The possible existence of a specific pharmacological antidepressant effect has become one of the major controversies in current medicine.Researchers are anticipating that a new “mega-analysis” shall end the ongoing controversy regarding antidepressants including selective serotonin reuptake inhibitors (SSRIs), being effective for depression or not.Previous research suggested that antidepressants’ superiority is “merely a psychological consequence of the side effects of the drugs enhancing the expectation of improvement.But in recent study ,the review of 15 studies, with more than 3300 patients, showed that compared with those who received placebo, participants without early adverse events (AEs) who received either of the SSRIs citalopram (multiple brands) or paroxetine (multiple brands) had significantly greater reductions in symptoms, as assessed with the Hamilton Depression Rating Scale (HDRS) depressed mood item.
E Eriksson et al conducted a placebo-controlled trials of citalopram or paroxetine in adult major depression that used the Hamilton Depression Rating Scale (HDRS) and included a week 6 symptom assessment (n=15). The primary analyses, which compared completers on active treatment without early adverse events to completers on placebo (with or without adverse events) with respect to reduction in the HDRS depressed mood item showed larger symptom reduction in patients given active treatment, the effect sizes being 0.48 for citalopram and 0.33 for paroxetine. In actively treated subjects reporting early adverse events, who also outperformed those given placebo, the severity of the adverse events did not predict response. Several sensitivity analyses, for example, including (i) those using change of the sum of all HDRS-17 items as effect parameter, (ii) those excluding all subjects with adverse events (that is, also those on placebo) and (iii) those based on the intention-to-treat population, were all in line with the primary analyses.
It was found that both paroxetine and citalopram are clearly superior to placebo also when not producing adverse events, as well as the lack of association between adverse event severity and response, argue against the theory that antidepressants outperform placebo solely or largely because of their side effects.
It was concluded that that the placebo-breaking-the-blind theory has come to influence the current view on the efficacy of antidepressants to a greater extent than can be justified by available data.
Principal investigator Elias Eriksson PhD, professor of pharmacology at the University of Gothenburg, Sweden while speaking to Medscape Medical News rebutted the side-effects theory and said that the number one takeaway message for clinicians? “It’s that SSRIs work. They may not work for every patient, but they work for most patients. And it’s a pity if their use is discouraged because of newspaper reports,” he said.
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