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Pharmacoeconomic analysis of antidepressants for major depressive disorder in the United Kingdom |
Freeman H, Arikian S, Lenox-Smith A |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology Antidepressants for major depressive disorder (MDD). The serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (norepinephrine) reuptake inhibitor (SNRI) venlafaxine was compared with selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants.
Economic study type Cost-effectiveness analysis.
Study population Patients suffering from MDD.
Setting The practice setting was primary care (outpatients). The economic analysis was carried out at Wyeth Laboratories, Taplow, Berkshire, UK.
Dates to which data relate It was not clear when the effectiveness and resource data were collected for the study model. 1998 prices were used.
Source of effectiveness data The estimates for the effectiveness of antidepressants in the treatment of MDD were based on a review/synthesis of completed studies and opinion (consultations with a "Delphi panel").
Modelling A decision tree model was used to estimate benefits and costs.
Outcomes assessed in the review Success rates and dropout rates were computed from the results of the literature review.
Study designs and other criteria for inclusion in the review The inclusion criteria used were: primary studies had to be double-blind, prospective RCTs which examined at least one of the drugs assessed at acceptable levels in at least one research arm; patients had to be adult in- or outpatients with major depression (Hamilton Depression Rating Scale (HAM-D) greater than 14 or Montgomery-Asberg Depression Rating Scale (MADRS) greater than 17), washout period (1-2 weeks) at start of trial; efficacy clearly defined (50% reduction in rating score); and dropouts identified. Exclusion criteria were: atypical depression, double depression, resistant depression, bipolar depression, concurrent psychological illnesses (psychosis, mania, etc.), organic depression and depression secondary to other diseases (e.g. Myocardial Infarction).
Sources searched to identify primary studies The authors searched databases, including MEDLINE, EMBASE, and International Pharmaceutical Abstracts. All clinical papers analysing the treatment of MDD between January 1980 and December 1997 were identified. References from retrieved papers were used to identify additional studies.
Criteria used to ensure the validity of primary studies No details were provided.
Methods used to judge relevance and validity, and for extracting data Number of primary studies included 44 studies were included in the analysis.
Methods of combining primary studies Summary statistics were combined across arms of studies using meta-analytic techniques.
Investigation of differences between primary studies Results of the review The highest efficacy rate for outpatients with MDD was with venlafaxine use (73.7%) compared with 61.4% for SSRIs and 59.3% for TCAs.
The corresponding dropout rates, due to lack of efficacy, were 4.8% with venlafaxine , 8.4% with SSRIs and 6.8% with TCAs.
Methods used to derive estimates of effectiveness The authors consulted a "Delphi panel" of 3 psychiatrists and 2 GPs.
Estimates of effectiveness and key assumptions No details of estimates of effectiveness were given.
Measure of benefits used in the economic analysis Benefits were expressed in terms of symptom free days (SFDs).
Direct costs Direct costs included medication (source: MIMS 1998), doctor's time and hospitalisation (source: Centre for Health Economics, University of York 1998). Direct costs were computed from the perspective of a health service. 1998 prices were used. Discounting was not required as the period of study was only six months.
Indirect Costs Indirect costs were not included.
Sensitivity analysis Monte Carlo analysis (10,000 iterations) was used to vary success and drop out rates as well as costs. Univariate break-even analyses were conducted on drug prices, success rates and others. Rates were varied with 95% CI, while costs were varied +/- 10% to 20% of the estimated cost, based on a uniform distribution.
Estimated benefits used in the economic analysis SFDs were not reported. It was stated that venlafaxine yielded superior outcomes compared to TCAs and SSRIs.
Synthesis of costs and benefits Treatment with venlafaxine yielded the lowest outpatient cost for an SFD (10.53), compared with 13.23 (SSRIs) and 15.52 (TCAs). Incremental cost-effectiveness analysis was not performed and only the above average ratios were reported. The sensitivity analyses indicated the robustness of the model.
Authors' conclusions Using the economic model within the study the authors stated that venlafaxine appeared to be a cost-effective treatment for outpatients with MDD in the UK.
CRD COMMENTARY - Selection of comparators The selection of antidepressants used in the treatment of MDD was justified. They were commonly prescribed drug groups within the
Validity of estimate of measure of benefit The effectiveness evidence was derived from a meta-analysis based on a literature review published elsewhere, as well as on consultations with specialists (a "Delphi panel"), and, from the methodology reported in this paper, the review appears to have been systematic. However, there is insufficient detail to assess the quality of the methods used to derive the effectiveness evidence. The measure of benefit used in the economic analysis (SFD) appears to have been appropriate.
Validity of estimate of costs Detailed descriptions of the methods of cost estimation were provided. The UK National Health Service (NHS) perspective adopted in the analysis makes the study results particularly useful in the UK setting. However, it would have been very useful if more details had been provided about the results of the main analyses and sensitivity analyses performed. This could have enhanced the applicability of the study findings in various UK settings. The authors reported average cost-effectiveness ratios and only stated that venlafaxine was the dominant strategy. No attempt was made to perform incremental cost-effectiveness analysis which, according to the authors statements, appears not to have been relevant.
Other issues Extensive sensitivity analyses were performed in order to account for the uncertainties in the model. However, the authors could have provided more details regarding their findings. The authors did not compare their findings with other studies and only offered a brief discussion on the usefulness of the study for the UK NHS.
Implications of the study The study implies that increasing pharmacy budgets will, in the longer term, result in cost savings through the cost-effectiveness of the favoured treatment. The authors stated that in order to substantiate this claim further analysis is required in the shape of outpatient-based RCTs.
Source of funding Sponsored by an unrestricted grant from Wyeth Laboratories.
Bibliographic details Freeman H, Arikian S, Lenox-Smith A. Pharmacoeconomic analysis of antidepressants for major depressive disorder in the United Kingdom. PharmacoEconomics 2000; 18(2): 143-148 Other publications of related interest Einarson T R, Arikian S R, Casciano J, et al. Comparison of extended-release venlafaxine, selective serotonin reuptake inhibitors, and tricyclic antidepressants in the treatment of depression: a meta-analysis of randomized controlled trials. Clinical Therapeutics 1999;21(2):296-308.
Indexing Status Subject indexing assigned by NLM MeSH Antidepressive Agents /therapeutic use; Cost-Benefit Analysis; Depressive Disorder /drug therapy /economics; Humans; Meta-Analysis as Topic; Monte Carlo Method AccessionNumber 22000008281 Date bibliographic record published 31/05/2001 Date abstract record published 31/05/2001 |
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