Whitaker

Imagining a Different Future:

What Do History and Science Tell Us Is Possible?

Robert WhitakerMarch 2013

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.

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.”

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.

“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

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.

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.

“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

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.

Non-medicated Schizophrenia Outcomes in the Modern Era

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.

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.

WHO Findings, Continued

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.

Recovery Rates for Schizophrenia Patients Off Meds

0%

10%

20%

30%

40%

50%

2 years 4.5 years 7.5 years 10 years 15 years


Off Antipsychotics

On Antipsychotics

Spectrum of Outcomes in Harrow’s Study

On Antipsychotics

Off Antipsychotics

0% 25% 50% 75% 100%

16%

49%

46%

46%

40%

5%

Recovered Fair Uniformly Poor


Psychotic Symptoms in Schizophrenia Patients Over the Long Term

0%

25%

50%

75%

100%

10-year followup 15-year followup

64%

79%

28%23%


Off antipsychotics On Antipsychotics

Recovery RatesMedication 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.

Five-Year Outcomes for First-Episode Psychotic Patients in Finnish Western Lapland Treated with Open-Dialogue Therapy

Source: Seikkula, J. “Five-year experience of !rst-episode nona"ective psychosis in open-dialogue approach.” Psychotherapy Research 16 (2006):214-28.

Patients (N=75) Schizophrenia (N=30) Other psychotic disorders (N=45)Antipsychotic use Never exposed to antipsychotics 67% Occasional use during !ve years 33% Ongoing use at end of !ve years 20%Psychotic symptoms Never relapsed during !ve years 67% Asymptomatic at !ve-year followup 79%Functional outcomes at !ve years Working or in school 73% Unemployed 7% On disability 20%

The patients at Tornio “went back to their work, to their studies, to their families.”

--Jaakko Seikkula

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.

“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

“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

“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

Bipolar Outcomes in the Pre-Drug Era

0%

10%

20%

30%

40%

50%

8%

26%

17%

50%

Recovered Patients Chronically ill

No subsequent episodes

One episode Two or more Chronically ill

Swedish Study, 1945

103 manic patients

Source: Lundquist, G. “Prognosis and course in manic-depressive psychoses.” Acta Psychiat Neurol, Supp. 35 (1945):7-93.

Functional Bipolar Outcomes in the Pre-Drug Era

0%

10%

20%

30%

40%

50%

60%

70%

80%

Good Fair Poor

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.

Marital Status Residential Status Employment Symptoms

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

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.

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.

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.

Dopamine function before exposure to antipsychotics

Presynaptic neuron

Dopamine

Dopamine receptors

Postsynaptic neuron

Dopamine function after exposure to antipsychotics

Brain increases receptors to compensate for drug blockade

Dopamine

Presynaptic neuron

Antipsychoticblocks receptors

Postsynaptic neuron

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.

The Evidence Against Antipsychotics

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.

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.

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.

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.

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.

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.

The Iatrogenic Effects of Antipsychotics (in Harrow’s study)

0

1

2

3

4

5

6

7

8

2 years 4.5 years 7.5 years 10 years 15 years

Schizophrenia On Meds

Schizophrenia Off Meds

Milder Disorders On Meds

Milder Disorders Off Meds


Worstoutcomes

Bestoutcomes

“Is very long-term treatment with antipsychotic medications undesirable?”

--Martin Harrow, 2012

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

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.

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.”

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, Psychotherapy and Psychosomatics, 1995

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.

Depression in the Netherlands(Over the course of ten years)

0%

10%

20%

30%

40%

50%

60%

70%

80%

Only one episode Two episodes More than two episodes

13%11%

76%

31%

19%

50%

First episode treated with drugFirst episode treated without drug

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

One-Year Outcomes in WHO Screening Study for Depression

0%

10%

20%

30%

40%

50%

60%

Continuing Depression

25.2%28.3%

44.9%

51.6%

Diagnosed/Antidepressants Diagnosed/SedativesUndiagnosed/no drug Diagnosed/No drug

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

Canadian Study of Risk of Long-term Disability for Depressed Workers

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

Returned to work Long-term disability Quit/retiredfired

7%9%

84%

8%

19%

73%

Medicated Unmedicated

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

Antidepressants Lessen the Long-Term Benefits of Exercise

Treatment during first 16

weeks

Percentage of patients in

remission at end of 16 weeks

Percentage of patents who relapsed in

following six months

Percentage of all patients

depressed at end of ten 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.

NIMH’s Six-Year Study of Untreated Depression

0%

10%

20%

30%

40%

Cessation of role function Became Incapacitated1.3%

9.8% 8.6%

32.3%

Treated Untreated

Source: W. Coryell. “Characteristics and significance of untreated major depressive disorder.” American Journal of Psychiatry 152 (1995):1124-29.

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.

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

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

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.”

Acknowledgment of Worsening Outcomes for Bipolar Disorder in Modern Era

0

1

2

3

4

5

1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 2007 2009

U.S. Disability in the Prozac Era

Millions of adults, 18 to 66 years old

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

Disability Due to Psychiatric Disorders in New Zealand, 1998-2011

0

12000

24000

36000

48000

60000

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

Adults

Source: New Zealand Ministry of Social Development, “National Benefits Factsheets,” 2004-2011.

Disability Due to Psychiatric Disorders in Australia, 1990-2011

50000

100000

150000

200000

250000

1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010

Adults

Source: Australian Government, “Characteristics of Disability Support Pension Recipients, June 2011.”

Disability Due to Mental and Behavioural Disorders in Iceland, 1990-2007

0

75

150

225

300

1990-92 1993-1995 1996-98 1999-2001 2002-04 2005-07

WomenMen

Number of New Cases Annually per 100,000 Population

Source: Thoriacius, S. “Increased incidence of disability due to mental and behavioural disorders in Iceland, 1990-2007.” J Ment Health (2010) 19: 176-83.

New Cases of Disability in Denmark Due to Mental Illness

0

2250

4500

6750

9000

1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

You say you want a revolution?

. . . Then you have to fundamentally rethink the use of psychiatric drugs.

Whitaker

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