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
