1. Imagining a Different Future:
What Do History and Science Tell Us Is
Possible?
Robert Whitaker
March 2013

2. A Dialogue About What is Possible
1. In nature, there is often a natural capacity to
recover from psychiatric episodes, even the
most severe ones.
2. Psychiatric medications lower the long-term
recovery rates from psychiatric episodes.
3. The long-term effectiveness of open dialogue
and other dialogical therapies will be reduced if
such therapies are paired with routine use of
psychiatric medications.

3. Moral Therapy in the Early 1800s
Reported 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. Long-Term Outcomes With
Moral Therapy
In a long-term study of 984 patients discharged from
Worcester asylum from 1833 to 1846, which was
conducted in the 1880s, 58% had remained well
throughout their lives. Another 7% had relapsed but
had subsequently recovered and returned to the
community. Only 35% had become chronically ill or had
died while still mentally ill.

5. “I think it is not too much to assume that
insanity is more curable than any other
disease of equal severity; more likely to be
cured than intermittent fever, pneumonia, or
rheumatism.”
--Samuel Woodward, 1843

6. The Downfall of Moral Therapy and The
Rise of Therapeutic Pessimism
• After the early success of moral therapy asylums, they became
dumping grounds for people with neurological disorders, syphilitics,
and the demented elderly. Discharge rates plummeted.
• Eugenic attitudes, particularly in the United States, emphasized
segregating the mentally ill from society so they couldn’t pass on their
bad genes. Discharge rates plummeted even further.
• When Emil Kraepelin classified psychotic disorders, he identified a
subset of patients who presented with a lack of affect and
deteriorated into early dementia. However, many of these dementia
praecox patients were likely ill with encephalitis lethargica, a viral
infection.

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 1950
were living in the community.
• At the end of six years following hospitalization, 70% of 216 first-episode
patients admitted to Delaware State Hospital from 1948 to 1950 were
living in the community.
• At the end of five years, 76% of first-episode psychotic patients treated
at Boston Psychopathic Hospital were successfully living in the community.
• In studies of schizophrenia patients in England, where the disorder was
more narrowly defined, after five years 33% enjoyed a complete recovery,
and another 20 percent a social recovery, which meant they could support
themselves and live independently.
Source: J Cole, Psychopharmacology (1959): 142, 386-7. R. Warner, Recovery from Schizophrenia (1985):
74.

8. “The majority of mental illnesses, especially the most
severe, are largely self-limiting in nature if the patient is
not subjected to a demeaning experience or loss of rights
and liberties.”
-- Samuel Bockoven, 1975

9. Non-medicated Schizophrenia Outcomes in
the Modern Era
In a study of 1,413 first-episode schizophrenia
patients hospitalized in California in 1856, 88%
of those not prescribed a neuroleptic were
discharged within 18 months. Those treated
with a neuroleptic had a lower discharge rate;
only 74% were discharged within 18 months.

10. WHO Cross-Cultural Studies, 1970s/1980s
• In both studies, which measured outcomes at the end of two
years and five years, the patients in the three developing
countries had a “considerably better course and outcome.”
•The WHO researchers concluded that “being in a developed
country was a strong predictor of not attaining a complete
remission.”
• They also found that “an exceptionally good social outcome
characterized the patients” in developing countries.
Source: Jablensky, A. “Schizophrenia, manifestations, incidence and course in different cultures.” Psychological Medicine 20, monograph
(1992):1-95.

11. WHO Findings, Continued
Medication usage:
16% of patients in the developing countries were regularly
maintained on antipsychotics, versus 61% of the patients in rich
countries.
15-year to 20-year followup:
The “outcome differential” held up for “general clinical state,
symptomatology, disability, and social functioning.” In the
developing 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. 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 hospitalizations
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.

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 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.

14. Spectrum of Outcomes in Harrow’s Study
Recovered Fair Uniformly Poor
On 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. 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 followup
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.

16. Recovery Rates
Medication compliant patients throughout 20 years: 17%
had one period of recovery.
Those off antipsychotics by year two who then remained
off the drugs throughout next 18 years: 87% had two or
more sustained periods of recovery.
Source: Harrow M. “Do all schizophrenia patients need antipsychotic treatment continuously throughout their lifetime? A 20-year
longtitudinal study.” Psychological Medicine, (2012):1-11.

17. Five-Year Outcomes for First-Episode Psychotic Patients in Finnish
Western 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-dialogue
approach.” Psychotherapy Research 16 (2006):214-28.

18. The patients at Tornio “went back to their work,
to their studies, to their families.”
--Jaakko Seikkula

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 never
rehospitalized.
• The average time between recurrent episodes
was three years or more.

20. “Depression is, on the whole, one of the
psychiatric conditions with the best prognosis
for eventual recovery with or without
treatment. Most depressions are self-limited.”
--Jonathan Cole, NIMH, 1964

21. “In the treatment of depression, one always
has an ally the fact that most depressions
terminate in spontaneous remissions. This
means that in many cases regardless of what
one does the patient eventually will begin to
get better.”
--Nathan Kline, Journal of the American Medical
Association, 1964

22. “Assurance can be given to a patient and to his
family that subsequent episodes of illness after a
first depression will not tend toward a more
chronic course.”
--George Winokur, Washington University, 1969
Manic Depressive Illness

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. 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 Symptoms
Outcomes for 100 manic patients first hospitalized in U.S., 1935-1945, and followed for 30 to 40
years. A good rating for each category meant that the patient was married or widowed, owned
home 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. 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. What Is Possible in Absence of Long-term
Use of Psychiatric Medications?
• 60% to 80% of first-episode psychotic patients could
recover and function well, particularly if provided with
good psychosocial care.
• Recovery from an initial depressive or bipolar episode
could be expected, and over the long-term, the disorder
would run an episodic course. Perhaps 50% of patients
would never experience another episode severe enough
to require re-hospitalization.

27. The Problem With Psychiatric Drugs
1. The etiology of most mental disorders remains
unknown, and thus the drugs do not fix known
pathologies.
2. The drugs impede the normal functioning of
neurotransmitter pathways, which leads to significant side
effects.
3. Over the long-term, the drugs induce changes in the
brain the opposite of what is intended, and this increases
the risk that a person will become chronically ill.

28. A Paradigm for Understanding
Psychotropic Drugs
Stephen Hyman, former director of the NIMH, 1996:
• Psychiatric medications “create perturbations in neurotransmitter
functions.”
• In response, the brain goes through a series of compensatory adaptations
in order “to maintain their equilibrium in the face of alterations in the
environment 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. Dopamine function before exposure to antipsychotics
Presynaptic neuron
Dopamine
Dopamine receptors
Postsynaptic neuron

30. Dopamine function after exposure to antipsychotics
Presynaptic neuron
Antipsychotic Dopamine
blocks receptors
Brain increases
receptors to
Postsynaptic neuron
compensate for
drug blockade

31. The Consequences of
“Oppositional Tolerance”
“Continued drug treatment may induce processes that are
the opposite of what the medication originally produced.”
This may “cause a worsening of the illness, continue for a
period of time after discontinuation of the medication, and
may not be reversible.”
-Rif El-Mallakh, University of Louisville, 2011
Source: El-Mallakh, R. “Tardive dysphoria: The role of long-term antidepressant use in inducing chronic depression.
Medical Hypotheses 76 (2011): 769-773.

32. The Evidence Against Antipsychotics

33. 1. In the first one-year study conducted by the NIMH in
the 1960s, those treated with antipsychotics in the
hospital had higher rehospitalization rates than those
treated initially with placebo.
2. Clinicians in the 1960s observed that antipsychotic-
treated patients were returning to the hospital with
great frequency, which they dubbed the “revolving door”
syndrome.

34. 3. A retrospective study by Samuel Bockoven of the
five-year outcomes of psychotic patients found
higher relapse rates for those treated in 1967 with
antipsychotics than for those treated in 1947
without drugs. The 1967 cohort was also much more
socially dependent than the 1947 group at the end of
five years.
4. In three studies funded by the NIMH in the 1970s,
those treated in the experimental arm of the
studies, which involved limited or no use of
antipsychotics, had better outcomes than those
treated conventionally with antipsychotics. The
studies lasted one to three years.

35. The Oppositional Tolerance Question is Raised by NIMH
Researchers, in 1977:
“There is no question that, once patients are placed on
medication, they are less vulnerable to relapse if maintained on
neuroleptics. But what if these patients had never been treated
with drugs to begin with? . . . We raise the possibility that
antipsychotic medication may make some schizophrenic patients
more vulnerable to future relapse than would be the case in the
normal course of the illness.”
Source: Carpenter, W. “The treatment of acute schizophrenia without drugs.” Am J Psychiatry 134 (1977):14-20.

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. Study of Drug-Induced Tardive Psychosis
In 1982, Chouinard and Jones reported that 30% of the
216 schizophrenia outpatients they studied showed
sign of tardive psychosis, which meant their psychosis
was becoming chronic. When this happens, they
wrote, “the illness appears worse” than ever before.
“New schizophrenic symptoms of greater symptoms
will 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-induced
supersensitivity psychosis,” Schiz Res 5 (1991):21-33.

38. Confirming Evidence Since 1985
• In the WHO studies, outcomes were much better in the developing
countries, where only 16% of patients were regularly maintained on
antipsychotics.
• MRI studies show that antipsychotics shrink the brain. Nancy
Andreasen reported that as this shrinkage is associated with
increased negative symptoms, functional impairment and cognitive
decline.
• In Martin Harrow’s study, unmedicated patients had dramatically
better outcomes over the long-term than those who stayed on
antipsychotics.
• The best documented outcomes in the western World can be found
today in Western Lapland, where antipsychotics are used in a
selective, cautious manner.

39. The Iatrogenic Effects of Antipsychotics
(in Harrow’s study)
Worst 8
outcomes
7
6 Schizophrenia On Meds
5 Milder Disorders On Meds
4
Schizophrenia Off Meds
3
2 Milder Disorders Off Meds
Best 1
outcomes
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. “Is very long-term treatment with
antipsychotic medications undesirable?”
--Martin Harrow, 2012

41. Evidence that Antidepressants Worsen the Long-term
Course of Depression and Bipolar Disorder

42. 1. Clinicians in 1960s and 1970s observe that
antidepressants were inducing a “change to a more chronic
course.”
2. A Dutch researcher reports in 1973 that systematic
long-term antidepressant medication “exerts a paradoxical
effect on the recurrent nature of the vital depression. In
other words, this therapeutic approach was associated
with an increase in recurrent rate and a decrease in cycle
duration.”
3. Modern epidemiological studies find that depression
runs a more chronic course than in the pre-drug era.

43. Acknowledgment of Change in
Course of Depression in Modern Era
American Psychiatric Association’s Textbook of
Psychiatry, 1999: It used to be believed that “most
patients would eventually recover from a major
depressive episode. However, more extensive
studies have disproved this assumption.” It was
now known that “depression is a highly
recurrent and pernicious disorder.”

44. Are Antidepressants Depressogenic
Over the Long-Term?
“Antidepressant drugs in depression might be
beneficial in the short term, but worsen the
progression of the disease in the long term, by
increasing the biochemical vulnerability to
depression . . . Use of antidepressant drugs may propel
the illness to a more malignant and treatment
unresponsive course.”
--Giovanni Fava, Psyc hotherapy and
Psychosomatics, 1995

45. The STAR*D Trial Confirms That Medicated
Depression Runs a Chronic Course Today
Findings from the National Institute of Mental Health’s STAR*D study, which was
the “largest study” of depression ever conducted:
• Only 38% of the patients properly enrolled in the trial remitted during one of the
four stages of drug treatment.
• Only 3% of the patients remitted and then stayed well throughout the 12-month
followup. The remaining patients either failed to remit, relapsed during the
followup, or dropped out.
Conclusion: “Most individuals with major depressive disorders have a chronic
course, often with considerable symptomatology and disability even between
episodes.”
Source: Pigott, E. “Efficacy and effectiveness of antidepressants.” Psychother Psychosom 79 (2010):267-79.

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 episodes
Source: E. Weel-Baumgarten, “Treatment of depression related to recurrence,” J Clin Psychiatry &
Therapeutics 25 (2000):61-66.

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 Depression
Source: D. Goldberg. “The effects of detection and treatment of major depression in primary care.” British
Journal of General Practice 48 (1998):1840-44.

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/retiredfired
Source: C Dewa. “Pattern of antidepressant use and duration of depression-related absence from work.”
British Journal of Psychiatry 183 (2003):507-13.

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. 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. Tardive Dysphoria
“A chronic and treatment-resistant depressive state is
proposed to occur in individuals who are exposed to potent
antagonists of serotonin reuptake pumps (i.e. SSRIs) for
prolonged time periods. Due to the delay in the onset of this
chronic depressive state, it is labeled tardive dysphoria. Tardive
dysphoria manifests as a chronic dysphoric state that is initially
transiently relieved by -- but ultimately becomes unresponsive
to -- antidepressant medication. Serotonergic antidepressants
may be of particular importance in the development of tardive
dysphoria.”
-- Rif El-Mallakh, 2011
Source: El-Mallakh, R. “Tardive dysphoria: The role of long-term antidepressant use in inducing chronic depression.
Medical Hypotheses 76 (2011): 769-773.

52. Worsening Long-term Course of Bipolar
Illness in Drug Era
“The general impression of clinicians today is that
the course of recurrences of manic-depressive
illness has substantially changed in the last 20
years. The recurrences of many patients have
become more frequent. One sees more manias
and hypomanias . . . more rapid cyclers and more
chronic depressions.”
--Anthansious Koukoulos, 1983

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% to
85% in pre-drug era)
• Long-term cognitive impairment (which wasn’t seen in pre-drug
era)
• Physical problems related to long-term medication use
• Risk of early death

54. Acknowledgment of Worsening Outcomes for
Bipolar Disorder in Modern Era
Carlos Zarate, head of NIMH Mood Disorders Program, 2000:
“In the era prior to pharmacotherapy, poor outcome in mania was
considered a relatively rare occurrence. However, modern outcome studies
have found that a majority of bipolar patients evidence high rates of
functional impairment.”
Ross Baldessarini, Harvard Medical School, 2007.
“Prognosis for bipolar disorder was once considered relatively favorable, but
contemporary findings suggest that disability and poor outcomes are
prevalent, despite major therapeutic advances.”
Fred Goodwin, 2008
“The illness has been altered. Today we have a lot more rapid cycling than we
described in the first edition [of his book, Manic Depressive Illness], a lot more
mixed states than we described in the first edition, a lot more lithium
resistance, and a lot more lithium treatment failure than we described in the
first edition. The illness is not what Kraepelin described any more.”

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 2009
Source: U.S. Social Security Administration Reports, 1987-2010

56. Disability Due to Psychiatric Disorders
in New Zealand, 1998-2011
Adults
60000
48000
36000
24000
12000
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. Disability Due to Psychiatric Disorders
in Australia, 1990-2011
Adults
250000
200000
150000
100000
50000
1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010
Source: Australian Government, “Characteristics of Disability Support Pension Recipients, June 2011.”

58. Disability Due to Mental and Behavioural
Disorders in Iceland, 1990-2007
Number of New Cases Annually per 100,000 Population
300
225 Women
Men
150
75
0
1990-92 1993-1995 1996-98 1999-2001 2002-04 2005-07
Source: Thoriacius, S. “Increased incidence of disability due to mental and behavioural disorders in Iceland,
1990-2007.” J Ment Health (2010) 19: 176-83.

59. New Cases of Disability in Denmark Due
to Mental Illness
9000
6750
4500
2250
0
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

60. You say you want a revolution?
. . . Then you have to fundamentally rethink
the use of psychiatric drugs.