Evidence Table TxMN10What is the effectiveness of beta-blockers vs. placebo or levodopa in the treatment of functionally disabled early Parkinson’s disease?

Bibliographic referenceCrosby, N. J., Deane, H. O., & Clarke, C. E. 2004, “Beta-blocker therapy for tremor in Parkinson’s disease.(Cochrane Review)”, The Cochrane Library no. Issue 2.
Study typeCochrane Systematic Review (of randomised, placebo-controlled, double-blinded trials)
Evidence level1++
Study objectiveTo compare the efficacy and safety of adjuvant beta-blocker (BB) therapy against placebo for the treatment of tremor in patients with Parkinson’s disease
Number of patientsN=72 Parkinson’s disease (PD) patients

Location: UK (Claveria and Marsden) and Australia (Corbett, Henderson)
Sites: One (all studies)
Patient characteristicsThe baseline characteristics were not given in two trials (Claveria, Marsden)
Two trials gave baseline characteristics but did not compare the distribution of the characteristics been actively treated and placebo treated groups (Corbett, Henderson)
InterventionAdjuvant oral BB therapy:
Claveria: oxprenolol 160 mg/day over 6 weeks
Corbett: Oxprenolol 160–320 mg/day over 4 weeks
Marsden: propanolol 40 mg/day 1st week, 80 mg/day 2nd week, 120 mg/day last 2 weeks
Henderson: propanolol 20mg/day, 40 mg/day and 80 mg/day (each dose was administered once over a period of 2 days and each dose was followed by an assessment of its effect-therefore single doses and not long-term effects were assessed in this trial).
ComparisonPlacebo
Length of follow-up2 days to 6 weeks
Outcome measuresQuality of life, PD activities of daily living rating scales, PD motor impairment rating scales, individual motor performance tests, accelerometer outcomes, electromyographic activity outcomes, patient self-evaluation rating scales, adverse event frequency, number of withdrawals
Effect sizeClinical outcomes:
➢ Corbett, Marsden, and Henderson (cross-over trials) did not present data from the end of first arms
➢ Since there is a carry-over risk the systematic review did not analyse the data from these trials
➢ Claveria was also a cross-over trial but did present data from first arm of trial
➢ Only mean total score for tremor in each group in the first arm was reported
➢ They did not state baseline scores, numbers of patients in each group, or standard deviations
➢ Magnitude and significance of effect of any changes due to BB therapy could not calculated
➢ They did report there was no significant difference between oxprenolol and placebo
➢ Details of the data analysis are not given so it is not possible to tell whether the non-significance is based on comparison between the first and second arms (which could have been affected by a possible cross-over effect) or between the therapy and placebo groups at the end of each arms

Adverse events
➢ Marsden reported mean pulse rate fell from 84 on placebo to 74 with maximum dose of propanolol
➢ 14/22 patients showed a ‘substantial’ fall in rate but author’s did not define what this constituted
➢ One patient was withdrawn from the study when his pulse rate dropped to 56 per minute
➢ Claveria reported no adverse events
➢ Henderson did not state whether any adverse events occurred
➢ Corbett reported adverse events but it is unclear which occurred in the trial with parkinsonism patients and which occurred in a separate trial with patients with essential tremor
Source of fundingNo sources of support supplied
Additional comments➢ None of the preparations used controlled-release forms of BB
➢ Pervious anti-Parkinson medication was unaltered in 3 studies- but Henderson stopped propanolol treatment 1 week before study and levodopa stopped 12 h before each test dose
➢ All 4 trials failed to provide details of the methods of randomisation and concealment allocation
➢ No trials defined the criteria used to differentiate IPD from other forms of parkinsonism
➢ Small sample size (n=72)- could affect generalisability of results
➢ All four trials were double-blinded
➢ All trials too short in duration for long-term effects to be determined
➢ Trials were too small for the frequency of adverse events to be calculated
Systematic review conclusions: in view of this lack of evidence, it is impossible to determine whether BB therapy is a safe and effective treatment for the tremor of PD
➢ Included studies: Claveria (1975), Corbett (1976), Henderson (1994), Marsden (1974)
NCC CC ID (Ref Man)80

From: Evidence Tables

Cover of Parkinson's Disease
Parkinson's Disease: National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care.
NICE Clinical Guidelines, No. 35.
National Collaborating Centre for Chronic Conditions (UK).
Copyright © 2006, Royal College of Physicians of London.

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