drug treatment. After a period of stabilization, these patients were randomly reassigned to placebo and thus would be expected to relapse. Second, a basic problem in the crossover design is that withdrawal symptoms can mimic the recurrence of depressive symptoms. That is true for the SSRIs, particularly fluvoxamine and paroxetine, because of their relatively short half-lives. 

Selective serotonin reuptake inhibitors (SSRIs) are the first-line therapy for PTSD. Efficacy for fluoxetine, paroxetine, and sertraline has been demonstrated in well-designed double-blind placebo-controlled studies to reduce all symptom domains (intrusive recollection, avoidance/numbness, and hyperarousal). - Other treatment options include the tricyclic antidepressants (TCAs) amitriptyline and imipramine and the irreversible monoamine oxidase inhibitor (MAOl) phenelzine, which have been shown to reduce re-experiencing. However, in comparison with SSRIs, TCAs and phenelzine are associated with a higher incidence of side-effects, risk of overdose, and poor compliance. Alprazolam has demonstrated anecdotal efficacy however, regular use of benzodiazepines is not recommended. Benzodiazepines can be used on an as-needed basis for specific symptoms (e.g. sleep disturbances). CBT has shown beneficial effects in relatively well-controlled studies, while the results with exposure therapy are... 

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