Hari begins his book “Lost Connections” by describing his own struggles with depression, since adolescence, and his subsequent examination of medication treatment of depression. What makes this book particularly valuable and readable is that Hari weaves together his personal story with a clear eyed examination of the research on antidepressants (and summaries of interviews he had with researchers who have studied antidepressants).
In the first chapters he not only recounts how he came to question the benefits of his own medication treatment but his subsequent examination and questioning of the biological model of depression and the value of antidepressant medications. Hari’s own experience can best be summarized as follows: he struggled with depression; he tried multiple medications; he experienced some initial benefits but then these faded; he had to increase dosage and eventually change medications; he suffered from multiple side effects; and in the end the medications really did not benefit him to any meaningful degree. Many of us may recognize patients we have worked with who have had similar travails.
Hari then delves into the research and interviews the researchers. One of the researchers he cites is Irving Kirsch, Ph.D., who has done extensive research on antidepressant medication and placebo effectors. Kirsch, who Hari reports was once a strong advocate for medication based treatment of depression, comes away concluding that antidepressants have no more benefit than placebos (see Kirsch NIMH sponsored study, from 2014, noted below). Hari cites Kirsch and others who have pointed out that the standards for proving a medication’s benefits are woefully inadequate (only 2 studies that show a benefit are needed by FDA standards) and how drug companies discard and do not allow the publication of studies that do not support the benefits of medication treatment.
In addition to the weakness of data supporting the efficacy of antidepressant medication Hari also discusses the multiple side effects associated with many antidepressant medications and how these negative consequences of medication treatment also need to be considered when evaluating the medication treatment. He also calls into question the theory that a deficit in serotonin accounts for depression, noting a lack of clear evidence to support this. Finally, his discussion of the Placebo Effect, and its potential role in accounting the changes attributed to medication treatment is worth considering. However, it should be noted that there have been challenges to the importance of the placebo effect and to Krisch’s work, and that the evidence of its significance may not be as clear cut as Hari makes it seem.
The first chapters of Hari’s work are quite thought provoking, particularly given concerns that many critics of large pharmaceutical companies have raised about how these companies “sell” physicians on the value of medications and reward them for prescribing (the story of proliferation of opiate based pain medications being perhaps the most extreme example). While Hari is a persuasive writer it is important to keep in mind that he is also an advocate for a social model of depression. He appears to omit arguments/research that suggest that there is benefit for medication based treatment, particularly in adults with severe clinical depression. In addition, he neglects other research that indicates that depression does appear to “run in” families and likely has a genetic component. Finally, his selection of “experts” does exclude those who are consistently more supportive of a biological model of depression and the use of medication based treatment.
In conclusion, my aim here is not to advocate for the abandonment of medication treatment or the complete rejection of a biological model of depression. Rather it is to raise questions we all need to consider (as patients and as clinicians) in working to understand what accounts for different disorders and what treatments are most efficacious. In upcoming blogs I will continue to discuss Hari’s work and the challenges it raises to conventional thinking, the limitations of his arguments, and the questions we all need to keep in mind in living and working with a wide variety of disorders, illnesses and problems.
References:
For a summary of a 2013 examination of natural remission rates of depression: https://www.goodtherapy.org/blog/spontaneous-remission-occurs-in-majority-of-depression-cases-0913131 and a link to the actual study: https://www.cambridge.org/core/journals/psychological-medicine/article/abs/estimating-remission-from-untreated-major-depression-a-systematic-review-and-metaanalysis/52961032C5AFAB1C3B2C4E06A652B561
A 2020 analysis of the remission rates for untreated depression: https://sciforum.net/manuscripts/9025/manuscript.pdf
Irving Kirsch, Ph.D., on how antidepressant medications are not effective, and how the benefits derived from them are most likely placebo effects: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172306/
For an even more detailed discussion see Kirsch’s book: The Emperor’s New Drugs: Exploding the Antidepressant Myth, which elaborates on his arguments that antidepressant medications are of little benefit. A solid summary of this book can be found at: https://en.wikipedia.org/wiki/The_Emperor%27s_New_Drugs
Note: it is important to stress that there have been challenges to Kirsch’s research and conclusions, and that his findings are not universally accepted by any means.
Research documenting heritability of depression: https://www.ncbi.nlm.nih.gov/pmc/about/authorms/
For a brief but solid summary of Hari’s book (which I do recommend you read in its entirety) see: https://www.allencheng.com/lost-connections-book-summary-johann-hari/