Effect of sodium valproate on tardive dyskinesia. The effect of sodium valproate on tardive dyskinesia--revisited. Effect of sodium valproate and baclofen in tardive dyskinesia: clinical and neuroendocrine studies. Effect of baclofen on tardive dyskinesia. Brain gamma-aminobutyric acid abnormality in tardive dyskinesia. Reduction in cerebrospinal fluid GABA levels and therapeutic response to GABA agonist treatment.
The effect of sodium valproate, a drug which has been demonstrated to increase gamma-aminobutyric acid levels in the CNS, on tardive dyskinesia and psychiatric symptoms was investigated in a double-blind cross-over study on 32 chronic psychiatric patients. The oro-facial dyskinesias were totally or significantly relieved in 17 cases. During the active treatment period the involuntary movements of the extremities and dystonic spasms were also significantly relieved in 7 out of 9 patients. In two patients, however, the extrapyramidal symptoms became slightly worse. A significant improvement was noted in the psychiatric symptoms of 14 out of 32 patients during sodium valproate administration. The psychiatric state of 4 out of 32 patients deteriorated. Three was no correlation between the serum concentration of sodium valproate and its effect on the dyskinesia or on the psychiatric symptoms. Some of the elderly subjects showed a slight accumulation of the drug. As a treatment for tardive dyskinesia, sodium valproate was tested in a double-blind placebo-controlled parallel group trial, with 6-week base-line observation period followed by 6 weeks of treatment. Sodium valproate was not found to be an effective treatment for either tardive dyskinesia or drug-induced Parkinsonism, and did not affect mental state or behaviour. Concurrent neuroleptic administration is a necessary factor in the therapeutic response to GABAergic agents. In contrast to their effect on the striatum, neither BAC nor NaV influences hypothalamic-pituitary DA function mediating PRL secretion. Eighteen chronic psychiatric patients with neuroleptic-induced tardive dyskinesia of 1/2-9 years duration participated in a double-blind crossover study on the effect and side effects of baclofen and placebo in the treatment of tardive dyskinesia. Each treatment phase lasted 3 weeks. Evaluation of the results included an assessment of video-tape recording. Baclofen (20-120 mg daily) reduced the hyperkinesias (median score from 5 to 3, P less than 0.05) and increased the parkinsonism (median score from 5 to 7, P less than 0.01). The effect on the oral movement pattern of tardive dyskinesia was characterized by a reduced frequency, an unchanged or slightly reduced amplitude, and an increased duration of each separate mouth opening and tongue protrusion, a response pattern very similar to the response pattern of alpha-methyl-p-tyrosine, an inhibitor of the catecholamine synthesis. Sediation, muscular weakness, and confusion were observed in 50% of the patients. These side effects, appearing mainly in elderly patients, sometimes set in before the anti-hyperkinetic effect, thus limiting the practical usefulness of baclofen in the treatment of tardive dyskinesia. A double-blind, placebo-controlled trial of gamma-vinyl gamma-aminobutyric acid (GVG) and 4,5,6,7-tetrahydroisoxazolo-(5,4-c) pyridine-3-ol (THIP) was carried out in drug-free schizophrenic patients with tardive dyskinesia. A significant decrease in dyskinetic symptoms occurred with the administration of GVG, associated with a twofold increase in cerebrospinal fluid levels of GABA; THIP produced a more moderate, yet consistent decrease in the involuntary movements. A pathophysiologic role for gamma-aminobutyric acid (GABA)-mediated neuronal transmission in tardive dyskinesia was explored by analyzing cerebrospinal fluid GABA concentrations in drug-free schizophrenic patients with and without tardive dyskinesia. A significant reduction in cerebrospinal fluid levels of GABA was observed in the dyskinetic schizophrenics compared with the nondyskinetic controls. These data compliment a growing body of experimental evidence suggesting a critical role for GABA-ergic neurons in the pathophysiology of tardive dyskinesia.
Evidence of the effects of baclofen, progabide, sodium valproate, or THIP for people with antipsychotic-induced TD is inconclusive and unconvincing. Any possible benefits are likely to be outweighed by the adverse effects associated with their use.