scholarly journals Adjunctive Sleep Medications and Depression Outcome in the Treatment of Serotonin-Selective Reuptake Inhibitor Resistant Depression in Adolescents Study

2012 ◽  
Vol 22 (1) ◽  
pp. 29-36 ◽  
Author(s):  
Wael Shamseddeen ◽  
Gregory Clarke ◽  
Martin B. Keller ◽  
Karen Dineen Wagner ◽  
Boris Birmaher ◽  
...  
Keyword(s):  
Reuptake Inhibitor ◽  
Resistant Depression ◽  
Serotonin Selective Reuptake Inhibitor

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 Neonatal infant EEG bursts are altered by prenatal maternal depression and serotonin selective reuptake inhibitor use

2019 ◽  
Vol 130 (11) ◽  
pp. 2019-2025
Author(s):  
P.G. Grieve ◽  
W.P. Fifer ◽  
N.P. Cousy ◽  
C.E. Monk ◽  
R.I. Stark ◽  
...  
Keyword(s):  
Maternal Depression ◽  
Reuptake Inhibitor ◽  
Serotonin Selective Reuptake Inhibitor

scholarly journals Genome-wide association studies of antidepressant class response and treatment-resistant depression

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Qingqin S. Li ◽  
◽  
Chao Tian ◽  
David Hinds
Keyword(s):  
Reuptake Inhibitor ◽  
Meta Analysis ◽  
Genomic Region ◽  
Genome Wide Association Studies ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Significance Threshold ◽  
Genome Wide ◽  
Resistant Depression ◽  
Genome Wide Significance

Abstract The “antidepressant efficacy” survey (AES) was deployed to > 50,000 23andMe, Inc. research participants to investigate the genetic basis of treatment-resistant depression (TRD) and non-treatment-resistant depression (NTRD). Genome-wide association studies (GWAS) were performed, including TRD vs. NTRD, selective serotonin reuptake inhibitor (SSRI) responders vs. non-responders, serotonin-norepinephrine reuptake inhibitor (SNRI) responders vs. non-responders, and norepinephrine-dopamine reuptake inhibitor responders vs. non-responders. Only the SSRI association reached the genome-wide significance threshold (p < 5 × 10−8): one genomic region in RNF219-AS1 (SNP rs4884091, p = 2.42 × 10−8, OR = 1.21); this association was also observed in the meta-analysis (13,130 responders vs. 6,610 non-responders) of AES and an earlier “antidepressant efficacy and side effects” survey (AESES) cohort. Meta-analysis for SNRI response phenotype derived from AES and AESES (4030 responders vs. 3049 non-responders) identified another genomic region (lead SNP rs4955665, p = 1.62 × 10−9, OR = 1.25) in an intronic region of MECOM passing the genome-wide significance threshold. Meta-analysis for the TRD phenotype (31,068 NTRD vs 5,714 TRD) identified one additional genomic region (lead SNP rs150245813, p = 8.07 × 10−9, OR = 0.80) in 10p11.1 passing the genome-wide significance threshold. A stronger association for rs150245813 was observed in current study (p = 7.35 × 10−7, OR = 0.79) than the previous study (p = 1.40 × 10−3, OR = 0.81), and for rs4955665, a stronger association in previous study (p = 1.21 × 10−6, OR = 1.27) than the current study (p = 2.64 × 10−4, OR = 1.21). In total, three novel loci associated with SSRI or SNRI (responders vs. non-responders), and NTRD vs TRD were identified; gene level association and gene set enrichment analyses implicate enrichment of genes involved in immune process.

Esketamine for treatment-resistant depression

2020 ◽  
Vol 58 (12) ◽  
pp. 183-188
Keyword(s):  
Reuptake Inhibitor ◽  
Brand Name ◽  
Treatment Resistant ◽  
Major Depressive ◽  
Spray Solution ◽  
Noradrenaline Reuptake ◽  
Starting Dose ◽  
Resistant Depression ◽  
Authorisation Holder ◽  
Additional Monitoring

Generic name: Esketamine hydrochlorideBrand name: SpravatoFormulation: 28mg in 0.2ml nasal spray solutionMarket Authorisation holder: Janssen-Cilag International NVIndication: Treatment resistant major depressive disorder in adults who have failed to respond to at least two different antidepressants during the current moderate to severe episode. To be used in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin-noradrenaline reuptake inhibitor (SNRI).Dose: The starting dose is 56 mg for adults aged <65 years and 28 mg for adults aged ≥65 years 1 . Subsequent doses (56 mg or 84 mg for those <65 years; 28 mg, 56 mg or 84 mg for those ≥65 years) are given twice a week for 4 weeks, followed by once a week for 4 weeks, and then once a week or once every 2 weeks from week 9. Treatment is recommended for at least 6 months after symptoms improve.Cost: £163 for 28 mg (one device)Classification: Prescription only medicine (POM) subject to additional monitoring (▼). Controlled drug schedule 2.

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.

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