The Drugs That Changed Our Minds

by Lauren Slater

  Bonifácio de Andrada e Silva: Per Enghag, Encyclopedia of the Elements: Technical Data—History—Processing—Applications (New York: Wiley, 2004), 291.

  Lithium found on Utö: F. Neil Johnson, The History of Lithium Therapy (New York: Macmillan, 1984), 3.

  How lithium came to be called lithion: Ibid.

  Lithium’s ability to alkalise excessively acidic urine: Ibid., 8.

  Doctors believing that excess uric acid: David Healy, Mania: A Short History of Bipolar Disorder (Baltimore: Johns Hopkins University Press, 1984), 90.

  Lithium levels in tap water: N. Sugawara, ‘Lithium in Tap Water and Suicide Mortality in Japan’, International Journal of Environmental Research and Public Health 10 (2013): 6044–48.

  Japanese research on tap water: Hirochika Ohgami et al., ‘Lithium Levels in Drinking Water and Risk of Suicide’, British Journal of Psychiatry (2009): 464–65.

  ‘I was born in 1917’: Johnson, The History of Lithium Therapy, 18.

  Discovery and development of lithium’s medicinal uses: Ibid., 5–22.

  On the popularisation of lithium spas: Ibid., 18–19.

  ‘For a person to obtain a therapeutic dose’: Elliot Valenstein, Blaming the Brain: The Truth about Drugs and Mental Health (New York: Free Press, 1988) , 41.

  Lange first to use lithium prophylactically: Edward Shorter, ‘The History of Lithium Therapy’, Bipolar Disorders (2009): 4–9.

  John Aulde’s treatment: Johnson, The History of Lithium Therapy, 12.

  Cocoanut Grove fire: Kathiann M. Kowalski, Attack of the Superbugs: The Crisis of Drug-Resistant Diseases (New York: Enslow Publishing, 2005). See also Stuart B. Levy, The Antibiotic Paradox: How the Misuse of Antibiotics Destroys Their Curative Powers (Cambridge, MA: Da Capo Press, 2002), 1–4.

  By the 1940s you couldn’t get your hands on a lithium tablet: Johnson, The History of Lithium Therapy, 31. See also Healy, Mania, 96.

  Cade held as a prisoner of war in the Changi camp: Johnson, The History of Lithium Therapy, 32–34. See also Greg de Moore and Ann Westmore, Finding Sanity: John Cade, Lithium, and the Taming of Bipolar Disorder (Melbourne: Allen & Unwin, 2017). See also Jack F. Cade, ‘John Frederick Joseph Cade: Family Memories on the Occasion of the Fiftieth Anniversary of His Discovery of the Use of Lithium in Mania’, Australian and New Zealand Journal of Psychiatry 33, no. 5 (1999): 615–18. For conditions at the camp, see Roland Perry, The Changi Brownlow (Sydney: Hachette Australia, 2012).

  How and when Cade developed his ideas: Healy, Mania, 100; Johnson, The History of Lithium Therapy, 32–34.

  ‘mourning the wasted years’: John Cade, quoted in Johnson, The History of Lithium Therapy, 34.

  Cade’s powers of observation: David Healy, The Psychopharmacologists, vol. 2 (Boca Raton, FL: CRC Press, 1998), 262.

  ‘Because I did not know’: Johnson, The History of Lithium Therapy, 35.

  Cade storing urine samples in family refrigerator: Ibid., 36.

  Urine ‘from the manic patients’: Valenstein, Blaming the Brain, 44.

  ‘all that had been demonstrated so far’: Samuel Gershon et al., eds., Lithium: Its Role in Psychiatric Research and Treatment (New York: Springer, 1973), 9.

  Cade injected large doses: Johnson, The History of Lithium Therapy, 36.

  ‘the animals, although fully conscious’: Ibid., 36.

  Cade trying lithium on himself: Jack F. Cade, Australian and New Zealand Journal of Psychiatry, 33, no. 5 (1999): 615–18.

  Cade believed that ‘spontaneous remission is far less likely to occur’: John F. Cade, ‘Lithium Salts in the Treatment of Psychotic Excitement’, Bulletin of the World Health Organization 78, no. 4 (2000): 518–20.

  ‘How to proceed?’: Johnson, The History of Lithium Therapy, 108.

  ‘Our kitchen refrigerator’: Ibid., 37.

  In total Cade treated nineteen patients: Philip B. Mitchell, ‘On the 50th Anniversary of John Cade’s Discovery of the Anti-Manic Effect of Lithium’, Australian and New Zealand Journal of Psychiatry 33, no. 5 (1999): 624.

  ‘in a state of typical manic excitement’: Cade, ‘Lithium Salts in the Treatment of Psychotic Excitement’, 518–20.

  ‘enjoyed preeminent nuisance value’: Valenstein, Blaming the Brain, 44.

  Cade’s ‘expectant imagination’: Ibid., 46.

  ‘he found normal surroundings and liberty of movement strange at first’: Healy, Mania, 102.

  ‘I readmitted him to the hospital’: Johnson, The History of Lithium Therapy, 39.

  ‘very first scientific evidence’: Barry Blackwell, Bits and Pieces of a Psychiatrist’s Life (Bloomington, IN: Xlibris, 2012), 218.

  ‘E.A., a male, aged forty-six years’: Cade, ‘Lithium Salts in the Treatment of Psychotic Excitement’, 518–20.

  Patients lithium did and did not help: Johnson, The History of Lithium Therapy, 38.

  Cade’s hypothesis on the effects of lithium deficiency: Cade, ‘Lithium Salts in the Treatment of Psychotic Excitement’, 518–20.

  Young found that lithium salts: Johnson, The History of Lithium Therapy, 59.

  W. B. was ‘back to his old form again’: Cade, ‘Lithium Salts in the Treatment of Psychotic Excitement’, 518–20.

  Cade reported that W. B.’s skin: Johnson, The History of Lithium Therapy, 40.

  The paper stirred little interest: Healy, Mania, 105.

  Young ‘found a supply of effervescent lithium’: Johnson, The History of Lithium Therapy, 58–59.

  Schou recalled how his father: Healy, The Psychopharmacologists, vol. 2, 259.

  Schou clearly remembered: Ibid.

  Mogens Schou on Cade’s paper: Ibid., 263.

  Schou’s study was the first: Ibid.

  Schou publishes findings consistent with Cade’s: Shorter, ‘The History of Lithium Therapy’. See also Johnson, The History of Lithium Therapy, 68.

  Danish researchers learning to use the flame spectrophotometer: Johnson, The History of Lithium Therapy, 61.

  Two reports of thirty-five patients: Ibid., 69.

  A common substrate for mania and depression: Ibid., 70.

  Baastrup on patients who chose to continue lithium: Ibid., 71. See also Healy, Mania, 113.

  Baastrup’s findings: Healy, Mania, 114.

  Geoffrey P. Hartigan gives lithium to twenty of his patients: Ibid.

  Five of the seven recovered: Johnson, The History of Lithium Therapy, 72.

  Wife reporting that her husband: G. P. Hartigan, ‘Experience of Treatment with Lithium Salts’, cited ibid., 187.

  ‘has kept very well since’: Ibid.

  In 1961 Schou wrote to Hartigan: Ibid.; Johnson, The History of Lithium Therapy, 75.

  ‘From the age of twenty he suffered’: Ibid.

  Dangers of lithium-based salt substitutes: Ibid., 49.

  Most asylums had huge canisters of lithium left over: Ibid.

  On Shepherd and Blackwell’s criticisms of Schou: Healy, Mania, 115–19.

  It was an impression: Healy, The Psychopharmacologists, vol. 2, 267.

  He ‘clearly felt that when I showed gratification’: Ibid.

  Blackwell and Shepherd’s criticisms of Schou and Baastrup: Johnson, The History of Lithium Therapy, 80.

  ‘How . . . could I put him’: Ibid., 87.

  ‘He was a genial man’: Healy, The Psychopharmacologists, vol. 2, 249–50.

  ‘Critical debate is what science thrives on’: Ibid., 268.

  Blackwell countered that Schou’s entire professional life: Johnson, The History of Lithium Therapy, 85.

  Schou’s study design and trial: Ibid., 88.

  ‘They saw a killing here’: Healy, The Psychopharmacologists, vol. 2, 250.

  Clinicians in the United States began applying to the FDA: Johnson, The History of Lithium Therapy, 102.

  Lithium approved in the United States: Ibid.

  ‘therapeutic effects of complicated compounds’: Johnson, The History of Lithium Therapy, 67.

  ‘But it has never really exci
ted neuroscientists’: Personal interview with Alexander Vuckovic, McLean Hospital, Belmont, MA, 21 May 2015.

  ‘as good a symbol of the vacuity’: Healy Mania, 168.

  Valproate semisodium an effective treatment for mania: Daniel Goleman, ‘2 Drugs Get a New Use: Soothing Mania’, New York Times, 13 July 1994.

  Numerous anticonvulsants were repurposed: Healy, Mania, 168.

  The term ‘mood stabiliser’: Ibid., 174.

  Gabapentin grossed $1.3 billion: Ibid.

  ‘I’ve found it to be as effective’: Personal interview with Alexander Vuckovic, McLean Hospital, Belmont, MA, 21 May 2015.

  3. Early Antidepressants

  Evidence that depression is genetic: Maria Neves-Pereira, Emanuela Mundo, Pierandrea Muglia, Nicole King, Fabio Macciardi and James L. Kennedy, ‘The Brain Derived Neurotrophic Factor Gene Confers Susceptibility to Bipolar Disorder: Evidence from a Family Based Association Study’, American Journal of Human Genetics 71, no. 3 (September 2002): 651.

  Broadhurst’s first impressions of the Geigy office: Alan D. Broadhurst, ‘The Discovery of Imipramine from a Personal Viewpoint’, in The Rise of Psychopharmacology and the Story of CINP, eds. T. A. Ban, D. Healy and E. Shorter (Budapest: Animula Press, 1998), 69.

  ‘nothing intrinsically special’: David Healy, The Creation of Psychopharmacology (Cambridge, MA: Harvard University Press, 2002), 37.

  ‘making life did not require’: Ibid.

  Broadhurst and the executives at Geigy aware of developments: Broadhurst, ‘The Discovery of Imipramine from a Personal Viewpoint’, 69.

  Desire of Broadhurst to avoid creating a ‘me too’ drug: Ibid.

  ‘the spotlight fell on iminodibenzyl’: Ibid., 71.

  Geigy’s organic chemists created derivatives of the substance: Peter Kramer, Ordinarily Well: The Case for Antidepressants (New York: Farrar, Straus and Giroux, 2016), 5.

  Eventually the team narrowed in on G22150, the least toxic and most sedative: Ibid., 72.

  Kuhn agreed to test G22150 on patients at Münsterlingen: Broadhurst, ‘The Discovery of Imipramine from a Personal Viewpoint’, 69.

  Kuhn believed that the best way to test a drug was not through clinical trials: Holger Steinberg and Hubertus Himmerich, ‘Roland Kuhn—100th Birthday of an Innovator of Clinical Psychopharmacology’, Psychopharmacology Bulletin 45, no. 1 (2012): 48–50.

  Geigy abandoned G22150: David Healy, The Psychopharmacologists, vol. 2 (Boca Raton, FL: CRC Press, 1998), 72.

  Their scientists soon identified a new focus, G22355: Broadhurst, ‘The Discovery of Imipramine from a Personal Viewpoint’, 69.

  ‘The road to Münsterlingen was already well trodden’ and the trial of G22355: Ibid., 72–73.

  The word ‘antidepressant’ was not in existence: David Healy, The Creation of Psychopharmacology (Cambridge, MA: Harvard University Press, 2002), 52.

  ‘we wondered if the apparent mood elevation’: Ibid., 73.

  ‘I well remember the look of suspicious disbelief on his face’: Broadhurst, ‘The Discovery of Imipramine from a Personal Viewpoint’, 74.

  Kuhn’s new clinical trial, entirely uncontrolled: Ibid.

  Kuhn’s approach to patients: Kramer, Ordinarily Well, 30.

  The first patient to show a change was Paula J. F.: David Healy, The Antidepressant Era (Cambridge, MA: Harvard University Press, 1997), 52.

  ‘It was clear that G22355’: Broadhurst, ‘The Discovery of Imipramine from a Personal Viewpoint’, 74.

  ‘the last person [he] would have expected’: Ibid., 75.

  ‘I remember how amazed Abraham was’: Ibid.

  Kuhn’s claims and reputation: Ibid., 50.

  Kuhn’s style of psychotherapy: Healy, The Antidepressant Era, 49.

  Those suffering from vital depression: Steinberg and Himmerich, ‘Roland Kuhn—100th Birthday of an Innovator of Clinical Psychopharmacology’.

  Lehmann managed to get his hands on some samples: Healy, The Antidepressant Era, 57.

  The drug would be most useful: Ibid., 52.

  World Health Organization series of studies: Ibid., 59.

  Böhringer was made aware of Geigy’s work on G22355: Kramer, Ordinarily Well, 8.

  G22355 becoming imipramine; Kline, Kuhn and MAOIs: Healy, The Antidepressant Era, 54–69.

  Reserpine also an effective antipsychotic: A. A. Baumeister, M. F. Hawkins and S. M. Uzelac, ‘The Myth of Reserpine-Induced Depression: Role in the Historical Development of the Monoamine Hypothesis’, Journal of the History of the Neurosciences 12, no. 2 (2003): 207–20.

  Kline abandoned reserpine: David Healy, Let Them Eat Prozac (New York: NYU Press, 2004), 1–40. See also Chaitra T. Ramachandraih et al., ‘Antidepressants: From MAOIs to SSRIs and More’, Indian Journal of Psychiatry 53, no. 2 (2011): 180–82.

  Reserpine did become an indispensable research tool: Healy, The Antidepressant Era, 64.

  Rabbits pretreated with either imipramine: Ibid., 66.

  Pretreated rabbits’ synapses: C. Lebrand et al., ‘Transient Uptake and Storage of Serotonin in Developing Thalamic Neurons’, Neuron 17, no. 5 (1996): 823–35.

  Two-thirds showed marked improvement: Healy, The Antidepressant Era, 64.

  Kline alerted company executives to his findings: Ibid., 67.

  Kline reported his study results to the New York Times: Ibid.

  Within the first year 400,000 people: Rebecca Kreston, ‘The Psychic Energizer! The Serendipitous Discovery of the First Antidepressant’, Discover Magazine, 27 January 2016, Web.

  Kline preferred the term ‘psychic energiser’: M. Rapley, J. Moncrieff and J. Dillon, eds., De-Medicalizing Misery: Psychiatry, Psychology and the Human Condition (New York: Palgrave Macmillan, 2011), 179.

  Reserpine has been shown in other studies: Ramachandraih et al., ‘Antidepressants: From MAOIs to SSRIs and More’, 180.

  Rats treated with reserpine became more active: Alan A. Boulton, Glen B. Baker, William G. Dewhurst and Merton Sandler, eds., Neurobiology of the Trace Amines: Analytical, Physiological, Pharmacological, Behavioral, and Clinical Aspects (New York: Springer Science & Business Media, 12 March 2013), 221.

  Differing levels of serotonin in depressed people: Elliot Valenstein, Blaming the Brain: The Truth about Drugs and Mental Health (New York: Free Press, 2002), 104.

  Side effects of the tricyclics and the MAOIs: Healy, The Antidepressant Era, 116–17.

  Account of David Foster Wallace’s struggle: D. T. Max, Every Love Story Is a Ghost Story: A Life of David Foster Wallace (New York: Viking, 2012), 297–301. See also D. T. Max, ‘The Unfinished’, The New Yorker, 9 March 2009; David Lipsky, ‘The Lost Years and Last Days of David Foster Wallace’, Rolling Stone, 30 October 2008; and Los Angeles County coroner’s report, 13 September 2008.

  Pharmacist writes to Blackwell: Barry Blackwell, ‘Adumbration: A History Lesson’, International Network for the History of Neuropsychopharmacology (2014): 201.

  Blackwell and a colleague ingesting cheese: Ibid., 208.

  Patients on MAOIs having bad reactions to cheese: Barry Blackwell, Bits and Pieces of a Psychiatrist’s Life (Bloomington, IN: Xlibris, 2012), 156.

  Blackwell claimed that there were forty deaths: Barry Blackwell, ‘Adumbration’.

  A prominent study in Britain: Healy, The Antidepressant Era, 119.

  Debates about the safety of the medication: Robert Whitaker, Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs, and the Astonishing Rise of Mental Illness in America (New York: Crown, 2010), 54.

  4. SSRIs

  The monoamine hypothesis of depression: P. L. Delgado, ‘Depression: The Case for a Monoamine Deficiency’, Journal of Clinical Psychiatry 61, no. 6 (2000): 7–11.

  Theory predominated until Arvid Carlsson further refined it: David Healy, The Antidepressant Era (Cambridge, MA: Harvard University Press, 1997), 165–66.

  Zimelidine made some people ill: National Center for Biotechnology Information, PubChem Compound Database, CID=5365247, https://pubchem
.ncbi.nlm.nih.gov/­compound/­5365247.

  Serotonin is omnipresent in the body: Elizabeth DePoy and Stephen French Gilson, Human Behavior Theory and Applications: A Critical Thinking Approach (New York: Sage Publications, 2012), 107.

  Eli Lilly considering fluoxetine as a possible weight-loss drug: David Healy, Let Them Eat Prozac: The Unhealthy Relationship between the Pharmaceutical Industry and Depression (New York: NYU Press, 2004), 31.

  ‘more human suffering has resulted from depression’: Nathan S. Kline, M.D., ‘The Practical Management of Depression’, JAMA 190, no. 8 (1964): 732–40.

  Serotonin is one of the oldest neurotransmitters: Efrain C. Azmitia, ‘Serotonin and Brain: Evolution, Neuroplasticity, and Homeostasis’, International Review of Neurobiology 77 (2006): 31–56.

  Annual sales reached $350 million: Joseph Glenmullen, Prozac Backlash: Overcoming the Dangers of Prozac, Zoloft, Paxil, and Other Antidepressants with Safe, Effective Alternatives (New York: Simon and Schuster, 2001), 15.

  Americans receiving disability payments: Robert Whitaker, Anatomy of an Epidemic (New York: Crown, 2010), 6–7.

  Incidences of depression have increased a thousandfold: Healy, Let Them Eat Prozac, 31.

  Infant animals secrete the stress hormone cortisol: Xiaoli Feng et al., ‘Maternal Separation Produces Lasting Changes in Cortisol and Behavior in Rhesus Monkeys’, Proceedings of the National Academy of Sciences of the United States of America 108, no. 34 (2011): 14312–17.

  ‘I have forfeited my estate to the king’: Andrew Solomon, The Noonday Demon: An Atlas of Depression (New York: Scribner, 2001), 386.

  ‘The secret of life’s greatest mystery’: Happy [film], dir. Roko Belic (Wadi Rum Productions, 2011).

  Bolo grew despondent after the birth of her daughter: Personal interview with Ann Bolo, 7 July 2014.

  ‘the psychiatrist as psychotherapist is an endangered species’: Daniel J. Carlat, Unhinged: The Trouble with Psychiatry—A Doctor’s Revelations about a Profession in Crisis (New York: Free Press, 2010), 4–5.

  ‘Doing psychotherapy doesn’t pay well enough’: Ibid., 5.

  Even in Eli Lilly’s published research: Irving Kirsch, ‘Antidepressants and the Placebo Effect’, Zeitschrift für Psychologie 222, no. 3 (2014): 128–34.

  Pharmaceutical companies need only come up with two studies: Glenmullen, Prozac Backlash, 287.