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Psychopharmacology, Pharmacogenetics

Therapeutic Effects of Antidepressants

Over the past three decades, the therapeutic effect of various types of antidepressants has been successfully conceptualized based on monoaminergic system modifications. Although achieved via different mechanisms, all these modifications enhance the neurotransmitter signal transfer, which suggests that an inadequately low concentration of biogenic amines at synapses and in neurons, for whatever reason, predisposes or causes depression. A prominent argument against this fairly simple hypothesis of depression is the clinically postulated delay in the onset of action of antidepressant drugs. Indeed, such a time lag is difficult to reconcile with the almost immediate monoamine re-uptake blockade induced by tricyclics.

Delayed Onset-of-Action Hypothesis

Attempts have therefore been made to incorporate the delayed onset into the biogenic amine approach to depression, for example, in the form of a postulated imbalance of neuronal second messenger function. Such attempts, however, failed to support a general delayed onset-of-action for antidepressants.

Time Characteristics of Improvement

Our results —replicated for several different antidepressant drug classes in comparison to placebo— demonstrated that the onset of improvement occurred in more than 70% of the patients within the first 2 weeks of treatment. Antidepressants that differed greatly in their biochemical and pharmacological actions had a similar efficacy in terms of the proportion of patients in whom they induced a therapeutic response. Differences in efficacy between active drugs and placebo were reflected only by the total number of improvers, responders and premature withdrawals —but not by the time characteristics of improvement. Specifically, our studies of 2'788 patients yielded no indication for a delayed onset of action of antidepressants.

References

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recovery
Fig. 1: Under antidepressants we typically find —independently of substance class— approximately 35-40% of the patients to be in fact placebo responders; an additional 40% display either no or incomplete improvement, so that no more than 20% of the patients benefit from antidepressant drug treatment in the expected form. An especially puzzling point in the treatment of Major Depressive Disorders (MDD) is the observation that 25-35% of patients under antidepressants show incomplete response after initial improvement.
Please note: (1) patients showing early improvement (within the first 2 weeks of treatment) are at least 3 times more likely to become responders compared to patients with a late onset; (2) patients showing late onset of improvement are more likely to get "stuck" in their recovery; (3) the probability to become a treatment responder drops below 15% if there are no signs of improvement during the first 2 weeks of treatment.
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