J. D. Parkes

Deprenyl in the management of response fluctuations in patients with Parkinson's disease on levodopa.

Fluctuations in response to levodopa are a common and serious complication of long-term levodopa therapy. It may be possible to prolong the effect of each dose of levodopa by retarding the breakdown of dopamine. The selective monoamine oxidase type B inhibitor deprenyl, which is extensively metabolised to amphetamine and methamphetamine, has this effect as well as possible actions on dopamine release and re-uptake. In a double-blind crossover trial against placebo, deprenyl prolonged the action of levodopa and produced an objective improvement in mobility in five of 10 patients with dose-related response swings, and a subjective improvement in a further four patients. In another group of seven patients with random fluctuations in symptoms, only two noted subjective improvement, and there was an apparent increase in the severity of response swings in five patients. Deprenyl exacerbated dyskinesias, but had no serious side-effects. We conclude that deprenyl is unlikely to benefit patients with random response swings, and may cause deterioration in such cases. However, it may be a useful adjuvant in the management of dose-related response fluctuations in patients already on optional levodopa therapy.

Amphetamines in the treatment of Parkinson's disease.

Twenty-two patients with Parkinsonism were treated with levoamphetamine and 12 of these with dextroamphetamine. Levoamphetamine resulted in a significant improvement in disability from Parkinsonism, although the reduction in total disability, tremor, akinesia, and rigidity scores was slight (ca 20 percent). Dextroamphetamine in lower dosage also reduced disability by some 17 percent. The most disabled patients, including those also on levodopa, showed the greatest response to amphetamines. Previously, amphetamines have been reported to be a selective treatment for the oculogyric crises of post-encephalitic Parkinsonism. Amphetamines are thought to cause the release of catecholamines from central neurones. Their action in Parkinsons disease may be limited because of pre-existing striatal dopamine deficiency. Side-effects of amphetamines, anorexia, and CNS stimulation are different from those caused by levodopa in patients with Parkinsons disease.

Metoclopramide and pimozide in Parkinson's disease and levodopa-induced dyskinesias.

Metoclopramide is an antiemetic drug which occasionally produced acute dystonic reactions. Although known to interfere with central dopamine mechanisms, it is frequently used in Parkinsons disease to prevent levodopa-induced nausea and vomiting. In this study metoclopramide did not increase Parkinsonism or reduce levodopa-induced involuntary movements in patients with Parkinsons disease. Pimozide, by contrast, increased Parkinsonism and reduced involuntary movements. The capacity of metoclopramide to produce acute dyskinesias while being apparently free of Parkinsonism effects is pharmacologically unique and differentiates this drug from the phenothiazines and butyrophenones.

TREATMENT OF PARKINSON'S DISEASE WITH AMANTADINE AND LEVODOPA: A One-year Study

Abstract 66 patients with Parkinsons disease were studied during a year of treatment. 26 patients were given amantadine, and 40 more disabled patients were given amantadine combined with levodopa. Amantadine gave significant and persistent benefit and is the treatment of choice for the slightly disabled patient. The additional effect of levodopa was apparent in moderately disabled patients, for whom combined amantadine/levodopa therapy was the preferred treatment. Side-effects of amantadine were livedo reticularis and leg œdema, whereas levodopa caused involuntary movements and gastrointestinal toxicity. Amantadine caused physiological alterations in skin blood-vessels, and although it may have a catecholamine-mobilising action it had, unlike levodopa, no effect on the low homovanillic-acid concentration of the cerebrospinal fluid in parkinsonism. The indications for surgical treatment of patients with Parkinsons disease are few.

AMANTADINE DOSAGE IN TREATMENT OF PARKINSON'S DISEASE

Abstract Forty-three patients with parkinsonism were included in a trial of amantadine, doses of 100, 300, and 500 mg. per day being given each for a fortnight in random order to all patients. Every patient completed the trial. Results confirmed the benefit seen with amantadine in previous trials, and showed considerable individual variation in optimum dose, although the preferred dose was 300 mg. per day, resulting in a 26% reduction in initial disability score. The results at each dose level were independent of age, sex, duration of disease, concurrent medication, or type of disease. The response to amantadine at each dose level was greatest in the most disabled patients. Side-effects suggestive of atropine intoxication were seen in a quarter of patients at some stage of the trial, but could be abolished in some cases by reducing or stopping concurrent medication with benzhexol.

A double-blind trial of clonazepam in benign essential tremor.

Clonazepam has been reported to be of some value in the treatment of benign essential tremor in open trials. The efficacy of clonazepam was evaluated in a double-blind placebo-controlled study using up to 4 mg/day. By a variety of objective measures, clonazepam was not found to be an effective form of therapy.

Amphetamine, mazindol, and fencamfamin in narcolepsy.

Twenty patients with the narcoleptic syndrome were treated separately with dexamphetamine sulphate tablets 10 and 30 mg, Dexedrine Spansules 10 mg, mazindol 4 mg, and fencamfamin hydrochloride 60 mg daily. Each drug was given for four weeks and the effects compared. In these dosages the reported frequency of attacks of narcolepsy was roughly halved with each treatment, dexamphetamine 30 mg daily being only slightly more potent than 10 mg. The subjective effects of Dexedrine tablets and Spansules could not be distinguished by most patients. Effects on mood, alertness, and sympathomimetic side effects were largely inseparable with all these drugs, but a decrease in appetite was not reported by patients with narcolepsy.

COMBINED TREATMENT OF PARKINSONISM WITH L-DOPA AND AMANTADINE

Abstract A double-blind crossover trial of combined treatment with amantadine and L-dopa was conducted in twenty-four patients with parkinsonism. Twelve patients were on long-term treatment with L-dopa, and amantadine was added to their treatment; while twelve patients had L-dopa added to long-term treatment with amantadine. Further benefit was shown in the group in whom amantadine treatment was supplemented by the addition of L-dopa, whereas no additional benefit was detected in patients on optimal L-dopa therapy when amantadine was added. Combined treatment with these drugs is only indicated when the maximum tolerated dose of L-dopa is very small.

Comparative trial of benzhexol, amantadine, and levodopa in the treatment of Parkinson's disease

Fourteen slightly disabled patients with Parkinsonism were treated separately with benzhexol, amantadine, and levodopa. Benzhexol and amantadine both gave a 15% reduction in functional disability and levodopa a 36% reduction. Benzhexol lessened the rigidity and improved the flexion of posture of Parkinsons disease, but had little or no effect on akinesia and tremor. Amantadine and levodopa caused improvement in all these symptoms. The combination of benzhexol and amantadine was as effective after four weeks of treatment as levodopa was after six months.

Sodium valproate in the treatment of levodopa-induced dyskinesia.

The effect of sodium valproate 1200 mg daily on the disability of Parkinsonism and on levodopa-induced dyskinesia was assessed in a double-blind crossover trial with matched placebo in 12 patients with Parkinsons disease. No objective change in the severity of Parkinsonism or dyskinesias was noted. However, six out of nine patients who completed the trial noted a slight to moderate improvement in their dyskinesias with no change in their Parkinsonism. Excess salivation improved in four subjects on sodium valproate.