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Treatment of depression in Parkinson's disease: a meta-analysis |
Klaassen T, Verhey F R, Sneijders G H, Rozendaal N, de Vet H C, van Praag H M |
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Authors' objectives To evaluate the effect of antidepressants in depressed Parkinson's disease patients, with the aim of extracting guidelines for the pharmacological treatment of depression in Parkinson's disease if possible.
Searching MEDLINE was searched from 1966 to June 1993 using the following keywords: 'parkinson', 'Parkinson's disease', 'depression', 'mood', 'affective disorder', 'therapy', 'drugs' and 'antidepressant'. Mental Health abstracts and PsycLIT were searched from 1969 to 1993 and 1974 to 1993, respectively, using the same keywords. Textbooks on neuropsychiatry were also checked and relevant references were looked up. Seventeen pharmaceutical companies were asked to supply relevant literature. Only studies written in English, French, German or Dutch were included.
Study selection Study designs of evaluations included in the reviewPlacebo-controlled studies published after 1965.
Specific interventions included in the reviewThe following antidepressants were compared with placebo: selegiline (10 to 30 mg/day; NOTE, selegiline was originally introduced as an antidepressant, though it is now used as an antiparkinsonian drug), amitriptyline (25 mg/day), clomipramine (150 mg/day), desipramine (100 mg/day), imipramine (30 to 100 mg/day), bupropion (maximum dose 450 mg/day) and nomifensine (150 mg/day).
Participants included in the reviewThe majority of the participants suffered from idiopathic parkinsonism. Other participants included were those who suffered from encephalitis, vascular Parkinson's disease, Parkinson's disease after stereotactic surgery, de novo Parkinson's disease, advanced Parkinson's disease and Parkinson's disease with headaches. Some studies also included depressed patients who did not have Parkinson's disease.
Outcomes assessed in the reviewDepression or mood was measured using one of the following scales or methods: Hamilton depression rating scale, Zung self-rating depression scale, Beck Depression Inventory, Andersen scale, Global Clinical Impression scale for depression, or a clinical examination.
How were decisions on the relevance of primary studies made?The authors do not state how the papers were selected for the review, or how many of the authors performed the selection.
Assessment of study quality The list used was adapted from ter Riet et al. (see Other Publications of Related Interest).
Study population: description, randomisation, blinding, study size, baseline comparability, drop-outs, loss to follow-up.
Interventions: treatment group, placebo group, co-interventions.
Measurement of effect: blinding of patient, blinding of therapist, blinding of observer, outcome measures, measurement timing, side-effects.
Data presentation and analysis: results presented, intention to treat analysis, statistical methods.
The papers to be reviewed were blinded for author, name and location of institute, journal, date and treatment outcome. Two raters, who were not involved in the design of the methodological criteria, scored the papers using the criteria. Two raters then scored the papers for statistical quality. The raters did not know how much weight was given to each criterion. Disagreements were resolved by consensus at a subsequent meeting; where disagreement persisted a fourth blinded reviewer made the final decision.
Data extraction The authors do not state how the data were extracted for the review, or how many of the authors performed the data extraction.
Methods of synthesis How were the studies combined?The studies are presented in tabular format. There is some narrative synthesis.
How were differences between studies investigated?Differences between the studies were not investigated.
Results of the review Twelve studies (n=381) were included.
Only 4 of the 12 studies received a validity score higher than 50 (out of 100), the best scoring 78. The methodology of most papers was scored as poor to moderate. Only 1 of the 12 studies was restricted to patients with both Parkinson's disease and depression. The authors state that the clinical significance of the 4 articles that had scores above 50 is limited because the mean scores of the patients on the Hamilton and the Zung scales were in the nondepressed range. In 5 of the 12 studies antidepressants had a positive effect, and in seven they did not.
Authors' conclusions The question of how depression in Parkinson's disease should be treated cannot be answered authoritatively. Until more research is done, therapeutic directives are at best only provisional.
CRD commentary The review is methodologically sound with a clearly-defined research question, a comprehensive literature search, clearly-defined inclusion criteria and rigorous validity assessment. More details of the included studies could have been presented, and the results could have been presented more clearly. The authors explain why they do not regard the results of the studies as reliable and, therefore, their conclusions do follow from the evidence presented.
Implications of the review for practice and research Practice: Antidepressants with relatively strong anticholinergic potency, such as amitriptyline, should be avoided because of their impact on cognitive functions. Nortriptyline is preferred.
Research: The authors state that a critical review of the antiparkinsonian medication should be carried out to assess its effect on depressive symptoms. If an antidepressant is indicated, the authors recommend that the choice be based primarily on a favourable profile of side-effects since there is no evidence to indicate whether tricyclics are better or worse than newer antidepressants.
Bibliographic details Klaassen T, Verhey F R, Sneijders G H, Rozendaal N, de Vet H C, van Praag H M. Treatment of depression in Parkinson's disease: a meta-analysis. Journal of Neuropsychiatry and Clinical Neurosciences 1995; 7(3): 281-286 Other publications of related interest 1. ter Riet G, Kleynen J, Knipschild P. Acupuncture and chronic pain: a criterion based meta-analysis. J Clin Epidemiol 1995;48:691-704.
Indexing Status Subject indexing assigned by NLM MeSH Alzheimer Disease /complications; Antidepressive Agents /therapeutic use; Clinical Trials as Topic; Depressive Disorder /drug therapy /etiology /psychology; Humans; Parkinson Disease /complications; Placebos AccessionNumber 11995002127 Date bibliographic record published 31/05/2000 Date abstract record published 31/05/2000 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. |
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