Neuroleptics and Chronic Mental Illness

The Whitaker Affidavit

 The case against antipsychotic drugs: a 50-year record of doing more harm than good, by Robert Whitaker, Medical Hypotheses, Volume 62, Issue 1 , 2004, Pages 5-13 is the academically written presentation of the information in Mad in America: Bad Science, Bad Medicine and the Enduring Mistreatment of the Mentally Ill.  The research papers analyzed in both of these publications is set forth below.

This article was cited in the British Medical Journal, Vol. 328/414, February, 2004:

Maintaining people with schizophrenia on neuroleptics (the accepted standard care) may actually be doing them a disservice. According to a 50 year review, long term treatment worsens long term outcomes, and up to 40% of people would do better without neuroleptics. Initiation of treatment only after a subsequent episode and helping patients who are stabilised on neuroleptics to gradually withdraw from them would increase recovery rates and reduce the proportion of patients who become chronically ill (Medical Hypotheses 2004;62:5-13).

1. Leon Epstein, "An Approach to the Effect of Ataraxic Drugs on Hospital Release Rates," American Journal of Psychiatry, 119 (1962), 36-47. 

This was the first large scale study of hospital release rates in the 1950s for schizophrenia patients treated with and without neuroleptics, and it concluded that "drug-treated patients tend to have longer periods of hospitalization."  P. 44.

2. Nina Schooler, "One year after discharge: community adjustment of schizophrenic patients," American Journal of Psychiatry, 123 (1967), 986-995.

This NIMH study looked at one-year outcomes for 299 patients who had been treated either with neuroleptics or placebo upon their admission to a hospital, and was the first long-term study conducted by the NIMH.  The researchers found that "patients who received placebo treatment in the drug study were less likely to be rehospitalized than those who received any of the three active phenothiazines (thioridazine (Mellaril), fluphenazine (Prolixin), chlorpromazine (Thorazine)." However, in spite of this finding, which the researchers wrote "was so unexpected," the NIMH investigators stated that they "were unprepared to recommend placebo as treatment of choice." In other words, the NIMH researchers decided they wouldn't develop treatment guidelines based on their own research, which found that placebo patients did better than the drug-treated patients. SEE PAGE 991.

3. Robert Prien, "Relapse in Chronic Schizophrenics Following Abrupt Withdrawal of Tranquillizing Medication," British  Journal of Psychiatry, 115 (1968), 679-86. 

The critical finding of this NIMH study  was that relapse rates rose in direct relation to dosage--the higher the dosage patients were on before the drugs were withdrawn, the greater the relapse rates. At the start of the study, 18 patients were on placebo, and only one got worse over the next six months (6%). Sixty-five patients were on 300 mg. of chlorpromazine at the start of the study, and 54% of these patients worsened after the drug was withdrawn. One hundred thirteen patients were on more than 300 mg. of chlorpromazine at the start of the study, and 66% of these patients got worse after drug withdrawal. SEE TABLE THREE, PAGE 684.

4.  Robert Prien, "Discontinuation of Chemotherapy for Chronic Schizophrenics," Hospital and Community Psychiatry, 22 (1971), 20-23.

 In this NIMH study, the earlier finding that relapse rates rose in correlation with neuroleptic dosage was confirmed. Only 2 of 30 patients who were on placebo at the start of the study relapsed during the next 24 weeks (7%). Twenty-three percent of the 99 patients who were on under 300 mg. of chlorpromazine at the start of the study relapsed following drug withdrawal.  Fifty-two percent of the 91 patients who were on 300 to 500 mg. of chlorpromazine at the start of the study relapsed following drug withdrawal, and sixty-five percent of the 81 patients who were on more than 500 mg. of chlorpromazine at the start of the study relapsed following drug withdrawal. The researchers concluded: "Relapse was found to be significantly related to the dose of the tranquilizing medication the patient was receiving before he was put on placebo--the higher the dose, the greater the probability of relapse."  SEE PAGE 22, AND 23

5. J. Sanbourne Bockoven Comparison of Two Five-Year Follow-Up Studies: 1947 to 1952 and 1967 to 1972, American Journal of Psychiatry, 132 (1975), 796-801. 

In this study, Boston psychiatrists Sanbourne Bockoven and Harry Solomon compared relapse rates in the pre-drug era to those in the drug era, and found that patients in the pre-drug era had done better. Forty-five percent of the patients treated at Boston Psychopathic Hospital in 1947 had not relapsed in the five years following discharge, and 76% were successfully living in the community at the end of that follow-up period. In contrast, only 31% of patients treated in 1967 with drugs at a Boston community health center remained relapse-free for the next five years, and as a group they were much more "socially dependent"--on welfare, etc.--than those in the 1947 cohort.

Other researchers who reviewed relapse rates for New York psychiatric hospitals in the 1940s and early 1950s reported similar findings: roughly 50% of discharged schizophrenia patients had remained continuously well through lengthy follow-up periods, which was markedly superior to outcomes with neuroleptics. See Nathaniel Lehrman, "A state hospital population five years after admission: a yardstick for evaluative comparison of follow-up studies," Psychiatric Quarterly, 34 (1960), 658-681; and H.L. Rachlin, "Follow-up study of 317 patients discharged from Hillside Hospital in 1950," J. Hillside Hospital, 5 (1956), 17-40. 

6. William Carpenter, Jr., "The treatment of acute schizophrenia without drugs: an investigation of some current assumptions," American Journal of Psychiatry, 134 (1977), 14-20. 

In this 1977 NIMH study, 49 schizophrenia patients, placed into an experimental hospital program that provided them with psychosocial support, were randomized into drug and non-drug cohorts. Only 35% of the non-medicated patients relapsed within a year after discharge, compared to 45% of those treated with medication. The medicated patients also suffered more from depression, blunted emotions, and retarded movements.

7. Maurice Rappaport, "Are there schizophrenics for whom drugs may be unnecessary or contraindicated?" International Pharmacopsychiatry, 13 (1978), 100-111.   

In this 1978 study,  Maurice Rappaport and his colleagues at the University of California, San Francisco randomized 80 young male schizophrenics admitted to Agnews State Hospital to drug and non-drug groups. Only 27% of the drug-free patients relapsed in the three years following discharge, compared to 62% of the medicated group. Most notably, only two of 24 patients (8%) who weren’t medicated in the hospital and continued to forgo such treatment after discharge subsequently relapsed. At the end of the study, this group of 24 drug-free patients was functioning at a dramatically higher level than drug-treated patients.

8. Susan Mathews,  “A non-neuroleptic treatment for schizophrenia: analysis of the two-year postdischarge risk of relapse,” Schizophrenia Bulletin, 5 (1979), 322-332;  Loren Mosher, “Community residential treatment for schizophrenia: two year followup,” Hospital and Community Psychiatry, 29 (1978), 715-723;  Mosher, “The treatment of acute psychosis without neuroleptics: six-week psychopathology outcome data from the Soteria project,” International Journal of Social Psychiatry, 41 (1995), 157-173;  Mosher, “The Soteria project: twenty five years of swimming upriver,” Complexity and Change, 9 (2000), 68-73. 

During the 1970s, the head of schizophrenia studies at the NIMH, Loren Mosher, conducted an experiment that compared non-drug treatment to drug treatment, and he reported better outcomes for the non-drug patients.   See, e.g.: Mosher LR and Menn AZ.  Soteria:  An Alternative to Hospitalization for Schizophrenia.  In JH Masserman (Ed), Current Psychiatric Therapies, (Vol. XIV).  New York: Grune and Stratton, Inc., pp. 287‑296, 1974.  Menn AZ and Mosher LR.  The Soteria Project.  An Alternative to Hospitalization for Schizophrenics: Some Clinical Aspects.  In J Jorstad and E Ugelstad (Eds), Schizophrenia 75.  Oslo, Norway: Universitetsforlaget, pp. 347‑372, 1976.  Mosher LR and Menn AZ.  Dinosaur or Astronaut?  One‑Year Follow‑Up Data from the Soteria Project.  In M Greenblatt and RD Budson (Eds), "A Symposium: Follow‑up of Community Care".  American Journal of Psychiatry, 133:8, 919‑920, 1976.  Mosher LR and Menn AZ.  Lowered Barriers in the Community: The Soteria Model.  In LI Stein and MA Test (Eds), Alternatives to Mental Hospital Treatment.  New York: Plenum Press, pp. 75‑113, 1977. 

9. Pavel Muller and Philip Seeman, "Dopaminergic Supersensitivity after Neuroleptics: Time-Course and Specificity, Psychopharmacology 60 (1978), 1-11. Guy Chouinard, “Neuroleptic-induced supersensitivity psychosis,” American Journal of Psychiatry, 135 (1978), 1409-1410; Chouinard, “Neuroleptic-induced supersensitivity psychosis: clinical and pharmacologic characteristics,” American Journal of Psychiatry, 137 (1980), 16-20. 

In the late 1970s, Canadian investigators identified the biological changes induced in the brain by neuroleptics that led to the higher relapse rates. Because the drugs dampen down dopamine activity, the brain tries to compensate by becoming "supersensitive" to dopamine. (The drugs trigger an increase in the density of dopamine receptors.) This perturbation in dopamine function makes the patients more biologically prone to psychosis and to worse relapses upon drug withdrawal. Chouinard concluded: "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 . . . the need for continued neuroleptic treatment may itself be drug-induced."

10. George Gardos and Jonathan Cole, “Maintenance Antipsychotic Therapy: Is the Cure Worse than the Disease.” American Journal of Psychiatry, 133, January (1976), pager 32-36. After discussing the problems with neuroleptics, the authors conclude, "every chronic schizophrenic outpatient maintained on an antipsychotic medication should have the benefit of an adequate trial without drugs."

Jonathan Cole was the head of the NIMH, I believe, in the 1960s. This is just a general discussion paper, but note his conclusion: “An attempt should be made to determine the feasibility of drug discontinuance in every patient.”

The WHO Studies

The evidence of an association between use of neuroleptics and poor long-term outcomes can be seen in studies by the World Health Organization.

11. J. Leff, "The International Pilot Study of Schizophrenia: five-year follow-up findings," Psychological Medicine, 22 (1992), 131-145. 

The first World Health Organization study that compared schizophrenia outcomes in "developed" and "developing" countries was called The International Pilot Study of Schizophrenia. It began in 1968, and involved 1202 patients in nine countries. At both two-year and five-year follow-ups, the patients in the poor countries were doing much better. The researchers concluded that schizophrenia patients in the poor countries "had a considerably better course and outcome than (patients) in developed countries. This remained true whether clinical outcomes, social outcomes, or a combination of the two was considered." Two-thirds of the patients in India and Nigeria were asymptomatic at the end of five years. The WHO investigators, however, were unable to identify a variable that explained this notable difference in outcomes. SEE PAGES 132, 142, 143.

12. Assen Jablensky, "Schizophrenia: manifestations, incidence and course in different cultures, A World Health Organization ten-country study," Psychological Medicine, suppl. 20 (1992), 1-95. [Note: at least the last page is missing]

The second WHO organization study of this type was called the Determinants of Outcome of Severe Mental Disorders. It involved 1379 patients from 10 countries, and was designed as a follow-up study to the International Pilot Study of Schizophrenia. The patients in this study were first-episode patients, and 86% had been ill fewer than 12 months. This study confirmed the findings of the first: two-year outcomes were much better for the patients in the poor countries. In broad terms, 37 percent of the patients in the poor countries (India, Nigeria and Colombia) had a single psychotic episode and then fully recovered; another 26.7% of the patients in the poor countries had two or more psychotic episodes but still were in "complete remission" at the end of the two years. In other words, 63.7% of the patients in the poor countries were doing fairly well at the end of two years. In contrast, only  36.9% of the patients in the U.S. and six other developed countries were doing fairly well at the end of two years. The researchers concluded that "being in a developed country was a strong predictor of not attaining a complete remission." 

Although the WHO researchers didn't identify a variable that would explain this difference in outcomes, they did note that in the developing countries, only 15.9% of patients were continuously maintained on neuroleptics, compared to 61% of patients in the U.S. and other developed countries. This difference in outcomes is also consistent with research  in the U.S. showing that neuroleptics induce brain changes that make people more biologically prone to psychosis. One would expect that drugs that induced such changes would lead to increased chronic illness, and the failure of most patients to attain a complete remission.   See, Table  4.10 page 64 and page 90.  [Table 9.1 from Mad in America reproduced because of quality in original]

Also see, "Culture and Schizophrenia: Criticisms of WHO studies are answered," by A. Jablensky, N. Sartorius, J.E. Cooper, M. Anker, A. Korten and A. Bertelsen, British Journal of Psychiatry (1994) 165, 434-436.

13. Harding’s studies.

Studies by the esteemed Dr. Courtenay Harding show that it is the patients who do not use psychiatric medications regularly on a long-term basis that are the ones that tend to recover from schizophrenia. In Empirical Correction of Seven Myths About Schizophrenia with Implications for Treatment, by Courtenay M. Harding, Ph.D., and James H. Zahniser, ACTA Psyciatrica Scandinava, 1994: 90 (suppl 384): 140-146 found that

These Studies have consistently found that half to two thirds of patients significantly imporved or recovered, including some cohorts of very chronic cases.  The universal criteria for recovery have been defined as no current signs and symptoms of any mental illness, no current medications, working, relating well to family and friends, integrated into the community and behaving in such a way as to not being able to detect having ever hospitalized for any kind of psychiatric problems.

(p. 140)

Myth No. 5 in this paper is that "Patients must be on medication all their lives" with the Reality being: "It may be a small percentage who need medication indefinitely."

Evidence:  There are no data existing which support this myth [the need to by on medication all their lives].  When analyzing the results from the long term studies, it was clear that that a surprising number (at least 25% - 50%), were completely off their medications, suffered no further signs and sympoms of schizophrenia, and were functioning well.

(p. 143)

"Even in the second and third decades of illness, there is still potential for full or partial recovery."  All of the recent long-term follow-up investigators have recorded the same findings. 

  In The Vermont Longitudinal Study of Persons With Severe Mental Illness, II: Long-Term Outcomes of Subjects Who Retrospectively Met DSM-III Criteria for Schizophrenia, by Courtenay M. Harding, Ph.D., George W. Brooks, M.D., Takamaru Ashikaga, Ph.D., John S. Strauss, M.D., and Alan Breier, M.D., American Journal of Psychiatry 144:6, June 1987, 727 at p. 730, that 68% of people diagnosed with schizophrenia had recovered and of these 50% never took psychiatric medications and another 25% only took them periodically when they felt they needed them to control symptoms.  See, also Vermont 1, by Courtenay M. Harding, Ph.D., George W. Brooks, M.D., Takamaru Ashikaga, Ph.D., John S. Strauss, M.D., and Alan Breier, M.D., American Journal of Psychiatry 144:6, June 1987, 718

14. The One Hundred Years of Schizophrenia: A Meta-Analysis of the Outcome Literature by James D. Hegarty, M.D., MP.H., Ross J. Baldessarini, M.D., M.P.H., Maricio Tohen, M.D., Dr. P.H., Christine Waternaux, Ph.D., and Godehard Oepen, M.D. American Journal of Psychiatry: 151 (1994), 1409-1416.   At the same time that the WHO was reporting on poor outcomes in developed countries, Harvard Medical School researchers published a study concluding that outcomes for schizophrenia patients in the U.S. had declined  since the 1970s, to the point they were no better than they had been in 1900. They found that since 1986, only 36.4% of patients in the U.S. have had favorable outcomes  (or were "improved" during a follow-up period that averaged 5.6 years.)  The authors did not blame neuroleptic use for the poor outcomes; on the contrary, they argued that despite the poor outcomes in the modern era, neuroleptics still should be seen as beneficial, but this part of their conclusions is not supported with any research.

15. Clinical Risk Following Abrupt and Gradual Withdrawal by Adele C. Viguera, MD; Ross J. Baldessarini, MD; James D. Hegarty, MD, MPH; Daniel P. van Kammen, MD, PhD; Marucio Tohen, MD, DrPH, Archives of General Psychiatry: Vol 54, Jan 1997, quantified the how much the abrupt discontinuation of long-term neuroleptic use increased relapse rates.  This study concluded that the relapse risk was relatively high within six months; most patients who remained stable for 6 months continued to do so for long periods without medication; and the risk of relapse was lower when the medication withdrawal was gradually discontinued as compared to abrupt discontinuation.  On page 52 Figure three shows that two-thirds of those gradually withdrawn haven’t relapsed at the end of 24 weeks, and that after that, they have a good chance of remaining well indefinitely.

16. The Pilot Project Soteria Berne; Clincial Experiences and Results, Luc Ciompi, Hans Peter Dauwalder, Chistian Maier, Exixabeth Aebi, Karl Trütsch, Zeno Kupper and Charlotte Rutishauser  In this study, Switzerland researchers duplicate Mosher’s results (more or less.) Note on page 148 conclusion that: “patients who received no or very low-dosage medication demonstrated significantly better results.”

17. Two-year outcome in first episode psychosis treated according to an integrated model. Is immediate neuroleptisation always needed?, by Lehtinen V, Aaltonen J, Koffert T, Rakkolainen V, Syvalahti E., European Psychiatry August 2000; 15(5): 312-20.  In this study,  43% of the patients in the experimental group didn’t receive any neuroleptics at all, and that overall, the outcome for the experimental group “was equal or even somewhat better" than those treated conventionally with neuroleptics.  The recommendation out of this study by the authors was that an integrated approach stressing intensive psychosocial measures be used for first-episode psychosis.

19. Integrating intensive psychosocial therapy and low dose medical treatment in a total material of first episode psychotic patients compared to "treatment as usual" a 3 year follow-up.  Cullberg, J, Acta Psychiatry Scandinavia 1991 May;83(5):363-72.   This is study from Sweden in which they copied the Finnish project. Note that only 45 of the patients in the experimental group were on neuroleptics at 3-year followup, and those on it were on 62 milligrams of Thorazine a day (a very low dose) and that this experimental group had much lower hospital use than those treated conventionally over a three-year followup. In other words, they did better, and this of course saves money.

21. (A) Increase in Caudate Nuclei Volumes of First-Episode Schizophrenia Patients Taking Antipsychotic Drugs, Chakos, Lieberman, Bilder, Borenstein, Lerner, Bogerts, Wu, Kinon and Ashtari, American Journal of Psychiatry, October 1994; 151:1430-1436; (B)  Neuroleptics in progressive structural brain abnormalities in psychiatric illness by Madsen, Keiding, Karle, Esbjerg and Hemmingsen, The Lancet, Vol 32, September 5, 1998, 784-785; (C) Subcortical Volumes in Neuroleptic-Naïve and Treated Patients with Schizophrenia by Gur, Maany, Mozley, Swanson, Bilker and Gur, American Journal of Psychiatry December 1998; 155:12 1711-1717; (D)  Increased Volume and Glial Density in Primate Prefrontal Cortex Associated with Crhonic Antipsychotic Drug Exposure by Selemon, Lidow and Goldman-Rakic, Biologic Psychiatry 1999; 46:171-172; and (E) A Follow-up Magnetic Resonance Imaging Study of Schizophrenia: Relationship of Neuroanatomical Changes to Clinical and Beurobehavioral Measures, by Gur, Cowell, Turetsky, Gallacher Cannon, Bilker and Gur, Archives of General Pscychiatry: Feb 1998 Vo. 55:145-152.

These last five are studies showing that the drugs shrink frontal lobes, and cause an enlargement in the basal ganglia. Please see the Gur MRI study in which she notes that this enlargement of the basal ganglia were associated with greater severity of symptoms. In other words, we have here an MRI study that charts brain changes that lead to greater severity of symptoms. 

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