Evidence from medical journals that antipsychotic drugs cause psychosis

Researched by Vera Hassner Sharav
ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)

A review of the history of Tardive Dyskinesia (TD) demonstrates clearly that despite the evidence, physicians' disclosure and practice has remained unchanged.

The APA has opposed written informed consent from patients.

Behavioral toxicity of antipsychotic drugs. J Clin Psychiatry 1987 Sep;48 Suppl:13-9

The concept of supersensitivity psychosis. J Nerv Ment Dis 1992 Apr;180(4):265-70 Maryland Psychiatric Research Center, Department of Psychiatry, Univ Maryland School of Medicine, Baltimore 21228.
The hypothesis that chronic neuroleptic treatment may induce relapse in some schizophrenic patients

Rebound psychoses following the discontinuation of a high potency neuroleptic.
Can J Psychiatry 1989 Apr;34(3):227-9

Psychotic patients who become worse on neuroleptics. J Clin Psychopharmacol 1988 Dec;8(6):417-21 Yale University School of Medicine, Dept of Psychiatry, New Haven, Connecticut

During the last decade, newer "atypical" neuroleptics have been developed-clozapine, risperdone, olanzapine and quitepane-these drugs have a lower risk of EPS and TD, but are associated in varying degrees with sedation, cardiovascular and liver enzyme abnormalities, anticholinergic effects, extreme weight gain (30lbs to 50lbs) which significantly increases the risk for diabetes, sexual dysfunction, NMS, seizures, mania, and (in the case of clozapine) agranulocytosis.

Additionally, mounting clinical evidence and findings -from non-industry sponsored research-point to additional, severe, adverse neurological changes in response to long-term exposure to neuroleptics. These drugs' actions suppress certain brain receptors (e.g., dopamine, glutamate), and when such drugs are withdrawn (or a patient stops taking them) the drug-induced receptor changes are unmasked, causing an acute "discontinuation syndrome" (i.e., "rebound psychosis" ) that is often more severe than the original symptoms of the illness. Psychotic relapse can cause months of mental and emotional anguish and loss of functioning and violent and suicidal behavior in patients not previously violent. [Often, these drug-induced reactions are used to justify forcing the person back on the drugs.]

Recent Findings Corroborate high incidence of drug-induced movement disorders:
Neurologic approach to drug-induced movement disorders: a study of 125 patients. South Med J 1990 May;83(5):525-32 Department of Family Medicine, Baylor College of Medicine, HoustonTX.

Of 125 patients, 63% had tardive dyskinesia, 30% had parkinsonism, 24% had dystonia, 7% had akathisia, and 2% had isolated tremor. Two or more movement disorders coexisted in 31 patients (25%). …Many patients could have been treated with less potent drugs.

Underrecognition of tardive dyskinesia and drug-induced parkinsonism by psychiatric residents.

Gen Hosp Psychiatry 1992 Sept; 14(5):340-4 … presents a major challenge in modern clinical psychopharmacology. This study reports the occurrence of tardive dyskinesia and drug-induced parkinsonism (DIP) in 101 inpatients, and documents under recognition of both disorders by resident physicians. Researchers noted TD in 28% of cases and residents only described TD (or symptoms ofTD) in 12%. Residents tended to miss milder cases of TD, and to miss DIP in younger patients and in patients with affective disorders.

Neuroleptic drug induced psychotic relapse ("supersensitivity psychosis")
Withdrawal from clozapine: the "rebound phenomenon"

Isr J Psychiatry Relat Sci 1999;36(2):122-8 Jerusalem Mental Health Center, Kfar Shaul Hospital, Israel.

… manifested in two interwoven clinical forms: (1) psychotic exacerbation, and (2) cholinergic rebound.

Life-threatening neuroleptic malignant syndrome (NMS)
NMS is the result of dopamine receptor blockade in the brain, induced by ALL neuroleptic drugs [included is a sample of published NMS reports associated with the new, "atypical" drugs]

Clozapine-associated neuroleptic malignant syndrome: Ann Pharmacother 1999 May;33(5):623-30 Memorial University of Newfoundland, St. John's, Canada. Two new cases of clozapine-associated NMS, identified by using a MEDLINE search (1966-August 1998).Clozapine was deemed a highly probable cause of NMS in 14 cases, a medium probability cause in five cases, and a low probability cause in eight cases. The most commonly reported clinical features were tachycardia, mental status changes, and diaphoresis. Clozapine appears to cause NMS, although the presentation may be different than that of traditional antipsychotics.

Clozapine-induced neuroleptic malignant syndrome: review and report of new cases.

J Clin Psychopharmacol 1995 Oct;15(5):365-71 Neuropsychiatric Institute, Prince Henry Hospital, Sydney, Australia. … add three, and possibly four, new cases

Neuroleptic malignant syndrome associated with olanzapine. Ann Pharmacother 1998 Nov;32(11):1158-9 Infectious Disease Section, Veterans Affairs Medical Center, Minneapolis, MN 55417, USA.

A 67-year-old white man with bipolar disorder developed nausea and vomiting. After 12 days, he became confused, delirious, and manic. His only medications were olanzapine 10 mg/d and divalproex sodium 500 mg bid. Olanzapine was given on 6 of the first 7 hospital days. On hospital day 6, typical NMS. Olanzapine was stopped after hospital day 7, and the syndrome resolved by hospital day 12.

1998 MRI Studies demonstrate structural brain changes in schizophrenia patients treated with both standard and "atypical" neuroleptic drugs:

Non-industry sponsored researchers are coming to realize that this rebound reaction to antipsychotic drugs-both standard and the newer atypicals-- may be so great, it could be causing structural brain changes such as swelling of the brain. Gur, et al., (abstract below) conducted an NIMH-funded MRI imaging study to monitor changes in the size of the basal ganglia and thalamic regions of the brain in schizophrenia patients treated with neuroleptic drugs. They compared them to a group of patients who were never exposed to neuroleptic drugs, and to a group of healthy comparison subjects: As they put it: "… indicate that exposure to neuroleptics is associated with hypertrophy...Neuroleptics increased the area of both regions of the brain: a higher dose of standard neuroleptics was associated with a size increase in multiple areas, while atypcal neuroleptics increased the volume only of the thalamic portion. … [This] is associated with greater severity of symptoms: This association was evident for hallucinations...and bizarre behavior....In other words, the patient's brains were being changed in ways that would likely increase the severity of their disabling illness-- and make it more difficult for them to ever withdraw from neuroleptic drugs.

The researchers themselves say the brain changes visible in the MRI scan "seem to be medication-induced hypertrophy."

Subcortical MRI volumes in neuroleptic-naive and treated patients with schizophrenia.

American Journal of Psychiatry, 155 (12), 1711-1717. [Study was funded by NIMH]

For the full article online go to: http://ajp.psychiatryonline.org/cgi/content/full/155/12/1711#F1

… 96 patients with schizophrenia (50 men and 46 women) and 128 healthy comparison subjects (60 men and 68 women). Increased subcortical volumes in treated schizophrenic patients seem to be medication-induced hypertrophy. This … may moderate the effects of neuroleptic treatment.

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