Neuroleptic Treatment of Elderly Patients

Margaret G. Woerner, Ph.D., Jose Ma. J. Alvir, Dr. P.H., John M. Kane, M.D., Bruce L. Saltz, M.D., and Jeffrey A. Lieberman, M.D.
(Psychopharmacology Bulletin 1995, Volume 31(2): pages 333-337)

Neuroleptics are commonly used to treat psychosis and behavioral disturbance in elderly patients. A recent review indicated that 25% to 45% of geriatric nursing home residence are prescribed neuroleptics (Harrington et al. 1992). The few methodologically sound controlled trials of neuroleptic drugs in this population suggest a modest therapeutic effect in controlling agitation in demented or psychotic patients and provide no evidence for differential effectiveness of any single drug or class of drugs (Salzman 1987).

There is mounting evidence that geriatric patients are especially sensitive to neuroleptic side effects. Preliminary results from our ongoing prospective study of the development of tardive dyskinesia among elderly patients beginning neuroleptic treatment for the first time have indicated that 41% developed rigidity, tremor, or akinesia, and 5% developed akathisia after 4 weeks of treatment (Saltz et al. 1991b). After receiving 43 weeks of treatment, 31% developed tardive dyskinesia (Saltz et al. 1991a). It should be noted that these results were obtained with low doses of medication.

In the context of this ongoing study we have prospectively collected detailed treatment records and periodic assessments of psychopathology and cognitive status. We have used these data to examine characteristics of elderly patients who were prescribed neuroleptics in geriatric treatment facilities, the indications for neuroleptic treatment, and the dosage and course of their treatment. In addition, we have examined the ratings of psychopathology and cognitive function before and after treatment, in order to explore the therapeutic benefits of antipsychotic treatment in these patients.

Methods
The methods and preliminary results of the ongoing parent study have been described in detail elsewhere (Saltz et al. 1991a). The subjects were 355 patients, age 55 and over, recruited from the psychiatric and geriatric medical services of two major medical centers, a large geriatric institute, and three nursing homes in the New York metropolitan area for a prospective study of tardive dyskinesia development. All individuals who are about to start antipsychotic drug treatment for any clinical indications were screened for inclusion in the study. The present sample includes 266 patients who were treated for at least two weeks, and for whom we had complete medication and dosage information.

The following assessments were completed on study entry:
1. Chart reviews and interviews with patients, relatives, and staff to obtain medical, neurological, demographic, psychiatric, and medication histories.
2. Examination for abnormal movements: ratings of tardive dyskinesia on the Simpson Dyskinesia Scale ( Simpson et al. 1979) and ratings of extrapyramidal side effects (EPS) on the Simpson-Angus Extrapyramidal Side Effects Scale (Simpson and Angus 1970).
3. Semistructured interviews to enable ratings on the Mini-Mental State Examination (MMSE; Folstein et al. 1975), the Brief Psychiatric Rating Scale - Anchored Version (BPRS; Woerner et al. 1988), and the Global Assessment Scale (GAS; Guy 1976, Endicott et al. 1976). All ratings were repeated at one month. Tardive dyskinesias and EPS ratings were repeated quarterly BPRS and GAS every 6 months and MMSE every 12 months thereafter.

The research staff was not involved in any way in patients' treatment, which was uncontrolled and determined by the treating clinician. Subjects were all inpatients at study entry but continued to receive follow-up at other treatment facilities or their homes after discharge.

Results

Subject Characteristics
Subjects are predominantly (75%) female and average age of 77 years (range 55-101). Their mean age at onset of symptoms was 73 (+13). The majority presented with psychiatric (57%) or neurological (23%) complaints. Diagnosis recorded in the clinical charts (based on DSM- III-R; American Psychiatric Association 1987) revealed that one-third of the patients had a diagnosis of dementia and one-third had other organic mental syndromes (e.g., organic delusional syndrome, delirium). Another Axis I psychiatric diagnosis (e.g., major affective disorder, schizophrenia, anxiety disorder) was recorded in the clinical charts for 44%; the majority of these were affective disorders (Table 1).

Prior treatment with psychotropics was relatively uncommon: 30% had received anxiolytics, 27% antidepressants (10% of these were treated for over 6 months), 9% hypnotics, 5% lithium, and 4% stimulants. Five percent had had electroconvulsive therapy. Most patients had a history of one or more medical problems; the majority were cardiovascular (64%) or neurological (44%) in nature. Nine percent reported a history of alcohol abuse or dependence; two reported current heavy drinking. Cigarette smoking in the past was reported by 34% and current smoking by 7% of the patients.

Baseline Psychopathology
As shown in Table 2, baseline BPRS ratings suggest that for most patients, neuroleptic treatment was instituted in response to psychotic symptoms, either with agitation (51%) or alone (31%). As shown in Figure 1, ratings were more severe for psychosis (67% had a rating of moderate or higher on a psychotic item) than for agitation (38% had a rating of moderate or higher on an agitation item).

Neuroleptic Treatment
The clear drug of choice at all sites was haloperidol, prescribed for 68% of the patients; the second most popular drug perphenazine, was prescribed for 13%. A low potency neuroleptic was prescribed for only 12%, with thioridazine accounting for most of these (Table 3). Although treatment tended to be intermittent or discontinued prior to six months, 71% were treated continuously for the first month, 42% for the fist 6 months, and 34% for 49 weeks or more in the first year; 22% were treated for 2 months or less during the first year.

Medication dosage prescribed was very low for most patients. The average daily starting dose in chlorpromazine (CPZ) equivalence was 80mg (+ 156). The average daily dose was 50 mg or less in CPZ equivalence (<1mg haloperidol) for 38% of the patients at six months and for 36% of the patients at one year. Dosage was lower for patients with organic mental syndrome diagnosis than for those with other Axis I diagnoses. After one month of treatment, the latter group had a mean cumulative dose of 4,603 mg (+6,339) in CPZ equivalence compared with 1,960 (+2,045) for the former group. The number of days on medication was the same for the two groups.

Psychopathology Ratings
Ratings on the BPRS factors of Anxiety-Depression, Thought Disturbance, Psychoticism, Activation, and Hostile-Suspiciousness and the GAS score were significantly better at 1 month and 6 months than at baseline. The improvements were most salient for psychotic symptoms and the GAS scores (at 6 months, there was an average decrease of thirty percent in the psychosis factor and an increase of thirty-five percent on the GAS). Ratings of Anergia and the MMSE scores were not changed (Figure 2). Results at six months were similar for patients who received neuroleptics all or most of the time and those treated intermittently for only part of the six months. During follow-up, 29% of the patients were treated with anxiolytics, 28% with antidepressants and 4% with lithium. The same pattern of results was evident regardless of whether patients were treated with any of these medications during the follow-up period. Further, the findings were similar for the subgroups of patients with organic mental syndrome diagnoses and those with other Axis I psychiatric diagnosis, with the following exceptions: (1) Anxiety-Depression and MMSE scores at one month were significantly improved for patients with other Axis I psychiatric diagnoses but not for those with organic mental syndromes (the improvement in MMSE score was quite small, approximately one scale point); (2) anergia ratings were worse at one month and six months for patients with organic mental syndromes and better for those with other Axis I diagnoses. In general the improvements in BPRS psychosis and GAS ratings were larger for the patients with other psychiatric diagnoses than for those with organic mental syndromes (Figure 3).

Discussion
Most of the elderly patients treated with neuroleptics for the first time in the geriatric inpatient or nursing home settings we sampled exhibited symptoms of psychosis with or without agitation; thus, they appeared to be appropriate candidates for neuroleptics. Treatment appears to have been conservative; it was most often with low doses of haloperidol (less than 2 mg/day) and continuous for the first month. Fewer than one-third of these patients were treated continuously for one year. Patients with organic mental syndrome diagnoses were treated with significantly lower doses than were patients with other Axis I diagnoses.

Ratings scale measures showed statistically significant improvement in symptoms related to psychosis and agitation as well as global functioning, but no change in anergia and dementia ratings at one month and six months for the group as a whole. Changes for the subgroup of patients with Axis I psychiatric diagnoses were somewhat more pronounced than for the subgroup with organic mental syndromes. This interesting, suggestive finding merits further study in a controlled trial. In addition, other outcome measures, focusing on functioning and social behavior should be investigated. These domains may prove to be important and more sensitive indicators of improvement for the organic mental syndrome group.

Since treatment was not controlled in our study, none of the changes described can be unambiguously interpreted as treatment effects. However, they are consistent with controlled studies suggesting a beneficial effect of neuroleptics for similar patient groups. The extent to which these benefits outweigh the increased risks of EPS and tardive dyskinesias must be considered on an individual case basis.

References
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