Home > DARE Reviews > A review of intermittent subcutaneous...

PubMed Health. A service of the National Library of Medicine, National Institutes of Health.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

A review of intermittent subcutaneous apomorphine injections for the rescue management of motor fluctuations associated with advanced Parkinson's disease

JJ Chen and C Obering.

Review published: 2005.

CRD summary

This review assessed the efficacy of intermittent subcutaneous apomorphine injections for the management of 'off' episodes in patients with Parkinson's disease. The authors concluded that apomorphine provides prompt and consistent rescue from 'off' episodes. The review has several methodological weaknesses and it is unclear whether the results of the included studies and the synthesis of them can be relied upon.

Authors' objectives

To review the clinical efficacy and tolerability, as well as the pharmacology, of intermittent subcutaneous apomorphine injections for the management of 'off' episodes (motor fluctuations due to the waning effect of dopaminergic drugs) in patients with Parkinson's disease (PD).

Searching

MEDLINE and International Pharmaceutical Abstracts were searched up to July 2005 for English-language papers. The Cochrane Database of Systematic Reviews was also searched. The reference lists of papers were checked and the U.S. manufacturer of apomorphine provided information.

Study selection

Study designs of evaluations included in the review

Inclusion criteria for the study design were not specified.

Specific interventions included in the review

Studies of intermittent subcutaneous injections of apomorphine were eligible for inclusion. Studies of continuous infusion and nonsubcutaneous administration were excluded. The daily dose, where reported, was 2 to 34.29 mg in the open-label studies and 3 to 14.5 mg in the double-blind studies. The dose per injection varied between studies. The mean duration of therapy ranged from one dose to 22 months in the open-label studies and from one dose to 2 months in the double-blind studies. All but one of the comparative studies were placebo-controlled.

Participants included in the review

Studies of patients with PD were eligible for inclusion. The baseline daily dose of levodopa received by patients in the included open-label studies was 635 to 1,430 mg. Further patient details were limited.

Outcomes assessed in the review

Inclusion criteria for the outcomes were not specified. The outcomes reported in the review were daily levodopa dose following the intervention, daily 'off' time (number of hours or proportion of waking day) and motor functioning based on a number of different scales.

How were decisions on the relevance of primary studies made?

The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.

Assessment of study quality

The authors did not state that they assessed validity.

Data extraction

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction.

Methods of synthesis

How were the studies combined?

Study details were tabulated and some individual studies were summarised in the text.

How were differences between studies investigated?

Open-label and double-blind studies were grouped separately.

Results of the review

Twenty-one studies were included: 8 double-blind trials (n=126), six of which were of a crossover design, and 13 uncontrolled open-label studies (n=202).

Following administration of apomorphine, the decrease in daily 'off' time from baseline ranged from 2.6 to 4 hours (6 studies) and 20.5% and 22% (2 studies) of the waking day in the open-label studies. Two studies reported that the difference was statistically significant, while six did not report a statistical comparison. The mean delay of onset ranged from 6 to 14 minutes (6 studies). The mean duration of effect ranged from 36 to 61.9 minutes (5 studies).

In the double-blind trials, all of the studies except one reported a statistically significant difference between apomorphine and placebo (8 studies) or levodopa (1 study) for motor functioning, with the improvement in favour of apomorphine. The mean delay of onset ranged from 8.1 to 22 minutes (3 studies). The mean duration of effect ranged from 56.6 to 96 minutes (2 studies).

Based on one study of 29 participants, which the authors stated provided the most extensive data on adverse events in apomorphine-naive patients, several adverse events were reported. The most common adverse events (30% or greater) were injection-site reaction, yawning, dyskinesias, drowsiness and nausea or vomiting.

Authors' conclusions

In patients with PD, apomorphine is effective at providing prompt and consistent rescue from 'off' episodes.

CRD commentary

Inclusion criteria were stated for the intervention and the participants of interest, but not for the outcomes or study design. Since only English language studies were included and only limited attempts were made to locate unpublished studies, relevant data might have been missed. The review methodology was poorly described and it was unclear whether appropriate measures had been taken to minimise error and bias. Study quality was not assessed and the impact of quality on the study findings was not discussed. Although the results of individual studies were tabulated, the authors did not systematically synthesis the results of all the studies in the narrative. Some individual studies were discussed, but it is unclear why these had specifically been selected for discussion. The reliability of the authors' conclusions is unclear given the poor reporting of the review process, the lack of a quality assessment, and the selective synthesis. In addition, the conclusions were based on a fairly small number of patients and the data available for some outcomes were limited.

Implications of the review for practice and research

Practice: The authors recommended close medical supervision and anti-emetic prophylaxis when initiating apomorphine therapy.

Research: The authors did not state any implications for further research.

Bibliographic details

Chen J J, Obering C. A review of intermittent subcutaneous apomorphine injections for the rescue management of motor fluctuations associated with advanced Parkinson's disease. Clinical Therapeutics 2005; 27(11): 1710-1724. [PubMed: 16368444]

PubMedID

16368444

Indexing Status

Subject indexing assigned by NLM

MeSH

Antiparkinson Agents /administration & dosage /pharmacology /therapeutic use; Apomorphine /administration & dosage /pharmacology /therapeutic use; Clinical Trials as Topic; Dopamine Agonists /administration & dosage /pharmacology /therapeutic use; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Interactions; Economics, Pharmaceutical; Humans; Injections, Subcutaneous; Levodopa /therapeutic use; Parkinson Disease /drug therapy /physiopathology

AccessionNumber

12006000532

Date bibliographic record published

30/11/2006

Date abstract record published

30/11/2006

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 16368444

PubMed Health Blog...

read all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...