Prospective study of tardive dyskinesia incidence in the elderly.

OBJECTIVES: To investigate the incidence of tardive dyskinesia in elderly individuals beginning treatment with antipsychotic drugs and to identify risk factors for the development of tardive dyskinesia in the elderly. DESIGN: A cohort of previously neuroleptic-naive patients was identified at the time of initiation of antipsychotic drug treatment. Patients were evaluated at baseline and followed up at 3-month intervals for periods ranging from 3 to 119 weeks. SETTING: Subjects were recruited from the psychiatric and geriatric medical services of two medical centers, a geriatric institute, and three nursing homes in the metropolitan area of New York City, NY. PATIENTS: Two hundred fifteen individuals older than 55 years have entered the study thus far. Preliminary data are presented for 160 patients who were followed up for at least 1 month. Their age range was 57 to 99 years (mean, 77 years). Seventy-two percent were women and 87% were white. Sixty-seven percent of patients had a diagnosis of organic mental syndrome and 42% had a psychiatric diagnosis. INTERVENTIONS: A naturalistic, longitudinal, repeated assessment paradigm was employed. Assessments included abnormal involuntary movements, extrapyramidal signs, psychiatric symptoms, and medical and drug treatment histories. MAIN OUTCOME MEASURE: The incidence of tardive dyskinesia was determined using a standardized rating instrument and survival analysis. RESULTS: The incidence of neuroleptic-induced dyskinesia was 31% (95% confidence interval, 20%, 42%) after 43 weeks of cumulative neuroleptic treatment. Psychiatric (as opposed to organic) diagnosis and presence of extrapyramidal signs early in treatment were associated with increased tardive dyskinesia vulnerability.

The prevalence of tardive dyskinesia.

A total of 2250 subjects from psychiatric and geriatric settings was examined for abnormal involuntary movements by the same team of trained raters employing a standard examination technique and rating scale. "Spontaneous" dyskinesia rates were 1.3% among 400 healthy elderly people surveyed at senior citizens centers, 4.8% among medical geriatric inpatients and ranged from 0 to 2% among psychiatric patients never exposed to neuroleptics. For samples of neuroleptic-treated patients, prevalence rates ranged from 13.3% among patients at a voluntary psychiatric hospital to 36.1% among state hospital patients. Logistic regression analyses revealed a large effect of age on tardive dyskinesia prevalence and an interaction of age with sex. Among younger subjects, men had higher rates; among subjects over age 40, rates were higher for women. Edentulousness and presence of other neurological disorders were possible contributors to high rates for the elderly. Even with control for age, sex and duration of neuroleptic exposure, prevalence differed markedly across study site.

Cholinergic and dopaminergic mechanisms in Parkinson's disease after long-term L-DOPA administration.

A study of parkinsonian patients suffering from ON-OFF phenomena, who had been on long-term treatment with L-DOPA, to the parenteral administration of apomorphine and physostigmine is reported. All patients, whether of the end-dose failure type or of the randomly occurring variety, when given apomorphine in an OFF phase, showed prompt reversal to an ON phase. Physostigmine given during an ON phase produced the opposite effect with induction of parkinsonian symptoms. These findings are interpreted as indicating that the dopaminergic receptors are available for stimulation during the OFF phase but are not receiving sufficient neurotransmitter, that is, dopamine, to stimulate their activity. The response to physostigmine is indicative of a return of cholinergic supersensitivity after long-term L-DOPA administration, the mechanisms by which this may occur are discussed. Based on these findings, therapeutic strategies are suggested that may overcome this major limitation of the use of L-DOPA in the treatment of parkinsonism.

Treatment of Parkinson's disease in early and late phases. Use of pharmacological agents with special reference to deprenyl (selegiline).

There are at present numerous pharmacological agents available for the control of parkinson symptoms. None are ideal; all have their limitations. The most potent is levodopa administered with a peripheral decarboxylase inhibitor. However, because its effectiveness declines after long-term use and side effects increase in severity, it should be reserved for individuals with established symptoms which are functionally impairing. In patients with minimal symptoms, anticholinergic agents, or agents which facilitate dopaminergic mechanisms normally operative in the nervous system, should be used. In a limited trial, deprenyl has produced promising results during this phase of parkinsonism. Deprenyl's major usefulness however, has been demonstrated in patients under treatment with levodopa which has become complicated by fluctuating responses--particularly those of the end-start-dose variety. In such patients, it is possible to achieve an increase in "on" time and a decrease in the severity of parkinsonism. In most patients, such a response can maintained for a period of two years or longer.