Exploring psychotherapeutic issues and agents in clinical practice
The modern version of the Hippocratic Oath requires physicians to swear that they “will apply, for the benefit of the sick, all measures [that] are required, avoiding those twin traps of overtreatment and therapeutic nihilism” (Mamede & Schmidt, 2014, p. 35). Therapeutic nihilism has long existed in psychiatry. A recent example of this is illustrated in a head-to-head debate pitting Peter Gøtzsche against Allan Young and John Crace, published in The BMJ (Gøtzsche, Young, & Crace, 2015). The debate centered on the question “Does long-term use of psychiatric drugs cause more harm than good?” I would encourage you to read this short debate. Here are some of my thoughts.
The Cochrane Collaboration
In this BMJ commentary (Gøtzsche et al., 2015), Gøtzsche opened with the following statement:
Psychiatric drugs are responsible for the deaths of more than half a million people aged 65 and older each year in the Western world, as I show below. Their benefits would need to be colossal to justify this, but they are minimal. (p. 1)
After describing his analysis of selected data sources to support this opinion, Gøtzsche then concluded his commentary with the following statement (Gøtzsche et al., 2015):
Given their lack of benefit, I estimate we could stop almost all psychotropic drugs without causing harm—by dropping all antidepressants, ADHD [attention deficit hyperactivity disorder] drugs, and dementia drugs (as the small effects are probably the result of unblinding bias) and using only a fraction of the antipsychotics and benzodiazepines we currently use. This would lead to healthier and more long lived populations. Because psychotropic drugs are immensely harmful when used long term, they should almost exclusively be used in acute situations and always with a firm plan for tapering off, which can be difficult for many patients. We need new guidelines to reflect this. We also need widespread withdrawal clinics because many patients have become dependent on psychiatric drugs, including antidepressants, and need help so that they can stop taking them slowly and safely. (p. 2)
Gøtzsche is the director of the Nordic Cochrane Centre (NCC). The NCC is an independent research and information center that is part of The Cochrane Collaboration. The Cochrane Collaboration is an independent, non-profit, non-governmental organization consisting of an international network of individuals and institutions who prepare, maintain, and disseminate reviews of medical research information in a systematic way, according to the principles of evidence-based medicine. The group is best known for conducting systematic reviews (i.e., meta-analyses) of randomized controlled trials of health care interventions, which are published in The Cochrane Library.
In an article published in a Danish newspaper, Gøtzsche (2014) voiced a rather cynical perception about psychiatry and the use of antidepressant drugs, which provoked a major debate in the Danish media and among Danish health professionals (Middelboe, Nordentoft, Videbech, & Kessing, 2014). Gøtzsche’s provocative comments in the BMJ debate have also generated considerable criticism, even within the leadership of the Cochrane Collaboration. Four of the editors who are responsible for the Cochrane Reviews that relate to mental health published (in The BMJ) a rapid response to Gøtzsche’s comments, criticizing his analysis and conclusions (Tovey, Churchill, Adams, & Macdonald, 2015). Gøtzsche (2015a) published a response to their comments, but he also subsequently wrote a separate letter to David Tovey, Editor in Chief of the Cochrane Collaboration. In this letter, posted on Gøtzsche’s Deadly Medicines and Organised Crime website (access http://www.deadlymedicines.dk), Gøtzsche (2015b) made what I found to be a rather curious and interesting statement:
Some people who know that you [David Tovey] don’t have special knowledge about psychiatry and that you are the deputy CEO of Cochrane feel that you have protected the system, in a political, or should I say, managerial fashion, instead of protecting the patients (and me, whose detailed research based knowledge about psychiatric drugs is widely respected, also among psychiatrists who are not on industry payroll, which is why psychiatrists invite me to give talks all over the world to help them reform their specialty). (para. 3)
According to his biography published on the NCC website (access http://www.cochrane.dk/about/profiles/pcg-profile.htm), Gøtzsche graduated as a physician in 1984, is a specialist in internal medicine, worked with clinical trials and regulatory affairs in the drug industry from 1975–1983, and worked at hospitals in Copenhagen from 1984–1995. He helped start The Cochrane Collaboration in 1993 with founder Sir Iain Chalmers, and established the NCC the same year. He became professor of Clinical Research Design and Analysis in 2010 at the University of Copenhagen.
Translating Research into Clinical Practice
I would not denigrate Gøtzsche because of his non-psychiatric medical training and practice, his apparent lack of clinical activities during the past 20 years, or for his self-proclaimed detailed research-based knowledge about psychiatric drugs. I believe, however, that this background is inevitably restrictive, resulting in a narrowed perspective that does not take into account the history of psychiatry, does not deeply understand the nature and course of mental illness, and does not appreciate the complexity and nuances involved in the treatment of patients and families who experience psychiatric disorders.
Whether psychiatric drugs cause more harm than good is an important question to ask, but is difficult to answer because of the complexity of defining and measuring concepts of “harm” and “good” as they pertain to treating (or not treating) psychiatric disorders with medication. Even non-drug psychological therapies can cause harm (Lilienfeld, 2007).
What the research investigation is (e.g., observational study, clinical trial, animal laboratory experiment) and who or what is included in the investigation (e.g., healthy or diseased individuals, administrative claims records, type of animal) necessarily limits what can be learned and generalized from the study. Results must be interpreted in the context of inherent limitations of the study design and methodology. Whether this knowledge validly translates into the “real world” clinical setting can be debated, as it often is.
Ultimately, what is relevant to addressing the issue of psychiatric drug benefits and harms, and what is important to practicing nurses, physicians, and other health care providers, is the valid translation of preclinical and clinical research findings into clinical practice. Investigators who conduct clinical research as well as see patients in clinical settings understand what I mean. What is perceived by a “real world” patient to be beneficial or harmful by taking medication is not a mirror image experience of individuals who participate in a study.
A criticism of professionals who spend all of their time in research is that they exist in an ivory tower. I was intrigued that Gøtzsche held such a strongly, comprehensively, and uniformly negative view about psychiatric drugs. Because his published biography mainly emphasized academic credentials, I sent an e-mail to him asking about the extent of his actual clinical experiences. I also invited him to write a commentary on psychopharmacology for the Journal of Psychiatric Nursing and Mental Health Services. His brief response to me only was to say “I am overworked, wait and see my next book” (P.C. Gøtzsche, e-mail communication, June 4, 2015).
Historical Aspects of Psychiatric Treatment
President Jimmy Carter and challenger Ronald Reagan debated just once in the U.S. presidential contest of 1980. At the end of the debate, in his final statement, Reagan delivered what ultimately was a knockout blow to Carter’s reelection (Commission on Presidential Debates, 1980):
Next Tuesday is Election Day. Next Tuesday all of you will go to the polls, will stand there in the polling place and make a decision. I think when you make that decision, it might be well if you would ask yourself, are you better off than you were four years ago? Is it easier for you to go and buy things in the stores than it was four years ago? Is there more or less unemployment in the country than there was four years ago? Is America as respected throughout the world as it was? Do you feel that our security is as safe, that we’re as strong as we were four years ago? And if you answer all of those questions yes, why then, I think your choice is very obvious as to whom you will vote for. If you don’t agree, if you don’t think that this course that we’ve been on for the last four years is what you would like to see us follow for the next four, then I could suggest another choice that you have.
I think of this quote because I would ask analogous questions about the use of drug treatments for psychiatric patients. Are psychiatric patients better off or worse off now than they were 60 years ago, when chlorpromazine (Thorazine®) was introduced? If you experienced a major mental illness, would you prefer being a psychiatric patient treated according to today’s standards or as a patient treated according to the standards of the first half of the 20th century or the standards of the 19th century and even earlier?
Before 1955, the history of psychiatric therapeutics included, but was not limited to, the following treatments: trephination; exorcism and prayer; mesmerism; asylum treatment using isolation and physical restraints; instillation of “moral” discipline; psychoanalysis; cold water dunking or ice water baths; bleeding or purging using emetics, laxatives, leeches, and phlebotomy; malarial (fever) therapy; surgical excision of “infected” organs believed to cause mental illness; crudely performed frontal lobotomies; and insulin shock (coma) therapy.
In 1955, there were approximately 560,000 severely mentally ill patients in public psychiatric hospitals (Torrey, 1997). By 1994, this number had been reduced to less than 72,000 patients. The number is much less today. If private psychiatric hospitals and general hospital psychiatric beds are included, the proportion of psychiatric beds per 100,000 population has dropped from 264 in 1970 to 112 in 1998, and length of hospital stay has also declined (Eisenberg & Guttmacher, 2010). Deinstitutionalization occurred for three reasons: (a) the advent of psychotropic drugs; (b) the social–political movement in favor of community mental health services; and (c) financial cost-shifting from federal to state governments (Eisenberg & Guttmacher, 2010). Although adverse consequences of deinstitutionalization have been appropriately highlighted, if not rectified, the transition from in-patient to outpatient treatment, facilitated by the use of psychiatric drugs, has been beneficial for most patients and their families.
In his BMJ commentary, Gøtzsche (2015) expresses his Panglossian view that a contemporary world with limited use of psychotropic drugs would result in a healthier and more long lived population. This scenario is mindful of the 1998 film Pleasantville, which explores the ancient theme of utopia from the modern perspective of cable television nostalgia (McDaniel, 2002). Pleasantville (circa 1950s) appears to be idyllic—it never rains, the high and low temperatures rest at 72°, the fire department exists only to rescue treed cats, and the basketball team never misses the hoop—but the town represents a false hope (McDaniel, 2002). The faith that psychiatric drugs are a problem and that patients would be better off without them, as they were without them before 1955, is based on a similarly false hope.
Mental Illness, Drug Therapy, and Mortality
Mental illness itself is associated with significant morbidity, mortality, and disability (Walker, McGee, & Druss, 2015; Whiteford et al., 2013). In a systematic review of mortality among individuals with mental illness, Walker et al. (2015) determined that mortality was significantly higher among individuals with mental illness than among the comparison population. Moreover, two thirds of deaths were due to natural causes, but less than 20% were due to unnatural causes (a category that includes suicide). They estimated that 8 million deaths worldwide annually can be attributed to mental illness. One might argue, as Gøtzsche does, that psychotropic drugs are harmful and potentially lethal, perhaps contributing to these 8 million annual deaths. However, excess mortality and shortened life spans among mentally ill individuals, for natural and unnatural reasons, had been observed long before psychotropic drug treatments were introduced in the 1950s (Malzberg, 1937).
As recently as 1977, 64% of psychiatric visits were exclusively for psychotherapy with no prescription provided, but in 2002 this was true for less than 10% of visits to psychiatrists (Eisenberg & Guttmacher, 2010). Approximately 11% of Americans (more than 35 million individuals) take antidepressant medications, and the rate of antidepressant drug use increased 400% since fluoxetine (Prozac®) was marketed in 1988 (Pratt, Brody, & Gu, 2011). Various atypical antipsychotic drugs were introduced between 1990 and 2002. From 1996 to 2003, an estimated 47.7 million adult ambulatory care visits involved mention of an antipsychotic drug (Sankaranarayanan & Puumala, 2007). During these 8 years, visits involving atypical antipsychotic drugs and combinations of antipsychotic drugs increased by 195% and 149%, respectively. More of the atypical antipsychotic drug visits also involved antidepressant drugs. Given the explosive rise in use of antidepressant, antipsychotic, and other psychotropic drugs, and the common practice of polypharmacy, why has there not been an explosive increase in suicide rates or non-suicide mortality rates during the past half-century, as would be predicted if such drugs harbor especially lethal effects?
Limitations of Research Findings
I do not disagree with the premise that there is a tendency for psychotropic drugs to be overprescribed, and that their benefits are often oversold or their harms underemphasized. But the magnitude of these tendencies simply does not rise to the level of harm that Gøtzsche (2015) claims. His analysis of harms and benefits is largely based on observational studies and meta-analyses, without considering the limitations of these investigations. Causality cannot be established from observed associations or meta-analyses (Berlin & Golub, 2014). Most reported associations in observational clinical research are false, and the minority of associations that are true are often exaggerated (Grimes & Schulz, 2012). Weak or small magnitude associations, even if statistically significant, are more likely to be attributable to bias than to causal association. All observational research has one or more types of bias, and bias is especially true of epidemiological research using administrative databases (Grimes, 2010).
The conviction that meta-analysis provides the best level of evidence, because it includes mathematically combining a complete body of evidence from different studies, is flawed (Berlin & Golub, 2014). Because of heterogeneity (variation in true effect sizes and in factors that may influence those effect sizes) and because of various methodological problems, meta-analysis should be considered as an observational study, such that the findings are interpreted as associations rather than as causal effects (Berlin & Golub, 2014). Different approaches to including studies in a meta-analysis can lead to different estimates of effect sizes and different interpretations of the study findings (Dechartres, Altman, Trinquart, Boutron, & Ravaud, 2014).
To Gøtzsche, the harms and benefits of psychiatric drugs can be reduced to discrete quantifiable variables that can be measured, with certainty and precision, among a small subset of patients who agree to be participants in a research study or that can be gleaned from administrative databases. Collecting and statistically analyzing such data from as many studies as possible may form the basis for his detailed research-based knowledge about psychiatric drugs. But this data-rich soup of knowledge is nutritionally deficient in wisdom—the wisdom that comes from an appreciation of the history of psychiatry; the wisdom gained from hands-on experience working with psychiatric patients and their families; and the wisdom to be aware of one’s own limits and biases, not just the conflicts of interest and biases of others (Nickerson, 1998).
Gøtzsche’s antipathy to psychotropic drugs and his cynicism toward psychiatry is unfortunate. Such views are harmful not only to patients and families, but also to nurses, physicians, and other professionals whose mission is to treat mental disorders safely, effectively, and compassionately.
- Berlin, J.A. & Golub, R.M. (2014). Meta-analysis as evidence: Building a better pyramid. Journal of the American Medical Association, 312, 603–605. doi:10.1001/jama.2014.8167 [CrossRef]
- Commission on Presidential Debates. (1980). The Carter-Reagan presidential debate. Retrieved from http://www.debates.org/index.php?page=october-28-1980-debate-transcript
- Dechartres, A., Altman, D.G., Trinquart, L., Boutron, I. & Ravaud, P. (2014). Association between analytic strategy and estimates of treatment outcomes in meta-analyses. Journal of the American Medical Association, 312, 623–630. doi:10.1001/jama.2014.8166 [CrossRef]
- Eisenberg, L. & Guttmacher, L.B. (2010). Were we all asleep at the switch? A personal reminiscence of psychiatry from 1940 to 2010. Acta Psychiatrica Scandinavica, 122, 89–102. doi:10.1111/j.1600-0447.2010.01544.x [CrossRef]
- Gøtzsche, P.C. (2014). Psychiatry gone astray. Retrieved from http://www.deadlymedicines.dk/wp-content/uploads/2015/05/3-G%C3%B8tzsche-Psychiatry-gone-astray.pdf
- Gøtzsche, P.C. (2015a, May17). Re: Does long term use of psychiatric drugs cause more harm than good? Retrieved from http://www.bmj.com/content/350/bmj.h2435/rr-4
- Gøtzsche, P.C. (2015b, May18). [Letter to David Tovey]. Retrieved from http://www.deadlymedicines.dk/wp-content/uploads/2015/05/11-G%C3%B8tzsche-Maudsley-letter-to-Tovey-about-debate-one-word-changed.pdf
- Gøtzsche, P.C., Young, A.H. & Crace, J. (2015). Does long term use of psychiatric drugs cause more harm than good?BMJ, 350, h2435. doi:10.1136/bmj.h2435 [CrossRef]
- Grimes, D.A. (2010). Epidemiologic research using administrative databases: Garbage in, garbage out. Obstetrics and Gynecology, 116, 1018–1019. doi:10.1097/AOG.0b013e3181f98300 [CrossRef]
- Grimes, D.A. & Schulz, K.F. (2012). False alarms and pseudo-epidemics: The limitations of observational epidemiology. Obstetrics and Gynecology, 120, 920–927. doi:10.1097/AOG.0b013e31826af61a [CrossRef]
- Lilienfeld, S.O. (2007). Psychological treatments that cause harm. Perspectives in Psychological Science, 2, 53–70. doi:10.1111/j.1745-6916.2007.00029.x [CrossRef]
- Mamede, S. & Schmidt, H.G. (2014). The twin traps of overtreatment and therapeutic nihilism in clinical practice. Medical Education, 48, 34–43. doi:10.1111/medu.12264 [CrossRef]
- Malzberg, B. (1937). Mortality among patients with involution melancholia. American Journal of Psychiatry, 93, 1231–1238. doi:10.1176/ajp.93.5.1231 [CrossRef]
- McDaniel, R. (2002). Pleasantville [Motion picture, G. Ross (Director) 1998]. Film & History: An Interdisciplinary Journal of Film and Television Studies, 32, 85–86.
- Middelboe, T., Nordentoft, M., Videbech, P. & Kessing, L.V. (2014, March5). [Letter to Cochrane Schizophrenia Group/ Depression-Anxiety Group]. Retrieved from http://www.deadlymedicines.dk/wp-content/uploads/2015/05/2-Middelboe-letter-to-Cochrane-March-5.pdf
- Nickerson, R.S. (1998). Confirmation bias: A ubiquitous phenomenon in many guises. Review of General Psychology, 2, 175–220. doi:10.1037/1089-26220.127.116.11 [CrossRef]
- Pratt, L.A., Brody, D.J. & Gu, Q. (2011). Antidepressant use in persons aged 12 and over: United States, 2005–2008 (NCHS data brief, no 76). Retrieved from http://www.cdc.gov/nchs/data/databriefs/db76.htm
- Sankaranarayanan, J. & Puumala, S.E. (2007). Antipsychotic use at adult ambulatory care visits by patients with mental health disorders in the United States, 1996–2003: National estimates and associated factors. Clinical Therapeutics, 29, 723–741. doi:10.1016/j.clinthera.2007.04.017 [CrossRef]
- Torrey, E.F. (1997). Out of the shadows: Confronting America’s mental illness crisis. New York, NY: John Wiley & Sons.
- Tovey, D., Churchill, R., Adams, C.E. & Macdonald, G. (2015, May13). Re: Does long term use of psychiatric drugs cause more harm than good? Retrieved from http://www.bmj.com/content/350/bmj.h2435/rr
- Walker, E.R., McGee, R.E. & Druss, B.G. (2015). Mortality in mental disorders and global disease burden implications: A systematic review and meta-analysis. JAMA Psychiatry, 72, 334–341. doi:10.1001/jamapsychiatry.2014.2502 [CrossRef]
- Whiteford, H.A., Degenhardt, L., Rehm, J., Baxter, A.J., Ferrari, A.J., Erskine, H.E. & Vos, T. (2013). Global burden of disease attributable to mental and substance use disorders: Findings from the Global Burden of Disease Study 2010. Lancet, 382, 1575–1586. doi:10.1016/S0140-6736(13)61611-6 [CrossRef]