Pharmageddon

by David Healy

  2. Neil Pearce, Adverse Reaction: The Fenoterol Story (Aukland: Auckland University Press, 2007).

  3. For example, diacetyl put in processed foods as a butter flavoring leads to a bronchiolitis—referred to as popcorn lung.

  4. Walter O. Spitzer et al., The use of beta agonists and the risk of death and near death from asthma, NEJM 326, 501–506 (1992); Shelley Salpeter, Nicholas S. Buckley, Thomas M. Ormiston, and Edwin Salpeter, Meta-analysis: Effect of long-acting beta agonist on severe asthma exacerbations and asthma related deaths, Annals of Internal Medicine 144, 904–912 (2006).

  5. John Berger, A Lucky Man (Harmondsworth, UK: Penguin Books, 1973); M. Winckler, The Case of Doctor Sachs (New York: Seven Stories Press, 1998).

  6. Steven Timmermans and Marc Berg, The Gold Standard: The Challenge of Evidence Based Medicine and Standardization in Health Care (Philadelphia: Temple University Press, 2003).

  7. Edward Shorter and David Healy, Shock Therapy (New Brunswick, NJ: Rutgers University Press, 2008).

  8. Hillel Schwartz, Never Satisfied: A Cultural History of Diets, Fantasies and Fat (New York: The Free Press, 1986).

  9. Schwartz, Never Satisfied.

  10. It is, however, difficult to know with any certainty what the prevalence of anorexia nervosa was before the 1960s. Whatever the prevalence of the disorder in some absolute sense, the number of patients accessing services for treatment was minimal compared with what came later. At one point in the 1970s and 1980s, almost all heads of psychiatric departments in London were eating-disorder researchers.

  11. T. R. Dawber, G. F. Meadors, and F. E. Moore, National Heart Institute, National Institutes of Health, Public Health Service, and Federal Security Agency, Washington, DC, Epidemiological Approaches to Heart Disease: The Framingham Study, Presented at a Joint Session of the Epidemiology, Health Officers, Medical Care, and Statistics Sections of the American Public Health Association at the 78th Annual Meeting in St. Louis, MO, Nov. 3, 1950.

  12. Theodore Eisenberg and Martin T. Wells, Statins and adverse cardiovascular events in moderate-risk females: A statistical and legal analysis with implications for FDA pre-emption, Journal of Empirical Legal Studies 5, 507–550 (2008).

  13. In men who have had a previous cardiovascular event, lowering cholesterol levels with drugs appears to reduce their risk of dying from a further cardiovascular event. Yet even in this case, it is now clear that the statin group of drugs have anti-inflammatory properties, just like aspirin, which also reduces the risk of a further heart attack, and it may be their benefits stem from this effect rather than any action on cholesterol. These drugs act on a range of systems around the body, and it may turn out that in some cases the statins can be helpful for other reasons, but despite the vast sales of these drugs today and the numbers of people taking them, there has been almost no research looking beyond blood cholesterol levels—almost certainly because this could spoil a good marketing story.

  14. John Abramson, Overdosed America: The Broken Promise of American Medicine (New York: Harper Perennial, 2004).

  15. Ramon Estruch et al., Effects of a Mediterranean-style diet on cardiovascular risk factors: A randomized trial, Annals of Internal Medicine 146, 1–11 (2006).

  16. Isabelle Savoie and Arminee Kazanjian, Utilization of lipid-lowering drugs in men and women: A reflection of the research evidence, Journal of Clinical Epidemiology 55, 97–98 (2002); Peter S. Sever et al., Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower than average cholesterol concentrations in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid lowering arm (ASCOT-LLA), Lancet 361, 1149–1155 (2003).

  17. Savoie and Kazanjian, Utilization of lipid-lowering drugs in men and women.

  18. Colette B. Raymond et al., Population-based analysis of statin utilization in British Columbia, Clinical Therapeutics 29, 2107–2115 (2007).

  19. Dudley Gentles et al., Serum lipid levels for a multicultural population in Auckland, New Zealand, New Zealand Medical Journal 120, 1–12 (2008).

  20. Gentles et al., Serum lipid levels for a multicultural population in Auckland, New Zealand.

  21. Robert A. Wilson, Feminine Forever (New York: M. Evans, 1966).

  22. Gillian Sansom, The Myth of Osteoporosis (Ann Arbor, MI: Century Publications, 2003); Elaine S. Berman, Too Little Bone: The Medicalization of Osteoporosis, Journal of Women's Health and Law 1, 257–277 (1999).

  23. K. Bassett, “On trying to stop the measurement of bone density to sell drugs,” in Tales from the Other Drug Wars, ed. M. L. Barer et al. (Vancouver: Centre for Health Services and Policy Research, 2000).

  24. http://www.npr.org/templates/story/story.php?storyId=121609815.

  25. Tamir Ali and Roger H. Jay, Spontaneous femoral shaft fracture after long-term alendronate, Age and Ageing 38, 625–626 (2009).

  26. E. E. Roughead, K. McGeehan, and G. P. Sayer, Biphosphonate use and subsequent prescription of acid suppressants, British Journal of Clinical Pharmacology 57, 813–816 (2004); Redonda G. Miller et al., Incidence of gastro-intestinal events among biphosphonate patients in an observational setting, American Journal of Managed Care 10, 207–215 (2004).

  27. J. J. Wolff et al., The effect of exercise training programs on bone mass: A meta-analysis of published controlled trials in pre and post-menopausal women, Osteoporosis International 9, 1–12 (1999).

  28. Max Hamilton, A rating scale for depression, Journal of Neurology, Neurosurgery and Psychiatry 23, 56–62 (1960).

  29. Max Hamilton, “Rating Scales in Depression,” in Depressive Illness, Diagnosis, Assessment, Treatment, ed. P. Kielholz, 100–108 (Berne: Hanns Huber Publishers, 1972).

  30. David Healy, Derelie Mangin, and Barbara Mintzes, The ethics of controlled trials in prenatal depression, International Journal of Risk and Safety in Medicine 22, 1–10 (2010), doi:10.3233/JRS-2010–048.

  31. Ray Moynihan and David Henry, The fight against disease mongering: Generating knowledge for action, Public Library of Science Medicine 3 (2006). All articles in this issue of the journal were on disease mongering.

  32. Leonore Tiefer, Female sexual dysfunction: A case study of disease mongering and activist resistance, Public Library of Science Medicine 3, e178 (2006), doi:10.1371/journalpmed.0030178.

  33. Jennifer Berman and Laura Berman, For Women Only (New York: Henry Holt, 2001).

  34. Diagnostic and Statistical Manual, Third Edition (Washington, DC: American Psychiatric Association, 1980).

  35. Kimberly A. Yonkers et al., The management of depression during pregnancy: A report from the American Psychiatric Association and American College of Obstetricians and Gynecologists, General Hospital Psychiatry 31, 403–413 (2009).

  36. Now these drugs all carry warnings on their labels about the risk of suicide.

  37. Jason Lazarou, Bruce H. Pomeranz, and Paul N. Corey, Incidence of adverse drug reactions in hospitalized patients: A meta-analysis of prospective studies, JAMA 279, 1200–1205 (1998).

  38. The Institute for Safe Medication Practices, QuarterWatch 1–3 (2009), http://www.ismp.org/QuarterWatch/2009Q3.pd.

  39. Thomas E. Bittker, The industrialization of American psychiatry, American Journal of Psychiatry 142, 149–154 (1985).

  40. Philip M. Sinaikin, Categorical diagnosis and a poetics of obligation: An ethical commentary on psychiatric diagnosis and treatment, Ethical Human Sciences and Services 5, 141–148 (2003); Philip M. Sinaikin, Coping with the medical model in clinical practice or “How I learned to stop worrying and love DSM,” Journal of Critical Psychology, Counselling and Psychotherapy, 204–213 (2004).

  41. http://www.ahrq.gov/clinic/USpstfab.htm.

  42. Kimberly S. Yarnall, Kathryn I. Pollak, and Truls Ostbye, Primary care: Is there enough time for prevention? American Journal of Public Health 93, 635–641 (2003).

  43. Larry Eliot and Daniel Atkinson, The Gods That Failed: How Blind Faith in the Markets Has Cost Us Our Future (London: Bodley Head, 2008).

  44. Jame
s Spence, The Purpose and Practice of Medicine (Oxford: Oxford University Press, 1960).

  45. James Lind, A Treatise of the Scurvy (1752; Edinburgh: Edinburgh University Press, 1953).

  46. Mark Bostridge, Florence Nightingale (Harmondsworth, UK: Penguin Books, 2009).

  47. L. J. Rather, Collected Essays on Public Health and Epidemiology of Rudolf Virchow (New York: Science History Publications, 1985).

  48. Kenneth F. Kiple, Plagues, Pox and Pestilence: Disease in History (London: Weidenfeld and Nicolson, 1997).

  49. Richard Harris, The Real Voice (New York: Macmillan Press, 1964), 64.

  50. Eric Kimbuende, Usha Ranji, Janet Lundy, and Alina Salganicoff, US Health Care Costs (2010), http://www.kaiseredu.org/topics_im.asp?imID=i&parentID=61&id=358 (accessed May 6, 2011); David Leonhardt, “The choice: A longer life or more stuff,” New York Times, Sept. 27, 2006, http://www.nytimes.com/2006/09/27/business/27leonhardt.html (accessed May 9, 2011).

  51. The World Health Organization's ranking of the world's health systems, http://www.photius.com/rankings/who_world_health_ranks.html.

  52. Bob Roehr, Healthcare in the US ranks lowest among developed countries, BMJ 337, 889 (2008).

  53. Nananda Col, James E. Fanale, and Penelope Kronholm, The role of medication noncompliance and adverse drug reactions in hospitalizations of the elderly, Archives of Internal Medicine 150, 841–845 (1990).

  54. US Congress, Congressional Budget Office, Technological Change and the Growth of Health Care Spending (Jan. 2008).

  CHAPTER 7

  1. Padmaja Chalassani, David Healy, Richard Morriss, Presentation and frequency of catatonia in new admissions to two acute psychiatric admission units in India and Wales, Psychological Medicine 35, 1667–1675 (2005).

  2. Ray Moynihan and David Henry, Disease Mongering is now part of the global health debate, PLoS Medicine (2008), doi:10.1371/journal .pmed.0050106; Steven Woloshin and Lisa Schwartz, Giving legs to Restless Legs. A case study of how the media makes people sick, PLoS Medicine (2006), doi:10.1371/journal.pmed.0030170.

  3. Jerome Groopman, How Doctors Think (New York: Norton, 2007).

  4. Jason Lazarou, Bruce Pomeranz, and Paul Corey, Incidence of adverse drug reactions in hospitalized patients: A meta-analysis of prospective studies, JAMA 279, 1200–1205 (1998).

  5. The Institute for Safe Medication Practices, QuarterWatch 1–3 (2009), http://www.ismp.org/QuarterWatch/2009Q3.pd.

  6. Other options include pharmakosepsis, pharmacoscotoma, pharmacotoxicity, pharmakonosis.

  7. Annemarie Mol, The Logic of Care (London: Routledge, 2008).

  8. Michael Bliss, The Discovery of Insulin (Toronto: McClelland and Stewart, 1982).

  9. Edward Shorter and David Healy, Shock Therapy (New Brunswick, NJ: Rutgers University Press, 2008).

  10. Thomas Hager, The Demon under the Microscope (New York: Harmony Books, 2006).

  11. Jeremy A. Greene, Prescribing by Numbers: Drugs and the Definition of Disease (Baltimore: Johns Hopkins University Press, 2007).

  12. Greene, Prescribing by Numbers.

  13. Louis Lasagna, Congress, the FDA, and new drug development: Before and after 1962, Perspectives in Biology and Medicine 32, 322–343 (1989).

  14. Greene, Prescribing by Numbers.

  15. http://www.aace.com/meetings/consensus/hyperglycemia/hyperglycemia.pdf.

  16. Action to Control Cardiovascular Risk in Diabetes (ACCORD), Effects of intensive glucose lowering in type 2 diabetes, NEJM 358, 2545–2559 (2008).

  17. John Abrahams, Science, Politics and the Pharmaceutical Industry (London: UCL and St. Martin's Press, 1995).

  18. Dwight L. Evans et al., Mood disorders in the medically ill: Scientific review and recommendations, Biological Psychiatry 58, 175–189 (2005).

  19. “Best Practice: Translating Scientific Discovery into CNS Therapeutic Advantage,” http://www.best-practice.net (accessed June 6, 2008).

  20. Gabrielle A. Carlson et al., Methodological issues and controversies in clinical trials with child and adolescent patients with bipolar disorder: Report of a consensus conference, Journal of Child and Adolescent Psychopharmacology 13, 13–27 (2003).

  21. Peter S. Jensen et al., Consensus report on impulsive aggression as a symptom across diagnostic categories in child psychiatry: Implications for medication studies, Journal of the American Academy of Child and Adolescent Psychiatry 6, 309–322 (2007).

  22. Testimony of David J. Graham MD, MPH, to Congress, Nov. 18, 2004, http://www.consumersunion.org/pub/core_health_care/001651.html.

  23. Joseph S. Ross et al., Pooled analysis of rofecoxib placebo-controlled clinical trial data: Lessons for postmarketing pharmaceutical surveillance, Archives of Internal Medicine 169, 1976–1984 (2009).

  24. Martin H. Teicher, Carol Glod, and Jonathan O. Cole, Emergence of intense suicidal preoccupation during fluoxetine treatment, American Journal of Psychiatry 147, 207–210 (1990).

  25. David Healy, The antidepressant tale: Figures signifying nothing? Advances in Psychiatric Treatment 12, 320–328 (2006).

  26. Charles M. Beasley et al., Fluoxetine and suicide: A meta-analysis of controlled trials of treatment for depression, BMJ 303, 685–692 (1991).

  27. Using these data the relative risk for suicidal acts is 1.9 times greater on Prozac than placebo, with a 95 percent confidence interval from 0.2 to 16. This means while there is a chance that there is no increase in risk, the likeliest guess from these data is that the increase in risk is 1.9 fold, but the data also show it could be a 16-fold greater risk.

  28. Beasley et al., Fluoxetine and suicide; emphasis added by the author.

  29. David E. Wheadon et al., Lack of an association between fluoxetine and suicidality in bulimia nervosa, Journal of Clinical Psychiatry 53, 235–241

  (1992).

  30. Food and Drug Administration, Psychopharmacological Drugs Advisory Committee, 34th Meeting, Sept. 20, 1991.

  31. David Healy, Did regulators fail over selective serotonin reuptake inhibitors? BMJ 333, 92–95 (2006).

  32. Carol Bombardier et al., VIGOR Study Group, Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis, NEJM 343, 1520–1528 (2000).

  33. David Armstrong, “Bitter Pill: How the New England Journal missed warning signs on Vioxx. Medical weekly waited years to report flaws in article that praised pain drug,” Wall Street Journal, May 15, 2006.

  34. Louis Lasagna, “Back to the future: Evaluation and drug development 1956 to 1996,” in The Psychopharmacologists, ed. David Healy, 2 (London: Arnold, 1998).

  35. Sandor Greenland, Bayesian perspectives for epidemiological research, International Journal of Epidemiology 35, 777–778 (2006).

  36. Ezra Hauer, The harm done by tests of significance, Accident Analysis and Prevention 36, 495–500 (2004).

  37. Charles Poole, Why published epidemiology is really junk science, Congress of Epidemiology, Toronto, June 13, 2001.

  38. US Supreme Court, Matrixx Initiatives Inc. et al. v. Siracusano et al., No. 09–1156, decided March 22, 2011, 563 US.

  39. Kenneth J. Rothman, Writing for Epidemiology, Epidemiology 9, 333–337 (1998).

  40. Arif Khan et al., Suicide risk in patients with anxiety disorders; A metaanalysis of the FDA database, Journal of Affective Disorders 68, 183–190 (2002).

  41. Khan et al., Suicide risk in patients with anxiety disorders.

  42. Arif Khan et al., Suicide rates in clinical trials of SSRIs, other antidepressants and placebo: Analysis of FDA reports, American Journal of Psychiatry 160, 790–792 (2003).

  43. Paul Anthony, FDA “Drug Watch ” early warnings will have lasting negative effect, PhRMA says, The Pink Sheet, no. 001, June 2005.

  44. Chris Bushe and Richard Holt, Prevalence of diabetes and impaired glucose tolerance in patients with schizophrenia, British Journal of Psychiatry (Supplement 47) 184, s67–71 (2004). This entire issue of the journal was a supplement paid for by Lilly. Several if not all articles will have b
een authored by company personnel. The other main British journal dealing with psychotropic drugs (Journal of Psychopharmacology) also included a Lilly-sponsored symposium shortly afterward. These supplements are worth a lot of money to journals and are often not peer-reviewed. The Maudsley quote appears in several of the articles in these two supplements.

  45. Joanna Le Noury et al., The incidence and prevalence of diabetes in patients with serious mental illness in North West Wales: Two cohorts 1875–1924 and 1994–2006 compared, BMC Psychiatry 8, 67 (2004), doi:10.1186/1471–244X-8–67.

  46. Barry G. Firkin and J. A. Whitworth, Dictionary of Medical Eponyms (Carnforth, UK: Parthenon Publishing, 1987). This volume, ironically in this context, was made available to British doctors as an educational gift from Glaxo.

  47. David Michaels, Doubt Is Their Product (New York: Oxford University Press, 2008).

  48. Parents Med Guide, The use of medication in treating childhood and adolescent depression: Information for patients and families, prepared by the American Psychiatric Association and American Academy of Child and Adolescent Psychiatry (2005), http://www.ParentsMedGuide.org (accessed Feb. 1, 2005).

  49. American Psychiatric Association, “APA responds to FDA's new warning on antidepressants,” news release, Oct. 15, 2004, http://www.psych.org/news_room/press_releases/04–55apaonfdablackboxwarning.pdf.

  50. The session was convened on October 10—the 43rd anniversary of Kefauver's bill.

  51. David Sheahan, “Angles on panic,” in The Psychopharmacologists, ed. David Healy, 3, 479–504 (London: Arnold, 2000).

  52. Food and Drug Administration, Psychopharmacological Drugs Advisory Committee, 34th Meeting, Sept. 20, 1991.

  53. Lyam Kilker and Michelle David v. SmithKline Beecham, First Judicial District of Pennsylvania, Civil Trial Division 1813 (Sept. 2009).

  54. The Tobacco Institute Inc., Tobacco and the Health of the Nation (San Francisco: Legacy of Tobacco Documents Library, UCSF, 1969), http://legacy.library.ucsf.edu/cgi/getdoc?tid=dxb34f00&fmt=pdf&ref=results. In a quite comparable fashion, pharmaceutical companies have promoted a series of studies that apparently showed declining suicide rates in line with rising antidepressant sales during the 1990s. For a list of such studies see Goran Isacsson et al., Decrease in suicides among the individuals treated with antide-pressants: A controlled study of antidepressants in suicide, Sweden 1995–2005, Acta Psychiatrica Scandinavia 120, 37–44 (2009). This was most probably explained by factors like declining autopsy rates in the 1990s—a large number of suicides are only diagnosed at autopsy; see Svein Reseland et al., National suicide rates 1961–2003: Further analysis of Nordic data for suicide, autopsies and ill-defined death rates, Psychotherapy and Psychosomatics 77, 78–82 (2008).