*the translation of human conditions and unmet social needs into opportunities for pharmaceutical intervention.
Helen Stokes-Lampard, chair of the Royal College of General Practitioners, when commenting about “the record number of antidepressants prescribed last year” claimed that “research has shown (antidepressants) can be very effective when used appropriately” and the figures “could indicate rising awareness of mental health conditions in society and more patients feeling able to seek medical care” (1). This opinion about whether the number of prescriptions is appropriate is one-sided. Below we present the counter arguments.
First, there is evidence that only 1 in 9 people benefit from antidepressants, while the remaining 8 are unnecessarily put at risk of adverse drug effects (2).
Second, the effect size for antidepressants is low to moderate, plateauing at around 0.30 vs placebo (2). While this effect is statistically significant, it represents only a 1.5 to 2 point decrease in scores from scales which are, to begin with, of questionable clinical relevance. Only 1 in 17 items deal with well-being in the Hamilton Depression Rating Scale and there are no such items in Montgomery-Åsberg Depression Rating Scale. Furthermore, sexual function which is frequently worsen by antidepressants, is ignored in both scales (3).
Third, mood perturbations commonly reflect real life circumstances. Entertaining a diagnosis of major depression two weeks after bereavement, as advocated in DSM 5, cannot be an advance for anyone suffering the death of a loved one. Many depressive presentations respond to judicious “watchful waiting” and most cases of depression, even major or persisting, are often successfully treated with psychosocial interventions which are robustly evidence-based in the real-life setting over the long term; often preferred by patients, beneficial for self-esteem and social functioning and finally, without adverse effects (3).
Fourth, serious adverse effects of antidepressants, including suicide, cannot be overlooked. In 2004, the US Food and Drug Administration issued a black-box warning for all antidepressants indicating an association with increased suicidality. Another adverse effect that can be serious is severe withdrawal reaction after discontinuation of long-term pharmacotherapy.
Finally, treating resistant depression remains a challenge, due to poor research, not only about aetiology but also concerning trials. Critical evaluations have exposed how pharmaceutical industry-sponsored studies have overestimated benefits and underestimated harms (4-7). The treatment of “resistant depression” may be complex for most general practitioners and access to specialists is frequently limited. But even so, writing a prescription should only be cautiously undertaken after ruling out substance use (alcohol, tobacco and cannabis), which causes or worsens depression, limits treatment effectiveness and increases adverse effects, ensuring better care for physical health problems and eliminating barriers to implementation of lifestyle enhancements.
In 2012 Allen Frances, the chair of the task force that produced DSM-IV, was a lone voice crying in the wind when he warned that DSM-5 “will medicalize normality and result in a glut of unnecessary and harmful drug prescription” (8). Unfortunately, he seems to have been proven correct.
1 Iacobucci G. NHS prescribed record number of antidepressants last year. BMJ 2019;364:l1508.
2 Hengartner MP, Plöderl M. Statistically significant antidepressant-placebo differences on subjective symptom-rating scales do not prove that the drugs work: Effect size and method bias matter! Front Psychiatry 2018;9:517.
3 Braillon A, Lexchin J, Noble JH et al. Challenging the promotion of antidepressants for non-severe depression. Acta Psychiatr Scand 2019;139:294-295.
4 Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med 2008;358:252-60.
5Jureidini JN, Amsterdam JD, McHenry LB. The citalopram CIT-MD-18 pediatric depression trial: Deconstruction of medical ghostwriting, data mischaracterisation and academic malfeasance. Int . J Risk Saf Med 2016,28:33-43.
6 Le Noury J, Nardo JM, Healy D et al. Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence. BMJ 2015 ;351:h4320.
7 Ebrahim S, Bance S, Athale A, Malachowski C, Ioannidis JP. Meta-analyses with industry involvement are massively published and report no caveats for antidepressants. J Clin Epidemiol. 2016;70:155-63.
8 Frances A. Diagnosing the D.S.M. New York Times May 11, 2012. Accessed April 9, 2019. Available at: https://www.nytimes.com/2012/05/12/opinion/break-up-the-psychiatric-mono….
Competing interests: No competing interests
Source: The BMJ