scholarly journals Trazodone Addition to Paroxetine and Mirtazapine in a Patient with Treatment-Resistant Depression: The Pros and Cons of Combining Three Antidepressants

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Rui Lopes ◽  
José Carlos Alves ◽  
Raquel Garcia Rego
Keyword(s):  
Clinical Practice ◽  
Depressive Symptoms ◽  
Sleep Problems ◽  
Treatment Options ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Pros And Cons ◽  
Effective Doses ◽  
Resistant Depression ◽  
Antidepressant Combination

Dual antidepressant combination for treatment-resistant depression is a strategy well supported by literature and accepted in clinical practice. Rather, the usefulness of the combination of more than two antidepressants is controversial. This may be related to the possibility of higher side-effect burden and to doubts about its pharmacological effectiveness and therapeutic advantage compared to other standard treatment options. We report a relapse of moderate-to-severe depressive symptoms with insomnia that successfully remitted after the addition of trazodone to a dual combination of paroxetine and mirtazapine (in standard effective doses) in a patient with treatment-resistant depression. We also review the literature and discuss the utility of triple antidepressant combination in treatment-resistant depression. This clinical case highlights the utility of combining trazodone as a third antidepressant for the relapse of depressive symptoms after the failure of a dual antidepressant combination. Trazodone may be advantageous in patients presenting recurrence of moderate-to-severe depressive symptoms that include sleep problems and/or insomnia and may be particularly useful when benzodiazepines are not recommended. Although its use may be controversial and associated with higher risk of side-effects, more investigation is needed to determine the efficacy and safety for triple antidepressant combinations as reliable strategies for treatment-resistant depression in clinical practice.

scholarly journals Role of the Pharmacist in Managing Treatment-Resistant Depression: A Focus on Ketamine

Pharmacy ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 118
Author(s):  
Linda Xing Yu Liu ◽  
Marina Golts ◽  
Virginia Fernandes
Keyword(s):  
Current Practice ◽  
Quality Care ◽  
Treatment Options ◽  
Critical Role ◽  
Transitions Of Care ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression ◽  
Multiple Treatments ◽  
The Impact

The impact of depression is well described in the literature, and it is most prominent in patients who have trialed multiple treatments. Treatment-resistant depression (TRD) is particularly debilitating, and it is associated with significant morbidity and mortality. Despite this, there seems to be therapeutic inertia in adopting novel therapies in current practice. Ketamine is an N-methyl-D-aspartate receptor antagonist and anesthetic agent which has recently been shown to be effective in the management of TRD when administered intravenously or intranasally. The treatments, however, are not easily accessible due to restrictions in prescribing and dispensing, high costs, and the slow uptake of evidence-based practice involving ketamine within the Canadian healthcare system. Given the limited treatment options for TRD, novel approaches should be considered and adopted into practice, and facilitated by a multi-disciplinary approach. Pharmacists play a critical role in ensuring access to quality care. This includes dissemination of evidence supporting pharmacological treatments and facilitating translation into current practice. Pharmacists are uniquely positioned to collaborate with prescribers and assess novel treatment options, such as ketamine, address modifiable barriers to treatment, and triage access to medications during transitions of care. Extending the reach of these novel psychiatric treatments in both tertiary and primary care settings creates an emerging role for pharmacists in the collaborative effort to better manage treatment-resistant depression.

scholarly journals Prolonged ketamine infusion modulates limbic connectivity and induces sustained remission of treatment-resistant depression

2021 ◽  
Author(s):  
Joshua S. Siegel ◽  
Ben J. A. Palanca ◽  
Beau M. Ances ◽  
Evan D. Kharasch ◽  
Julie A. Schweiger ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Limbic System ◽  
Anterior Cingulate ◽  
Sustained Remission ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Open Label ◽  
Subgenual Anterior Cingulate Cortex ◽  
Post Infusion ◽  
Resistant Depression

AbstractKetamine produces a rapid antidepressant response in over 50% of adults with treatment-resistant depression. A long infusion of ketamine may provide durable remission of depressive symptoms, but the safety, efficacy, and neurobiological correlates are unknown. In this open-label, proof-of-principle study, adults with treatment-resistant depression (N = 23) underwent a 96-h infusion of intravenous ketamine (0.15 mg/kg/h titrated toward 0.6 mg/kg/h). Clonidine was co-administered to reduce psychotomimetic effects. We measured clinical response for 8 weeks post-infusion. Resting-state functional magnetic resonance imaging was used to assess functional connectivity in patients pre- and 2 weeks post-infusion and in matched non-depressed controls (N = 27). We hypothesized that responders to therapy would demonstrate response-dependent connectivity changes while all subjects would show treatment-dependent connectivity changes. Most participants completed infusion (21/23; mean final dose 0.54 mg/kg/h, SD 0.13). The infusion was well tolerated with minimal cognitive and psychotomimetic side effects. Depressive symptoms were markedly reduced (MADRS 29 ± 4 at baseline to 9 ± 8 one day post-infusion), which was sustained at 2 weeks (13 ± 8) and 8 weeks (15 ± 8). Imaging demonstrated a response-dependent decrease in hyperconnectivity of the subgenual anterior cingulate cortex to the default mode network, and a treatment-dependent decrease in hyperconnectivity within the limbic system (hippocampus, amygdala, medial thalamus, nucleus accumbens). In exploratory analyses, connectivity was increased between the limbic system and frontal areas, and smaller right hippocampus volume at baseline predicted larger MADRS change. A single prolonged infusion of ketamine provides a tolerated, rapid, and sustained response in treatment-resistant depression and normalizes depression-related hyperconnectivity in the limbic system and frontal lobe.ClinicalTrials.gov: Treatment Resistant Depression (Pilot), NCT01179009.

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

BJPsych Open ◽  
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.

Baseline Working Memory Predicted Response to Low-Dose Ketamine Infusion in Patients with Treatment-Resistant Depression

2021 ◽  
Author(s):  
Mu-Hong Chen ◽  
Wei-Chen Lin ◽  
Cheng-Ta Li ◽  
Shih-Jen Tsai ◽  
Hui-Ju Wu ◽  
...  
Keyword(s):  
Working Memory ◽  
Depressive Symptoms ◽  
Treatment Response ◽  
Low Dose ◽  
Memory Function ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Ketamine Infusion ◽  
Treatment Groups ◽  
Resistant Depression

Abstract Introduction Pretreatment neurocognitive function may predict the treatment response to low-dose ketamine infusion in patients with treatment-resistant depression (TRD). However, the association between working memory function at baseline and the antidepressant efficacy of ketamine infusion remains unclear. Methods A total of 71 patients with TRD were randomized to one of three treatment groups: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, or normal saline. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale (HDRS) at baseline and after treatment. Cognitive function was evaluated using working memory and go-no-go tasks at baseline. Results A generalized linear model with adjustments for demographic characteristics, treatment groups, and total HDRS scores at baseline revealed only a significant effect of working memory function (correct responses and omissions) on the changes in depressive symptoms measured by HDRS at baseline (F=12.862, p<0.05). Correlation analysis further showed a negative relationship (r=0.519, p=0.027) between pretreatment working memory function and changes in HDRS scores in the 0.5 mg/kg ketamine group. Discussion An inverse relationship between pretreatment working memory function and treatment response to ketamine infusion may confirm that low-dose ketamine infusion is beneficial and should be reserved for patients with TRD.

scholarly journals Pharmacological Treatments for Patients with Treatment-Resistant Depression

2020 ◽  
Vol 13 (6) ◽  
pp. 116 ◽  
Author(s):  
Valerie L. Ruberto ◽  
Manish K. Jha ◽  
James W. Murrough
Keyword(s):  
Treatment Options ◽  
Symptom Relief ◽  
Antidepressant Medication ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Qualitative Synthesis ◽  
Course Of Illness ◽  
Effective Strategies ◽  
Increased Risk ◽  
Resistant Depression

Over a third of patients with major depressive disorder (MDD) do not have an adequate response to first-line antidepressant treatments, i.e., they have treatment-resistant depression (TRD). These patients tend to have a more severe course of illness and are at an increased risk of suicide. Next step treatment options for patients with TRD, include switching to a different antidepressant, combining more than one antidepressant, or augmenting an antidepressant with another (non-antidepressant) medication. It is unclear which of these treatment approaches should be applied to a given patient, and in what order. Due to this ambiguity, comparing antidepressants and augmentation agents on the basis of their efficacy, tolerability, and speed of symptom relief would be beneficial for clinicians. To accomplish this, a systematic search was conducted following PRISMA guidelines. Only randomized controlled trials were included in this qualitative synthesis, resulting in 66 articles. This review identified several effective pharmaco-therapeutic strategies that are currently available for patients with TRD. Ketamine and esketamine appear to be effective for the treatment of TRD. Augmentation with certain second generation antipsychotics, such as quetiapine or aripiprazole is likewise effective, and may be preferred over switching to antidepressant monotherapy. While the combination of olanzapine and fluoxetine was one of the first pharmacotherapy approved for TRD, and its use may be limited by metabolic side-effects. Other effective strategies include augmentation with lithium, liothyronine (T3), lamotrigine, or combination of antidepressants including bupropion, tricyclics, or mirtazapine. There is insufficient research to demonstrate the efficacy of ziprasidone or levothyroxine (T4). A shared decision-making approach is recommended to guide treatment selection to address each patient’s individual needs.

scholarly journals Esketamine for treatment resistant depression: a trick of smoke and mirrors?

2019 ◽  
Vol 29 ◽  
Author(s):  
C. Gastaldon ◽  
D. Papola ◽  
G. Ostuzzi ◽  
C. Barbui
Keyword(s):  
Clinical Practice ◽  
Severe Depression ◽  
Practice Research ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Off Label ◽  
The Us ◽  
The Usa ◽  
Resistant Depression ◽  
Spray Formulation

Abstract In March 2019, the US Food and Drug Administration (FDA) approved a nasal spray formulation of esketamine for the treatment of resistant depression in adults. Esketamine is the S-enantiomer of ketamine, an FDA-approved anaesthetic, known to cause dissociation and, occasionally, hallucinations. While ketamine has not been approved for depression in the USA or in any other country, it has been used off-label in cases of severe depression. This commentary critically reviewed the evidence on esketamine submitted to the FDA, aiming to draw implications for clinical practice, research and regulatory science.

scholarly journals 118 Use of Patient Health Questionnaire to Predict Relapses in Patients with Treatment-resistant Depression Treated With Esketamine + Oral Antidepressant

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 276-277
Author(s):  
Carol Jamieson ◽  
Nan Li ◽  
Ella Daly ◽  
Adam Janik ◽  
Rosanne Lane ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Patient Health Questionnaire ◽  
Controlled Study ◽  
Health Questionnaire ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Relapse Risk ◽  
Total Score Range ◽  
Patient Health ◽  
Resistant Depression

Abstract:Objective:To assess the Patient Health Questionnaire (PHQ-9) as a predictor of relapse of depressive symptoms in treatment-resistant depression (TRD).Method:Analysis included maintenance phase data from SUSTAIN-1 (NCT02493868), a randomized, double-blind, active-controlled study in TRD patients that evaluated efficacy of intranasal esketamine (ESK) + oral antidepressant (AD) vs AD + intranasal placebo in delaying relapse of depressive symptoms. A ≥50% reduction in initial symptom score and total score of ≤12 were considered as response and remission, respectively, using the Montgomery-Asberg Depression Rating Scale. PHQ-9 total score (range, 0–27), PHQ-2 total score (0–6), and individual items of the PHQ-9 (0–3) were examined as predictors of relapse. Data were collected every 2 weeks. Association between time-varying PHQ-9 and event of depression relapse was evaluated in Andersen-Gill Cox model.Results:Of 176 stable remitters, 63 had a relapse event (ESK+AD [n=24]; AD+placebo [n=39]). Of 121 stable responders, 50 had a relapse event (ESK+AD [n=16]; AD+placebo [n=34]). Among stable remitters, PHQ-9 total score (HR; 95% CI [1.12; 1.04–1.21]) and PHQ-2 total score (1.58; 1.25–1.99) were associated with relapse risk. PHQ-9 items #1 (loss of pleasure, 2.07; 1.38–3.09), #2 (feeling down, 2.18; 1.51–3.15), #4 (feeling tired, 1.54; 1.13–2.11), and #6 (negative self-view, 2.27; 1.41–3.66) were associated with relapse risk. PHQ-2 total scale yielded the smallest Akaike’s Information Criterion among stable remitters and responders.Conclusion:PHQ-9, PHQ-2 total scores or individual items may be useful for predicting relapse of depressive symptoms among stable TRD patients.Funding Acknowledgements:This study was sponsored by Janssen Research and Development, LLC.

scholarly journals Additional intranasal oxytocin to escitalopram improves depressive symptoms in resistant depression: An open trial

2015 ◽  
Vol 30 (1) ◽  
pp. 65-68 ◽  
Author(s):  
G. Scantamburlo ◽  
M. Hansenne ◽  
V. Geenen ◽  
J.J. Legros ◽  
M. Ansseau
Keyword(s):  
Depressive Symptoms ◽  
Rating Scale ◽  
Open Trial ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Hamilton Depression Rating Scale ◽  
Resistant Depression ◽  
Synthetic Oxytocin

AbstractThe aim of this open trial was to assess the antidepressant/anxiolytic effects of oxytocin used as an adjunct to antidepressant in treatment-resistant depression. Fourteen patients, who have not responded to 40 mg of escitalopram, received intranasal synthetic oxytocin during 4 weeks, in association with antidepressant. This is the first open trial study suggesting OT in association with escitalopram significantly reduced scores on Hamilton Depression Rating Scale.

Magnetic seizure therapy in treatment-resistant depression: clinical, neuropsychological and metabolic effects

2014 ◽  
Vol 45 (5) ◽  
pp. 1073-1092 ◽  
Author(s):  
S. Kayser ◽  
B. H. Bewernick ◽  
A. Matusch ◽  
R. Hurlemann ◽  
M. Soehle ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Depressive Symptoms ◽  
Fdg Pet ◽  
Metabolic Effects ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Magnetic Seizure Therapy ◽  
Resistant Depression ◽  
Pet Scans

Background.Magnetic seizure therapy (MST), despite being in an early phase of clinical research, has been demonstrated to be associated with antidepressant efficacy. However, safety, tolerability and efficacy data in connection with functional brain activity from larger samples are lacking. The aim of this study was to determine clinical and cognitive effects of MST and the influence of MST on regional brain glucose metabolism.Method.Twenty-six patients suffering from treatment-resistant depression (TRD) underwent MST. Ten patients underwent a randomized trial and 16 patients an open-label study design. The primary outcome criterion was the severity of depressive symptoms assessed with the Hamilton Depression Rating Scale (HAMD). Depressive symptoms, tolerability and cognitive safety, along with social functioning and quality of life parameters, were assessed using various rating scales. A clinical follow-up visit 6 months following the completion of a course of MST and [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) scans of 12 patients were analysed.Results.A significant response to MST was demonstrated by 69% of the patient sample, with 46% meeting remission criteria. Anxiety ratings were significantly reduced in responders and their quality of life was improved. Half of the responders relapsed within 6 months. No cognitive side-effects were observed. FDG-PET scans showed a metabolic increase in the frontal cortex bilaterally and a decrease in the left striatum.Conclusions.Robust antidepressant and anti-anxiety efficacy of MST was demonstrated, and found to be associated with localized metabolic changes in brain areas that are strongly implicated in depression. Thus, MST presents an effective, well-tolerated and safe treatment option for patients unable to respond to other forms of therapy for depression.

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