scholarly journals Combining mirtazapine with SSRIs or SNRIs for treatment-resistant depression: the MIR RCT

2018 ◽  
Vol 22 (63) ◽  
pp. 1-136 ◽  
Author(s):  
David Kessler ◽  
Alison Burns ◽  
Debbie Tallon ◽  
Glyn Lewis ◽  
Stephanie MacNeill ◽  
...  
Keyword(s):  
Primary Care ◽  
Health Technology Assessment ◽  
Usual Care ◽  
Reuptake Inhibitor ◽  
Technology Assessment ◽  
Primary Outcome ◽  
Health Technology ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression

Background Depression is usually managed in primary care and antidepressants are often the first-line treatment, but only half of those treated respond to a single antidepressant. Objectives To investigate whether or not combining mirtazapine with serotonin–noradrenaline reuptake inhibitor (SNRI) or selective serotonin reuptake inhibitor (SSRI) antidepressants results in better patient outcomes and more efficient NHS care than SNRI or SSRI therapy alone in treatment-resistant depression (TRD). Design The MIR trial was a two-parallel-group, multicentre, pragmatic, placebo-controlled randomised trial with allocation at the level of the individual. Setting Participants were recruited from primary care in Bristol, Exeter, Hull/York and Manchester/Keele. Participants Eligible participants were aged ≥ 18 years; were taking a SSRI or a SNRI antidepressant for at least 6 weeks at an adequate dose; scored ≥ 14 points on the Beck Depression Inventory-II (BDI-II); were adherent to medication; and met the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, criteria for depression. Interventions Participants were randomised using a computer-generated code to either oral mirtazapine or a matched placebo, starting at a dose of 15 mg daily for 2 weeks and increasing to 30 mg daily for up to 12 months, in addition to their usual antidepressant. Participants, their general practitioners (GPs) and the research team were blind to the allocation. Main outcome measures The primary outcome was depression symptoms at 12 weeks post randomisation compared with baseline, measured as a continuous variable using the BDI-II. Secondary outcomes (at 12, 24 and 52 weeks) included response, remission of depression, change in anxiety symptoms, adverse events (AEs), quality of life, adherence to medication, health and social care use and cost-effectiveness. Outcomes were analysed on an intention-to-treat basis. A qualitative study explored patients’ views and experiences of managing depression and GPs’ views on prescribing a second antidepressant. Results There were 480 patients randomised to the trial (mirtazapine and usual care, n = 241; placebo and usual care, n = 239), of whom 431 patients (89.8%) were followed up at 12 weeks. BDI-II scores at 12 weeks were lower in the mirtazapine group than the placebo group after adjustment for baseline BDI-II score and minimisation and stratification variables [difference –1.83 points, 95% confidence interval (CI) –3.92 to 0.27 points; p = 0.087]. This was smaller than the minimum clinically important difference and the CI included the null. The difference became smaller at subsequent time points (24 weeks: –0.85 points, 95% CI –3.12 to 1.43 points; 12 months: 0.17 points, 95% CI –2.13 to 2.46 points). More participants in the mirtazapine group withdrew from the trial medication, citing mild AEs (46 vs. 9 participants). Conclusions This study did not find convincing evidence of a clinically important benefit for mirtazapine in addition to a SSRI or a SNRI antidepressant over placebo in primary care patients with TRD. There was no evidence that the addition of mirtazapine was a cost-effective use of NHS resources. GPs and patients were concerned about adding an additional antidepressant. Limitations Voluntary unblinding for participants after the primary outcome at 12 weeks made interpretation of longer-term outcomes more difficult. Future work Treatment-resistant depression remains an area of important, unmet need, with limited evidence of effective treatments. Promising interventions include augmentation with atypical antipsychotics and treatment using transcranial magnetic stimulation. Trial registration Current Controlled Trials ISRCTN06653773; EudraCT number 2012-000090-23. Funding This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 63. See the NIHR Journals Library website for further project information.

scholarly journals Stratified versus usual care for the management of primary care patients with sciatica: the SCOPiC RCT

2020 ◽  
Vol 24 (49) ◽  
pp. 1-130
Author(s):  
Nadine E Foster ◽  
Kika Konstantinou ◽  
Martyn Lewis ◽  
Reuben Ogollah ◽  
Benjamin Saunders ◽  
...  
Keyword(s):  
Primary Care ◽  
Health Technology Assessment ◽  
Usual Care ◽  
Technology Assessment ◽  
Fast Track ◽  
Primary Outcome ◽  
Health Technology ◽  
Care Pathways ◽  
Care Model ◽  
Stratified Care

Background Sciatica has a substantial impact on patients and society. Current care is ‘stepped’, comprising an initial period of simple measures of advice and analgesia, for most patients, commonly followed by physiotherapy, and then by more intensive interventions if symptoms fail to resolve. No study has yet tested a model of stratified care in which patients are subgrouped and matched to different care pathways based on their prognosis and clinical characteristics. Objectives The objectives were to investigate the clinical effectiveness and cost-effectiveness of a stratified care model compared with usual, non-stratified care. Design This was a two-parallel group, multicentre, pragmatic, 1 : 1 randomised controlled trial. Setting Participants were recruited from primary care (42 general practices) in North Staffordshire, North Shropshire/Wales and Cheshire in the UK. Participants Eligible patients were aged ≥ 18 years, had suspected sciatica, had access to a mobile phone/landline, were not pregnant, were not receiving treatment for the same problem and had not had previous spinal surgery. Interventions In stratified care, a combination of prognostic and clinical criteria associated with referral to spinal specialist services was used to allocate patients to one of three groups for matched care pathways. Group 1 received advice and up to two sessions of physiotherapy, group 2 received up to six sessions of physiotherapy, and group 3 was fast-tracked to magnetic resonance imaging and spinal specialist opinion. Usual care was based on the stepped-care approach without the use of any stratification tools/algorithms. Patients were randomised using a remote web-based randomisation service. Main outcome measures The primary outcome was time to first resolution of sciatica symptoms (six point ordinal scale, collected via text messages). Secondary outcomes (at 4 and 12 months) included pain, function, psychological health, days lost from work, work productivity, satisfaction with care and health-care use. A cost–utility analysis was undertaken over 12 months. A qualitative study explored patients’ and clinicians’ views of the fast-track care pathway to a spinal specialist. Results A total of 476 patients were randomised (238 in each arm). For the primary outcome, the overall response rate was 89.3% (88.3% and 90.3% in the stratified and usual care arms, respectively). Relief from symptoms was slightly faster (2 weeks median difference) in the stratified care arm, but this difference was not statistically significant (hazard ratio 1.14, 95% confidence interval 0.89 to 1.46; p = 0.288). On average, participants in both arms reported good improvement from baseline, on most outcomes, over time. Following the assessment at the research clinic, most participants in the usual care arm were referred to physiotherapy. Conclusions The stratified care model tested in this trial was not more clinically effective than usual care, and was not likely to be a cost-effective option. The fast-track pathway was felt to be acceptable to both patients and clinicians; however, clinicians expressed reluctance to consider invasive procedures if symptoms were of short duration. Limitations Participants in the usual care arm, on average, reported good outcomes, making it challenging to demonstrate superiority of stratified care. The performance of the algorithm used to allocate patients to treatment pathways may have influenced results. Future work Other approaches to stratified care may provide superior outcomes for sciatica. Trial registration Current Controlled Trials ISRCTN75449581. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 49. See the NIHR Journals Library website for further project information.

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

2020 ◽  
Vol 34 (12) ◽  
pp. 1342-1349
Author(s):  
Raphael Rifkin-Zybutz ◽  
Stephanie MacNeill ◽  
Simon JC Davies ◽  
Christopher Dickens ◽  
John Campbell ◽  
...  
Keyword(s):  
Primary Care ◽  
Reuptake Inhibitor ◽  
Secondary Analysis ◽  
Anxiety Symptoms ◽  
Generalized Anxiety ◽  
Depression And Anxiety ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Likelihood Ratio Testing ◽  
Resistant Depression

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.

scholarly journals Mirtazapine added to SSRIs or SNRIs for treatment resistant depression in primary care: phase III randomised placebo controlled trial (MIR)

BMJ ◽  
2018 ◽  
pp. k4218 ◽  
Author(s):  
David S Kessler ◽  
Stephanie J MacNeill ◽  
Deborah Tallon ◽  
Glyn Lewis ◽  
Tim J Peters ◽  
...  
Keyword(s):  
Primary Care ◽  
Adverse Effects ◽  
Confidence Interval ◽  
Beck Depression Inventory ◽  
Reuptake Inhibitor ◽  
Controlled Trial ◽  
Phase Iii ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression

AbstractObjectiveTo 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 TrialsISRCTN06653773.

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

2018 ◽  
Vol 68 (675) ◽  
pp. e673-e681 ◽  
Author(s):  
Nicola Wiles ◽  
Abigail Taylor ◽  
Nicholas Turner ◽  
Maria Barnes ◽  
John Campbell ◽  
...  
Keyword(s):  
Primary Care ◽  
Mixed Methods ◽  
Usual Care ◽  
Antidepressant Medication ◽  
Mixed Methods Study ◽  
Active Management ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression ◽  
Medication Changes

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.

scholarly journals An open randomised study of autoinflation in 4- to 11-year-old school children with otitis media with effusion in primary care

2015 ◽  
Vol 19 (72) ◽  
pp. 1-150 ◽  
Author(s):  
Ian Williamson ◽  
Jane Vennik ◽  
Anthony Harnden ◽  
Merryn Voysey ◽  
Rafael Perera ◽  
...  
Keyword(s):  
Primary Care ◽  
Young Children ◽  
Adverse Events ◽  
Health Technology Assessment ◽  
Usual Care ◽  
Middle Ear ◽  
School Children ◽  
Technology Assessment ◽  
Otitis Media With Effusion ◽  
Health Technology

BackgroundOtitis media with effusion (OME) is a very common problem in primary care, but one that lacks an evidence-based non-surgical treatment.ObjectiveTo determine the clinical effectiveness of nasal balloon autoinflation for the treatment of OME in children.DesignA pragmatic, two-arm, open randomised controlled trial.SettingForty-three general practices from 17 UK primary care trusts recruited between January 2012 and February 2013.ParticipantsSchool children aged 4–11 years with a history of OME symptoms or related concerns in the previous 3 months, and a type B tympanogram, diagnostic of a middle ear effusion, in one or both ears.InterventionThree hundred and twenty children were randomised, 160 to each group, using independent web-based computer-generated randomisation (with minimisation based on age, sex and baseline severity of OME) to either nasal balloon autoinflation performed three times per day for 1–3 months plus usual care, or usual care alone.Main outcome measuresThe proportion of children demonstrating clearance of middle ear fluid in at least one ear (with normal tympanograms) at 1 and 3 months, assessed blind to treatment. An ear-related measure of quality of life (QoL) [a 14-point questionnaire on the impact of OME (OMQ-14)], weekly diary recorded symptoms, compliance and adverse events were all secondary outcomes.ResultsAt 1 month, the proportion of children with normal tympanograms was 47.3% (62/131) in those allocated to autoinflation and 35.6% (47/132) in those receiving usual care [adjusted relative risk (RR) 1.36, 95% confidence interval (CI) 0.99 to 1.88]. At 3 months, the proportions were 49.6% (62/125) and 38.3% (46/120), respectively (adjusted RR 1.37, 95% CI 1.03 to 1.83; number needed to treat = 9). The change in OMQ-14 also favoured the intervention arm (adjusted global score difference –0.42;p = 0.001). Reported compliance was good: 89% in the first month and 80% in months 2 and 3. Adverse events included otalgia in 4% of treated children compared with 1% in the control group. Minor nosebleeds (14% vs. 15%) and respiratory tract infections (18% vs. 13%) were noted.ConclusionWe found the use of autoinflation in young children with OME to be feasible in primary care and effective in both clearing effusions and improving child and parent ear-related QoL and symptoms. This method has scope to be used more widely. Further research is needed for very young children, and to inform prudent use in different health settings.Trial registrationCurrent Controlled Trials ISRCTN55208702.FundingThis project was funded by the National institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment, Vol. 19, No. 72. See the NIHR Journals Library website for further project information.

scholarly journals From idealistic rookies to a regional leader: The history of health technology assessment in Poland

2009 ◽  
Vol 25 (S1) ◽  
pp. 156-162 ◽  
Author(s):  
Rafał Niżankowski ◽  
Norbert Wilk
Keyword(s):  
Primary Care ◽  
Health Care ◽  
Decision Making ◽  
Health Technology Assessment ◽  
Technology Assessment ◽  
Health Technology ◽  
The Public ◽  
History Of ◽  
Decision Making Processes ◽  
Public Payer

In 1989, Poland started to slowly release itself not only from the burden of a half-century of communist indoctrination and soviet exploitation, but also from the consequences of the Semashko model of healthcare organization: low doctors' salaries, primary care based on multispecialty groups, overdeveloped hospital infrastructure, and limited access to sophisticated interventions overcome by patients' unofficial payments.A few years after the 1998 workshop on health technology assessment (HTA) in Budapest, the first HTA reports were elaborated in the National Center for Quality Assessment in Health Care, which could mark the beginning of HTA in Poland. Several individuals and organizations have been involved in developing HTA, both from noncommercial and commercial standpoints.A goal to establish a national HTA agency appeared among the priorities of the Polish Ministry of Health in 2004 and was realized a year later. The Agency for HTA in Poland published guidelines on HTA and established a sound and transparent two-step (assessment-appraisal) process for preparing recommendations on public financing of both drugs and nondrug technologies. The recommendations of the Agency's Consultative Council were warmly welcomed by the public payer. However, the recent major restructuring of the Agency and new drug reimbursement decisions aroused doubts as to keeping transparency of the decision-making processes.

scholarly journals Three wound-dressing strategies to reduce surgical site infection after abdominal surgery: the Bluebelle feasibility study and pilot RCT

2019 ◽  
Vol 23 (39) ◽  
pp. 1-166 ◽  
Author(s):  
Barnaby C Reeves ◽  
Leila Rooshenas ◽  
Rhiannon C Macefield ◽  
Mark Woodward ◽  
Nicky J Welton ◽  
...  
Keyword(s):  
Abdominal Surgery ◽  
Surgical Site Infection ◽  
Health Technology Assessment ◽  
Technology Assessment ◽  
Value Of Information ◽  
Primary Outcome ◽  
Health Technology ◽  
Controlled Trials ◽  
Site Infection ◽  
Pilot Rct

Background Surgical site infection (SSI) affects up to 20% of people with a primary closed wound after surgery. Wound dressings may reduce SSI. Objective To assess the feasibility of a multicentre randomised controlled trial (RCT) to evaluate the effectiveness and cost-effectiveness of dressing types or no dressing to reduce SSI in primary surgical wounds. Design Phase A – semistructured interviews, outcome measure development, practice survey, literature reviews and value-of-information analysis. Phase B – pilot RCT with qualitative research and questionnaire validation. Patients and the public were involved. Setting Usual NHS care. Participants Patients undergoing elective/non-elective abdominal surgery, including caesarean section. Interventions Phase A – none. Phase B – simple dressing, glue-as-a-dressing (tissue adhesive) or ‘no dressing’. Main outcome measures Phase A – pilot RCT design; SSI, patient experience and wound management questionnaires; dressing practices; and value-of-information of a RCT. Phase B – participants screened, proportions consented/randomised; acceptability of interventions; adherence; retention; validity and reliability of SSI measure; and cost drivers. Data sources Phase A – interviews with patients and health-care professionals (HCPs), narrative data from published RCTs and data about dressing practices. Phase B – participants and HCPs in five hospitals. Results Phase A – we interviewed 102 participants. HCPs interpreted ‘dressing’ variably and reported using available products. HCPs suggested practical/clinical reasons for dressing use, acknowledged the weak evidence base and felt that a RCT including a ‘no dressing’ group was acceptable. A survey showed that 68% of 1769 wounds (727 participants) had simple dressings and 27% had glue-as-a-dressing. Dressings were used similarly in elective and non-elective surgery. The SSI questionnaire was developed from a content analysis of existing SSI tools and interviews, yielding 19 domains and 16 items. A main RCT would be valuable to the NHS at a willingness to pay of £20,000 per quality-adjusted life-year. Phase B – from 4 March 2016 to 30 November 2016, we approached 862 patients for the pilot RCT; 81.1% were eligible, 59.4% consented and 394 were randomised (simple, n = 133; glue, n = 129; no dressing, n = 132); non-adherence was 3 out of 133, 8 out of 129 and 20 out of 132, respectively. SSI occurred in 51 out of 281 participants. We interviewed 55 participants. All dressing strategies were acceptable to stakeholders, with no indication that adherence was problematic. Adherence aids and patients’ understanding of their allocated dressing appeared to be key. The SSI questionnaire response rate overall was 67.2%. Items in the SSI questionnaire fitted a single scale, which had good reliability (test–retest and Cronbach’s alpha of > 0.7) and diagnostic accuracy (c-statistic = 0.906). The key cost drivers were hospital appointments, dressings and redressings, use of new medicines and primary care appointments. Limitations Multiple activities, often in parallel, were challenging to co-ordinate. An amendment took 4 months, restricting recruitment to the pilot RCT. Only 67% of participants completed the SSI questionnaire. We could not implement photography in theatres. Conclusions A main RCT of dressing strategies is feasible and would be valuable to the NHS. The SSI questionnaire is sufficiently accurate to be used as the primary outcome. A main trial with three groups (as in the pilot) would be valuable to the NHS, using a primary outcome of SSI at discharge and patient-reported SSI symptoms at 4–8 weeks. Trial registration Phase A – Current Controlled Trials ISRCTN06792113; Phase B – Current Controlled Trials ISRCTN49328913. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 39. See the NIHR Journals Library website for further project information. Funding was also provided by the Medical Research Council ConDuCT-II Hub (reference number MR/K025643/1).

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