Bupropion for Treatment-Resistant Depression

Switching to monotherapy after failure with a first antidepressant resulted in no significant difference in efficacy and tolerability among bupropion, sertraline, and venlafaxine. In treatment-resistant depression, augmentation of previous treatment with bupropion did not result in significant differences in remission compared with switching to bupropion monotherapy, augmentation with aripiprazole, or augmentation with buspirone. Switching to bupropion monotherapy or augmentation with bupropion was associated with significantly higher incidence of anxiety, decreased appetite, dry mouth, and increased blood pressure, but lower incidence of increased appetite, increased weight, somnolence, akathisia, and laboratory test abnormality compared to augmentation with aripiprazole. Augmentation therapy with bupropion or aripiprazole may be a cost-effective option relative to switching to bupropion in treatment-resistant depression. Among the monotherapies, switching to vortioxetine appeared to be the most cost-effective option relative to other medications such as agomelatine, bupropion, venlafaxine, or sertraline; bupropion, venlafaxine, and sertraline monotherapies were not significantly different from one another in terms of cost-effectiveness.

Download Full-text

Reply to Drs Munkholm and Paludan-Müller’s comment on our paper “Augmentation therapy with minocycline in treatment-resistant depression patients with low-grade peripheral inflammation: results from a double-blind randomised clinical trial”

Neuropsychopharmacology ◽

10.1038/s41386-021-01042-1 ◽

2021 ◽

Author(s):

Maria A. Nettis ◽

Carmine M. Pariante ◽

Valeria Mondelli

Keyword(s):

Clinical Trial ◽

Randomised Clinical Trial ◽

Peripheral Inflammation ◽

Low Grade ◽

Treatment Resistant Depression ◽

Augmentation Therapy ◽

Treatment Resistant ◽

Double Blind ◽

Resistant Depression

Download Full-text

Epidemiology and current treatment patterns of treatment-resistant depression in Scotland: a CPRD study

BJPsych Open ◽

10.1192/bjo.2021.876 ◽

2021 ◽

Vol 7 (S1) ◽

pp. S334-S334

Author(s):

Timothy Ming ◽

Tom Denee ◽

Gemma Scott ◽

Joachim Morrens ◽

Christopher Weatherburn

Keyword(s):

Clinical Practice ◽

Incidence Rates ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Treatment Resistant Depression ◽

Augmentation Therapy ◽

Treatment Resistant ◽

First Line ◽

Resistant Depression

AimsTo assess the incidence and treatments currently used in clinical practice for the treatment of treatment-resistant depression (TRD) in Scotland.BackgroundPatients with major depressive disorder (MDD) who have not responded to at least two successive antidepressant (AD) treatments in a single episode are described as having Treatment-Resistant Depression (TRD). Epidemiological data on TRD in Scotland is lacking. Furthermore, there is no data to our knowledge on therapies prescribed in Scottish clinical practice to treat TRD.MethodA retrospective, longitudinal cohort study was conducted using Clinical Practice Research Datalink (CPRD) medical records. Adult patients were indexed on AD prescription, requiring MDD diagnosis within 90 days, from Jan 2011-May 2018 with 360-day baseline and 180-day minimum follow-up periods. Failure of ≥2 adequate oral AD regimens following indexing constituted TRD classification. Incidence rates of MDD and TRD (within the MDD cohort) and treatment lines following TRD classification were derived.ResultThe analysis included 20,059 patients with MDD (mean age 44 years, 63% female, median follow-up 59 months); 1,374 (6.8%) were classified as TRD. Median time-to-TRD classification was 25 months. The incidence rate of MDD was 15.9 per 1,000 patient-years and for TRD was 14.7 per 1,000 MDD-patient-years. For all first four post-TRD treatment lines, SSRI monotherapy was the most commonly prescribed therapy, followed by combination (dual/triple) therapy and augmentation therapy (at least one oral AD supplemented with lithium, an antipsychotic or an anticonvulsant therapy). At first-line of TRD treatment, 1,050 (76.4%) patients received monotherapy AD, 212 (15.4%) received combination AD therapy and 112 (8.2%) received augmentation therapy. The most common monotherapy treatments at first-line TRD were sertraline (15.6%), mirtazapine (13.8%), fluoxetine (12.2%) and venlafaxine (11.6%). Among combination therapies, mirtazapine, venlafaxine, sertraline and amitriptyline were frequently used. Among the TRD and MDD cohort, no somatic treatments were coded in CPRD, although the use of these treatments was likely underestimated.ConclusionMonotherapy AD treatment was the most common therapy type for all four post-TRD treatment lines. These data support the need for new treatments that can achieve and maintain therapeutic response, and avoid continuous cycling through similar AD therapies.This study was sponsored by Janssen Cilag Ltd.

Download Full-text

Deep Brain Stimulation Is Effective for Treatment-Resistant Depression: A Meta-Analysis and Meta-Regression

Journal of Clinical Medicine ◽

10.3390/jcm9092796 ◽

2020 ◽

Vol 9 (9) ◽

pp. 2796

Author(s):

Frederick L. Hitti ◽

Andrew I. Yang ◽

Mario A. Cristancho ◽

Gordon H. Baltuch

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Meta Analysis ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Significant Difference ◽

Resistant Depression ◽

Meta Regression ◽

K 12 ◽

Deep Brain

Major depressive disorder (MDD) is a leading cause of disability and a significant cause of mortality worldwide. Approximately 30–40% of patients fail to achieve clinical remission with available pharmacological treatments, a clinical course termed treatment-resistant depression (TRD). Numerous studies have investigated deep brain stimulation (DBS) as a therapy for TRD. We performed a meta-analysis to determine efficacy and a meta-regression to compare stimulation targets. We identified and screened 1397 studies. We included 125 citations in the qualitative review and considered 26 for quantitative analysis. Only blinded studies that compared active DBS to sham stimulation (k = 12) were included in the meta-analysis. The random-effects model supported the efficacy of DBS for TRD (standardized mean difference = −0.75, <0 favors active stimulation; p = 0.0001). The meta-regression did not demonstrate a statistically significant difference between stimulation targets (p = 0.45). While enthusiasm for DBS treatment of TRD has been tempered by recent randomized trials, this meta-analysis reveals a significant effect of DBS for the treatment of TRD. Additionally, the majority of trials have demonstrated the safety and efficacy of DBS for this indication. Further trials are required to determine the optimal stimulation parameters and patient populations for which DBS would be effective. Particular attention to factors including electrode placement technique, patient selection, and long-term follow-up is essential for future trial design.

Download Full-text

Augmentation Therapy With Serial Intravenous Ketamine Over 18 Months in a Patient With Treatment Resistant Depression

Clinical Neuropharmacology ◽

10.1097/wnf.0000000000000104 ◽

2015 ◽

Vol 38 (5) ◽

pp. 212-216 ◽

Cited By ~ 7

Author(s):

Sameer Hassamal ◽

Margaret Spivey ◽

Ananda K. Pandurangi

Keyword(s):

Treatment Resistant Depression ◽

Augmentation Therapy ◽

Treatment Resistant ◽

Resistant Depression ◽

Intravenous Ketamine

Download Full-text

Intranasal esketamine: A novel drug for treatment-resistant depression

American Journal of Health-System Pharmacy ◽

10.1093/ajhp/zxaa191 ◽

2020 ◽

Vol 77 (17) ◽

pp. 1382-1388

Author(s):

Farah Khorassani ◽

Om Talreja

Keyword(s):

Blood Pressure ◽

English Language ◽

Severe Depression ◽

Antidepressant Therapy ◽

Inadequate Response ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Included Review ◽

Resistant Depression ◽

Novel Drug

Abstract Purpose To review the efficacy, safety, and place in therapy of intranasal esketamine, a treatment modality for treatment-resistant depression. Summary An electronic literature search of PubMed, MEDLINE, and the ClinicalTrials.gov and Food and Drug Administration (FDA) websites covering the period April 2015 through June 2020 was performed using the following search terms: esketamine, intranasal esketamine, depression, and treatment-resistant depression. Other resources included review articles and the manufacturer’s product labeling. All relevant English-language articles and reports on clinical trials conducted in humans were included. Esketamine (Spravato, Janssen Pharmaceuticals) is an intranasal antidepressant approved by FDA for management of treatment-resistant depression (TRD) in patients with inadequate response to traditional antidepressant therapy. Esketamine is self-administered under the supervision of a healthcare provider and is used as an adjunct to oral antidepressant therapy. Patients are supervised for 2 hours after self-administering the medication to monitor for sedation, dizziness, dissociation reactions, and increased blood pressure. Esketamine has a favorable risk-to-benefit profile, with demonstrated efficacy in reducing depressive symptoms more rapidly than monotherapy with traditional oral antidepressants. Reported adverse effects include sedation, dizziness, dissociation reactions, and blood pressure elevations, but these effects are primarily confined to the 2-hour postdose monitoring window. Conclusion Patients with moderate to severe depression who are not sufficiently responsive to traditional strategies for managing TRD may benefit from adjunctive esketamine therapy.

Download Full-text

Cost-utility analysis of esketamine and electroconvulsive therapy in adults with treatment-resistant depression

BMC Psychiatry ◽

10.1186/s12888-021-03601-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Kinza Degerlund Maldi ◽

Peter Asellus ◽

Anna Myléus ◽

Fredrik Norström

Keyword(s):

Cost Effectiveness ◽

Electroconvulsive Therapy ◽

Cost Effective ◽

Sensitivity Analyses ◽

Base Case ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Case Scenario ◽

Base Case Scenario ◽

Resistant Depression

Abstract Background Electroconvulsive therapy (ECT) has long been used for treating individuals with treatment-resistant depression (TRD). Esketamine has recently emerged as a new treatment for TRD due to its rapid antidepressant effects. To further inform the decision regarding choice of treatment, this paper aims to evaluate whether ECT or esketamine is the more cost-effective option. Methods The cost-effectiveness was derived as cost per quality-adjusted life-year (QALY) using a Markov model from a societal and life-time perspective. The incremental cost-effectiveness ratio (ICER) was calculated. Health states included different depression and remission states and death. Data to populate the model was derived from randomised controlled trials and other research. Various sensitivity analyses were carried out to test the robustness of the model. Results The base case scenario shows that ECT is cost-effective compared to esketamine and yields more QALYs at a lower cost. The sensitivity analysis shows that ECT is cost-effective in all scenarios and ECT dominates esketamine in 12 scenarios. Conclusions This study found that, from a cost-effectiveness point of view, ECT should be the first-hand option for individuals with TRD, when other first line treatments have failed. Considering the lack of economic evaluation of ECT and esketamine, this study is of great value to decision makers.

Download Full-text

Effects of subcutaneous esketamine on blood pressure and heart rate in treatment-resistant depression

Journal of Psychopharmacology ◽

10.1177/0269881120922955 ◽

2020 ◽

Vol 34 (10) ◽

pp. 1155-1162

Author(s):

Lorena Catarina Del Sant ◽

Luciana Maria Sarin ◽

Eduardo Jorge Muniz Magalhães ◽

Ana Cecília Lucchese ◽

Marco Aurélio Tuena ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Vital Signs ◽

Response To Treatment ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Post Dose ◽

Before And After ◽

Resistant Depression ◽

The Impact

Introduction and objectives: The impact of multiple subcutaneous (s.c.) esketamine injections on the blood pressure (BP) and heart rate (HR) of patients with unipolar and bipolar treatment-resistant depression (TRD) is poorly understood. This study aimed to assess the cardiovascular safety of multiple s.c. doses of esketamine in patients with TRD. Methods: Seventy TRD patients received 394 weekly s.c. esketamine injections in conjunction with oral antidepressant therapy for up to six weeks. Weekly esketamine doses were 0.5, 0.75 or 1.0 mg/kg according to each patient’s response to treatment. Participants were monitored before each treatment and every 15 minutes thereafter for 120 minutes. We assessed systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR measurements for the entire treatment course. Results: BP increased after the first s.c. esketamine injection, reaching maximum mean SBP/DBP levels of 4.87/5.54 mmHg within 30–45 minutes. At the end of monitoring, 120 minutes post dose, vital signs returned to pretreatment levels. We did not detect significant differences in BP between doses of 0.5, 0.75, and 1 mg/kg esketamine. Mean HR did not differ significantly between doses or before and after s.c. esketamine injection. Conclusions: The BP changes observed with repeated s.c. esketamine injections were mild and well tolerated for doses up to 1 mg/kg. The s.c. route is a simple and safe method of esketamine administration, even for patients with clinical comorbidities, including obesity, hypertension, diabetes, and dyslipidemia. However, 14/70 patients experienced treatment-emergent transient hypertension (SBP >180 mmHg and/or a DBP >110 mmHg). Therefore, we strongly recommend monitoring BP for 90 minutes after esketamine dosing. Since s.c. esketamine is cheap, requires less frequent dosing (once a week), and is a simpler procedure compared to intravenous infusions, it might have an impact on public health.

Download Full-text

Somatic Comorbidities and Cardiovascular Safety in Ketamine Use for Treatment-Resistant Depression

Medicina ◽

10.3390/medicina57030274 ◽

2021 ◽

Vol 57 (3) ◽

pp. 274

Author(s):

Joanna Szarmach ◽

Wiesław Jerzy Cubała ◽

Adam Włodarczyk ◽

Maria Gałuszko-Węgielnik

Keyword(s):

Diabetes Mellitus ◽

Blood Pressure ◽

Heart Rate ◽

Small Sample ◽

Tolerability Profile ◽

Acute Administration ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Somatic Comorbidities ◽

Resistant Depression

Background and Objectives: There is evidence for ketamine efficacy in treatment-resistant depression (TRD). Several safety and tolerability concerns arise that some psychotropic agents may provide blood pressure or/and heart rate alterations. The aim of this study is to review blood pressure measurements in course of the treatment with ketamine on treatment refractory inpatients with somatic comorbidities in the course of MDD and BP. Materials and Methods: The study population of 49 patients comprised MDD and BP subjects treated with ketamine registered in the naturalistic observational protocol of treatment-resistant mood disorders (NCT04226963). Results: The conducted analysis showed that among people suffering from hypertension there is a higher increase in systolic blood pressure (RR) after infusion 2 (p = 0.004) than among people who do not suffer from hypertension. Patients with hypertension have a higher increase in diastolic RR compared to those not suffering from hypertension (p = 0,038). Among the subjects with diabetes mellitus, significant differences occurred for infusions 2 (p = 0.020), 7 (p = 0.020), and 8 (p = 0.035) for heart rate (HR), compared to subjects without diabetes mellitus. A higher increase in diastolic RR was noted in the group of subjects suffering from diabetes mellitus (p = 0.010) compared to those who did not. In the hyperlipidemic patients studied, a significantly greater decrease in HR after infusion 5 (p = 0.031) and systolic RR after infusion 4 (p = 0.036) was noted compared to nonpatients. People after a stroke had significantly higher increases in diastolic RR after infusions 4 (p = 0.021) and 6 (p = 0.001) than those who did not have a stroke. Patients suffering from epilepsy had a significantly greater decrease in systolic RR after the 8th infusion (p = 0.017) compared to those without epilepsy. Limitations: The study may be underpowered due to the small sample size. The observations apply to inhomogeneous TRD population in a single-site with no blinding and are limited to the acute administration. Conclusions: This study supports evidence for good safety and tolerability profile for short-term IV ketamine use in TRD treatment. However, risk mitigation measures are to be considered in patients with metabolic and cardiovascular comorbidities.

Download Full-text