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

ABSTRACT: 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.

SUBMITTER: Rifkin-Zybutz R

PROVIDER: S-EPMC7708671 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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

Rifkin-Zybutz Raphael R MacNeill Stephanie S Davies Simon Jc SJ Dickens Christopher C Campbell John J Anderson Ian M IM Chew-Graham Carolyn A CA Peters Tim J TJ Lewis Glyn G Wiles Nicola N Kessler David D

Journal of psychopharmacology (Oxford, England) 20201104 12

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 33143538

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Project description:ObjectiveTo investigate the effectiveness of combining mirtazapine with serotonin-noradrenaline reuptake inhibitor (SNRI) or selective serotonin reuptake inhibitor (SSRI) antidepressants for treatment resistant depression in primary care.DesignTwo parallel group multicentre phase III randomised placebo controlled trial.Setting106 general practices in four UK sites; Bristol, Exeter, Hull, and Keele/North Staffs, August 2013 to October 2015.Participants480 adults aged 18 or more years who scored 14 or more on the Beck depression inventory, second revision, fulfilled ICD-10 (international classification of diseases, 10th revision) criteria for depression, and had used an SSRI or SNRI for at least six weeks but were still depressed. 241 were randomised to mirtazapine and 239 to placebo, both given in addition to usual SSRI or SNRI treatment. Participants were stratified by centre and minimised by baseline Beck depression inventory score, sex, and current psychological therapy. They were followed up at 12, 24, and 52 weeks. 431 (89.8%) were included in the (primary) 12 week follow-up.Main outcome measuresDepressive symptoms at 12 weeks after randomisation, measured using the Beck depression inventory II score as a continuous variable. Secondary outcomes included measures of anxiety, quality of life, and adverse effects at 12, 24, and 52 weeks.ResultsBeck depression inventory II scores at 12 weeks were lower in the mirtazapine group after adjustment for baseline scores and minimisation or stratification variables, although the confidence interval included the null (mean (SD) scores at 12 weeks: 18.0 (12.3) in the mirtazapine group, 19.7 (12.4) in the placebo group; adjusted difference between means -1.83 (95% confidence interval -3.92 to 0.27); P=0.09). Adverse effects were more common in the mirtazapine group and were associated with the participants stopping the trial drug.ConclusionThis study did not find evidence of a clinically important benefit for mirtazapine in addition to an SSRI or SNRI over placebo in a treatment resistant group of primary care patients with depression. This remains an area of important unmet need where evidence of effective treatment options is limited.Trial registrationCurrent Controlled Trials ISRCTN06653773.

Project description:BACKGROUND:People 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/DESIGN:MIR 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. DISCUSSION:The 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 REGISTRATION:EudraCT Number: 2012-000090-23 (Registered January 2012); ISRCTN06653773 (Registered September 2012).

Project description:Co-occurring depression is common in patients seeking treatment for anxiety; however, the literature on the effects of depression on anxiety treatment outcomes is inconclusive. The current study evaluated prescriptive and prognostic effects of depression on anxiety treatment outcomes in a large primary care sample.Data were analyzed from a randomized controlled effectiveness trial that compared coordinated anxiety learning and management (CALM) to usual care. The study enrolled 1,004 patients between June 2006 and April 2008. Patients were referred by their primary care provider and met DSM-IV criteria for generalized anxiety disorder, panic disorder, posttraumatic stress disorder, and/or social anxiety disorder. They were treated for approximately 3 to 12 months with CALM (computer-assisted cognitive-behavioral therapy, medication management, or their combination) or usual care. Outcomes were evaluated by blinded assessment at 6, 12, and 18 months. Effects of baseline major depressive disorder (MDD) on anxiety symptoms, anxiety-related disability, and response/remission rates were evaluated using statistical models accounting for baseline anxiety and patient demographics.MDD did not moderate the effects of CALM (relative to usual care) on anxiety symptoms, anxiety-related disability, or response/remission rates. Greater improvements in anxiety symptoms and anxiety-related disability were observed in depressed patients, regardless of treatment assignment (P values < .005). However, cross-sectionally depressed patients displayed higher anxiety symptom and anxiety-related disability scores at baseline and all subsequent assessments (P values < .001). Depressed patients also displayed lower remission rates at each follow-up (P values < .001).CALM had comparable advantages over usual care for patients with and without MDD. Depressed patients displayed more severe anxiety symptoms and anxiety-related disability at baseline, but their clinical improvement was substantial and larger in magnitude than that observed in the nondepressed patients. Results support the use of empirically supported interventions for anxiety disorders in patients with co-occurring depression.ClinicalTrials.gov identifier: NCT00347269.

Project description:BACKGROUND:Pregnant women with symptoms of depression or anxiety often do not receive adequate treatment. In view of the high incidence of these symptoms in pregnancy and their impact on pregnancy outcomes, getting treatment is of the utmost importance. A guided internet self-help intervention may help to provide more women with appropriate treatment. OBJECTIVE:This study aimed to examine the effectiveness of a guided internet intervention (MamaKits online) for pregnant women with moderate to severe symptoms of anxiety or depression. Assessments took place before randomization (T0), post intervention (T1), at 36 weeks of pregnancy (T2), and 6 weeks postpartum (T3). We also explored effects on perinatal child outcomes 6 weeks postpartum. METHODS:This randomized controlled trial included pregnant women (<30 weeks) with depressive symptoms above threshold (ie, Center for Epidemiological Studies Depression scale [CES-D] >16) or anxiety above threshold (ie, Hospital Anxiety and Depression Scale-Anxiety subscale [HADS-A] >8) or both of them. Participants were recruited via general media and flyers in prenatal care waiting rooms or via obstetricians and midwives. After initial assessment, women were randomized to (1) MamaKits online in addition to treatment as usual or (2) treatment as usual (control condition). MamaKits online is a 5-week guided internet intervention based on problem solving treatment. Guidance was was provided by trained students pursuing a Master's in Psychology. Outcomes were based on a Web-based self-report. Women in the control condition were allowed to receive the intervention after the last assessment (6 weeks postpartum). RESULTS:Of the 159 included women, 79 were randomized to MamaKits online, 47% (79/37) of whom completed the intervention. Both groups showed a substantial decrease in affective symptoms on the CES-D, HADS-A, and Edinburgh Postnatal Depression Scale over time. In the intervention group, affective symptoms decreased more than that in the control group, but between-group effect sizes were small to medium (Cohen d at T3=0.45, 0.21, and 0.23 for the 3 questionnaires, respectively) and statistically not significant. Negative perinatal child outcomes did not differ between the 2 groups (?21=0.1; P=.78). Completer analysis revealed no differences in outcome between the treatment completers and the control group. The trial was terminated early for reasons of futility based on the results of an interim analysis, which we performed because of inclusion problems. CONCLUSIONS:Our study did show a significant reduction in affective symptoms in both groups, but the differences in reduction of affective symptoms between the intervention and control groups were not significant. There were also no differences in perinatal child outcomes. Future research should examine for which women these interventions might be effective or if changes in the internet intervention might make the intervention more effective. TRIAL REGISTRATION:Netherlands Trial Register NL4162; https://tinyurl.com/sdckjek.

Dataset Information

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

Publications

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

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