Treatment-Resistant Depressive Disorder

Failure to respond to two or more trials of antidepressant monotherapy or failure to respond to four or more trials of different antidepressant therapies. (Campbell's Psychiatric Dictionary, 9th ed.)

Also Known As:

Depressive Disorder, Treatment-Resistant; Refractory Depression; Therapy-Resistant Depression; Treatment Resistant Depression; Depression, Refractory; Depression, Therapy-Resistant; Depression, Treatment Resistant; Depressions, Refractory; Depressions, Therapy-Resistant; Depressions, Treatment Resistant; Depressive Disorder, Treatment Resistant; Depressive Disorders, Treatment-Resistant; Disorder, Treatment-Resistant Depressive; Disorders, Treatment-Resistant Depressive; Refractory Depressions; Resistant Depression, Treatment; Resistant Depressions, Treatment; Therapy Resistant Depression; Therapy-Resistant Depressions; Treatment Resistant Depressions; Treatment-Resistant Depressive Disorders

Networked: 2937 relevant articles (464 outcomes, 681 trials/studies)

Relationship Network

Disease Context: Research Results

Mental Disorders: 24177
- Mood Disorders: 9968
  - Depressive Disorder: 6574
    - Treatment-Resistant Depressive Disorder: 2937

Related Diseases

1.	Bipolar Disorder (Manic Depressive Psychosis)
2.	Major Depressive Disorder (Major Depressive Disorders)
3.	Post-Traumatic Stress Disorders (Post Traumatic Stress Disorder)
4.	Mood Disorders (Mood Disorder)
5.	Mental Disorders (Mental Disorder)

Experts

1.	Daskalakis, Zafiris J: 40 articles (12/2022 - 10/2007)
2.	McIntyre, Roger S: 39 articles (07/2022 - 01/2019)
3.	Fava, Maurizio: 37 articles (03/2022 - 03/2002)
4.	Blumberger, Daniel M: 36 articles (12/2022 - 01/2012)
5.	Mayberg, Helen S: 34 articles (01/2022 - 03/2005)
6.	Rosenblat, Joshua D: 33 articles (07/2022 - 01/2019)
7.	Li, Cheng-Ta: 33 articles (03/2022 - 07/2014)
8.	Zarate, Carlos A: 33 articles (01/2022 - 04/2003)
9.	Mathew, Sanjay J: 32 articles (06/2022 - 05/2008)
10.	Su, Tung-Ping: 29 articles (03/2022 - 07/2008)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Treatment-Resistant Depressive Disorder:

1.	Ketamine FDA LinkGeneric 03/01/2015 - "Each study demonstrated a rapid and clinically significant reduction in SI, with results similar to previously described data on ketamine and treatment-resistant depression. " 01/01/2023 - "Baseline cognitive function predicts full remission of suicidal symptoms among patients with treatment-resistant depression and strong suicidal ideation after low-dose ketamine infusion." 01/01/2021 - "Ketamine treatment is capable of significant and rapid symptom improvement in adults with treatment-resistant depression (TRD). " 02/01/2020 - "Some patients with refractory depression who fail to respond to rapid injection of standard-dose ketamine are injected with high doses, but the safety and efficacy of this practice are unclear. " 12/01/2016 - "Ketamine has emerged as a novel strategy to treat refractory depression, producing rapid remission, but elicits some side effects that limit its use. "
2.	Antidepressive Agents (Antidepressants)IBA 01/01/2012 - "Preliminary evidence from current published trials indicates that the use of cognitive-behavioral therapy in combination with antidepressant medication yields the best outcome for treatment-resistant depression in adolescents. " 11/01/2014 - "An important determinant of treatment-resistant depression is so called subthreshold bipolarity which is connected with worse efficacy of antidepressant drugs. " 03/01/1994 - "Recently, several studies have suggested that newer, "second generation" antidepressants might be beneficial in treatment resistant depression (TRD). " 10/01/2021 - "The effectiveness of antidepressants shows high interindividual variability ranging from full symptomatologic remission to treatment-resistant depression. " 01/01/2021 - "Generally, people are treated successfully with antidepressants or psychotherapy, but some people do not respond to these treatments (called treatment-resistant depression [TRD]). "
3.	EsketamineIBA 01/01/2021 - "Combination of Electroconvulsive Therapy Alternating With Intravenous Esketamine Can Lead to Rapid Remission of Treatment Resistant Depression." 10/01/2020 - "Esketamine is unlikely to be cost-effective for management of treatment-resistant depression in the United States unless its price falls by more than 40%." 01/01/2023 - "Intranasal esketamine effectively treats treatment-resistant depression in adults regardless of baseline irritability." 06/01/2022 - "Intranasal esketamine was demonstrated to be safe, well tolerated, and rapidly effective in individuals with treatment resistant depression, suicidal ideation, and suicidal behavior." 01/01/2019 - "Controlled studies have shown short-term efficacy of esketamine for treatment-resistant depression (TRD), but long-term effects remain to be established. "
4.	LithiumIBA 01/01/2003 - "Although considerable evidence exists on the efficacy of lithium as an augmenting agent in refractory depression, the underlying neurobiology of this phenomenon is unknown. " 02/01/2013 - "Lithium augmentation has been shown to be effective in treatment-refractory depression. " 09/01/2000 - "The combination of maintenance ECT and lithium may be safe and effective in selected cases of refractory depression." 05/01/2001 - "The efficacy of lithium augmentation in therapy-resistant depression has been shown in a series of well-designed, placebo-controlled studies. " 01/01/1998 - "The available literature highlights the efficacy of lithium as an augmenting agent in refractory depression and serves as an impetus for additional neurobiological and clinical studies of this phenomenon."
5.	Psilocybin (Psilocibin)IBA 01/01/2023 - "Psilocybin, for example, has now been shown in several clinical trials to induce a rapid (within days) and persistent (3-12 months) improvement in human treatment-resistant depression and other neuropsychiatric conditions. " 07/01/2016 - "This study provides preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach. " 12/01/2023 - "The paper will examine whether three one-to-one psychotherapies identified as effective in the treatment of treatment-resistant depression are compatible with the psilocybin experience. " 12/01/2023 - "There is evidence to support the use of some psychotherapies in treating 'treatment-resistant' depression, and emerging evidence for the efficacy of psilocybin. " 08/22/2023 - "A recent randomized double-blind phase-IIb study demonstrated the safety and efficacy of COMP360, COMPASS Pathways' proprietary synthetic formulation of psilocybin, in participants with treatment-resistant depression. "
6.	Nasal SpraysIBA 01/01/2019 - "New Nasal Spray for Treatment-Resistant Depression." 07/11/2023 - "Long-term remission following esketamine nasal spray sessions in a patient with severe and highly treatment-resistant depression: a single-case report." 07/23/2019 - "Esketamine Nasal Spray Effective in Treatment-Resistant Depression." 01/01/2023 - "Predictors of response and remission in patients with treatment-resistant depression: A post hoc pooled analysis of two acute trials of esketamine nasal spray." 01/01/2020 - "This post hoc study assessed the evidence-base for esketamine nasal spray for management of treatment-resistant depression (TRD) using number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH). "
7.	Fluoxetine (Prozac)FDA LinkGeneric 07/01/2004 - "We report a case of a patient, suffering from a bipolar treatment resistant depression, who dramatically improved after substituting VPD to VPA in association with fluoxetine. " 03/01/1994 - "4. The present observations suggest that fluoxetine treatment of adequate duration may be beneficial for some patients with a prior history of refractory depression." 01/01/2021 - "Post-weaning Social Isolated Flinders Sensitive Line Rats Display Bio-Behavioural Manifestations Resistant to Fluoxetine: A Model of Treatment-Resistant Depression." 05/01/2004 - "Effect of medical comorbidity on response to fluoxetine augmentation or dose increase in outpatients with treatment-resistant depression." 03/01/1994 - "Fluoxetine efficacy in treatment resistant depression."
8.	Selective Serotonin Reuptake Inhibitors (Serotonin Reuptake Inhibitors)IBA 04/01/2006 - "The results suggest that the ability of atypical APDs to augment the therapeutic efficacy of SSRIs in major depression and treatment-resistant depression may be due, at least in part, to potentiation of SSRI-induced increases in cortical DA and NE. " 01/01/2007 - "Treatment-resistant depression is a relatively common clinical occurrence: between 60-70% of depressive patients fail to achieve total remission to the initial treatment with selective serotonin reuptake inhibitors (SSRI). " 08/01/2012 - "CLINICAL TRIALS.GOV IDENTIFIER: NCT00093847; titled 'Optimizing the Effectiveness of Selective Serotonin Reuptake Inhibitors (SSRIs) in Treatment-Resistant Depression', accessible at: http://clinicaltrials.gov/ct2/show/NCT00093847." 01/01/2020 - "The present characterization of related clinical features describes the use of nonselective serotonin reuptake inhibitors in adolescents with treatment-resistant depression and raises the possibility that those with the greatest medication treatment resistance are less likely to have had recurrent episodes. " 11/01/2018 - "Alternate day dTMS combined with SSRIs for chronic treatment resistant depression: A prospective multicenter study."
9.	Aripiprazole (Abilify)FDA Link 01/01/2018 - "This is a secondary analysis of data from a late-life treatment resistant depression trial examining the safety and efficacy of aripiprazole augmentation. " 01/01/2018 - "To identify which specific depressive symptoms predict remission to aripiprazole augmentation in late-life treatment resistant depression. " 01/01/2018 - "Specific depressive symptoms predict remission to aripiprazole augmentation in late-life treatment resistant depression." 04/01/2016 - "Set-shifting performance indicates which older adults with treatment-resistant depression may respond favorably to augmentation with aripiprazole and thus may help to personalize treatment. " 01/01/2018 - "Efficacy, acceptability, and safety of adjunctive aripiprazole in treatment-resistant depression: a meta-analysis of randomized controlled trials."
10.	Antipsychotic Agents (Antipsychotics)IBA 04/01/2016 - "Among the several "add-on" strategies with established efficacy for treatment-resistant depression, the second-generation antipsychotics have become the most commonly used in psychiatric settings. " 04/01/2008 - "Atypical antipsychotics (AAPs) have been hypothesized to be beneficial in treatment-resistant depression (TRD). " 05/25/2015 - "We performed a network meta-analysis, which integrates direct and indirect evidence from randomized controlled trials (RCTs), to investigate the comparative efficacy and tolerability of adjunctive atypical antipsychotics for treatment-resistant depression (TRD). " 11/05/2014 - "Randomized clinical trials (RCTs) with atypical antipsychotic augmentation treatment for treatment-resistant depression will be considered. " 01/01/2013 - "We included randomized trials comparing adjunctive antipsychotic medication to placebo for treatment-resistant depression in adults. "

Therapies and Procedures

1.	Transcranial Magnetic Stimulation 01/01/2022 - "Transcranial magnetic stimulation (TMS) is a proven intervention for treatment-resistant depression in younger adults but the efficacy of TMS to treat depressed older adults is still unclear. " 01/01/2023 - "The aim of this study is to compare the efficacy of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) to left dorsolateral prefrontal cortex (DLPFC) with that of pharmacological augmentation strategies in unipolar non-psychotic treatment-resistant depression. " 11/01/2020 - "Repetitive transcranial magnetic stimulation (rTMS) is a treatment option for treatment resistant depression (TRD) with response and remission rates in open-label studies being as high as 58% and 37% respectively. " 01/01/2019 - "Clinical trials and meta-analyses have demonstrated the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left prefrontal cortex in treatment-resistant depression. " 02/08/2023 - "A promising treatment option for adolescents with treatment-resistant depression is high-frequency repetitive transcranial magnetic stimulation (rTMS) delivered to the left dorsolateral prefrontal cortex (L-DLPFC). "
2.	Therapeutics 01/01/2019 - "Electroconvulsive therapy (ECT) is the most effective treatment for MDD and the gold-standard therapy for treatment-resistant depression (TRD), yet it remains underutilized due to factors such as limited availability, stigma, and concerns about cognitive side effects. " 12/01/2016 - "Electroconvulsive therapy (ECT) is a highly effective and well-tolerated therapy for severe and treatment-resistant depression. " 11/01/2011 - "Electroconvulsive therapy (ECT) is the most effective treatment for therapy-refractory depression. " 12/20/2022 - "Despite many proven treatments with multiple medications or therapies, approximately 30% of patients fail to achieve remission and are considered to have treatment-refractory depression (TRD). " 01/01/2020 - "Electroconvulsive therapy (ECT) is an important therapy for treatment-resistant depression and is especially effective for elderly individuals with depression. "
3.	Deep Brain Stimulation 06/15/2013 - "In this pilot study, we assessed safety and efficacy of deep brain stimulation to the supero-lateral branch of the medial forebrain bundle in seven patients with highly refractory depression. " 01/01/2017 - "Deep brain stimulation (DBS) of the subgenual cingulate gyrus (area CG25) is beneficial in treatment resistant depression. " 08/30/2020 - "Deep Brain Stimulation Is Effective for Treatment-Resistant Depression: A Meta-Analysis and Meta-Regression." 10/01/2009 - "There is also emerging evidence that deep brain stimulation (DBS) is effective for otherwise treatment resistant depression, but this is an investigational approach in 2009. " 06/01/2014 - "Clinical trials have shown promising results with the use of subcallosal cingulate gyrus deep brain stimulation (DBS) for treatment-resistant depression. "
4.	Vagus Nerve Stimulation 09/01/2017 - "Sustained remission in patients with treatment-resistant depression receiving vagal nerve stimulation: A case series." 11/01/2022 - "This study is the first to assess the safety and therapeutic efficacy of vagus nerve stimulation (VNS) as an adjunctive treatment for Chinese patients suffering from treatment-resistant depression (TRD). " 01/01/2022 - "Previous studies found that transcutaneous auricular vagus nerve stimulation (taVNS) was clinically effective in treating a case of treatment-resistant depression (TRD). " 01/01/2022 - "Among few available therapeutic options for patients with treatment-resistant depression, chronic stimulation of the vagus nerve using an implanted stimulator, the so-called vagal nerve stimulation (VNS), has been shown to be both effective and safe technique, based on the multitude of studies. " 08/01/2014 - "The purpose of this study was to evaluate the efficacy of vagus nerve stimulation (VNS) as a therapeutic option for treatment-resistant depression (TRD), with follow-up periods of 1, 3 and 5 years after VNS surgery. "
5.	Drug Therapy (Chemotherapy) 01/01/2023 - "Electroconvulsive therapy (ECT) is a highly effective treatment for severe and treatment-resistant depression, but relapse rates remain high despite maintenance pharmacotherapy. " 01/01/2011 - "Treatment-resistant depression (TRD) is a severely disabling disorder with no proven treatment options; novel treatment methods like rTMS can be used as augmentation to ongoing pharmacotherapy or as a solitary method of treatment. " 11/28/2023 - "However, a significant percentage of depressive individuals do not achieve remission even after an adequate trial of pharmacotherapy, a condition known as treatment-resistant depression (TRD). " 09/01/2016 - "One of the major drawbacks of current depression pharmacotherapy is the delay in symptom improvement, aside from the untoward side effects and lack of efficacy against refractory depression. " 01/01/2023 - "Empirical evidence on the relative efficacy of rTMS treatment compared with standard pharmacotherapy in Treatment-Resistant Depression (TRD) were extracted. "