INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, VOL. 9: 41 5-41 7 (1994)

CASE REPORT

THE USE OF RISPERIDONE, AN ATYPICAL NEUROLEPTIC, IN LEWY BODY DISEASE

HElDl LEE Research Registrar in Old Age Psychiatry, St James’s Hospital, Dublin 8, Ireland

JOHN M. COONEY Registrar in Psychiatry, St James’s and St Patrick’s Hospitals, Dublin 8, Ireland

Consultant in Old Age Psychiatry, St James’s Hospital, Dublin 8, Ireland BRIAN A. LAWLOR

SUMMARY A case of senile dementia of Lewy body type (SDLBT) who developed severe and incapacitating extrapyramidal side-effects (EPSE) following treatment with typical neuroleptics, but responded to and tolerated the new atypical neuroleptic risperidone, is described. The potential benefits of atypical neuroleptics for elderly dementia patients with concurrent psychotic and behavioural symptoms are discussed.

KEY woms-Risperidone, Lewy body dementia, case report, extrapyramidal side-effects.

Clinically, the usefulness of typical high-potency neuroleptics in dementia populations is limited by the frequent emergence of extrapyramidal side- effects (EPSE) and cognitive toxicity. In Alz- heimer’s disease (AD), EPSE and cognitive impair- ment can develop at very low doses of haloperidol (Devanand ef al., 1989).

A related dementing disorder, senile dementia of Lewy body type (SDLBT), is emerging as the second most common neuropathological diagnosis coming to autopsy and is characterized pathologi- cally by the presence of subcortical, limbic and neo- cortical Lewy bodies (Perry et al., 1990; Lennox et af., 1989). Fluctuating cognitive impairment and extrapyramidal symptoms have been described in operational diagnostic criteria associated with SDLBT (Byrne et al., 1991), and in addition McKeith et al. (1992) have suggested that visual or auditory hallucinations may be prominent and that severe, even fatal, sensitivity to neuroleptics in dementia patients may be diagnostic of this con- dition,

Correspondence to first author. Tel: (01) 537822. Fax: (01) 6798865.

Atypical neuroleptics are defined by their low EPSE potential. Risperidone, a new neuroleptic with potent serotonin 5 HT2 and dopamine D, anta- gonist activity, has demonstrated antipsychotic activity and a low likelihood of inducing EPSE (Mesotten et al., 1989).

This case report illustrates the benefits of using this atypical agent to treat distressing psychotic symptoms in a patient meeting clinical criteria for SDLBT.

CASE REPORT

Mrs A, a 74-year-old white female, was referred to the Department of Medicine for the Elderly with an 18-month history of memory loss. At the time of the initial referral she was living at home. In addition to her memory loss, she complained of distressing and vivid visual hallucinations asso- ciated with paranoid delusions. She described see- ing a man sitting in the living room with her, to whom she offered a drink. She also reported seeing dead bodies in her home. She felt that her neigh- bours were ‘closing in’ on her, and that her family

CCC 0885-6230/94/0504 I 5 4 3 0 1994 by John Wiley & Sons, Ltd.

Received 18 October 1993 Accepted I5 December 1993

416 H. LEE, J . M. COONEY AND B . A. LAWLOR

was plotting to harm her. Her cognitive symptoms had followed a fluctuating course and during the previous year she had been admitted on one occasion for investigation of a rapid decline in cog- nitive function. No cause was found, and CT brain scan at the time was normal. Her cognitive function improved spontaneously, and she was discharged home.

The patient was referred to psychiatry for control of her psychotic symptoms. Physical examination was normal apart from generalized hypokinesis and decreased associated movement. A full dementia work-up including CT brain, chest X-ray, ECG, full blood count, ESR, SMAC, thyroid function tests, Biz, folate and VDRL were all within normal limits. There was no past psychiatric history. Of interest was that her father had died aged 58 of a dementing disorder.

At interview, she presented as tearful and depressed as a result of her delusional thinking. There was no sleep or appetite disturbance, no diur- nal mood variation and no suicidal ideation. Her Mini Mental State Examination (MMSE, Folstein et al., 1975) score was 21/30; Brief Psychiatric Rat- ing Scale (BPRS, Overall and Gorham, 1962) score was 49. Personal activities of daily living (ADL, eg dressing, toileting, feeding, etc) were intact (14/ 14); however, instrumental activities of daily living (IADL, eg use of telephone, budgeting, etc) were impaired (7/14) (OARS, Duke Collaborative Study, 1968). In the day hospital she was com- menced on low-dose haloperidol-0.5 mg bd. Within 3 days she began to complain of dizziness and nausea and by the end of a week she had a pill-rolling tremor, cog-wheel rigidity in both upper limbs, shuffling gait and masked facies. Her psycho- tic symptoms persisted. There was also a marked decline in her cognitive and functional abilities, with MMSE falling to 14/30, ADL to 7/14 and IADL to 0/14. Because of this deterioration she had to move in with her daughter. Haloperidol was discontinued. Over the next 2 weeks the EPSE improved, as did her cognition (MMSE 17/30), but her psychotic symptoms continued unabated. At this point Mrs A. was unable to manage in the community in spite of her family’s support, and was admitted to the inpatient unit.

On the ward she was frightened and paranoid about other patients stealing her belongings and was seen to place chairs against her wardrobe to keep it safe. Perphenazine was started and the dose was gradually increased to 6 mg per day over the next 4 weeks. The patient’s target psychotic symp-

toms remained prominent and very problematic (she was convinced that someone had been shot on the ward, and was unable to attend occupational therapy because she feared that other patients would undress her and tie her feet together), she became more cognitively impaired (MMSE 11/30), once again developed EPSE (cog-wheel rigidity, reduced affective range and poor mobility) and additionally developed postural hypotension. Fol- lowing discontinuation of the perphenazine, per- mission was gained from the National Drug Advisory Board (NDAB) to give risperidone on a named patient basis.

The dose was titrated up to 5 mg a day over 10 days. At this dose, she developed drowsiness and increased confusion (MMSE 9/30). The dose was reduced to 1 mg bd, and her mental and cogni- tive state gradually improved over the following 4 weeks (MMSE 21/30). On the ward she was no longer paranoid or frightened, had no hallucina- tions (BPRS score 41) and was notably less agitated and more restful. Because her psychosis was in remission, it was possible to discharge her to a nurs- ing home where she continues to remain free of psychotic symptoms 6 months later.

DISCUSSION

Although there was no pathological confirmation of the diagnosis in this case, Mrs A met clinical criteria for SDLBT with coexistent fluctuating dementia, parkinsonism and psychiatric symptoms (Byrne et al., 1991).

Additionally, in their retrospective study, McKeith et al. (1992) found that 80% of SDLBT patients developed neuroleptic sensitivity, with over 50% having a severe reaction and a subse- quently higher mortality rate. The case history illus- trates the toxic potential of classical neuroleptics in SDLBT, and suggests that, for this patient group the new atypical agent risperidone may be an effec- tive antipsychotic agent, without causing the same degree of EPSE. Risperidone was not free of side- effects as, on 5 mg per day, the patient developed drowsiness, a known side-effect of risperidone usually seen at higher doses (Mesotten et al., 1989) and increasing confusion (with marked reduction in MMSE score); however, these side-effects were not in evidence at the lower dose (2 mg per day).

It is possible that this was a spontaneous remission of psychotic symptoms, unrelated to medication. However, the fact that the improve-

RISPERIDONE IN LEWY BODY DISEASE 417

ment has been maintained consistently throughout the 6 months’ follow-up period makes this less likely.

The primary pathophysiological factor under- lying EPSE is believed to be dopamine D, receptor blockade in the striatum (Seeman, 1980). In both AD and SDLBT there is increased dopamine neur- onal fallout with resultant decreases in brain dopa- mine levels (Wallin and Gottfries, 1990; Perry et al., 199 1). This may explain the increased sensitivity to typical D2 blocking agents in these patient popu- lations. By contrast, the newer atypicals, such as risperidone, have greater 5-HT2 than D2 antagonist properties, and it may be this relative balance that results in the lower propensity to induce EPSE (See- man, 1992).

Controlled studies are now needed to further clarify the efficacy and side-effect profile of these new atypicals in the treatment of psychiatric and behavioural disturbances in our growing popula- tions of dementia sufferers. The future development of these agents may represent a significant advance in the pharmacological management of behaviour- ally disturbed dementia patients.

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