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The mid-twentieth century saw a burgeoning of pharmacological therapies for mental health issues. By 1939, lithium had been introduced; the 1950s saw the introduction of antidepressants[1] and antipsychotics;[2] and benzodiazepines proliferated during the 1960s and 1970s.[3] This flourish of the pharmaceutical, and the optimism in terms of treating mental ill health that it brought, was accompanied by a notable prediction by psychiatrist William Sargant. Drugs such as these, Sargant prophesied, ‘would enable doctors to “cut the cackle” of mental illness by the 1990s’.[4]

Despite Sargant’s foretelling, pharmaceuticals — notably anti-depressants, which remain the most-prescribed class of drug for mental health issues today[5] — are perhaps far from a cure-all. This is evidenced by the fact that in the UK, between 2008 and 2018, the number of prescriptions dispensed for anti-depressants increased twofold.[6] Simultaneously, the rates of Depression and Anxiety, at best, remained constant[7] at a rate of 25%[8] or, at worst, increased.[9] This has been compounded by the Covid-19 pandemic, with an Institute of Fiscal Studies report finding that mental health in the UK during this time has ‘worsened substantially [...] by 8.1%’.[10] Although it is possible that the increase in prescriptions for anti-depressants is the result of psychiatry’s medicalisation of what were previously considered to be normal emotional states or personality traits,[11] it cannot be denied that people seem to be increasingly dealing with their psychological distress in ineffective and harmful ways: self-harm and suicidal thoughts are becoming more prevalent.[12] Given this, it is worth questioning the efficacy and appropriateness of anti-depressants as treatments for mental health issues.[13]

In order to do this, it is salient to review the evidence behind this class of drug’s effectiveness. Perhaps surprisingly, it is not as robust as anti-depressants’ popularity would suggest. British doctor Ben Goldacre notes in his scathing critique of UK big pharma, that there is a far greater likelihood — up to a 20-fold increase, in fact — that industry-sponsored clinical trials demonstrate a given drug’s effectiveness than trials which are placebo-controlled or independent.[14] Indeed, Goldacre observes that these trials are oftentimes carried out by the very same individuals who are involved in a given drug’s manufacture. Moreover, the trials themselves,[15] and the statistics associated with them,[16] are manipulated such that results appear more favourable than the trials would actually suggest.

It is not unheard of, Goldacre continues, for trials to not be of the appropriate length or size; for the drug in question to be compared to a drug which is not analogous — that is, it is not given at the correct dose or even intended to treat the same malady — or a drug which is known to be ineffective.[17] And, if all of these strategies should still not yield the desired outcome, the trial’s results remain unpublished.[18] When results are published, Goldacre tells us that it is not unusual for journal articles to have been authored by individuals employed by the drug’s manufacturer (but, crucially, this conflict of interest tends to be kept under wraps).[19]

Since Goldacre’s Bad Pharma was published, many major medical journals have taken steps to curb what Goldacre has called ‘wily tricks, close calls, and elegant mischief at the margins of acceptability’.[20] For instance, The Lancet requires funding declarations, and the New England Journal of Medicine insists that all authors list study sponsorship and complete disclosure forms which are displayed alongside the full text of each article. Moreover, authors of editorials and reviews for NEJM are not permitted to have significant financial interests in the biomedical company relevant to the topics and products being discussed, and editors are not permitted to have any financial relationships with any biomedical companies whatsoever.

With that said, one facet of what Goldacre has dubbed ‘elegant mischief’ that warrants further discussion is the placebo effect. This has been the focus of academic and author Irving Kirsch.[21] In the case of anti-depressants, Kirsch contends that trials’ data — including that which pharmaceutical companies have elected not to publish — reveal that this class of drug, in comparison to placebo, does not confer substantive benefit. In cases where benefits are evident, they are so small that they are below the National Institute for Health and Care Excellence’s (NICE) threshold of clinical significance. Kirsch tells us that when these (small) benefits above placebo are visible, they likely arise due to participants ‘break[ing] blind’:[22] anti-depressants can cause a myriad of physical side effects, especially on initiation, thereby allowing doctors and/or patients to infer who has been given the ‘real’ drug. While it is worth acknowledging that both doctors and patients attest to anti-depressants’ efficacy, patients visiting their GP with symptoms of Depression or Anxiety are never given merely a placebo instead: we never see how they might improve given a ‘dummy’ pill.[23]

Anti-depressants are still recommended by NICE for treating Depression and Anxiety,[24] although it is worth examining the role that lengthy waiting lists for talking therapies have to play. One in five patients waits longer than a year for Cognitive Behavioural Therapy,[25] and the increase in demand,[26] and reduction in provision,[27] of mental health services caused by the Covid-19 pandemic has only seen this worsen.  Even before the pandemic, due to welfare reform and austerity, GPs were — and are — under increasing pressure ‘to provide for a range of medical and social support needs within consultations as other key services have been stripped back.’[28] As such, many primary care physicians give accounts of feeling as though they have no choice but to prescribe anti-depressants when the alternative is a length waiting list for talking therapies.[29] This calls to mind the remarks of sociologist Allan Horwitz, who notes that ‘drugs [are] clearly both faster and cheaper than years of psychoanalysis.’[30]  

On this point, a large and recent systematic review of anti-depressants by Cipriani and colleagues notes that ‘because of inadequate resources, antidepressants are used more frequently than psychological interventions’, and therefore ‘[p]rescription of these agents should be informed by the best available evidence.’ [31] This systematic review includes several double-blind, randomised controlled trials (RCTs), which compare a number of antidepressants with either another antidepressant or placebo. This meta-analysis would suggest that anti-depressants do have more of an effect than Kirsch contends, but, on the other hand, this meta-analysis does not address Kirsch’s key tenet: that ‘placebo-controlled’ is somewhat of a misnomer, since the physical side effects of antidepressants — which are described to patients as part of obtaining informed consent — enable patients (and clinicians, for that matter) to infer who has been given the ‘real’ drug.[32]

Since the publication of Cipriani and colleagues’ meta-analysis, Kirsch has authored another article which maintains his position, arguing that ‘most (if not all) of the benefits of antidepressants in the treatment of depression and anxiety are due to the placebo response’, again citing ‘breaking blind’ due to the drugs’ side effects as the culprit.[33] On this point, he cites a trial which circumvents the difficulties associated with maintaining ‘blindness’, wherein patients with Social Anxiety Disorder were all treated with a Selective Serotonin Reuptake Inhibitor (SSRI). Half of the patients were correctly told that they were being treated with an SSRI, whereas the other half were ‘treated deceptively with the SSRI described, by the psychiatrist, as active placebo’[34] — that is, ‘a drug that produces side effects but has no therapeutic effect on the condition being treated’.[35] Even though all patients were receiving treatment with the same drug, at the same dose, the trial’s outcome showed that ‘telling patients that they were being treated by an active medication doubled its effectiveness on a continuous measure of anxiety and tripled the response rate’,[36] thus corroborating Kirsch’s contention that placebo has a large role to play in anti-depressants’ efficacy.

As previously mentioned, anti-depressants incur a number of negative side effects — sexual dysfunction, nausea, and diarrhoea, to name but a few — and, if treatment is ceased, withdrawal can ensue.[37] Moreover, those whose who have taken anti-depressants for their mental health issues have a higher likelihood of experiencing relapse than those who have undergone other modes of treatment.[38] In addition to these potential harms, and the contention that this class of drugs is ineffective,[39] we still do not actually know how they are meant to work (or not, as the case may be). Their purported mechanism of action is the ‘correcti[on of] the neurotransmitter imbalances that cause mental disorders’.[40] The neurotransmitter in question tends to be serotonin, a lack of which the anti-depressant allegedly restores[41] — it is worth noting that the most prominent drug in the anti-depressant class is arguably the SSRI (Selective Serotonin Reuptake Inhibitor). The low-serotonin model has bled into popular conceptions of mental distress, yet, this half-a-century-old model has been described by prominent figures in the scientific community as being reductive[42] and simplistic.[43] A key observation by Kirsch which serves to debunk the low-serotonin explanatory model, is that anti-depressants’ efficacy is independent of whether they decrease or increase serotonin, or act on an entirely different neurotransmitter[44] (such as norepinephrine or dopamine). He therefore troubles the effectiveness and appropriateness of treatment with anti-depressants for mental ill health more broadly in asking: ‘What do you call pills, the effects of which are independent of their chemical composition? I call them “placebos.”’[45]

Katie Masters

[1] David Healy, ‘The Antidepressant Drama’, in The Treatment of Depression: Bridging the 21st Century, ed. by Myrna Weissman (Washington: American Psychiatric Publishing Inc., 2001), 10–11.

[2] Caroline King and Lakshmi N. P. Voruganti, ‘What’s in a Name? The Evolution of the Nomenclature of Antipsychotic Drugs’, Journal of Psychiatry and Neuroscience, 27.3 (2002), 168–75 <https://pubmed.ncbi.nlm.nih.gov/12066446/> [accessed 4 January 2021].

[3] Hugh J. Parry, ‘Use of Psychotropic Drugs by US Adults’, Public Health Reports, 83.10 (1968), 799–810 <doi: 10.2307/4593420> [accessed 4 January 2021].

Hugh J. Parry, Mitchell B. Balter, Glen D. Mellinger, Ira H. Cisin, and Dean I. Manheimer, ‘National Patterns of Psychotherapeutic Drug Use’, Archives of General Psychiatry, 28.6 (1973), 769–38 <doi: 10.1001/archpsyc.1973.01750360007002> [accessed 4 January 2021].

Mitchell B. Balter, Jerome Levine, and Dean I. Manheimer, ‘Cross-National Study of the Extent of Anti-Anxiety/Sedative Drug Use’, New England Journal of Medicine, 290 (1974), 769–74 <doi: 10.1056/NEJM197404042901404> [accessed 4 January 2021].

All cited in Jonathan M. Metzl, ‘“Mother’s Little Helper”: The Crisis of Psychoanalysis and the Miltown Resolution’, Gender and History, 15.2 (2003), 228–55 <doi: 10.1111/1468-0424.00300> [accessed 4 January], p. 228.

[4] Porter, The Greatest Benefit to Mankind, p. 521.

[5] Sara G. Miller, ‘1 in 6 Americans Takes a Psychiatric Drug’, Scientific American (13 December, 2016) <https://www.scientificamerican.com/article/1-in-6-americans-takes-a-psychiatric-drug/> [accessed 10 August 2021]

[6] Gareth Iacobucci, ‘NHS Prescribed Record Number of Antidepressants Last Year’, British Medical Journal, 364.1508 (2019), <doi: 10.1136/bmj.l1508> [accessed 25 September 2020].

[7] Mind, Mental Health Facts and Statistics (2013) <https://www.mind.org.uk/information-support/types-of-mental-health-problems/statistics-and-facts-about-mental-health/how-common-are-mental-health-problems/#one> [accessed 10 June 2019].

[8] S. McManus, H. Meltzer, T. S. Brugha, P. E. Bebbington, and R. Jenkins, Adult Psychiatric Morbidity in England, 2007: Results of a Household Survey (2009) <https://digital.nhs.uk/data-and-information/publications/statistical/adult-psychiatric-morbidity-survey/adult-psychiatric-morbidity-in-england-2007-results-of-a-household-survey> [accessed 10 June 2019], cited in Mind, Mental Health Facts and Statistics.

[9] J. Evans, I. Macrory, and C. Randall, Measuring National Well-being: Life in the UK (2016) <https://www.ons.gov.uk/peoplepopulationandcommunity/wellbeing/articles/measuringnationalwellbeing/2016#how-good-is-our-health> [accessed 3 October 2016] cited in Mental Health Foundation, Fundamental Facts about Mental Health 2016 (2016) <https://www.mentalhealth.org.uk/publications/fundamental-facts-about-mental-health-2016> [accessed 10 June 2019], p. 14.

[10] James Banks and Xiaowei Xu, ‘The Mental Health Effects of the First Two Months of Lockdown and Social Distancing During the Covid-19 Pandemic in the UK’, Institute of Fiscal Studies Working Paper W20/16 (2020) <doi: 10.1920/wp.ifs.2020.1620> [accessed 22 February 2021]. My emphasis.

[11] Felicity Thomas, Lorraine Hansford, Joseph Ford, Katrina Wyatt, Rosemarie McCabe, and Richard Byng. ‘Moral Narratives and Mental Health: Rethinking Understandings of Distress and Healthcare Support in Contexts of Austerity and Welfare Reform’, Palgrave Communications , 4.1 (2018): 1–8 <doi: 10.1057/s41599-018-0091-y> [accessed 5th November 2021].

[12] McManus et al., Mental Health and Wellbeing in England, cited in Mind, Mental Health Facts and Statistics.

[13] Masters, Katie M., Putting the ‘Social’ in ‘Social Anxiety Disorder’: Exploring Women’s Experiences from the Perspectives of Feminism and Anti-psychiatry, PhD Thesis, University of Birmingham (2021).

[14] Michael E. Thase, ‘Do Antidepressants really Work? A Clinicians’ Guide to Evaluating the Evidence’, Current Psychiatry Reports, 10.6 (2008) 487–94 <doi: 10.1007/s11920-008-0078-2> [accessed 6 January 2021].

Lisa Bero, Fieke Oostvogel, Peter Bacchetti, and Kirby Lee, ‘Factors Associated with Findings of Published Trials of Drug-Drug Comparisons: Why Some Statins Appear More Efficacious than Others’, PLoS Medicine, 4.6 (2007) e184 <doi: 10.1371/journal.pmed.0040184> [accessed 6 January 2021], cited in Ben Goldacre, Bad Pharma (London: Fourth Estate, 2012), p. 2.

[15] Goldacre, Bad Pharma, p. xi.

[16] Ibid., pp. 216–17.

[17] Ibid., p. 176, 180–87, 191–93.

[18] Ibid., p. 12, 407.

[19] Ibid.

[20] Ibid., p. 171.

[21] Irving Kirsch, ‘Antidepressants and the Placebo Effect’, ZeitschriftfürPsychologie, 222.3 (2014), 128–34 <doi: 10.1027/2151-2604/a000176> [accessed 5 January 2021], p. 128.

[22] Ibid.

[23] Johnson and Kirsch, ‘Do Antidepressants Work?’, p. 56.

[24] National Institute for Health and Care Excellence, Antidepressant Drugs (2021) <https://bnf.nice.org.uk/treatment-summary/antidepressant-drugs.html> [accessed 2nd November 2021].

[25] Mind, We Need To Talk: Getting the Right Therapy at the Right Time (n.d.) <https://www.mind.org.uk/media/280583/We-Need-to-Talk-getting-the-right-therapy-at-the-right-time.pdf> [accessed 10 June 2019].

[26] Mind, Mind Warns of ‘Second Pandemic’ as it Reveals More People in Mental Health Crisis than ever Recorded and Helpline Calls Soar (2020) <https://www.mind.org.uk/news-campaigns/news/mind-warns-of-second-pandemic-as-it-reveals-more-people-in-mental-health-crisis-than-ever-recorded-and-helpline-calls-soar/> [accessed 22 February 2021].

[27] British Medical Association, Pressure Points in the NHS (2021) <https://www.bma.org.uk/advice-and-support/nhs-delivery-and-workforce/pressures/pressure-points-in-the-nhs> [accessed 22 February 2021].
NHS England, Consultant-led Referral to Treatment Waiting Times Data 2020–21 (2020) <https://www.england.nhs.uk/statistics/statistical- work-areas/rtt-waiting-times/rtt-data-2020-21/> [accessed 22 February 2021].

[28] Thomas, et al., ‘Moral Narratives and Mental Health’, p. 2.

[29] Julia Hyde, Michael Calnan, Lindsay Prior, Glyn Lewis, David Kessler, and Deborah Sharp, ‘A Qualitative Study Exploring how GPs Decide To Prescribe Antidepressants’, British Journal of General Practice, 55.519 (2005), 755–62 <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1562347/> [accessed 25th September 2020], pp. 759–60.     

Royal Pharmaceutical Society, ‘Most GPs are Over-prescribing Antidepressants’, The Pharmaceutical Journal Online, 272.7293 (2004), 407 <https://www.pharmaceutical-journal.com/pj-online-news-most-gps-are-over-prescribing-antidepressants/20011591.article?firstPass=false> [accessed 10 June 2019].

Emily Wooster on behalf of the We Need To Talk campaign, While We are Waiting: Experiences of Waiting for and Receiving Psychological Therapies on the NHS (2019) <https://www.mentalhealth.org.uk/publications/while-we-are-waiting [accessed 10 June 2019], p. 8.

[30] Allan V. Horwitz, Creating Mental Illness (London: University of Chicago Press, 2002), cited in Olivia Goldhill, 30 Years After Prozac Arrived, We Still Buy the Lie that Chemical Imbalances Cause Depression (2019) <https://qz.com/1162154/30-years-after-prozac-arrived-we-still-buy-the-lie-that-chemical-imbalances-cause-depression/> [accessed 10 June 2019].

[31] Andrea Cipriani, Toshi A. Furukawa, Georgia Salanti, Anna Chaimani, Lauren Z. Atkinson, Yusuke Ogawa, Stefan Leucht, Henricus G. Ruhe, Erick H. Turner, Julian P. T. Higgins, Matthias Egger, Nozomi Takeshima, Yu Hayasaka, Hissei Imai, Kiyomi Shinohara, Aran Tajika, John P. A. Ioannidis, and John R. Geddes. ‘Comparative Efficacy and Acceptability of 21 Antidepressant Drugs for the Acute Treatment of Adults with Major Depressive Disorder: A Systematic Review and Network Meta-analysis’, Focus, 16.4 (2018), 420–429 <doi: 10.1176/appi.focus.16407> [accessed 2nd November 2021], p. 1357.

[32] Irving Kirsch, ‘Placebo Effect in the Treatment of Depression and Anxiety’, Frontiers in Psychiatry, 10. 407 (2019) <doi: 10.3389/fpsyt.2019.00407> [accessed 2nd November 2021].

[33] Kirsch, ‘Placebo Effect in the Treatment of Depression and Anxiety’.

[34] Vanda Faria, Malin Gingnella, Johanna M.Hoppea, Olof Hjorth, Iman Alai, Andreas Frick, Sara Hultberg, Kurt Wahlsted, Jonas Engman, Kristoffer N. T. Månsson, Per Carlbring, Gerhard Andersson, Margareta Reis, Elna-Marie Larsson, Mats Fredrikson, and Tomas Furmark, ‘Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder: A Randomized Trial’, EBioMedicine, 24 (2017), 179–88 <doi: 10.1016/j.ebiom.2017.09.031> [accessed 4th November 2021], p. 179.

[35] Kirsch, ‘Placebo Effect in the Treatment of Depression and Anxiety’.

[36] Ibid.

[37]  Kirsch, ‘Antidepressants and the Placebo Effect’, p. 132.

[38] Paul W. Andrews, J. Anderson Thomson, Jr., Ananda Amstadter, and Michael C. Neale, ‘Primum Non Nocere: An Evolutionary Analysis of whether Antidepressants Do More Harm than Good’, [Review], Frontiers in Psychology, 3.117 (2012) <doi: 10.3389/fpsyg.2012.00117> [accessed 6 January 2021].

M. A. Babyak, J. A. Blumenthal, S. Herman, P. Khatri, P. M. Doraiswamy, K. A. Moore, and K. R. Krishnan, ‘Exercise Treatment for Major Depression: Maintenance of Therapeutic Benefit at 10 Months’, Psychosomatic Medicine, 62 (2000), 633–38 <doi: 10.1097/00006842-200009000-00006> [accessed 6 January 2021].

Keith S. Dobson, Steven D. Hollon, Sona Dimidjian, Karen B. Schmaling, Robert J. Kohlenberg, Robert Gallop, Shireen L. Rizvi, Jackie K. Gollan, David L. Dunner, and Neil S. Jacobson, ‘Randomized Trial of Behavioral Activation, Cognitive Therapy, and Antidepressant Medication in the Prevention of Relapse and Recurrence in Major Depression’, Journal of Consulting and Clinical Psychology, 76.3 (2008), 468–77 <doi: 10.1037/0022-006X.76.3.468> [accessed 6 January 2021].

All cited Kirsch, ‘Antidepressants and the Placebo Effect’, p. 132.

[39] Kirsch, ‘Antidepressants and the Placebo Effect’, p. 128.

[40] Deacon, ‘The Biomedical Model of Mental Disorder’, p. 846.

[41] Kirsch, ‘Antidepressants and the Placebo Effect’, p. 128.

[42] Kenneth S. Kendler and Kenneth F. Schaffner, ‘The Dopamine Hypothesis of Schizophrenia: An Historical and Philosophical Analysis’, Philosophy in Psychiatry and Psychology, 18.1 (2011), 41–63 <doi: 10.1353/ppp.2011.0005> [accessed 6 January 2021].

Irving Kirsch, The Emperor’s New Drugs: Exploding the Antidepressant Myth (New York: Basic Books, 2010).

Lacasse and Leo, ‘Serotonin and Depression’.

All cited in Deacon, ‘The Biomedical Model of Mental Disorder’, p. 852.

[43] Philip J. Cowen and Michael Browning. ‘What Has Serotonin To Do with Depression?’ World Psychiatry, 14.2 (2015), 158–60 <doi: 10.1002/wps.20229> [accessed 6 January 2021], p. 160.

[44] Kirsch, ‘Antidepressants and the Placebo Effect’, p. 128.

[45] Ibid., p. 131.