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Antidepressants (f)utility: clinical reality lost in translation

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“Reality is that which, when you stop believing in it, doesn't go away.”

Philip K. Dick

In 2022, an article published in a psychiatry scientific journal questioned the role of the neurotransmitter serotonin in the pathophysiology of depression. Despite multiple methodological criticisms by international clinicians and scientists, conclusions from the article were indirectly used to kindle the latest wave of media flame on the alleged (f)utility of antidepressants, which are supposed to target serotonin and other similar neurotransmitters.

I am a clinical psychologist, certified psychotherapist, and researcher in psychiatric epidemiology. I have seen several of these media-amplified flames criticising antidepressants outbursting cyclically. Nevertheless, in the current age of social media, where the news cycle is mainly oriented toward enhancing the polarization of opinions, the resulting crude oversimplification of the arguments has completely lost touch with the clinical reality, its complexities and imperfections.

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The clinical reality

In international clinical guidelines, antidepressants are listed among first-line treatments for depression. This indication is supported by research data: large meta-analyses (a type of study that combines and analyses data from multiple clinical trials) showed that, on average, patients on antidepressants had a higher likelihood of responding (reducing by more than half the severity of their depressive symptoms) as compared to those on a placebo. Of course, there is complexity hidden in this reality: antidepressants do not produce significant response in all subjects (⅓ do not respond after different combinations of drugs); they have side effects; and their discontinuation needs to be carefully planned and require careful handling in certain categories of subjects (e.g., adolescents, or older subject with somatic multimorbidity and using multiple medicines). Nevertheless, the mentioned issues are a common aspect of the reality of all pharmacological treatments for all conditions, psychiatric and somatic.

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What could be an alternative to antidepressant medication? We know that certain psychotherapy approaches work: large meta-analyses showed that psychotherapy and pharmacotherapy have comparable effects (and their combination is more effective than either psychotherapy or pharmacotherapy alone) in the short term. I am a psychotherapist and I have seen the improvement in patients applying tools from cognitive behavioural therapy for instance. However, this type of approach requires a level of engagement and active work that may be difficult to achieve in the acute phase of depression. For this reason, I often collaborated with psychiatrists initially prescribing antidepressants to fend off the most severe symptoms and regain some energy to start the psychotherapy work. Furthermore, evidence-based psychotherapies are not accessible to all persons struggling with depression. In the country where I live, The Netherlands, more than 80,000 persons are currently on waiting lists for mental health care; the long waiting time is one of the first things to be discussed with a depressed person opting for psychotherapy. While in a parallel ideal world we are certainly going to train legions of psychotherapists to match immediately this unmet need, what are we going to do in this real world for those who are suffering now? Any argument against antidepressants that does not contextually address this practical question is merely ignoring (the clinical) reality.

Osheroff v. Chestnut Lodge: a legal battle for medications

In this period of anti-antidepressant media flame, it was interesting for me to re-discover the story of Osheroff v. Chestnut Lodge, a landmark (legal) case in American psychiatry involving a patient suing a psychiatric hospital for failing to treat him with antidepressants. Dr. Raphael (Ray) Osheroff was a nephrologist who at age 41 started to develop severe depressive symptoms. In 1979, he decided to seek care at a prestigious private psychiatric hospital, the Chestnut Lodge in Rockville (Maryland), which was strictly proposing a psychoanalytic approach not contemplating the use of psychopharmacology. Over several months after his admission, Ray's mental and physical condition alarmingly deteriorated, causing concern among his friends and mother, who repeatedly asked the hospital to give him antidepressants. Eventually, Ray’s mother decided to transfer him to another hospital where he was treated with medications and was able to regain his functionality. The legal dispute that followed, which involved eminent civil rights attorneys and psychiatrists, profoundly impacted American psychiatric culture with multiple ramifications that goes beyond the scope of the present brief piece. Here, I just wanted to mention a historical case in which a patient fought hard to have his right to be treated with antidepressants acknowledged.

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The clinical reality that does not go away

The reality of depression treatment (either with psychopharmacology or psychotherapy) is not perfect. The endless cycle of media-amplified flames on antidepressants terribly oversimplifies the clinical reality, its complexities and imperfections. This crude attitude unfortunately unfairly hits persons struggling with depression who could benefit from this treatment. I tend to agree with the perspective proposed by Dr. Joseph F. Goldberg (Mount Sinai, New York): “To paraphrase Winnicott, a “good enough” psychopharmacology often means coming to terms with the reality of imperfection. It serves no one’s interests to pretend that psychiatric problems hold an immunity from that reality in ways that are somehow different from other chronic nonpsychiatric medical conditions.”


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