Loss, Grief, and Betrayal: Psychiatric Survivors Reflect on the Impact of New Serotonin Study
Janusz Rybakowski comment
In my opinion, the recent article in Molecular Psychiatry (Moncrieff, Cooper, Stockmann et al. 2022) can be regarded the greatest media success of Joanna Moncrieff in her psychiatric career. However, an assessment of the scientific value of the paper may be less favorable.
It should be noted that the start of Moncrieff’s activity of looking for a hole all over and making herself visible in the area of psychopharmacology, dates back to the mid-1990s when she published articles questioning the prophylactic efficacy of lithium (Moncrieff 1995, 1997). Although the articles were noticed they were generally regarded as something anecdotal and not having any impact on the practice of lithium therapy.
In the first decade of the 21st century, she tried to undermine the dopamine hypothesis of schizophrenia and psychosis (Moncrieff 2009). Again, the article was noted but the development of new antipsychotic drugs having antidopaminergic activity as an essential element of their antipsychotic action was occuring, although at a slower pace than in 1990s.
The issue of the treatment of depression has been always a hot topic, significantly augmented by social media. More than a half-century ago, catecholaminergic and serotonergic hypotheses of depression were formulated for elucidating the mechanism of action of antidepressant drugs. Surprisingly, the effect of antidepressants on three neurotransmitters: norepinephrine, dopamine and serotonin, have remained still the best for interpreting not only antidepressant activity but also specific action on particular symptoms of depression. In such an explanation, new findings on neurotransmitter various receptors and transporters are taken into account.
Furthermore, the serotonergic hypothesis was the basis of the first non-serendipitous category of antidepressant drugs, of which the main mechanism of action was inhibition of serotonergic transporter, i.e., selective serotonin reuptake inhibitors – SSRIs. The introduction of the SSRI drug, fluoxetine, in the USA in the late 1980s, was a cultural event.
The advent of SSRI antidepressants implied that some serotonin inadequacy in the brain could make an element of pathogenic mechanisms of depression. Serotonin became a symbol of depression in popular books (Houellebecq 2019). As the SSRIs were entering the American market, publications appeared to constitute a backlash to them (Glenmullen 2001). The climax was in 2009 when a paper and a book by Kirsch appeared claiming that antidepressant drugs are no better than placebo (Kirsch 2009a,b). The discussion about the media and intellectuals' response to medical publications on antidepressants was summarized by an article written by eminent depression researchers (Fountoulakis, Hoschl, Kasper et al. 2013).
Joanna Moncrieff had waited the next decade to make an impact on this issue in her article in Molecular Psychiatry (Moncrieff, Cooper, Stockmann et al, 2022). The first aim was to discredit a serotonin hypothesis of depression based on the results of some studies. Implicitly, the second intent was to show that serotonergic antidepressant drugs are no better than a placebo. And while the first information may be an argument for pathogenic discussion of depression, the second may appear very harmful for psychiatrists prescribing these drugs and the millions of patients who benefit from them.
Furthermore, in a recent paper published in Psychological Medicine, Moncrieff joined John Read in questioning the efficacy of electroconvulsive therapy (ECT) (Read and Moncrieff 2022). Three years ago, Read published an article suggesting no therapeutic effect of ECT, concluding that such therapy should be immediately banned. Although he claims to have compared “real” and “sham” ECT (Read, Kirsch and McGrath 2019), it looks like his knowledge of the procedure comes mostly from the movie “One flew over the cuckoo’s nest” released in 1975.
Observing the destructive activity of Joanna Moncrieff over the last three decades, she deserves rightly to be named an “enfant terrible” of contemporary psychopharmacology. However, she may be reminded of an oriental proverb: “The dogs bark but the caravan moves on.” “The caravan” presumably pertains to contemporary psychopharmacology, where, paraphrasing Mark Twain, the reports on its fall are greatly exaggerated.
Fountoulakis KN, Hoschl C, Kasper S, Lopez-Ibor J, Möller HJ. The media and intellectuals' response to medical publications: the antidepressants' case. Ann Gen Psychiatry 2013;12:11.
Glenmullen J. Prozac Backlash: Overcoming the Dangers of Prozac, Zoloft, Paxil, and Other Antidepressants with Safe, Affective Alternatives. Simon & Schuster, New York; 2001.
Houellebecq M. Sérotonine. Flammarion, Paris; 2019.
Kirsch I. Antidepressants and the placebo response. Epidemiologia e Psichiatria Sociale 2009;18:318-22.
Kirsch I. The Emperor’s New Drugs. Exploding the Antidepressant Myth. The Bodley Head, London, 2009.
Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry 2022. Online ahead of print.
Moncrieff J. Lithium revisited. A reexamination of the placebo-controlled trial of lithium prophylaxis in manic-depressive disorder. Br J Psychiatry 1995;167:569-74.
Moncrieff J. Lithium: evidence reconsidered. Br J Psychiatry 1997;171:113-19.
Moncrieff J. A critique of the dopamine hypothesis of schizophrenia and psychosis. Harv Rev Psychiatry 2009;17:214-25.
Read J, Moncrieff J. Depression: why drugs and electricity are not the answer. Psychol Med. 2022;52(8):1401-10.
Read J, Kirsch I, McGrath L. Electroconvulsive therapy for depression: A review of the quality of ECT versus sham ECT trials and meta-analyses. Ethical Hum Psychol Psychiatry 2019; 21:64–85.
October 13, 2022