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| Year : 1983 | Volume
: 29
| Issue : 3 | Page : 181-3 |
metoclopramide in Gilles de la Tourette's syndrome (a case report).
Desai AB, Doongaji DR, Satoskar RS
How to cite this article:
Desai A B, Doongaji D R, Satoskar R S. metoclopramide in Gilles de la Tourette's syndrome (a case report). J Postgrad Med 1983;29:181 |
Gilles de la Tourette's syndrome is a stereotyped movement disorder. Basal ganglion dysfunction is thought to be responsible for this syndrome. Various aetiological theories have been postulated. A disturbance in central dopamine metabolism is thought to be related to its causation and clinical manifestations.[9] Its treatment with the dopamine antagonists haloperidol[9], pimozide[8] and penfluridol[6] has been described.
Metoclopramide, a benzamide derivative commonly used as an anti-emetic,[7] is a potent dopamine blocking agent.[4] We describe the use of metoclopramide in a case of Gilles de la Tourette's syndrome.
M. J., a right-handed, unmarried, 21 year old male was referred to us for involuntary movements and meaningless utterances. On examination, he had jerky movements of the neck, shrugging of the shoulders and brief, sudden, jerky, repetitive, irregular movements of fingers and feet. The movements were more prominent on the left side. They were accompanied by spontaneous, explosive, involuntary, vocal grunting and coughing. There were no obscenities. These symptoms were present since childhood. They occurred even when the patient was alone although they were aggravated in the presence of people and in times of emotional stress. They were absent during sleep.
The patient was born at full-term and there was no history of perinatal or neonatal complications. Developmental milestones were normal. He is a reserved and meticulous person. He has a good academic record and is presently working as an accountant. There was no family history of mental illness, epilepsy, alcoholism or involuntary movements. A detailed physical examination revealed no abnormalities apart from the involuntary movements. Mental status examination was normal. The electroencephalogram (EEG) was within normal limits.
Routine laboratory investigations done initially revealed no abnormality. These were repeated at weekly intervals throughout the trial period.
The patient's consent for treatment with metoclopramide was obtained after explaining the details of the trial procedure. He was initially prescribed metoclopramide 40 mg thrice daily for 7 days. A flexible dosage schedule was adopted and the dose adjusted depending on the response. The maximum dose administered was 80 mg thrice daily. The involuntary movements were rated on the Abnormal Involuntary M6vement Scale (AIMS).[3] The patient was observed unobstrusively for a period of 5 minutes for recording the vocal tics. These assessments were done initially and at weekly intervals by the same observer.
A steady improvement was noted at the end of the first week after starting metoclopramide and this continued till the end of twelve weeks. The AIMS scores decreased from an initial score of 14 to 2 (86% reduction) at the end of 12 week. The vocal utterances disappeared completely by the end of the second week from an initial frequency of 15 utterances every 5 minutes. Subjectively, the patient felt improvement in the motor tics and vocal utterances by the end of the second week. There was a reappearance of symptoms at the eighth week when the dose of metoclopramide was reduced from 240 mg/day to 120 mg/day.
The patient developed a dystonic reaction on the second day while on a metoclopramide 120 mg/day. This was successfully treated with intramuscular promethazine hydrochloride 50 mg. Subsequently, the patient was maintained on trihexiphenidyl hydrochloride 6 mg/day orally. No extrapyramidal side effects were observed thereafter.
The routine biochemical studies including methaemoglobin levels revealed no abnormality during the course of the treatment.
The Diagnostic and Statistical Manual of Mental Disorders (DSM-III) classifies Gilles de la Tourette's syndrome (307.23) as a stereotyped movement disorder. A disturbance in the functions of the basal ganglia is suspected in this syndrome.[9] Improvement in symptoms with haloperidol, a potent dopaminergic blocking agent, suggests the possibility of involvement of brain dopamine. An excess of dopamine after the administration of I-dopa has resulted in the production of similar tics in patients with Parkinson's disease.[9] The daily dose of haloperidol effective in controlling the symptoms of this syndrome ranges from 6 to 180 mg and the drug is often poorly tolerated at the higher dosage levels which are often required.
Metoclopramide has potent dopamine blocking properties[4] and has also been found to be useful in the diagnosis of phenothiazine-induced tardive dyskinesia.[1], [2] Kababian and Calne[5] have shown that the nigrostriatal dopamine receptors are of two types viz. D1 and D2. Most of the available antipsychotics are antagonists of both D1 and D2, receptors, while metoclopramide is a selective D2 antagonist.[5], [10] Central dopaminergic hyperactivity is suspected in both, Gilles de la Tourette's syndrome and tardive dyskinesia. This could explain the beneficial effects of metoclopramide in Gilles de la Tourette's syndrome.
In our patient, a steady improvement was seen to occur after the first week of medication as reflected by the steady reduction in the AIMS scores. When the dose of metoclopramide was reduced at the eighth week, there was a reappearance of the symptoms. When the dose was again increased there was an improvement in the patient's condition which was maintained till the end of the trial. This suggests that the improvement observed was a dose related phenomenon. The drug was well tolerated in the dosages used and, except for a dystonic reaction, no other adverse effects were observed.
It would have been worthwhile to have done a double blind study of the efficacy of metoclopramide in a series of patients with Gilles de la Tourette's syndrome. However, this is not possible, as either the syndrome or its diagnosis is rare in India, and only six cases have been reported so far.[6]
The authors thank Dr. C. K. Deshpande, Dean, Seth G.S. Medical College and K.E.M. Hospital for permission to publish this report. Acknowledgement is made to Ipca Laboratories Pvt. Ltd. for supply of metoclopramide.
| 1. | Doongaji, D. R., Jeste, D. V., Jape, N. M., Seth, A. S., Apte, J. S., Vahia, V. N., Desai, A. B., Parikh, M. D., Rathi, L. G., Gandhi, M. I-L, Parikh, R. M., Thatte, S. S. and Bharadwaj, J.: Effects of intravenous metoclopramide in 81 patients with tardive dyskinesia. J. Clin. Psychopharmacol., 2: 376-379, 1982.  |
| 2. | Doongaji, D. R., Sheth, A. S., Desai, A. B., Apte, J. S., Thatte, S. S.., Vahora. S. A., Parikh, M. D., Gandhi, M. H., Meherhomji, J. B., Jeste, D. V. and Satoskar, R. S.: Use of metoclopramide in the differential diagnosis of drug induced involuntary movements. J. Postgrad. Med., 28: 101-106, 1982. |
| 3. | Guy, W.: ECDEU Assessment Manual for Psychopharmacology," Department of Health, Education and Welfare, Washington D.C., 1976, pp. 534-537. |
| 4. | Jenner, P., Elliott, P. N. C., Clow, A., Reavill, C. and Marsden, C. D.: A comparison of in vitro and in vivo dopamine receptor antagonism produced by substituted benzamide drugs. J. Pharm. & Pharmacol., 30: 46-48, 1978. |
| 5. | Kababian, J. and Calne, D.: Multiple receptors for dopamine. Nature, 277: 93-96, 1979. |
| 6. | Parikh, M. D., Abhyankar, R. R., Bajaj, N. and Doongaji, D. R.: Penfluridol in the treatment of Gilles de la Tourette's syndrome. Neurology (India), 27: 174-177, 1979. |
| 7. | Finder, R. M., Brogden, R. N., Sawyer, P. R., Speight, T. M. and Avery, G. S.: Metoclopramide: A review of its pharmacological properties and clinical use. Drugs, 12: 81-131, 1976. |
| 8. | Ross, M. S. and Moldofsky, H.: A comparison of pimozide with haloperidol in the treatment of Gilles de la Tourette's syndrome. Amer. J. Psychiat, 135: 585587, 1978. |
| 9. | Silver, L. B.: Stereotyped movement and speech disorders of childhood and adolescene. In, "Comprehensive Textbook of Psychiatry," Editors: Kaplan, H. I., Freedman, A. M. and Sadock, B. J., Williams and Wilkins, Baltimore, 1980, pp.. 2571-2578. |
| 10. | Stanley, M., Lantin, A., Rotrosen, J., Gershon, S. and Kleinberg, D.: Metoclopramide: Antipsychotic efficacy of a drug lacking potency in receptor models. Psychopharmacology, 71: 219-225, 1980. |
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