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  1. 1. Imagining a Different Future: What Do History and Science Tell Us Is Possible?Robert WhitakerMarch 2013
  2. 2. A Dialogue About What is Possible1. In nature, there is often a natural capacity torecover from psychiatric episodes, even themost severe ones.2. Psychiatric medications lower the long-termrecovery rates from psychiatric episodes.3. The long-term effectiveness of open dialogueand other dialogical therapies will be reduced ifsuch therapies are paired with routine use ofpsychiatric medications.
  3. 3. Moral Therapy in the Early 1800sReported Recovery Rates for First Episode Patients • At the York Retreat, 70 percent of the patients who had been ill for less than 12 months recovered, which was defined as never relapsing into illness. (1813). • At McLean Hospital in Boston, 59% of the 732 patients admitted between 1818 and 1830 were discharged as “recovered,” “much improved,” or “improved.” • At Bloomingdale Asylum in New York, 60% of the 1,841 patients between 1821 and 1844 were discharged as either “cured” or “improved.” • At Friends Asylum in Philadelphia, approximately 50% of all first admissions left “cured.’” • During Worcester State Lunatic Asylum’s first seven years, more than 80% who had been ill for less than a year “recovered.”
  4. 4. Long-Term Outcomes With Moral TherapyIn a long-term study of 984 patients discharged fromWorcester asylum from 1833 to 1846, which wasconducted in the 1880s, 58% had remained wellthroughout their lives. Another 7% had relapsed buthad subsequently recovered and returned to thecommunity. Only 35% had become chronically ill or haddied while still mentally ill.
  5. 5. “I think it is not too much to assume thatinsanity is more curable than any otherdisease of equal severity; more likely to becured than intermittent fever, pneumonia, orrheumatism.” --Samuel Woodward, 1843
  6. 6. The Downfall of Moral Therapy and The Rise of Therapeutic Pessimism• After the early success of moral therapy asylums, they becamedumping grounds for people with neurological disorders, syphilitics,and the demented elderly. Discharge rates plummeted.• Eugenic attitudes, particularly in the United States, emphasizedsegregating the mentally ill from society so they couldn’t pass on theirbad genes. Discharge rates plummeted even further.• When Emil Kraepelin classified psychotic disorders, he identified asubset of patients who presented with a lack of affect anddeteriorated into early dementia. However, many of these dementiapraecox patients were likely ill with encephalitis lethargica, a viralinfection.
  7. 7. Schizophrenia Outcomes, 1945-1955• At end of three years following hospitalization, 73 percent of first-episode patients admitted to Warren State Hospital from 1946 to 1950were living in the community.• At the end of six years following hospitalization, 70% of 216 first-episodepatients admitted to Delaware State Hospital from 1948 to 1950 wereliving in the community.• At the end of five years, 76% of first-episode psychotic patients treatedat Boston Psychopathic Hospital were successfully living in the community.• In studies of schizophrenia patients in England, where the disorder wasmore narrowly defined, after five years 33% enjoyed a complete recovery,and another 20 percent a social recovery, which meant they could supportthemselves and live independently.Source: J Cole, Psychopharmacology (1959): 142, 386-7. R. Warner, Recovery from Schizophrenia (1985):74.
  8. 8. “The majority of mental illnesses, especially the mostsevere, are largely self-limiting in nature if the patient isnot subjected to a demeaning experience or loss of rightsand liberties.” -- Samuel Bockoven, 1975
  9. 9. Non-medicated Schizophrenia Outcomes in the Modern EraIn a study of 1,413 first-episode schizophreniapatients hospitalized in California in 1856, 88%of those not prescribed a neuroleptic weredischarged within 18 months. Those treatedwith a neuroleptic had a lower discharge rate;only 74% were discharged within 18 months.
  10. 10. WHO Cross-Cultural Studies, 1970s/1980s• In both studies, which measured outcomes at the end of twoyears and five years, the patients in the three developingcountries had a “considerably better course and outcome.”•The WHO researchers concluded that “being in a developedcountry was a strong predictor of not attaining a completeremission.”• They also found that “an exceptionally good social outcomecharacterized the patients” in developing countries.Source: Jablensky, A. “Schizophrenia, manifestations, incidence and course in different cultures.” Psychological Medicine 20, monograph(1992):1-95.
  11. 11. WHO Findings, ContinuedMedication usage:16% of patients in the developing countries were regularlymaintained on antipsychotics, versus 61% of the patients in richcountries.15-year to 20-year followup:The “outcome differential” held up for “general clinical state,symptomatology, disability, and social functioning.” In thedeveloping countries, 53% of schizophrenia patients were“never psychotic” anymore, and 73% were employed. Source: Jablensky, A. “Schizophrenia, manifestations, incidence and course in different cultures.” Psychological Medicine 20, monograph (1992):1-95. See table on page 64 for medication usage. For followup, see Hopper, K. “Revisiting the developed versus developing country distinction in course and outcome in schizophrenia.” Schizophrenia Bulletin 26 (2000):835-46.
  12. 12. Martin Harrow’s Long-Term Study of Psychotic Patients Patient Enrollment • 64 schizophrenia patients • 81 patients with other psychotic disorders 37 psychotic bipolar patients 28 unipolar psychotic patients 16 other milder psychotic disorders • Median age of 22.9 years at index hospitalization • Previous hospitalization 46% first hospitalization 21% one previous hospitalization 33% two or more previous hospitalizationsSource: Harrow M. “Factors involved in outcome and recovery in schizophrenia patients not on antipsychotic medications.” Journal ofNervous and Mental Disease 195 (2007):406-14.
  13. 13. Recovery Rates for Schizophrenia Patients Off Meds 50% 40% Off Antipsychotics 30% 20% 10% On Antipsychotics 0% 2 years 4.5 years 7.5 years 10 years 15 yearsSource: Harrow M. “Factors involved in outcome and recovery in schizophrenia patients not on antipsychotic medications.” Journal ofNervous and Mental Disease 195 (2007):406-14.
  14. 14. Spectrum of Outcomes in Harrow’s Study Recovered Fair Uniformly PoorOn Antipsychotics 5% 46% 49%Off Antipsychotics 40% 46% 16% 0% 25% 50% 75% 100% Source: Harrow M. “Factors involved in outcome and recovery in schizophrenia patients not on antipsychotic medications.” Journal of Nervous and Mental Disease 195 (2007):406-14.
  15. 15. Psychotic Symptoms in Schizophrenia Patients Over the Long Term Off antipsychotics On Antipsychotics 100% 75% 79% 64% 50% 25% 28% 23% 0% 10-year followup 15-year followupSource: Harrow M. “Factors involved in outcome and recovery in schizophrenia patients not on antipsychotic medications.” Journal ofNervous and Mental Disease 195 (2007):406-14.
  16. 16. Recovery RatesMedication compliant patients throughout 20 years: 17%had one period of recovery.Those off antipsychotics by year two who then remainedoff the drugs throughout next 18 years: 87% had two ormore sustained periods of recovery.Source: Harrow M. “Do all schizophrenia patients need antipsychotic treatment continuously throughout their lifetime? A 20-yearlongtitudinal study.” Psychological Medicine, (2012):1-11.
  17. 17. Five-Year Outcomes for First-Episode Psychotic Patients in FinnishWestern Lapland Treated with Open-Dialogue Therapy Patients (N=75) Schizophrenia (N=30) Other psychotic disorders (N=45) Antipsychotic use Never exposed to antipsychotics 67% Occasional use during five years 33% Ongoing use at end of five years 20% Psychotic symptoms Never relapsed during five years 67% Asymptomatic at five-year followup 79% Functional outcomes at five years Working or in school 73% Unemployed 7% On disability 20%Source: Seikkula, J. “Five-year experience of first-episode nonaffective psychosis in open-dialogueapproach.” Psychotherapy Research 16 (2006):214-28.
  18. 18. The patients at Tornio “went back to their work,to their studies, to their families.” --Jaakko Seikkula
  19. 19. Outcomes for Hospitalized Depression in Pre-Drug Era• Recovery from index episode was expected.• In four of five long-term studies, more than 50%hospitalized for an index episode were neverrehospitalized.• The average time between recurrent episodeswas three years or more.
  20. 20. “Depression is, on the whole, one of thepsychiatric conditions with the best prognosisfor eventual recovery with or withouttreatment. Most depressions are self-limited.” --Jonathan Cole, NIMH, 1964
  21. 21. “In the treatment of depression, one alwayshas an ally the fact that most depressionsterminate in spontaneous remissions. Thismeans that in many cases regardless of whatone does the patient eventually will begin toget better.”--Nathan Kline, Journal of the American MedicalAssociation, 1964
  22. 22. “Assurance can be given to a patient and to hisfamily that subsequent episodes of illness after afirst depression will not tend toward a morechronic course.” --George Winokur, Washington University, 1969 Manic Depressive Illness
  23. 23. Bipolar Outcomes in the Pre-Drug Era Swedish Study, 1945 103 manic patients Recovered Patients Chronically ill 50% 50% 40% 30% 26% 20% 17% 10% 8% 0% No subsequent One episode Two or more Chronically ill episodes Source: Lundquist, G. “Prognosis and course in manic-depressive psychoses.” Acta Psychiat Neurol, Supp. 35 (1945):7-93.
  24. 24. Functional Bipolar Outcomes in the Pre-Drug Era Good Fair Poor 80% 70% 60% 50% 40% 30% 20% 10% 0% Marital Status Residential Status Employment SymptomsOutcomes for 100 manic patients first hospitalized in U.S., 1935-1945, and followed for 30 to 40years. A good rating for each category meant that the patient was married or widowed, ownedhome or lived with family members, was employed or had retired, and had no psychiatric symptoms.Seventy percent of the patients had good functional outcomes, and half were asymptomatic. Source:Tsuang, M. “Long-term outcome of major psychoses.” Arch Gen Psych 36 (1979):1295-1301.
  25. 25. Summary of Bipolar Outcomes in Pre-Drug Era There is “no basis to consider that manic depressive psychosis permanently affected those who suffered from it. In this way, it is of course different from schizophrenia.” While some people suffered multiple episodes, each episode was usually only a “few months in duration” and “in a significant number of patients, only one episode of illness occurs.” Once patients recovered, they usually had “no difficulty resuming their usual occupations.” --George Winokur, Washington University, 1969 Manic Depressive Illness
  26. 26. What Is Possible in Absence of Long-term Use of Psychiatric Medications?• 60% to 80% of first-episode psychotic patients couldrecover and function well, particularly if provided withgood psychosocial care.• Recovery from an initial depressive or bipolar episodecould be expected, and over the long-term, the disorderwould run an episodic course. Perhaps 50% of patientswould never experience another episode severe enoughto require re-hospitalization.
  27. 27. The Problem With Psychiatric Drugs1. The etiology of most mental disorders remainsunknown, and thus the drugs do not fix knownpathologies.2. The drugs impede the normal functioning ofneurotransmitter pathways, which leads to significant sideeffects.3. Over the long-term, the drugs induce changes in thebrain the opposite of what is intended, and this increasesthe risk that a person will become chronically ill.
  28. 28. A Paradigm for Understanding Psychotropic DrugsStephen Hyman, former director of the NIMH, 1996:• Psychiatric medications “create perturbations in neurotransmitterfunctions.”• In response, the brain goes through a series of compensatory adaptationsin order “to maintain their equilibrium in the face of alterations in theenvironment or changes in the internal milieu.”• The “chronic administration” of the drugs then cause “substantial and long-lasting alterations in neural function.”• After a few weeks, the person’s brain is now functioning in a manner that is“qualitatively as well as quantitatively different from the normal state.” Source: Hyman, S. “Initiation and adaptation: A paradigm for understanding psychotropic drug action.” Am J Psychiatry 153 (1996):151-61.
  29. 29. Dopamine function before exposure to antipsychotics Presynaptic neuron Dopamine Dopamine receptors Postsynaptic neuron
  30. 30. Dopamine function after exposure to antipsychotics Presynaptic neuron Antipsychotic Dopamineblocks receptors Brain increases receptors to Postsynaptic neuron compensate for drug blockade
  31. 31. The Consequences of “Oppositional Tolerance”“Continued drug treatment may induce processes that arethe opposite of what the medication originally produced.”This may  “cause a worsening of the illness, continue for aperiod of time after discontinuation of the medication, andmay not be reversible.” -Rif El-Mallakh, University of Louisville, 2011Source: El-Mallakh, R. “Tardive dysphoria: The role of long-term antidepressant use in inducing chronic depression.Medical Hypotheses 76 (2011): 769-773.
  32. 32. The Evidence Against Antipsychotics
  33. 33. 1. In the first one-year study conducted by the NIMH inthe 1960s, those treated with antipsychotics in thehospital had higher rehospitalization rates than thosetreated initially with placebo.2. Clinicians in the 1960s observed that antipsychotic-treated patients were returning to the hospital withgreat frequency, which they dubbed the “revolving door”syndrome.
  34. 34. 3. A retrospective study by Samuel Bockoven of thefive-year outcomes of psychotic patients foundhigher relapse rates for those treated in 1967 withantipsychotics than for those treated in 1947without drugs. The 1967 cohort was also much moresocially dependent than the 1947 group at the end offive years.4. In three studies funded by the NIMH in the 1970s,those treated in the experimental arm of thestudies, which involved limited or no use ofantipsychotics, had better outcomes than thosetreated conventionally with antipsychotics. Thestudies lasted one to three years.
  35. 35. The Oppositional Tolerance Question is Raised by NIMHResearchers, in 1977:“There is no question that, once patients are placed onmedication, they are less vulnerable to relapse if maintained onneuroleptics. But what if these patients had never been treatedwith drugs to begin with? . . . We raise the possibility thatantipsychotic medication may make some schizophrenic patientsmore vulnerable to future relapse than would be the case in thenormal course of the illness.” Source: Carpenter, W. “The treatment of acute schizophrenia without drugs.” Am J Psychiatry 134 (1977):14-20.
  36. 36. The Dopamine Supersensitivity Theory The Mechanism: Antipsychotics block D2 receptors in the brain. As a compensatory response, the brain then increases the density of its D2 receptors by 30% or more. The Consequence: Two Canadian investigators at McGill University, Guy Chouinard and Barry Jones, reasoned that this made the patient more biologically prone to psychosis, and to worse relapses upon drug withdrawal. “Neuroleptics can produce a dopamine supersensitivity that leads to both dyskinetic and psychotic symptoms . . . An implication is that the tendency toward psychotic relapse in a patient who has developed such a supersensitivity is determined by more than just the normal course of the illness.”Source: Chouinard, G. “Neuroleptic-induced supersensitivity psychosis,” Am J Psychiatry 135 (1978): 1409-10; and“Neuroleptic-induced supersensitivity psychosis,” Am J Psychiatry 137 (1980): 16-20.
  37. 37. Study of Drug-Induced Tardive PsychosisIn 1982, Chouinard and Jones reported that 30% of the216 schizophrenia outpatients they studied showedsign of tardive psychosis, which meant their psychosiswas becoming chronic. When this happens, theywrote, “the illness appears worse” than ever before.“New schizophrenic symptoms of greater symptomswill appear.Source: Chouinard, C. “Neuroleptic-induced supersensitivity psychos, the ‘Hump Course,’ and tardive dyskinesia.”J Clin Psychopharmacology 2 (1982):143-44. Also, Chouinard, C. “Severe cases of neuroleptic-inducedsupersensitivity psychosis,” Schiz Res 5 (1991):21-33.
  38. 38. Confirming Evidence Since 1985• In the WHO studies, outcomes were much better in the developingcountries, where only 16% of patients were regularly maintained onantipsychotics.• MRI studies show that antipsychotics shrink the brain. NancyAndreasen reported that as this shrinkage is associated withincreased negative symptoms, functional impairment and cognitivedecline.• In Martin Harrow’s study, unmedicated patients had dramaticallybetter outcomes over the long-term than those who stayed onantipsychotics.• The best documented outcomes in the western World can be foundtoday in Western Lapland, where antipsychotics are used in aselective, cautious manner.
  39. 39. The Iatrogenic Effects of Antipsychotics (in Harrow’s study) Worst 8outcomes 7 6 Schizophrenia On Meds 5 Milder Disorders On Meds 4 Schizophrenia Off Meds 3 2 Milder Disorders Off Meds Best 1outcomes 0 2 years 4.5 years 7.5 years 10 years 15 years Source: Harrow M. “Factors involved in outcome and recovery in schizophrenia patients not on antipsychotic medications.” Journal of Nervous and Mental Disease 195 (2007):406-14.
  40. 40. “Is very long-term treatment withantipsychotic medications undesirable?” --Martin Harrow, 2012
  41. 41. Evidence that Antidepressants Worsen the Long-term Course of Depression and Bipolar Disorder
  42. 42. 1. Clinicians in 1960s and 1970s observe thatantidepressants were inducing a “change to a more chroniccourse.”2. A Dutch researcher reports in 1973 that systematiclong-term antidepressant medication “exerts a paradoxicaleffect on the recurrent nature of the vital depression. Inother words, this therapeutic approach was associatedwith an increase in recurrent rate and a decrease in cycleduration.”3. Modern epidemiological studies find that depressionruns a more chronic course than in the pre-drug era.
  43. 43. Acknowledgment of Change inCourse of Depression in Modern EraAmerican Psychiatric Association’s Textbook ofPsychiatry, 1999: It used to be believed that “mostpatients would eventually recover from a majordepressive episode. However, more extensivestudies have disproved this assumption.” It wasnow known that “depression is a highlyrecurrent and pernicious disorder.”
  44. 44. Are Antidepressants Depressogenic Over the Long-Term?“Antidepressant drugs in depression might bebeneficial in the short term, but worsen theprogression of the disease in the long term, byincreasing the biochemical vulnerability todepression . . . Use of antidepressant drugs may propelthe illness to a more malignant and treatmentunresponsive course.” --Giovanni Fava, Psyc hotherapy and Psychosomatics, 1995
  45. 45. The STAR*D Trial Confirms That Medicated Depression Runs a Chronic Course TodayFindings from the National Institute of Mental Health’s STAR*D study, which wasthe “largest study” of depression ever conducted:• Only 38% of the patients properly enrolled in the trial remitted during one of thefour stages of drug treatment.• Only 3% of the patients remitted and then stayed well throughout the 12-monthfollowup. The remaining patients either failed to remit, relapsed during thefollowup, or dropped out.Conclusion: “Most individuals with major depressive disorders have a chroniccourse, often with considerable symptomatology and disability even betweenepisodes.”Source: Pigott, E. “Efficacy and effectiveness of antidepressants.” Psychother Psychosom 79 (2010):267-79.
  46. 46. Depression in the Netherlands (Over the course of ten years) First episode treated with drug First episode treated without drug 80% 70% 76% 60% 50% 50% 40% 30% 31% 20% 19% 10% 11% 13% 0% Only one episode Two episodes More than two episodesSource: E. Weel-Baumgarten, “Treatment of depression related to recurrence,” J Clin Psychiatry &Therapeutics 25 (2000):61-66.
  47. 47. One-Year Outcomes in WHO Screening Study for Depression Diagnosed/Antidepressants Diagnosed/Sedatives Undiagnosed/no drug Diagnosed/No drug 60% 50% 51.6% 44.9% 40% 30% 28.3% 25.2% 20% 10% 0% Continuing DepressionSource: D. Goldberg. “The effects of detection and treatment of major depression in primary care.” BritishJournal of General Practice 48 (1998):1840-44.
  48. 48. Canadian Study of Risk of Long-term Disability for Depressed Workers Medicated Unmedicated 90% 80% 84% 70% 73% 60% 50% 40% 30% 20% 19% 10% 9% 8% 7% 0% Returned to work Long-term disability Quit/retiredfiredSource: C Dewa. “Pattern of antidepressant use and duration of depression-related absence from work.”British Journal of Psychiatry 183 (2003):507-13.
  49. 49. Antidepressants Lessen the Long-Term Benefits of Exercise Percentage of Percentage of Percentage of all Treatment patents who patients in patients during first 16 relapsed in remission at end depressed at end weeks following six of 16 weeks of ten months months Zoloft alone 69% 38% 52% Zoloft plus exercise 66% 31% 55% Exercise alone 60% 8% 30% Source: Babyak, M. “Exercise treatment for major depression.” Psychosomatic Medicine 62 (2000):633-8.
  50. 50. NIMH’s Six-Year Study of Untreated Depression Treated Untreated 40% 30% 32.3% 20% 10% 9.8% 8.6% 0% 1.3% Cessation of role function Became Incapacitated Source: W. Coryell. “Characteristics and significance of untreated major depressive disorder.” American Journal of Psychiatry 152 (1995):1124-29.
  51. 51. Tardive Dysphoria“A chronic and treatment-resistant depressive state isproposed to occur in individuals who are exposed to potentantagonists of serotonin reuptake pumps (i.e. SSRIs) forprolonged time periods. Due to the delay in the onset of thischronic depressive state, it is labeled tardive dysphoria. Tardivedysphoria manifests as a chronic dysphoric state that is initiallytransiently relieved by -- but ultimately becomes unresponsiveto  -- antidepressant medication. Serotonergic antidepressantsmay be of particular importance in the development of tardivedysphoria.” -- Rif El-Mallakh, 2011Source: El-Mallakh, R. “Tardive dysphoria: The role of long-term antidepressant use in inducing chronic depression.Medical Hypotheses 76 (2011): 769-773.
  52. 52. Worsening Long-term Course of Bipolar Illness in Drug Era“The general impression of clinicians today is thatthe course of recurrences of manic-depressiveillness has substantially changed in the last 20years. The recurrences of many patients havebecome more frequent. One sees more maniasand hypomanias . . . more rapid cyclers and morechronic depressions.” --Anthansious Koukoulos, 1983
  53. 53. The Modern Course of Bipolar Illness• More recurrent episodes and more rapid cycling• Low-level depression between episodes• Only 33% enjoy good functional outcomes (compared to 70% to85% in pre-drug era)• Long-term cognitive impairment (which wasn’t seen in pre-drugera)• Physical problems related to long-term medication use• Risk of early death
  54. 54. Acknowledgment of Worsening Outcomes for Bipolar Disorder in Modern EraCarlos Zarate, head of NIMH Mood Disorders Program, 2000:“In the era prior to pharmacotherapy, poor outcome in mania wasconsidered a relatively rare occurrence. However, modern outcome studieshave found that a majority of bipolar patients evidence high rates offunctional impairment.”Ross Baldessarini, Harvard Medical School, 2007.“Prognosis for bipolar disorder was once considered relatively favorable, butcontemporary findings suggest that disability and poor outcomes areprevalent, despite major therapeutic advances.”Fred Goodwin, 2008“The illness has been altered. Today we have a lot more rapid cycling than wedescribed in the first edition [of his book, Manic Depressive Illness], a lot moremixed states than we described in the first edition, a lot more lithiumresistance, and a lot more lithium treatment failure than we described in thefirst edition. The illness is not what Kraepelin described any more.”
  55. 55. U.S. Disability in the Prozac Era Millions of adults, 18 to 66 years old 5 4 3 2 1 0 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 2007 2009Source: U.S. Social Security Administration Reports, 1987-2010
  56. 56. Disability Due to Psychiatric Disorders in New Zealand, 1998-2011Adults6000048000360002400012000 0 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 Source: New Zealand Ministry of Social Development, “National Benefits Factsheets,” 2004-2011.
  57. 57. Disability Due to Psychiatric Disorders in Australia, 1990-2011Adults250000200000150000100000 50000 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010Source: Australian Government, “Characteristics of Disability Support Pension Recipients, June 2011.”
  58. 58. Disability Due to Mental and Behavioural Disorders in Iceland, 1990-2007 Number of New Cases Annually per 100,000 Population300225 Women Men15075 0 1990-92 1993-1995 1996-98 1999-2001 2002-04 2005-07Source: Thoriacius, S. “Increased incidence of disability due to mental and behavioural disorders in Iceland,1990-2007.” J Ment Health (2010) 19: 176-83.
  59. 59. New Cases of Disability in Denmark Due to Mental Illness9000675045002250 0 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
  60. 60. You say you want a revolution? . . . Then you have to fundamentally rethinkthe use of psychiatric drugs.