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Risperidone in levodopa induced dyskinesiae
  1. GIUSEPPE MECO,
  2. EDITO FABRIZIO,
  3. ANDREA ALESSANDRI,
  4. NICOLA VANACORE,
  5. VINCENZO BONIFATI
  1. Department of Neurological Sciences, Viale dell’Università 30, 00185 Roma, Italy.
  1. Dr G Meco, Department of Neurological Sciences, Viale dell’Università 30, 00185 Roma, Italy Telephone 0039 6 49914706; fax 0039 6 49914840.

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Levodopa induced dyskinesiae represent a common complication of the chronic treatment of patients with Parkinson’s disease.1 Refining the schedule of levodopa administration and adding controlled release preparations of levodopa, or dopamine agonists, or both often prove insufficient to control these problems. Pharmacological agents which exert a mild antagonism on striatal dopamine receptors or modulate the dopamine systems by interacting with serotoninergic pathways have recently shown beneficial effects in levodopa induced dyskinesiae.2 3

Risperidone is a new, atypical neuroleptic drug with potent serotonin-S2 and secondary dopamine-D2 antagonist properties.4 It has antipsychotic effects with a low incidence of extrapyramidal side effects, a feature which makes this drug a candidate for the treatment of levodopa induced psychosis and dyskinesia in patients with Parkinson’s disease. We have previously obtained beneficial effects with low dosages of risperidone in levodopa induced psychosis in patients with Parkinson’s disease.5Here we report our open experience with low dosages of risperidone in levodopa induced dyskinesiae.

Eight patients (five women, three men) with advanced Parkinson’s disease, motor fluctuations, and levodopa induced dyskinesiae took part in the study. All gave informed consent. Clinical details were as follows: mean age 67.3 (range 57-81) years; mean Parkinson’s disease duration 12.7 (8-20) years; Hoehn-Yahr stage in “off” phase: IV in five patients, III in three patients; mean duration of levodopa therapy 9.6 (range 6-14) years; duration of levodopa induced dyskinesiae 4.3 (range 2-7) years. All but one had peak dose dyskinesiae. The remaining patient had diphasic (beginning and end of dose) dyskinesiae. The risperidone dosages ranged from 0.125 to 0.25 mg once a day, at bedtime. The chronic antiparkinsonian treatment (levodopa/dopa decarboxylase inhihbitors monotherapy in four patients; levodopa plus bromocriptine or pergolide in four patients) remained unchanged during the trial. The severity of parkinsonism and dyskinesiae was assessed at regular intervals during the trial using the unified Parkinson’s disease rating scale (UPDRS; part III-motor scale) and the abnormal involuntary movement scale (AIMS). All patients but one were evaluated during the period of maximum benefit from therapy (“best on” condition); the remaining patient, with diphasic dyskinesiae, was evaluated during the beginning of the levodopa effects. Patients were asked to fill in diaries at home with the number of hours spent in “on” and “off” conditions, but data were available only in a few cases and were not reported.

The table summarises the results. After risperidone therapy all the patients had moderate to pronounced reduction in dyskinesiae. These effects have been maintained during the follow up (mean 11 (range 6-21) months). The final AIMS score of the group was significantly lower compared to the baseline score (P<0.01, Wilcoxon test). Three patients (2, 4, 6) took 0.25 mg risperidone/day with no modification of their parkinsonism. Three other patients (1, 3, 5) were unable to tolerate the initial 0.25 mg dosage owing to a worsening of parkinsonism (increase of number of hours spent in “off” conditions or worsening of “on” conditions) and their dosage was therefore reduced to 0.125 mg/day after some weeks. This produced a smaller improvement in the dyskinesiae with no great worsening of parkinsonism (table). One patient (7) received 0.125 mg risperidone/day from the beginning of the trial. The last patient (8), with diphasic dyskinesiae, received 0.25 mg risperidone/day for about one year, with considerable improvement in the dyskinesiae. Subsequently, owing to a worsening of parkinsonism, the risperidone dosage of this patient was reduced to 0.25 mg twice a week, although some improvement in dyskinesiae was maintained. The final UPDRS score of the group showed no significant changes when compared with the baseline score (Wilcoxon test) (table). No serious side effects were encountered during this risperidone trial.

The results of this open experience suggest that in some patients with Parkinson’s disease low dosages of risperidone might have beneficial effects on levodopa induced dyskinesiae, without causing significant worsening of parkinsonism. In the light of the pharmacological properties of risperidone, both dopamine and serotonin antagonism might play a part in the effects we found on levodopa induced dyskinesiae. It has to be stressed that, owing to the extreme sensitivity of patients with Parkinson’s disease to both the beneficial and undesirable effects of neuroleptic drugs, treatment with risperidone must be started with very low dosages (0.125 mg daily) and continued with caution. In conclusion, these results warrant larger, controlled studies to test the therapeutic potential of risperidone in levodopa induced dyskinesiae.

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