A Research Timeline for Antipsychotic Drugs

Robert Whitaker

1883     Phenothiazines developed as synthetic dyes

1934     USDA develops phenothiazines as insecticides

1938     Phenothiazines used to kill swine parasites

1949     Phenothiazines used to hinder rope-climbing abilities in rats

1950     Rhone Poulenc synthesizes chlorpromazine, a phenothiazine, for use as an anesthetic

1952     French psychiatrists use chlorpromazine as part of a drug cocktail that can put mental  patients into “hibernation”

1952     Chlorpromazine described as producing a chemical lobotomy

1954     Chlorpromazine, marketed in the U.S. as Thorazine, found to induce symptoms of Parkinson’s Disease

1955     Chlorpromazine said to induce symptoms similar to encephalitis lethargica

1959     First reports of permanent motor dysfunction linked to neuroleptics, later named tardive dyskinesia

1960     French physicians describe a potentially fatal toxic reaction to neuroleptics, later named neuroleptic malignant syndrome

1962     California Mental Hygiene Department determines that chlorpromazine and other neuroleptics prolong hospitalization

1965     Neuroleptics found to impair learning in animals and humans

1966     NIMH study of one-year outcomes find that drug-treated patients are more likely than placebo patients to be rehospitalized

1972     Tardive dyskinesia is said to resemble Huntington’s disease, or “postencephalitic brain damage”

1973     Neuroleptics shown to cause decrease of nerve cells in basal ganglia in rats

1975     Boston researchers report that relapse rates were lower in pre-neuroleptic era, and that drug-treated patients are more likely to be socially dependent

1977     In animal studies, neuroleptics found to cause significant increases in dopamine receptors in the brain, which is the very pathology hypothesized to be a cause of schizophrenia

1978     California investigator Maurice Rappaport reports markedly superior three-year outcomes for patients treated without neuroleptics

1978     Canadian researchers describe drug-induced changes in the brain that make a patient more vulnerable to relapse, which they dub “neuroleptic induced supersensitivity psychosis”

1978     Neuroleptics found to cause 10% cellular loss in brains of rats

1979     Prevalence of TD in drug-treated patients is reported to range from 24% to 56%

1979     TD found to be associated with cognitive impairment.

1979     Relapse in patients on injectable fluphenazine found to lead to “severe clinical deterioration”

1979     Loren Mosher, head of schizophrenia studies at the NIMH, reports superior one-year and two-year outcomes for Soteria patients treated without neuroleptics

1980     NIMH researchers find an increase in “blunted effect” and “emotional withdrawal in drug-treated patients who don’t relapse, and determine that neuroleptics do not improve “social and role performance” in non-relapsers

1982     Anticholinergic medications used to treat Parkinsonian symptoms induced by neuroleptics reported to cause cognitive impairment

1985    Drug-induced akathisia is linked to suicide and to violent homicides

1992    World Health Organization reports that schizophrenia outcomes are much superior in poor countries, where few patients are maintained on neuroleptics

1992     Researchers acknowledge that neuroleptics cause a recognizable pathology, which they named neuroleptic induced deficit syndrome

1994     Neuroleptics found to cause an increase in the volume of caudate region in the brain, which is a sign of brain damage

1994     Harvard investigators report that schizophrenia outcomes have worsened over past 20 years, and are now no better than in first decades of 20th century

1995     “Real-world” relapse rates for schizophrenia patients treated with neuroleptics said to be above 80% in two years following hospital discharge, which is much higher than in pre-neuroleptic era

1995     “Quality of life” in drug-treated patients reported to be “very poor”

1998     MRI studies show that neuroleptics appear to cause hypertrophy of the caudate, putamen, and thalamus, with the increase “associated with greater severity of both negative and positive symptoms”

1998     Neuroleptic use is found to be associated with atrophy of the cerebral cortex

1998     Harvard researchers conclude that “oxidative stress” may be the process by which neuroleptics cause neuronal damage in the brain

1998    Treatment with two or more neuroleptics is found to increase risk of early death

2000    Neuroleptics linked to fatal blood clots

2000    TD linked to early death

2003    Risk of early death for schizophrenia patients is found to have increased since introduction of atypical antipsychotics

2005    NIMH researchers report that atypical antipsychotics provide few, if any, benefits compared to old neuroleptics

2006    Suicide rate for schizophrenic patients is reported to be 20 times higher today than it was a century ago

2007    British researchers report that quality-of-life was better on old drugs than on atypicals

2007    Illinois investigators report that long-term recovery rates for unmedicated schizophrenia patients are eight times higher than for medicated patients


Mad in America Documents

The evidence for antipsychotics

Antipsychotics and chronic illness

Antipsychotics and progressive brain dysfunction

Early death associated with antipsychotic drugs

Outcomes in the era of atypical antipsychotics

Modern experimental programs producing better outcomes

Timeline for antipsychotics


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