therapy TARDIVE DYSKINESIA - A FEW CLUES IN THE SEARCH FOR A SOLUTION Thiopropazate hydrochloride helps. but benztropine mesylate makes the condition worse Eight of 1 0 patients with tardive dyskinesia improved significantly and) were free of symptoms after 6 months on thiopropazate He l (' Dartalan ') J Omg daily. [5 patients completed at least 3 months on the dr ug and 8 showed improvement after I and J mont hs, but this is nOl significant compar ed with drug-fr ee control period. Thiopropazate seemed to be effecti ve in controlling tardive dyskinesia with out aggravation of its underlying pathophysiol ogy and may be valuable as an adjunct in patients on other antipsychotic dru gs. The study showed no benefit with previous therapy with the anticholinergic antiparkinson agent benztropi ne mesylate ('Cogentin '); in fact. 10 of the I 5 patients improved on stopping il. 'These findings support the hypothesis that tardive d ys k inesia may result from dopamine rgic hyperactivity and cholinergic hypoactivity in the corpus striatum ,' Smith. J.S. and KiJoh. L G.; Journal of Neurology. Neurosurgery. and Psychiatry 42: S760un 1979) Effects of muscimol suggest that GABA augmentation may be worth a try Muscimol. a dr ug capable of augmenting y-aminobutyric acid (GABA) neuronal acti vity. significantly diminis hed choreiform movements in 7 chroni c schizophrenics with tardive dyskinesia. Pa ti ents received mus ci mol once daily in doses of 3-9mg PO after stopping amipsychotics at least 5 days previously. The effect of musci mol at 2 hours, when a 48 % decrease in involuntary movements occurred. T wo of 3 patients with Par kinsonian movements showed exacerbation of symptoms for up to 5 hours after receiving muscimol. Behavioural side effects may limit the use of muscimol, but use of other GA BA stim ul ating therapies may be acceptable. Tamminga. CA. et at, of General Psychiatry )6: 595 (May 1979) The value of drug holidays seems doubtful The commonly held notion that frequent len gt hy interruptions of long term drug lreatment reduces the incidence of pe rsistent dyskinesia was not borne out in 21 hos pi talised patients over 50 years of age with lardive dyski nesia. Nine of lhe 2 I had persistent dyskinetic symptoms 3 months after stopping ant ipsychoti cs and antidepressants. These 9 patients had received antipsychotics for significantly longer than the pa tients with reversible dyskinesia (mean 10.8 years) and had had more (mean 5.6) drug interruptions of at least 2 mont hs' duration. )este. D.V. et a1. : of General 36: 585 iMay 1979) Results with clozapine give little cause for optimism Clozapine was beneficial in only 2 o f I 0 w ith various abnormal invol untary movement disorders. These included Huntington's disease. Gilles de la Toureue's syndro me, and atypical persistent dyskinesia. Two patients with Huntington 's d isease showed marked reduction in abnormal movements. The remain ing patients fa il ed to i mprove. Seven of the 10 patients had moderate to marked s ide effects. Caine. E_D. c\ a1, American Journal of Psychiatry 136, 311 (Mar 1979) 0156-2703/79/0908-0IXl9 $00.50 /0 Cl ADIS Press INPHARMA 8 Sep 1979 9

TARDIVE DYSKINESIA — A FEW CLUES IN THE SEARCH FOR A SOLUTION

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therapy

TARDIVE DYSKINESIA - A FEW CLUES IN THE SEARCH FOR A SOLUTION

Thiopropazate hydrochloride helps. but benztropine mesylate makes the condition worse Eight of 1 0 patients with tardive dyskinesia improved significantly and) were free of symptoms after 6 months on thiopropazate He l (' Dartalan ') J Omg daily. [5 patients completed at least 3 months on the drug and 8 showed improvement after I and J months, but this is nOl significant compared with drug-free control period. Thiopropazate seemed to be effective in controlling tardive dyskinesia without aggravation of its underlying pathophysiology and may be valuable as an adjunct in patients on other antipsychotic drugs. The study showed no benefit with previous therapy with the anticholinergic antiparkinson agent benztropine mesylate ('Cogentin '); in fact. 10 of the I 5 patients improved on s topping il.

'These findings support the hypothesis that tardive dyskinesia may res ult from dopaminergic hyperactivity and c holinergic hypoactivity in the corpus striatum,'

Smith. J.S. and KiJoh. L G.; Journal of Neurology. Neurosurgery. and Psychiatry 42: S760un 1979)

Effects of muscimol suggest that GABA augmentation may be worth a try Muscimol. a drug capable of augmenting y-aminobutyric acid (GABA) neuronal activity. s ignificantly diminished choreiform movements in 7 chronic schizophrenics with tardive dyskinesia. Patients received muscimol once daily in doses of 3-9mg PO after stopping amipsychotics at least 5 days previously. The effect of musci mol ~ked at 2 hours, when a 48 % decrease in involuntary movements occurred. Two of 3 patients with Parkinsonian movements showed exacerbation of symptoms for up to 5 hours after receiving muscimol. Behavioural side effects may limit the use of muscimol, but use of o ther GA BA stim ulating therapies may be

acceptable. Tamminga. CA. et at, Archi~es of General Psychiatry )6: 595 (May 1979)

The value of drug holidays seems doubtful The commonly held notion that freq uent lengthy interruptions of long term drug lreatment reduces the incidence of persistent dyskinesia was not borne out in 21 hospi talised patients over 50 years of age with lardive dyski nesia. Nine of lhe 2 I had persistent dyskinet ic symptoms 3 months after stopping antipsychotics and antidepressants. These 9 patients had received antipsychotics for significantly longer than the patients with reversible dyskinesia (mean 10.8 years) and had had more (mean 5.6) drug interruptions of at least 2 months' duration. )este. D.V. et a1. : Archi~es of General Psy~hiatry 36: 585 iMay 1979)

Results with clozapine give little cause for optimism Clozapine was beneficial in only 2 of I 0 patient~ with various abnormal involuntary movement disorders. These included

Huntington's disease. Gilles de la Toureue's syndrome, and atypical persistent dyskinesia. Two patients with Huntington's disease showed marked reduction in abnormal movements. The remaining patients failed to improve. Seven of the 10 patients had moderate to marked side effects. Caine. E_D. c\ a1, American Journal of Psychiatry 136, 311 (Mar 1979)

0156-2703 /79/0908-0IXl9 $00.50 /0 Cl ADIS Press INPHARMA 8 Sep 1979 9