Neuroleptics and Chronic Mental Illness

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Neuroleptics and Chronic Mental Illness

 

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withdrawn, the greater the relapse rates.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and 54% of these patients worsened after the drug was withdrawn.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#8209;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#8209;372, 1976. Mosher LR and Menn AZ. Dinosaur

or Astronaut? One#8209;Year Follow#8209;Up Data from the Soteria Project. In M

Greenblatt and RD Budson (Eds), " A Symposium: Follow#8209;up of Community Care " .

American Journal of Psychiatry, 133:8, 919#8209;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#8209;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 Metta-Analysis of the Outceom

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

200; 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; © 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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Last modified 6/29/2003

2003 Law Project for Psychiatric Rights.

 

 

 

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