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Selective serotonin reuptake inhibitors (SSRIs) in the treatment of elderly depressed patients: a qualitative analysis of the literature on their efficacy and side-effects |
Menting J E, Honig A, Verhey F R, Hartmans M, Rozendaal N, de Vet H C, van Praag H M |
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Authors' objectives To assess the efficacy and side-effects of selective serotonin re-uptake inhibitors (SSRIs) for the treatment of elderly people with depression.
Searching MEDLINE was searched from January 1980 until December 1994 using the keywords 'fluvoxamine', 'paroxetine', 'fluoxetine' and 'sertraline' combined with 'aged', 'elderly' or 'geriatric'. The citations in all of the identified papers were also examined for additional studies.
Study selection Study designs of evaluations included in the reviewThe studies had to be placebo-controlled or controlled with a known antidepressant agent; assess the efficacy of fluvoxamine, paroxetine, fluoxetine or sertraline; and be written in English, French, German or Dutch.
Specific interventions included in the reviewSSRIs were compared with placebo or tricyclic antidepressants (TCAs). The SSRIs were fluoxetine (20 to 80 mg/day), paroxetine (10 to 40 mg/day), sertraline (50 to 200 mg/day) and fluvoxamine (50 to 200 mg/day). The TCAs were amitriptyline (50 to 150 mg/day), clomipramine (20 to 75 mg/day), dothiepin (50 to 100 mg/day), doxepin (50 or 150 mg/day), imipramine (160 mg/day), mianserin (20 to 80 mg/day) and tradodone (50 to 400 mg/day).
Participants included in the reviewElderly adults (aged over 59 years) who were being treated for depression were included.
Outcomes assessed in the reviewAntidepressant efficacy was measured using 15 different measurement scales for depression. In addition, the total number of drop-outs, drop-outs due to side-effects, and sideeffects, were assessed.
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 Four of the authors designed a list of 46 items covering 11 methodological aspects of a pharmacological study. These items assessed the quality of each study according to: the internal validity and precision of the study; the adequacy of the study population and interventions; and the effect parameters. Papers blinded for the author, the name of the institution and its location, were assessed by two reviewers who had not been involved in the design of the quality assessment. The reviewers met to achieve consensus on the criteria when there was disagreement, and in cases of disagreement at that stage, a third reviewer made the final decision. The blinding was also assessed in a separate process.
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 Mantel-Haenszel fixed-effect model was used to calculate the pooled odds ratios (ORs), along with 95% confidence intervals (CIs), in order to assess whether SSRIs led to more side-effects, drop-outs and drop-outs due to side-effects.
How were differences between studies investigated?The ORs of the individual studies were tested for heterogeneity using Woolf's method (see Other Publications of Related Interest).
Results of the review Eighteen papers with 16 studies met the inclusion criteria. After applying a methodological quality score cut-off point of 55 (out of 100), only 6 studies were included in the review. There was a total of 416 patients in the SSRI group and 307 patients in the TCA comparison group.
The quality scores ranged from 25 to 72.
No significant difference between the SSRIs and the comparator drugs was found in any of the studies, as measured by the mean reduction in the total scores (Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale) after treatment (4 to 8 weeks).
The total drop-outs were 40.7% in the SSRI group and 50% in the TCA group (OR 0.67, 95% CI: 0.47, 0.97, p=0.03).
The drop-outs due to side-effects were 24.5% in the SSRI group and 31.7% in the TCA group (OR 0.67, 95% CI: 0.45, 1.00, p=0.05).
The side-effects were 76.2% in the SSRI group and 86.6% in the TCA group (OR 0.34, 95% CI: 0.15, 0.76, p=0.007).
Authors' conclusions The authors tentatively concluded that SSRIs were as effective as TCAs in the treatment of elderly people, but this cannot be concluded for both in- and out-patients since no in-patient study was included in the review. The results were also doubtful for the population-at-large. Side-effects occurred less frequently with SSRIs than with TCAs, and different side-effect profiles were found. Significantly fewer SSRI-treated patients than TCA-treated patients dropped out, both overall and due to side-effects.
CRD commentary The authors included non-English trials (French, Dutch and German) in the review, but it was unclear whether an attempt was made to search for abstracts or unpublished data. The inclusion criteria for the individual trials and their participants were stated, and the authors made a detailed assessment of the quality of the included studies. However, the method used to select the studies for inclusion was not reported.
The authors listed the studies and the data extracted in a tabular format, and also discussed these data in the review. The studies were discussed in a narrative format for the review of effectiveness, but the pooled ORs were calculated for the three outcomes relating to the side-effects and drop-outs.
The results of the review should be viewed with caution due to the very large number of drop-outs from the included studies, which are not explained in the original studies, and the wide range of different tests used to measure study outcomes in the original studies. It is doubtful whether ORs should have been pooled when the characteristics of the included studies were so different for the treatment (drug and dosage) and outcome measurement.
The authors' conclusion that SSRIs are as effective as TCAs is not shown in the narrative discussion, but is drawn from studies which did not meet the methodological quality score for inclusion.
Implications of the review for practice and research The authors state that the application of detailed, standardised, side-effect questionnaires would increase knowledge of adverse effects and the ability to compare studies. They also state that, given the large number of elderly patients suffering depression and the poor state of current knowledge regarding the efficacy and side-effects of current drug treatments, well-designed research programmes in elderly patients and those with somatic comorbidity are urgently needed.
Bibliographic details Menting J E, Honig A, Verhey F R, Hartmans M, Rozendaal N, de Vet H C, van Praag H M. Selective serotonin reuptake inhibitors (SSRIs) in the treatment of elderly depressed patients: a qualitative analysis of the literature on their efficacy and side-effects. International Clinical Psychopharmacology 1996; 11(3): 165-175 Other publications of related interest Kleinbaum DG, Kupper LL, Morgenstern H. Epidemiologic research. Principles and quantitative methods. London: Lifetime Learning Publications; 1982.
Indexing Status Subject indexing assigned by NLM MeSH 1-Naphthylamine /adverse effects /analogs & Aged; Anorexia /chemically induced; Antidepressive Agents /adverse effects /therapeutic use; Depressive Disorder /drug therapy; Diarrhea /chemically induced; Fluoxetine /adverse effects /therapeutic use; Fluvoxamine /adverse effects /therapeutic use; Humans; Meta-Analysis as Topic; Nausea /chemically induced; Paroxetine /adverse effects /therapeutic use; Patient Dropouts; Serotonin Uptake Inhibitors /adverse effects /therapeutic use; Sertraline; Single-Blind Method; derivatives /therapeutic use AccessionNumber 11997003205 Date bibliographic record published 31/10/1999 Date abstract record published 31/10/1999 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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