Current issue provides critical review of data concerned with antidepressant drugs

A paper in the current issue of Psychotherapy and Psychosomatics by Giovanni Fava, MD (University of Bologna)  provides a critical review of the data concerned with antidepressant drugs. Their use should be guided by consideration of the potential benefits, probability of responsiveness and likelihood of side effects. If we consider the data this way, a picture, that is very different from what is done, currently emerges. Indeed, to place the benefits and harms of antidepressant (AD) in the context of risk, responsiveness and vulnerability, and choose the most appropriate approach to an individual patient, we should be aware that several adverse events have been documented during AD treatment (loss of AD efficacy, tachyphylaxis, resistance, paradoxical effects, switching to a bipolar course and withdrawal reactions). AD were developed and found to be effective in the treatment of severe depression, but the better tolerability of newer AD has stretched their original indications. As a consequence, a large body of randomized controlled trials concerned with AD is available, but there is still a paucity of studies encompassing risks, responsiveness and vulnerability.

A rational use of AD should restrict their application to only the most severe and persistent cases of depression, limiting their use to the shortest possible duration and reducing their utilization in anxiety disorders (unless a major depressive disorder is present or other treatments have been ineffective). Indeed, the magnitude of benefit from AD medication compared with placebo increases with the severity of depression. If a patient suffers from severe depression, there is little doubt that pharmacotherapy may yield substantial benefits, even though, of course, the response may vary from patient to patient. However, if symptoms of mild or moderate intensity are present, the benefits may be minimal or nonexistent. Furthermore, the neglect of the clinical phenomena related to tolerance may urge a clinician to give it a trial, a position that does not reflect the evidence in the field on the effectiveness of placebo, that is, the likelihood that depressive symptoms remit with nonspecific ingredients. An alternative is to postpone prescribing an AD and to see the patient again after a couple of weeks. This may be particularly important in the setting of medical disease, when depression may subside with the improvement of the medical condition and/or discharge from the hospital. If the symptoms have improved to a certain degree, the need of AD treatment may be low; in case of the persistence (or, at times, of worsening) of symptoms, the use of AD appears to be more justified and worth pursuing.

As for anxiety disorders, in the past years, a progressive change in prescribing pattern from benzodiazepines (BDZ) to second-generation AD has been observed in anxiety disorders. In a recent systematic review, no consistent evidence emerged supporting the advantage of using AD over BDZ in treating anxiety disorders. Indeed, BDZ showed fewer treatment withdrawals and adverse events than AD. In panic disorder with and without agoraphobia, BDZ treatment was more effective than AD in reducing the number of panic attacks.

AD are important and potentially lifesaving drugs if the proper indications are endorsed. However, currently, the prescribing physician is driven by an overestimated consideration of potential benefits, little attention to the likelihood of responsiveness and neglect of potential vulnerabilities to the adverse effects of treatment.