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.
IN animal experiments several investigators have demonstrated the depletoxy action of reserpine on the stores of catecholamines (CARLSON and HILLARP, 1956; BERTLER, CARLSSON and ROSENGREN, 1956; HOLZBAUER and VOCT, 1956; BRODIE, OLIN, K u " and SHORE, 1957; CARLSSON, ROSENGREN, BERTLER and NILSON, 1957; STJ-and SCHAPIRO, 1958). In patients treated with reserpine BURGER (1957) found a decrease in blood noradrenaline, and GADDUM et al. (1958) reported a diminished excretion in urine of adrenaline and noradrenaline. As part of an investigation of the excretion of catecholamines in mental patients under treatment with various drugs, a group of male schizophrenic patients under reserpine treatment were examined. The dosage of reserpine varied from 1 to 9 mg daily, usually 3 mg. Duration of treatment: 6 to 45 months. METHODS Determination of catecholamines in urine. The urine was collected for 24 hr in bottles containing U ) o d N-perchloric acid. One hundred mg ethylene diamine tetraacetic acid (disodium salt) and 5 mg ascorbic acid were added to two urine samples of 10 ml each. To one sample was added 2 pg noradredhe in order to check the recovery. (Recoveries of both adrenaline (A) and noradrenaline (NA)are usually about 80 per cent.) By means of a Beckman-titrator or bromthymol blue the samples were neutralized to pH 7. centrifuged, and passed through a Dowex 50, X-8, column (2W-400 mesh, dimensions 5.5 x I5 mm), loaded with 0.1 M-phosphate buffer, pH 6.5. The flow rate was kept at 0.5-1 ml/min. The column was washed with 40 ml distilled water. A and NA were eluted with 7 9 ml N-HC~. The eluates were neutralized to pH about 6.5 (checked with indicator paper) by means
In his attempts to estimate the comparative value and potency of a neuroleptic agent the clinician may frequently find his primary impressions corrected or modified through prolonged and extensive use of the drug in question,The "fate" of the butyrophenone derivative floropipamide (DipiperonB) in this hospital may serve as an illustration. As a result of a pilot study conducted in 1963 on 70 schizophrenic women we were inclined to classify this drug as a potent anti-psychotic agent, similar in action to the piperazinated phenothiazines. At a later period a controlled comparative trial on 16 schizophrenic patients of both sexes failed to demonstrate any difference in action and side effects between floropipamide and chlorpromazine. To-day being more familiar with the drug we feel justified in our estimation of floropipamide as belonging to the predominantly sedative neuroleptics, with an anti-psychotic potency and side-effects placing it at a level between chlorpromazine and chlorprothixene.As on the other hand the first representative of the butyrophenone-series, haloperidol (SerenaseB) seems to maintain its position as a potent, low dosage neuroleptic agent, a retrospective review of clinical trials of this drug might possibly reveal some points of interest.Numerous uncontrolled studies of the clinical effects of haloperidol, from various parts of Europe and the British Commonwealth show much conformity.All investigators agree on the efficacy of the drug against mania and states of acute agitation.Bohacek (1964) collected information on about 100 cases of mania treated with haloperidol, showing satisfactory results in more than 90 per cent, which is in accordance with the author's own finding.In a review of 39 clinical studies from 11 European countries comprising more than 500 manic patients, excellent results were reported in 78 per cent and good results in a further 15 per cent, totalling 93 per cent of the cases treated. The only phenothiazine derivative with which corresponding results are reported is thioproperazine (Majeptil), but with more frequent and severe side-effects.
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