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Cost effectiveness of representatives of three classes of antidepressants used in major depression in the UK |
Lenox-Smith A, Conway P, Knight C |
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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 Three different classes of antidepressants used in major depression were under examination. The three classes were serotonin and noradrenaline reuptake inhibitors (venlafaxine), selective serotonin reuptake inhibitors (SSRIs; fluoxetine, paroxetine and fluovoxamine) and tricyclic antidepressants (TCAs; amitriptyline).
Economic study type Cost-effectiveness analysis.
Study population The study population comprised patients with major depressive disorders.
Setting The setting was primary care. The economic analysis was conducted in the UK.
Dates to which data relate The effectiveness data were gathered from two studies published in 1993 and 2001. The dates to which the resource data related were not reported. The price year was 2001.
Source of effectiveness data The effectiveness data were derived from a non-systematic review of the literature.
Modelling A decision analytic model was constructed to estimate the cost-effectiveness of the antidepressant treatments. This model was based on another model (Freeman et al., see Other Publications of Related Interest" below) and was amended in discussion with a five-member Delphi panel (UK general practitioners and UK psychiatrists). Each treatment phase had a duration of 8 weeks. The model allowed patients who had failed on venlafaxine to be switched to either an SSRI or a TCA. Those who failed on an SSRI could be switched to venlafaxine or to a TCA. Those who failed on a TCA could be switched to venlafaxine or an SSRI. The model assumed that, once a patient was in remission, he or she would continue to receive treatment until the end of the time horizon (6 months).
Outcomes assessed in the review The outcomes assessed were remission, response rate and the dropout rate to adverse events. Remission was defined as a score of 7 or less on the 17-item Hamilton Depression Rating Scale (HAM-D). The response rate was defined as a 50% reduction in the 21-item HAM-D score.
Study designs and other criteria for inclusion in the review Remission and response rates for venlafaxine and the SSRIs were taken from the published meta-analysis of Thase et al. (see Other Publications of Related Interest). The meta-analysis included 8 double-blind studies of venlafaxine versus SSRIs. Some of the studies were also placebo-controlled. Overall, 2,045 patients were evaluated for efficacy in the intention to treat analysis.
Remission and response rates for the TCAs were taken from the randomised study of fluoxetine versus amitriptyline (Beasley et al., see Other Publications of Related Interest). This included 136 outpatients with major depressive disorders.
Sources searched to identify primary studies Criteria used to ensure the validity of primary studies From the meta-analysis, all the patients were largely homogenous. They met standard entry criteria (either the Diagnostic and Statistical Manual of Mental Disorders 3rd edition, revised or 4th Edition criteria for depression) and had to have either a minimum HAM-D score of 20 or a minimum Montgomery-Asberg Depression Rating Scale score of 25.
The definitions of remission and response for the TCA study were the same as those used in the study of Thase et al. The dropout rate due to adverse events for the TCA (22.5%) was comparable to the value of 23.1% obtained in the meta-analysis of Einarson et al. (see Other Publications of Interest). The TCA study was considered representative of the class, as the response rate was within the 95% confidence interval (CI) of the Einarson meta-analysis.
Methods used to judge relevance and validity, and for extracting data Number of primary studies included Two studies were included in the review. One was a meta-analysis of 8 primary studies, while the other was a randomised study.
Methods of combining primary studies Investigation of differences between primary studies Results of the review The remission rate was 45% with venlafaxine, 35% with SSRIs and 24% with TCAs.
The response rate was 64% with venlafaxine, 57% with SSRIs and 54% with TCAs.
The dropout rate due to adverse events was 9.8% with venlafaxine, 7.6% with SSRIs and 22.5% with TCAs.
Measure of benefits used in the economic analysis The measure of benefit was the number of symptom-free days (SFDs). A patient was considered to have SFDs once he or she was in remission.
Direct costs The perspective of the UK NHS was adopted. The direct costs estimated were for drugs, physicians' time, blood tests for monitoring, nursing time, hospital inpatient stay and psychotherapy. It appears that the resource quantities have been derived from UK data sources, although these sources were not reported. The latest UK unit costs were obtained from different sources published in 2000 and 2001. All the costs were inflated to 2001 values using an inflation rate of 2.5%. The resource quantities and the costs were not reported separately. No discount rate was applied since the costs were incurred during less than one year.
Statistical analysis of costs No statistical analysis of the costs was performed.
Indirect Costs The indirect costs were not included, which was consistent with the study perspective adopted.
Sensitivity analysis One-way sensitivity analyses were conducted using the rank-order stability analysis (ROSA). The ROSA changed remission rate and (separately) treatment cost, leaving all other rates unchanged. The efficacy and cost of the three main drugs were individually increased and decreased, to establish at what levels the rank-order of expected 6-monthly cost changed.
Estimated benefits used in the economic analysis Patients on venlafaxine, SSRIs and TCAs were likely to have 61 (venlafaxine), 52 (SSRIs) and 44 (TCAs) SFDs, respectively.
Cost results The mean expected cost of treating major depressive disorders over a 6-month time horizon was 1,285 for patients initially treated with venlafaxine, 1,348 for patients initially on SSRIs, and 1,385 for patients initiated on TCAs.
Venlafaxine contributed to around 9% of the overall costs, SSRIs 8% and TCAs 5%.
Synthesis of costs and benefits The authors calculated the average cost per SFD.
The cost of one SFD was 21.20 for venlafaxine, 26.12 for an SSRI and 31.80 for a TCA.
One of the most common combinations used in primary care (start with a TCA and switch to an SSRI if this fails) turned out to be the least cost-effective (33.00). One of the least common combinations (start with venlafaxine and switch to an SSRI or a TCA if this fails) was the most cost-effective option (20.90 or 21.50, respectively).
Looking at a typical primary care organisation (with 150,000 patients), the overall cost was 1,609,319, with 785 patients attaining remission.
If first-line venlafaxine use doubled to 12%, there would have been an extra 2 patients in remission with a saving of $4,094.
Looking at the NHS as a whole (with 56 million people), increasing venlafaxine usage from 6 to 12% would have increased the number of remissions by 665 each year with annual savings of $1,528,298.
The sensitivity analysis showed that the model was robust.
The daily treatment cost of a TCA could be reduced to zero, or the daily treatment cost of an SSRI could be reduced to 4 pence, before venlafaxine ceased to be the most cost-effective option.
The remission rate for venlafaxine could be reduced to 19% before venlafaxine became less cost-effective than the SSRI.
The daily cost of venlafaxine could rise from 71 pence to 1.23 before it became less cost-effective than the SSRI.
Authors' conclusions The serotonin and noradrenaline reuptake inhibitor, venlafaxine, may be a cost-effective option in comparison with selective serotonin reuptake inhibitors and tricyclic antidepressants when used as a first-line drug for depression in primary care in the UK.
CRD COMMENTARY - Selection of comparators The choice of the comparators appears to have been appropriate. Venlafaxine, SSRIs and TCAs represent different classes of antidepressants used in major depression. You should decide whether these antidepressant treatments represent valid comparators in your own setting.
Validity of estimate of measure of effectiveness The authors did not state whether a systematic review of the literature had been undertaken, but it is likely that few other studies were available. The authors did not report the method used to judge the validity of the studies included in the review. Only limited details of the treatment regimens were provided, no information being given on the dose or the number of doses per week, for example. Only the remission rates were investigated in a sensitivity analysis. The ranges over which the parameters were varied were justified. The reporting of the methods of the review was limited, thus making it difficult to give an overall assessment of the quality of the results.
Validity of estimate of measure of benefit The estimation of benefits was modelled. The decision analysis model used to derive the measure of heath benefit appears to have been appropriate. The number of SFDs was chosen as the measure of benefit. This specific measure of benefit did not allow comparisons with other studies.
Validity of estimate of costs The authors limited their analysis to the direct costs. The sources and dates to which the resource data related were not reported. Details of the unit costs and the quantities of resources used were not reported separately. These facts limit the possibility of replicating the study in other settings. The price year was given, thus enhancing reflation exercises in other time periods or contexts. Statistical tests were not carried out and the costs were treated deterministically. Sensitivity analyses were performed, which would assist the transferability of the results to other settings. No discount rate was necessary.
Other issues The generalisability of the results was not addressed. In addition, the authors did not compare their findings with those from other studies. The authors highlighted a few limitations of their study. In particular, the fact that the study was a model and only one primary study was used for TCAs. Incremental cost-effectiveness ratios were investigated. However, because venlafaxine was a dominant strategy (more effective and less costly), the incremental cost-effectiveness analysis was not applicable. Only limited details of the methodology were provided which, in turn, limits the assessment of the validity of the study.
Implications of the study The authors recommended that, with unified budgets becoming more common, venlafaxine is more widely used as first-line therapy in primary care.
Source of funding Funded in full by Wyeth. A Lenox-Smith and P Conway are full-time employees of Wyeth.
Bibliographic details Lenox-Smith A, Conway P, Knight C. Cost effectiveness of representatives of three classes of antidepressants used in major depression in the UK. PharmacoEconomics 2004; 22(5): 311-319 Other publications of related interest Freeman H, Arikian S, Lenox-Smith A. Pharmacoeconomic analysis of antidepressants for major depressive disorders in the United Kingdom. Pharmacoeconomics 2000;18:143-8.
Thase ME, Entsuah AR, Rudolph RL, et al. Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. British Journal of Psychiatry 2001;178:234-41.
Beasley CM Jr, Sayler ME, Potvin JH, al. Fluoxetine versus amitriptyline in the treatment of major depression: a multicenter trial. International Clinical Psychopharmacology 1993;8:143-9.
Einarson TR, Arikian SR, Casciano J, et al. Pharmacoeconomic analysis of venlafaxine in the treatment of major depressive disorder. Pharmacoeconomics 1997;12:286-96.
Indexing Status Subject indexing assigned by NLM MeSH Antidepressive Agents /classification /economics /therapeutic use; Cost-Benefit Analysis; Decision Trees; Depressive Disorder /drug therapy /economics; Economics, Pharmaceutical; Great Britain; Humans; Treatment Outcome AccessionNumber 22004008190 Date bibliographic record published 30/11/2004 Date abstract record published 30/11/2004 |
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