Treatment-resistant Depression In Primary Care Research Articles

Evaluation, Treatment, and Referral of Treatment-Resistant Depression in Primary Care.

Evaluation, Treatment, and Referral of Treatment-Resistant Depression in Primary Care.

Does anxiety moderate the effectiveness of mirtazapine in patients with treatment-resistant depression? A secondary analysis of the MIR trial.

Background:There is a lack of evidence to guide treatment of comorbid depression and anxiety. Preliminary evidence suggests mirtazapine may be effective in treating patients with both depression and anxiety symptoms.Methods:We undertook a secondary analysis of mirtazapine (MIR): a placebo-controlled trial of the addition of mirtazapine to a selective serotonin reuptake inhibitor or serotonin–norepinephrine reuptake inhibitor in treatment-resistant depression (TRD) in primary care. We subdivided participants into three groups by baseline generalized anxiety disorder score (GAD-7): severe (GAD-7 ⩾ 16), moderate (GAD-7 = 11–15), no/mild (GAD-7 ⩽ 10). We used linear regression including likelihood-ratio testing of interaction terms to assess how baseline anxiety altered the response of participants to mirtazapine as measured by 12-week GAD-7 and Beck Depression Inventory II (BDI-II) scores.Results:Baseline generalized anxiety moderated mirtazapine’s effect as measured by GAD-7 (p = 0.041) and BDI-II (p = 0.088) at 12 weeks. Participants with severe generalized anxiety receiving mirtazapine had lower 12-week GAD-7 score (adjusted difference between means (ADM) −2.82, 95% confidence interval (CI) −0.69 to −4.95) and larger decreases in BDI-II score (ADM −6.36, 95% CI −1.60 to −10.84) than placebo. Conversely, there was no anxiolytic benefit (ADM 0.28, 95% CI −1.05 to 1.60) or antidepressant benefit (ADM −0.17, 95% CI −3.02 to 2.68) compared with placebo in those with no/mild generalized anxiety.Conclusions:These findings extend the evidence for the effectiveness of mirtazapine to reduce generalized anxiety in TRD in primary care. These results may inform targeted prescribing in depression based on concurrent anxiety symptoms, although these conclusions are constrained by the post-hoc nature of this analysis.

Antidepressant treatment with sertraline for adults with depressive symptoms in primary care: the PANDA research programme including RCT

Antidepressant treatment with sertraline for adults with depressive symptoms in primary care: the PANDA research programme including RCT

Management of treatment-resistant depression in primary care: a mixed-methods study.

BackgroundNon-response to antidepressant medication is common in primary care. Little is known about how GPs manage patients with depression that does not respond to medication.AimTo describe usual care for primary care patients with treatment-resistant depression (TRD).Design and settingMixed-methods study using data from a UK primary care multicentre randomised controlled trial.MethodIn total, 235 patients with TRD randomised to continue with usual GP care were followed up at 3-month intervals for a year. Self-report data were collected on antidepressant medication, number of GP visits, and other treatments received. In addition, 14 semi-structured face-to-face interviews were conducted with a purposive sample after the 6-month follow-up and analysed thematically.ResultsMost patients continued on the same dose of a single antidepressant between baseline and 3 months (n = 147/186 at 3 months, 79% (95% confidence interval [CI] = 73 to 85%)). Figures were similar for later follow-ups (for example, 9–12 months: 72% (95% CI = 63 to 79%). Medication changes (increasing dose; switching to a different antidepressant; adding a second antidepressant) were uncommon. Participants described usual care mainly as taking antidepressants, with consultations focused on other (physical) health concerns. Few accessed other treatments or were referred to secondary care.ConclusionUsual care in patients with TRD mainly entailed taking antidepressants, and medication changes were uncommon. The high prevalence of physical and psychological comorbidity means that, when these patients consult, their depression may not be discussed. Strategies are needed to ensure the active management of this large group of patients whose depression does not respond to antidepressant medication.

Mirtazapine added to selective serotonin reuptake inhibitors for treatment-resistant depression in primary care (MIR trial): study protocol for a randomised controlled trial.

BackgroundPeople with depression are usually managed in primary care and antidepressants are often the first-line treatment, but only one third of patients respond fully to a single antidepressant. This paper describes the protocol for a randomised controlled trial (MIR) to investigate the extent to which the addition of the antidepressant mirtazapine is effective in reducing the symptoms of depression compared with placebo in patients who are still depressed after they have been treated with a selective serotonin reuptake inhibitor (SSRI) or serotonin and noradrenaline reuptake inhibitor (SNRI) for at least 6 weeks in primary care.Methods/DesignMIR is a two-parallel group, multi-centre, pragmatic, placebo controlled, randomised trial with allocation at the level of the individual. Eligible participants are those who: are aged 18 years or older; are currently taking an SSRI/SNRI antidepressant (for at least 6 weeks at an adequate dose); score ≥14 on the Beck Depression Inventory (BDI-II); have adhered to their medication; and meet ICD-10 criteria for depression (assessed using the Clinical Interview Schedule-Revised version).Participants who give written, informed consent, will be randomised to receive either oral mirtazapine or matched placebo, starting at 15 mg daily for 2 weeks and increasing to 30 mg daily thereafter, for up to 12 months (to be taken in addition to their usual antidepressant). Participants, their GPs, and the research team will all be blind to the allocation. The primary outcome will be depression symptoms at 12 weeks post randomisation, measured as a continuous variable using the BDI-II.Secondary outcomes (measured at 12, 24 and 52 weeks) include: response (reduction in depressive symptoms (BDI-II score) of at least 50 % compared to baseline); remission of depression symptoms (BDI-II <10); change in anxiety symptoms; adverse effects; quality of life; adherence to antidepressant medication; health and social care use, time off work and cost-effectiveness. All outcomes will be analysed on an intention-to-treat basis.A qualitative study will explore patients’ views and experiences of either taking two antidepressants, or an antidepressant and a placebo; and GPs’ views on prescribing a second antidepressant in this patient group.DiscussionThe MIR trial will provide evidence on the clinical and cost-effectiveness of mirtazapine as an adjunct to SSRI/SNRI antidepressants for patients in primary care who have not responded to monotherapy.Trial registrationEudraCT Number: 2012-000090-23 (Registered January 2012); ISRCTN06653773 (Registered September 2012)

Long-term effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: follow-up of the CoBalT randomised controlled trial

Cognitive behavioural therapy (CBT) is an effective treatment for people whose depression has not responded to antidepressants. However, the long-term outcome is unknown. In a long-term follow-up of the CoBalT trial, we examined the clinical and cost-effectiveness of cognitive behavioural therapy as an adjunct to usual care that included medication over 3-5 years in primary care patients with treatment-resistant depression. CoBalT was a randomised controlled trial done across 73 general practices in three UK centres. CoBalT recruited patients aged 18-75 years who had adhered to antidepressants for at least 6 weeks and had substantial depressive symptoms (Beck Depression Inventory [BDI-II] score ≥14 and met ICD-10 depression criteria). Participants were randomly assigned using a computer generated code, to receive either usual care or CBT in addition to usual care. Patients eligible for the long-term follow-up were those who had not withdrawn by the 12 month follow-up and had given their consent to being re-contacted. Those willing to participate were asked to return the postal questionnaire to the research team. One postal reminder was sent and non-responders were contacted by telephone to complete a brief questionnaire. Data were also collected from general practitioner notes. Follow-up took place at a variable interval after randomisation (3-5 years). The primary outcome was self-report of depressive symptoms assessed by BDI-II score (range 0-63), analysed by intention to treat. Cost-utility analysis compared health and social care costs with quality-adjusted life-years (QALYs). This study is registered with isrctn.com, number ISRCTN38231611. Between Nov 4, 2008, and Sept 30, 2010, 469 eligible participants were randomised into the CoBalT study. Of these, 248 individuals completed a long-term follow-up questionnaire and provided data for the primary outcome (136 in the intervention group vs 112 in the usual care group). At follow-up (median 45·5 months [IQR 42·5-51·1]), the intervention group had a mean BDI-II score of 19·2 (SD 13·8) compared with a mean BDI-II score of 23·4 (SD 13·2) for the usual care group (repeated measures analysis over the 46 months: difference in means -4·7 [95% CI -6·4 to -3·0, p<0·001]). Follow-up was, on average, 40 months after therapy ended. The average annual cost of trial CBT per participant was £343 (SD 129). The incremental cost-effectiveness ratio was £5374 per QALY gain. This represented a 92% probability of being cost effective at the National Institute for Health and Care Excellence QALY threshold of £20 000. CBT as an adjunct to usual care that includes antidepressants is clinically effective and cost effective over the long-term for individuals whose depression has not responded to pharmacotherapy. In view of this robust evidence of long-term effectiveness and the fact that the intervention represented good value-for-money, clinicians should discuss referral for CBT with all those for whom antidepressants are not effective. National Institute for Health Research Health Technology Assessment.

Conditional Beliefs of Primary-Care Patients with Treatment-Resistant Depression.

Cognitive behaviour therapy (CBT) for patients with treatment-resistant depression (TRD) aims to reframe underlying conditional beliefs that are thought to maintain depression. To systematically explore conditional beliefs expressed by primary-care based patients with TRD, defined as non-response to at least 6 weeks of antidepressants. Conditional beliefs (stated in an "If...then..." format) were extracted from a random sample of 50 sets of therapist notes from the CoBalT trial, a large randomized controlled trial of CBT for TRD in primary care. The beliefs were separated into their two constituent parts; the demands (Ifs) and consequences (thens). An approach based on framework analysis provided a systematic way of organizing the data, and identifying key themes. Four main themes emerged from the demand part of the conditional beliefs (Ifs): 1. High standards; 2. Putting others first/needing approval; 3. Coping; and 4. Hiding "true" self. Three main themes emerged from the consequence part of the conditional beliefs (thens): 1. Defectiveness; 2. Responses of others; 3. Control of emotions. Identifying common themes in the conditional beliefs of patients with TRD adds to our clinical understanding of this client group, providing useful information to facilitate the complex process of collaborative case conceptualization and working with conditional beliefs within CBT interventions.

Moderators of response to cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care

BackgroundStratified medicine aims to improve clinical and cost-effectiveness by identifying moderators of treatment that indicate differential response to treatment. Cognitive behavioural therapy (CBT) is often offered as a ‘next-step’ for patients who have not responded to antidepressants, but no research has examined moderators of response to CBT in this population. We aimed, therefore, to identify moderators of response to CBT in treatment resistant depression. MethodsWe used linear regression to test for interactions between treatment effect and 14 putative moderator variables using data from the CoBalT randomised controlled trial. This trial examined the effectiveness of CBT given in addition to usual care (n=234) compared with usual care alone (n=235) for primary care patients with treatment resistant depression. ResultsAge was the only variable with evidence for effect modification (p Value for interaction term=0.012), with older patients benefiting the most from CBT. We found no evidence of effect modification by any other demographic, life, illness, personality trait, or cognitive variable (p≥0.2). ConclusionsGiven the largely null findings, a stratified approach that might limit offering CBT is premature; CBT should be offered to all individuals where antidepressant medication has failed.

Treatment-resistant depression in primary care across Canada.

Treatment-resistant depression (TRD) represents a considerable global health concern. The goal of the InSight study was to investigate the prevalence of TRD and to evaluate its clinical characterization and management, compared with nonresistant depression, in primary care centres. Physicians completed a case report on a consecutive series of patients with major depressive disorder (n = 1212), which captured patient demographics and comorbidity, as well as current and past medication. Using failure to respond to at least 2 antidepressants (ADs) from different classes as the definition of TRD, the overall prevalence was 21.7%. There were no differences in prevalence between men and women or among ethnicities. Patients with TRD had longer episode duration, were more likely to receive polypharmacy (for example, psychotropic, lipid-lowering, and antiinflammatory agents), and reported more AD related side effects. Higher rates of disability and comorbidity (axes I to III) were associated with treatment resistance. Obesity and being overweight were also associated with treatment resistance. While the selection and sequencing of pharmacotherapy by family physicians in this sample was in line with recommendations from evidence-based treatment guidelines, the wait time to make a change in treatment was 6 to 8 weeks in both groups, which exceeds guideline recommendations. These real-world data demonstrate the high prevalence of TRD in primary care settings, and underscore the substantial burden of illness associated with TRD.

ACP Journal Club. In treatment-resistant depression, adding cognitive-behavioral therapy to usual care was cost-effective at 1 y.

Source Citation Hollinghurst S, Carroll FE, Abel A, et al. Cost-effectiveness of cognitive-behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: e...

Clinical effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: the CoBalT randomised controlled trial.

Only one-third of patients with depression respond fully to treatment with antidepressant medication. However, there is little robust evidence to guide the management of those whose symptoms are 'treatment resistant'. The CoBalT trial examined the clinical effectiveness and cost-effectiveness of cognitive behavioural therapy (CBT) as an adjunct to usual care (including pharmacotherapy) for primary care patients with treatment-resistant depression (TRD) compared with usual care alone. Pragmatic, multicentre individually randomised controlled trial with follow-up at 3, 6, 9 and 12 months. A subset took part in a qualitative study investigating views and experiences of CBT, reasons for completing/not completing therapy, and usual care for TRD. General practices in Bristol, Exeter and Glasgow, and surrounding areas. Patients aged 18-75 years who had TRD [on antidepressants for ≥ 6 weeks, had adhered to medication, Beck Depression Inventory, 2nd version (BDI-II) score of ≥ 14 and fulfilled the International Classification of Diseases and Related Health Problems, Tenth edition criteria for depression]. Individuals were excluded who (1) had bipolar disorder/psychosis or major alcohol/substance abuse problems; (2) were unable to complete the questionnaires; or (3) were pregnant, as were those currently receiving CBT/other psychotherapy/secondary care for depression, or who had received CBT in the past 3 years. Participants were randomised, using a computer-generated code, to usual care or CBT (12-18 sessions) in addition to usual care. The primary outcome was 'response', defined as ≥ 50% reduction in depressive symptoms (BDI-II score) at 6 months compared with baseline. Secondary outcomes included BDI-II score as a continuous variable, remission of symptoms (BDI-II score of < 10), quality of life, anxiety and antidepressant use at 6 and 12 months. Data on health and social care use, personal costs, and time off work were collected at 6 and 12 months. Costs from these three perspectives were reported using a cost-consequence analysis. A cost-utility analysis compared health and social care costs with quality adjusted life-years. A total of 469 patients were randomised (intervention: n = 234; usual care: n = 235), with 422 participants (90%) and 396 (84%) followed up at 6 and 12 months. Ninety-five participants (46.1%) in the intervention group met criteria for 'response' at 6 months compared with 46 (21.6%) in the usual-care group {odds ratio [OR] 3.26 [95% confidence interval (CI) 2.10 to 5.06], p < 0.001}. In repeated measures analyses using data from 6 and 12 months, the OR for 'response' was 2.89 (95% CI 2.03 to 4.10, p < 0.001) and for a secondary 'remission' outcome (BDI-II score of < 10) 2.74 (95% CI 1.82 to 4.13, p < 0.001). The mean cost of CBT per participant was £ 910, the incremental health and social care cost £ 850, the incremental QALY gain 0.057 and incremental cost-effectiveness ratio £ 14,911. Forty participants were interviewed. Patients described CBT as challenging but helping them to manage their depression; listed social, emotional and practical reasons for not completing treatment; and described usual care as mainly taking medication. Among patients who have not responded to antidepressants, augmenting usual care with CBT is effective in reducing depressive symptoms, and these effects, including outcomes reflecting remission, are maintained over 12 months. The intervention was cost-effective based on the National Institute for Health and Care Excellence threshold. Patients may experience CBT as difficult but effective. Further research should evaluate long-term effectiveness, as this would have major implications for the recommended treatment of depression. Current Controlled Trials ISRCTN38231611.

Cost-effectiveness of cognitive–behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: economic evaluation of the CoBalT Trial

BackgroundDepression is expensive to treat, but providing ineffective treatment is more expensive. Such is the case for many patients who do not respond to antidepressant medication.AimsTo assess the cost-effectiveness of cognitive–behavioural therapy (CBT) plus usual care for primary care patients with treatment-resistant depression compared with usual care alone.MethodEconomic evaluation at 12 months alongside a randomised controlled trial. Cost-effectiveness assessed using a cost-consequences framework comparing cost to the health and social care provider, patients and society, with a range of outcomes. Cost-utility analysis comparing health and social care costs with quality-adjusted life-years (QALYs).ResultsThe mean cost of CBT per participant was £910. The difference in QALY gain between the groups was 0.057, equivalent to 21 days a year of good health. The incremental cost-effectiveness ratio was £14 911 (representing a 74% probability of the intervention being cost-effective at the National Institute of Health and Care Excellence threshold of £20 000 per QALY). Loss of earnings and productivity costs were substantial but there was no evidence of a difference between intervention and control groups.ConclusionsThe addition of CBT to usual care is cost-effective in patients who have not responded to antidepressants. Primary care physicians should therefore be encouraged to refer such individuals for CBT.

Prevalence of treatment-resistant depression in primary care: cross-sectional data

Antidepressants are often the first-line treatment for depression in primary care. However, not all patients respond to medication after an adequate dose and duration of treatment. Currently, there are no estimates of the prevalence of treatment-resistant depression (TRD) from UK primary care. To estimate the prevalence of TRD in UK primary care. Design and setting Data were collected as part of a multicentre randomised controlled trial, from 73 general practices in UK primary care. Potential participants (aged 18-75 years who had received repeated prescriptions for antidepressants) were identified from general practice records. Those who agreed to be contacted were mailed a questionnaire that included questions on depressive symptoms (Beck Depression Inventory [BDI-II]), and adherence to antidepressants. Those who scored ≥14 on the BDI-II and had taken antidepressants for at least 6 weeks at an adequate dose were defined as treatment resistant. A total of 2439 patients completed the questionnaire (84% of those who agreed to be contacted), of whom 2129 had been prescribed an adequate dose of antidepressants for at least 6 weeks. Seventy-seven per cent (95% CI = 75% to 79%) had a BDI score of ≥14. Fifty-five per cent (95% CI = 53% to 58%) (n = 1177) met the study's definition of TRD, of whom 67% had taken their antidepressants for more than 12 months. The high prevalence of TRD is an important challenge facing clinicians in UK primary care. A more proactive approach to managing this patient population is required to improve outcome.

Measuring Homework Completion in Behavioral Activation

The aim of this study was to develop and validate an observer-based coding system for the characterization and completion of homework assignments during Behavioral Activation (BA). Existing measures of homework completion are generally unsophisticated, and there is no current measure of homework completion designed to capture the particularities of BA. The tested scale sought to capture the type of assignment, realm of functioning targeted, extent of completion, and assignment difficulty. Homework assignments were drawn from 12 (mean age = 48, 83% female) clients in two trials of a 10-session BA manual targeting treatment-resistant depression in primary care. The two coders demonstrated acceptable or better reliability on most codes, and unreliable codes were dropped from the proposed scale. In addition, correlations between homework completion and outcome were strong, providing some support for construct validity. Ultimately, this line of research aims to develop a user-friendly, reliable measure of BA homework completion that can be completed by a therapist during session.