Dataset Information

Cost-Utility Analysis of Discontinuing Antidepressants in England Primary Care Patients Compared with Long-Term Maintenance: The ANTLER Study.

ABSTRACT:

Background

Depression is a common mental health condition with considerable negative impact on health and well-being. Although antidepressants are recommended as first-line treatment, there is limited evidence regarding the cost effectiveness of long-term maintenance antidepressants for preventing relapse.

Objectives

Our objective was to calculate the mean incremental costs and quality-adjusted life-years (QALYs) over 12 months of discontinuing long-term antidepressant medication in well patients compared with maintenance, using patient-level trial data.

Methods

We conducted a cost-utility analysis of 478 participants from 150 UK general practices recruited to a randomised, double-blind trial (ANTLER). QALYs were calculated from EQ-5D-5L and 12-Item Short Form survey (SF-12) results, with primary analysis using the EQ-5D-5L value set for England. Resource use was collected from primary care patient electronic medical records and self-completed questionnaires capturing mental-health-related resource use. Costs were calculated by applying standard UK unit costs to resource use. Adjustments were made for baseline variables.

Results

Participants randomised to discontinuation had significantly worse utility scores at 3 months (- 0.032; 95% confidence interval [CI] - 0.053 to - 0.011) but no significant difference in QALYs (- 0.011; 95% CI - 0.026 to 0.003) or costs (£3.11; 95% CI - 41.28 to 47.50) at 12 months. The probability that discontinuation was cost effective compared with maintenance was 12.9% at a threshold of £20,000 per QALY gained.

Conclusions

Discontinuation of antidepressants was unlikely to be cost effective compared with maintenance for currently well patients on long-term antidepressants. However, this analysis provides no information on the wider impact of antidepressants. Our findings provide information on the potential impact of discontinuing long-term maintenance antidepressants and facilitate improving guidance for shared patient-clinician decision making.

Trial registration

EudraCT number 2015-004210-26; ISRCTN number ISRCTN15969819.

SUBMITTER: Clarke CS

PROVIDER: S-EPMC8847280 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Cost-Utility Analysis of Discontinuing Antidepressants in England Primary Care Patients Compared with Long-Term Maintenance: The ANTLER Study.

Clarke Caroline S CS Duffy Larisa L Lewis Glyn G Freemantle Nick N Gilbody Simon S Kendrick Tony T Kessler David D King Michael M Lanham Paul P Mangin Derelie D Moore Michael M Nazareth Irwin I Wiles Nicola N Marston Louise L Hunter Rachael Maree RM

Applied health economics and health policy 20211108 2

<h4>Background</h4>Depression is a common mental health condition with considerable negative impact on health and well-being. Although antidepressants are recommended as first-line treatment, there is limited evidence regarding the cost effectiveness of long-term maintenance antidepressants for preventing relapse.<h4>Objectives</h4>Our objective was to calculate the mean incremental costs and quality-adjusted life-years (QALYs) over 12 months of discontinuing long-term antidepressant medication ...[more]

PMID: 34748164

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Project description:ImportanceThere is significant concern regarding increasing long-term antidepressant treatment for depression beyond an evidence-based duration.ObjectiveTo determine whether adding internet and telephone support to a family practitioner review to consider discontinuing long-term antidepressant treatment is safe and more effective than a practitioner review alone.Design, setting, and participantsIn this cluster randomized clinical trial, 131 UK family practices were randomized between December 1, 2018, and March 31, 2022, with remote computerized allocation and 12 months of follow-up. Participants and researchers were aware of allocation, but analysis was blind. Participants were adults who were receiving antidepressants for more than 1 year for a first episode of depression or more than 2 years for recurrent depression who were currently well enough to consider discontinuation and wished to do so and who were at low risk of relapse. Of 6725 patients mailed invitations, 330 (4.9%) were eligible and consented.InterventionsInternet and telephone self-management support, codesigned and coproduced with patients and practitioners.Main outcomes and measuresThe primary (safety) outcome was depression at 6 months (prespecified complete-case analysis), testing for noninferiority of the intervention to under 2 points on the 9-item Patient Health Questionnaire (PHQ-9). Secondary outcomes (testing for superiority) were antidepressant discontinuation, anxiety, quality of life, antidepressant withdrawal symptoms, mental well-being, enablement, satisfaction, use of health care services, and adverse events. Analyses for the main outcomes were performed on a complete-case basis, and multiple imputation sensitivity analysis was performed on an intention-to-treat basis.ResultsOf 330 participants recruited (325 eligible for inclusion; 178 in intervention practices and 147 in control practices; mean [SD] age at baseline, 54.0 [14.9] years; 223 women [68.6%]), 276 (83.6%) were followed up at 6 months, and 240 (72.7%) at 12 months. The intervention proved noninferior; mean (SD) PHQ-9 scores at 6 months were slightly lower in the intervention arm than in the control arm in the complete-case analysis (4.0 [4.3] vs 5.0 [4.7]; adjusted difference, -1.1; 95% CI, -2.1 to -0.1; P = .03) but not significantly different in an intention-to-treat multiple imputation sensitivity analysis (adjusted difference, -0.9 (95% CI, -1.9 to 0.1; P = .08). By 6 months, antidepressants had been discontinued by 66 of 145 intervention arm participants (45.5%) who provided discontinuation data and 54 of 129 control arm participants (41.9%) (adjusted odds ratio, 1.02; 95% CI, 0.52-1.99; P = .96). In the intervention arm, antidepressant withdrawal symptoms were less severe, and mental well-being was better compared with the control arm; differences were small but significant. There were no significant differences in the other outcomes; 28 of 179 intervention arm participants (15.6%) and 22 of 151 control arm participants (14.6%) experienced adverse events.Conclusions and relevanceIn this cluster randomized clinical trial of adding internet and telephone support to a practitioner review for possible antidepressant discontinuation, depression was slightly better with support, but the rate of discontinuation of antidepressants did not significantly increase. Improvements in antidepressant withdrawal symptoms and mental well-being were also small. There were no significant harms. Family practitioner review for possible discontinuation of antidepressants appeared safe and effective for more than 40% of patients willing and well enough to discontinue.Trial registrationISRCTN registry Identifiers: ISRCTN15036829 (internal pilot trial) and ISRCTN12417565 (main trial).

Project description:BackgroundAntidepressants are used both for treating acute episodes and for prophylaxis to prevent future episodes of depression, also called maintenance treatment. This article describes the protocol for a randomised controlled trial (ANTLER: ANTidepressants to prevent reLapse in dEpRession) to investigate the clinical effectiveness and cost-effectiveness in UK primary care of continuing on long-term maintenance antidepressants compared with a placebo in preventing relapse of depression in those who have taken antidepressants for more than 9 months and who are currently well enough to consider stopping maintenance treatment.Methods/designThe ANTLER trial is an individually randomised, double-blind, placebo-controlled trial in which participants are randomised to remain on active medication or to take an identical placebo after a tapering period of 2 months. Eligible participants are those who: are between the ages of 18 and 74 years; have had at least two episodes of depression; and have been taking antidepressants for 9 months or more and are currently taking citalopram 20 mg, sertraline 100 mg, fluoxetine 20 mg or mirtazapine 30 mg but are well enough to consider stopping their medication. The participants will be followed up at 6, 12, 26, 39 and 52 weeks. The primary outcome will be the time in weeks to the beginning of the first episode of depression after randomisation. This will be measured using a retrospective version of the Clinical Interview Schedule-Revised administered at 12, 26, 39 and 52 weeks. Secondary outcomes will include depressive and anxiety symptoms, adverse effects, withdrawal symptoms, emotional processing tasks, quality of life and the resources and costs used. We will also perform a cost-effectiveness analysis based on results of the trial.DiscussionThe ANTLER trial findings will inform primary care prescribing practice by providing a valid and generalisable estimate of the clinical effectiveness and cost-effectiveness of long-term maintenance treatment with antidepressants in UK primary care.Trial registrationControlled Trials ISRCTN Registry, ISRCTN15969819. Registered on 21 September 2015.

Project description:BackgroundAs depression has a recurrent course, relapse and recurrence prevention is essential.AimsIn our randomised controlled trial (registered with the Nederlands trial register, identifier: NTR1907), we found that adding preventive cognitive therapy (PCT) to maintenance antidepressants (PCT+AD) yielded substantial protective effects versus antidepressants only in individuals with recurrent depression. Antidepressants were not superior to PCT while tapering antidepressants (PCT/-AD). To inform decision-makers on treatment allocation, we present the corresponding cost-effectiveness, cost-utility and budget impact.MethodData were analysed (n = 289) using a societal perspective with 24-months of follow-up, with depression-free days and quality-adjusted life years (QALYs) as health outcomes. Incremental cost-effectiveness ratios were calculated and cost-effectiveness planes and cost-effectiveness acceptability curves were derived to provide information about cost-effectiveness. The budget impact was examined with a health economic simulation model.ResultsMean total costs over 24 months were €6814, €10 264 and €13 282 for AD+PCT, antidepressants only and PCT/-AD, respectively. Compared with antidepressants only, PCT+AD resulted in significant improvements in depression-free days but not QALYs. Health gains did not significantly favour antidepressants only versus PCT/-AD. High probabilities were found that PCT+AD versus antidepressants only and antidepressants only versus PCT/-AD were dominant with low willingness-to-pay thresholds. The budget impact analysis showed decreased societal costs for PCT+AD versus antidepressants only and for antidepressants only versus PCT/-AD.ConclusionsAdding PCT to antidepressants is cost-effective over 24 months and PCT with guided tapering of antidepressants in long-term users might result in extra costs. Future studies examining costs and effects of antidepressants versus psychological interventions over a longer period may identify a break-even point where PCT/-AD will become cost-effective.Declaration of interestC.L.H.B. is co-editor of PLOS One and receives no honorarium for this role. She is also co-developer of the Dutch multidisciplinary clinical guideline for anxiety and depression, for which she receives no remuneration. She is a member of the scientific advisory board of the National Insure Institute, for which she receives an honorarium, although this role has no direct relation to this study. C.L.H.B. has presented keynote addresses at conferences, such as the European Psychiatry Association and the European Conference Association, for which she sometimes receives an honorarium. She has presented clinical training workshops, some including a fee. She receives royalties from her books and co-edited books and she developed preventive cognitive therapy on the basis of the cognitive model of A. T. Beck. W.A.N. has received grants from the Netherlands Organisation for Health Research and Development and the European Union and honoraria and speakers' fees from Lundbeck and Aristo Pharma, and has served as a consultant for Daleco Pharma.

Project description:BackgroundTapering and discontinuing antidepressants are important aspects of the management of patients with depression and should therefore be considered in clinical practice guidelines.ObjectivesWe aimed to assess the extent and content, and appraise the quality, of guidance on tapering and discontinuing antidepressants in major clinical practice guidelines on depression.MethodsSystematic review of clinical practice guidelines on depression issued by national health authorities and major national or international professional organisations in the United Kingdom, the United States, Canada, Australia, Singapore, Ireland and New Zealand (PROSPERO CRD42020220682). We searched PubMed, 14 guideline registries and the websites of relevant organisations (last search 25 May 2021). The clinical practice guidelines were assessed for recommendations and information relevant to tapering and discontinuing antidepressants. The quality of the clinical practice guidelines as they pertained to tapering and discontinuation was assessed using the AGREE II tool.ResultsOf the 21 included clinical practice guidelines, 15 (71%) recommended that antidepressants are tapered gradually or slowly, but none provided guidance on dose reductions, how to distinguish withdrawal symptoms from relapse or how to manage withdrawal symptoms. Psychological challenges were not addressed in any clinical practice guideline, and the treatment algorithms and flow charts did not include discontinuation. The quality of the clinical practice guidelines was overall low.ConclusionCurrent major clinical practice guidelines provide little support for clinicians wishing to help patients discontinue or taper antidepressants in terms of mitigating and managing withdrawal symptoms. Patients who have deteriorated upon following current guidance on tapering and discontinuing antidepressants thus cannot be concluded to have experienced a relapse. Better guidance requires better randomised trials investigating interventions for discontinuing or tapering antidepressants.

Dataset Information

Cost-Utility Analysis of Discontinuing Antidepressants in England Primary Care Patients Compared with Long-Term Maintenance: The ANTLER Study.

Background

Objectives

Methods

Results

Conclusions

Trial registration

Publications

Cost-Utility Analysis of Discontinuing Antidepressants in England Primary Care Patients Compared with Long-Term Maintenance: The ANTLER Study.

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