NEW STUDY. In contrast to what has previously been claimed, low doses of antidepressants are clearly less effective than higher ones. This is the principal finding of a new study from the Sahlgrenska Academy at the University of Gothenburg in Sweden. The authors also suggest that antidepressants, when used at an optimal dose, are considerably more effective than usually assumed.
Selective serotonin reuptake inhibitors, or SSRIs, are antidepressants influencing the activity of the neurotransmitter serotonin. While the SSRIs remain the most commonly prescribed type of antidepressant, it has recently been questioned if these drugs actually display any antidepressant effect.
“It has never been convincingly shown that higher doses of SSRIs are more effective than lower ones and this alleged lack of dose-response has often been put forward as an argument for the view that they do not display any specific, pharmacological antidepressant action”, says Fredrik Hieronymus, PhD student in pharmacology at Sahlgrenska Academy, University of Gothenburg.
Three common SSRIs
In their analysis the researchers included all clinical trials in adult major depression conducted by the manufacturers of three common SSRIs where predefined doses were compared to placebo. In total the analysis comprises close to 3000 patients from eleven clinical studies, including all relevant studies for the SSRIs citalopram (Celexa™), sertraline (Zoloft™), and paroxetine (Paxil™).
“We find that low but commonly used doses of SSRIs are more effective than placebo but clearly less effective than higher doses. We did not, however, detect any additional improvement in patients that received what might be regarded as very high doses”, relates Fredrik Hieronymus.
When the scientists excluded those patients that had received suboptimal doses from the analysis, the antidepressant effect of the studied SSRIs turned out to be markedly higher than what has previously been suggested.
“One has tended to disregard the possible influence of dose in earlier assessments of these drugs, hence including suboptimal doses in the analyses, which we suggest has led to an underestimation of their efficacy”, says Fredrik Hieronymus, however adding that their results do not support the use of the highest recommended doses:
“For the individual patient, the choice of dose must be guided not only by the antidepressant response but also by possible side effects.”
The study also reveals that the SSRIs are significantly superior to placebo already after one week of treatment, which is in contrast with the conventional wisdom that the beneficial effects are not apparent until the treatment has been in effect for a couple of weeks.
“It does take several weeks for the full effect of the treatment to appear”, states Fredrik Hieronymus, “but the fact that there is a modest but significant decrease in depressed mood in many patients already after the first week of treatment is of theoretical interest and may be of importance when trying to clarify why drugs affecting serotonin yields an antidepressant response”.
The article, A mega-analysis of fixed-dose trials reveals a dose-dependency and a rapid onset of action for the antidepressant effect of three selective serotonin reuptake inhibitors, is published in the journal Translational Psychiatry.