Neuroleptics and Chronic Mental Illness

Copyright by PsychRights.org, Law Project for Psychiatric Rights. Posted by permission. Originally posted athttps://psychrights.org/Research/Digest/Chronicity/NeurolepticResearch.htm

 

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 onHospital Release Rates,” American Journal of Psychiatry, 119(1962), 36-47. 

This was the first large scale study of hospital release rates in the 1950sfor schizophrenia patients treated with and without neuroleptics, and itconcluded that “drug-treated patients tend to have longer periods ofhospitalization.”  P. 44.

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

This NIMH study looked at one-year outcomes for 299 patients who had beentreated either with neuroleptics or placebo upon their admission to a hospital,and was the first long-term study conducted by the NIMH.  The researchersfound that “patients who received placebo treatment in the drug study wereless likely to be rehospitalized than those who received any of the threeactive phenothiazines (thioridazine (Mellaril), fluphenazine (Prolixin),chlorpromazine (Thorazine).” However, in spite of this finding, which theresearchers wrote “was so unexpected,” the NIMH investigators statedthat they “were unprepared to recommend placebo as treatment ofchoice.” In other words, the NIMH researchers decided they wouldn’tdevelop treatment guidelines based on their own research, which found thatplacebo patients did better than the drug-treated patients. SEE PAGE 991.

3. Robert Prien, “Relapse in Chronic Schizophrenics Following AbruptWithdrawal of Tranquillizing Medication,” British  Journal ofPsychiatry, 115 (1968), 679-86. 

The critical finding of this NIMH study  was that relapse rates rose indirect relation to dosage–the higher the dosage patients were on before thedrugs 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 thestudy, and 54% of these patients worsened after the drug was withdrawn. Onehundred thirteen patients were on more than 300 mg. of chlorpromazine at thestart 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 ChronicSchizophrenics,” Hospital and Community Psychiatry, 22 (1971),20-23.

 In this NIMH study, the earlier finding that relapse rates rose incorrelation with neuroleptic dosage was confirmed. Only 2 of 30 patients whowere 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. ofchlorpromazine at the start of the study relapsed following drugwithdrawal.  Fifty-two percent of the 91 patients who were on 300 to 500mg. of chlorpromazine at the start of the study relapsed following drugwithdrawal, and sixty-five percent of the 81 patients who were on more than 500mg. of chlorpromazine at the start of the study relapsed following drugwithdrawal. The researchers concluded: “Relapse was found to besignificantly related to the dose of the tranquilizing medication the patientwas receiving before he was put on placebo–the higher the dose, the greaterthe probability of relapse.”  SEE PAGE 22, AND 23

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

In this study, Bostonpsychiatrists Sanbourne Bockoven and Harry Solomon compared relapse rates inthe pre-drug era to those in the drug era, and found that patients in thepre-drug era had done better. Forty-five percent of the patients treated at Boston Psychopathic Hospitalin 1947 had not relapsed in the five years following discharge, and 76% weresuccessfully living in the community at the end of that follow-up period. Incontrast, only 31% of patients treated in 1967 with drugs at a Boston communityhealth center remained relapse-free for the next five years, and as a groupthey were much more “socially dependent”–on welfare, etc.–thanthose in the 1947 cohort.

Other researchers who reviewed relapse rates for New York psychiatric hospitals in the 1940s and early1950s reported similar findings: roughly 50% of discharged schizophreniapatients had remained continuously well through lengthy follow-up periods,which was markedly superior to outcomes with neuroleptics. SeeNathaniel Lehrman, “A state hospital population five years afteradmission: a yardstick for evaluative comparison of follow-up studies,” PsychiatricQuarterly, 34 (1960), 658-681; and H.L. Rachlin, “Follow-up study of317 patients discharged from Hillside Hospital in 1950,” J.Hillside Hospital, 5 (1956), 17-40. 

6. William Carpenter, Jr., “The treatment ofacute schizophrenia without drugs: an investigation of some currentassumptions,” American Journal of Psychiatry, 134 (1977),14-20. 

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

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

In this 1978study,  Maurice Rappaport and his colleagues at the University of California, San Francisco randomized 80 young male schizophrenicsadmitted to Agnews State Hospital to drug and non-druggroups. Only 27% of the drug-free patients relapsed in the three yearsfollowing discharge, compared to 62% of the medicated group. Most notably, onlytwo of 24 patients (8%) who weren’t medicated in the hospital and continued toforgo such treatment after discharge subsequently relapsed. At the end of thestudy, this group of 24 drug-free patients was functioning at a dramaticallyhigher level than drug-treated patients.

8. Susan Mathews,”A non-neuroleptic treatment forschizophrenia: analysis of the two-year postdischarge risk of relapse,” SchizophreniaBulletin, 5 (1979), 322-332;  Loren Mosher, “Community residentialtreatment for schizophrenia: two year followup,” Hospital and CommunityPsychiatry, 29 (1978), 715-723; Mosher, “The treatment of acute psychosiswithout neuroleptics: six-week psychopathology outcome data from the Soteriaproject,” International Journal of Social Psychiatry, 41 (1995),157-173;  Mosher, “The Soteria project: twenty five years of swimmingupriver,” Complexity and Change, 9 (2000), 68-73.

During the 1970s, the head of schizophrenia studies at the NIMH, LorenMosher, conducted an experiment that compared non-drug treatment to drugtreatment, 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 PsychiatricTherapies, (Vol. XIV).New York: Grune and Stratton, Inc., pp. 287‑296,1974.Menn AZ and Mosher LR.The Soteria Project.An Alternative to Hospitalization forSchizophrenics: Some Clinical Aspects.In J Jorstad and E Ugelstad (Eds), Schizophrenia75.Oslo, Norway: Universitetsforlaget,pp. 347‑372, 1976.Mosher LR andMenn AZ.Dinosaur or Astronaut?One‑Year Follow‑Up Data from theSoteria Project.In M Greenblatt and RDBudson (Eds), “A Symposium: Follow‑up of Community Care”.American Journal of Psychiatry, 133:8,919‑920, 1976.Mosher LR and MennAZ.Lowered Barriers in the Community:The Soteria Model.In LI Stein and MATest (Eds), Alternatives to Mental Hospital Treatment.New York:Plenum Press, pp. 75‑113, 1977.

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

In the late 1970s, Canadian investigators identified the biological changesinduced in the brain by neuroleptics that led to the higher relapse rates.Because the drugs dampen down dopamine activity, the brain tries to compensateby becoming “supersensitive” to dopamine. (The drugs trigger anincrease in the density of dopamine receptors.) This perturbation in dopaminefunction makes the patients more biologically prone to psychosis and to worserelapses upon drug withdrawal. Chouinard concluded: “Neuroleptics canproduce a dopamine supersensitivity that leads to both dyskinetic and psychoticsymptoms. An implication is that the tendency toward psychotic relapse in apatient who has developed such a supersensitivity is determined by more thanjust the normal course of the illness . . . the need for continued neuroleptictreatment may itself be drug-induced.”

10. George Gardos and Jonathan Cole, “Maintenance Antipsychotic Therapy: Isthe 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 isjust a general discussion paper, but note his conclusion: “An attempt should bemade to determine the feasibility of drug discontinuance in every patient.”

The WHO Studies

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

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

The first World Health Organization study that compared schizophreniaoutcomes in “developed” and “developing” countries wascalled The International Pilot Study of Schizophrenia. It began in 1968, andinvolved 1202 patients in nine countries. At both two-year and five-yearfollow-ups, the patients in the poor countries were doing much better. The researchersconcluded that schizophrenia patients in the poor countries “had aconsiderably better course and outcome than (patients) in developed countries.This remained true whether clinical outcomes, social outcomes, or a combinationof the two was considered.” Two-thirds of the patients in Indiaand Nigeriawere asymptomatic at the end of five years. The WHO investigators, however,were unable to identify a variable that explained this notable difference inoutcomes. SEE PAGES 132, 142, 143.

12. Assen Jablensky, “Schizophrenia: manifestations, incidence andcourse in different cultures, A World Health Organization ten-countrystudy,” 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 Determinantsof Outcome of Severe Mental Disorders. It involved 1379 patients from 10countries, and was designed as a follow-up study to the International PilotStudy 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 ofthe first: two-year outcomes were much better for the patients in the poorcountries. 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 thepatients in the poor countries had two or more psychotic episodes but stillwere in “complete remission” at the end of the two years. In otherwords, 63.7% of the patients in the poor countries were doing fairly well atthe 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 twoyears. The researchers concluded that “being in a developed country was astrong predictor of not attaining a complete remission.” 

Although the WHO researchers didn’t identify a variable that would explainthis difference in outcomes, they did note that in the developing countries,only 15.9% of patients were continuously maintained on neuroleptics, comparedto 61% of patients in the U.S. and other developed countries. This differencein outcomes is also consistent with research  in the U.S.showing that neuroleptics induce brain changes that make people morebiologically prone to psychosis. One would expect that drugs that induced suchchanges would lead to increased chronic illness, and the failure of mostpatients to attain a complete remission. See, Table 4.10 page 64 and page90.  [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 wasreporting on poor outcomes in developed countries, Harvard Medical Schoolresearchers published a study concluding that outcomes for schizophreniapatients in the U.S. had declined  since the 1970s, to the point they wereno better than they had been in 1900. They found that since 1986, only 36.4% ofpatients 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, Ph.D.; 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, Switzerlandresearchers duplicate Mosher’s results (more or less.) Note on page 148conclusion that: “patients who received no or very low-dosage medicationdemonstrated significantly better results.”

17. Two-year outcome in first episode psychosis treated according to anintegrated model. Is immediate neuroleptisation always needed?, by Lehtinen V, Aaltonen J, Koffert T, Rakkolainen V, Syvalahti E., European PsychiatryAugust 2000; 15(5): 312-20.  In this study,  43% of the patients in the experimental group didn’t receive anyneuroleptics 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 Swedenin which they copied the Finnish project. Note that only 45 of the patients inthe experimental group were on neuroleptics at 3-year followup, and those on itwere on 62 milligrams of Thorazine a day (a very low dose) and that thisexperimental group had much lower hospital use than those treatedconventionally over a three-year followup. In other words, they did better, andthis 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 structuralbrain 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-Naïveand 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 GlialDensity in Primate Prefrontal Cortex Associated with Crhonic Antipsychotic DrugExposure 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, andcause an enlargement in the basal ganglia. Please see the Gur MRI study in whichshe notes that this enlargement of the basal ganglia were associated withgreater severity of symptoms. In other words, we have here an MRI study thatcharts brain changes that lead to greater severity of symptoms.