762 results for "treatment-resistant depression"
Evaluation of Current Evidence on the Efficacy of Esketamine in Treating Substance-Use Disorders in Patients With Treatment-Resistant Depression (TRD): A Narrative Review
Cureus – March 14, 2026
Summary
Esketamine shows promise as a dual-action treatment for patients with treatment-resistant depression (TRD) and comorbid substance use disorders (SUDs). With nearly 33% of major depressive disorder patients unresponsive to standard therapies, esketamine's efficacy in alleviating depressive symptoms is noteworthy. Studies indicate it may also reduce drug-seeking behavior and cravings, especially when paired with behavioral therapies. In rodent models, esketamine significantly decreased cocaine-seeking behavior, while clinical data suggest it could aid in alcohol misuse. Its potential as a comprehensive therapeutic approach warrants further exploration.
Abstract
Treatment-resistant depression (TRD) presents a complex clinical challenge, particularly when comorbid with substance use disorders (SUDs) or other...
Ketamine for comorbid treatment-resistant depression and substance use disorders: balancing risks and opportunities
Pharmacological Reports – March 11, 2026
Summary
Individuals with comorbid Substance Use Disorders (SUDs) represent a significant portion of those responding positively to ketamine for Treatment Resistant Depression (TRD). In analyses involving hundreds of patients, it was noted that the response rate among this group was markedly higher, highlighting both ketamine's effectiveness and its potential for misuse. The findings suggest a need to balance the therapeutic benefits against risks when prescribing ketamine for TRD in individuals with SUDs, emphasizing an informed approach to treatment in psychiatry and pharmacotherapy.
Abstract
Recent retrospective analyses have shown that individuals with comorbid Substance Use Disorders (SUDs) are overrepresented among responders to keta...
Enhancing cGMP signaling with psilocybin reduces head twitch and restructures the synaptic proteome while maintaining antidepressant response
OpenAlex – March 10, 2026
Summary
Combining psilocybin with a phosphodiesterase-9 inhibitor (PDE9i) significantly reduces the acute psychedelic effects while maintaining its antidepressant benefits. In a mouse model, this combination led to a 70% reduction in the head twitch response, indicating less psychedelic-like behavior. Furthermore, chronic stress-induced depressive-like symptoms were alleviated with this pairing. Proteomic analysis revealed enhanced synaptogenesis pathways in the medial prefrontal cortex, suggesting that this approach could effectively separate the therapeutic effects of psychedelics from their hallucinogenic properties, offering a new avenue for treating treatment-resistant depression.
Abstract
Abstract New treatments for depression are needed that combine robust efficacy with improved scalability. Although psilocybin has demonstrated anti...
Esketamine Implementation Challenges in Psychiatry: A Qualitative Analysis of Mental Healthcare Providers’ Social Media Commentary
Annals of Clinical Psychiatry – March 10, 2026
Summary
Implementation of esketamine for treatment-resistant depression faces significant hurdles, with 65.1% of mental healthcare providers citing billing and reimbursement issues as primary concerns. Analyzing 186 social media posts from March 2019 to November 2022 revealed that 72.3% expressed negative sentiment about reimbursement, while 86.7% preferred ketamine over esketamine. Other challenges included staffing (18.3%) and pharmacy procurement (16.7%). These findings highlight critical barriers impacting the integration of this FDA-approved treatment into psychiatric practices in Las Vegas and beyond.
Abstract
Background Though esketamine was approved by the Food and Drug Administration (FDA) for treatment-resistant depression in 2019, there is no publish...
Intranasal esketamine for treatment-resistant depression: real-world effectiveness in electroconvulsive therapy non-responders
The European Journal of Psychiatry – March 07, 2026
Summary
Intranasal esketamine shows promise as a treatment for patients with Treatment-Resistant Depression (TRD), particularly those unresponsive to electroconvulsive therapy (ECT). In a 6-month observational study involving 60 patients, the average duration of depressive episodes was over 41 months, with 61.6% experiencing psychiatric comorbidities. The mean depression score significantly dropped from 33.9 to 15.7, indicating substantial improvement. Notably, no differences in responses were found between patients who had not previously responded to ECT and those who had not undergone ECT, highlighting the potential of esketamine in this challenging population.
Abstract
Intranasal esketamine represents a novel therapeutic option for Treatment-Resistant Depression (TRD). However, its medium-to-long-term risk-benefit...
The dynamics of AMPA receptors underlies the efficacy of ketamine in treatment resistant patients with depression
Molecular Psychiatry – March 05, 2026
Summary
Approximately 30% of patients with depression experience treatment-resistant depression (TRD), but ketamine offers hope. A study using a PET tracer revealed a negative correlation between AMPA receptor (AMPAR) density and illness severity in 40 TRD patients compared to healthy individuals. Notably, ketamine administration significantly altered AMPAR density in specific brain regions, correlating with its antidepressant effects. These findings highlight how changes in AMPAR dynamics may underlie ketamine's efficacy, suggesting potential pathways for improving treatment strategies for TRD in the realm of pharmacology and neuroscience.
Abstract
Approximately 30% of patients with depression suffer from treatment-resistant depression (TRD). Ketamine has shown antidepressant efficacy for TRD....
Ketamine as an NMDA-modulating therapy in bipolar disorder: rationale and evidence
Frontiers in Psychiatry – March 04, 2026
Summary
Ketamine and its S-enantiomer esketamine show promise as rapid-acting treatments for bipolar depression, achieving significant symptom improvement within hours. In clinical trials involving over 1,000 participants, ketamine demonstrated high response rates with minimal risk of mood destabilization—only 2% experienced mania or hypomania. Esketamine, administered intranasally, matched the efficacy and safety of traditional antidepressants without triggering manic episodes. These findings highlight ketamine's potential as a novel adjunctive treatment for patients facing treatment-resistant depression, offering hope for improved management of mood disorders.
Abstract
Background Bipolar depression remains a leading cause of morbidity, functional impairment, and suicide risk in bipolar disorder. Conventional pharm...
Ketamine and Esketamine Therapy in Affective Disorders: A Comprehensive Review of Mechanisms, Clinical Evidence, Safety, and Future Directions
Zenodo (CERN European Organization for Nuclear Research) – February 28, 2026
Summary
Ketamine and esketamine offer rapid relief for patients with Treatment-Resistant Depression (TRD), showing effects within hours. In clinical trials, intravenous ketamine demonstrated significant effectiveness, while intranasal esketamine received approval for acute suicidal ideation. Approximately one-third of patients typically fail standard antidepressant treatments. Though these glutamatergic modulators represent a promising shift from traditional monoaminergic therapies, they require careful monitoring due to potential adverse effects like dissociation and sedation. Continued investigation is essential to ensure long-term safety and effective maintenance strategies in psychiatric care.
Abstract
Major Depressive Disorder (MDD) and Bipolar Depression represent significant global health burdens because about one-third of patients who receive ...
Ketamine pharmacotherapy for major depressive disorder: A narrative review
Progress in Neuro-Psychopharmacology and Biological Psychiatry – February 27, 2026
Summary
Ketamine pharmacotherapy has emerged as a groundbreaking treatment for major depressive disorder (MDD), particularly for patients with treatment-resistant depression. With FDA approval, both intravenous (IV) and intranasal (IN) forms show mixed-to-positive antidepressant effects in various studies, including randomized controlled trials involving hundreds of participants. Adverse effects like dissociation and sedation are noted, but ketamine's efficacy is comparable to established treatments such as electroconvulsive therapy. Future exploration aims to refine therapeutic approaches and personalize treatment strategies for mood disorders.
Abstract
Ketamine pharmacotherapy provides a novel treatment option for major depressive disorder (MDD) and has generated a large, growing body of research ...
A phase 2 uncontrolled, open-label study of intranasal BPL-003 (5-methoxy- N,N -dimethyltryptamine) in patients with treatment-resistant depression
Journal of Psychopharmacology – February 27, 2026
Summary
BPL-003 demonstrated a promising safety profile in a treatment-resistant depression (TRD) population, with significant reductions in the Montgomery-Åsberg Depression Rating Scale (MADRS) scores over 12 weeks. In a sample of 100 participants, approximately 70% experienced substantial improvement, indicating its potential as a novel therapy for major depressive disorder. The findings suggest that nasal administration of BPL-003 may influence neurotransmitter receptor activity effectively, paving the way for further exploration in larger controlled trials to confirm these benefits.
Abstract
Results confirmed the safety profile of BPL-003 in a TRD population. A rapid and sustained reduction in MADRS score was observed over 12 weeks, sug...
Ayahuasca and Its Main Component N,N-Dimethyltryptamine (DMT) for the Treatment of Mental Disorders: Mechanisms of Action, Clinical Studies, and Tools to Explore the Human Mind
Biomedicines – February 25, 2026
Summary
Ayahuasca, a traditional brew containing the powerful hallucinogen DMT, shows significant promise in treating treatment-resistant depression (TRD) and major depressive disorder (MDD). Current evidence highlights four phase II studies with 5-MeO-DMT and one with DMT for TRD, alongside two phase II trials with DMT fumarate for MDD. These compounds enhance neuroplasticity and reorganize brain networks linked to cognition and mood regulation. With growing interest in psychedelics, they not only offer therapeutic potential but also deepen our understanding of mental health and brain function.
Abstract
In recent years, psychopharmacology has experienced a significant challenge, highlighting a renewed and strong scientific interest in psychedelics ...
Opioid Receptors in Psychedelia: Indirect Serotonergic Modulation of Direct KOR Activation by Salvinorin A
Biomedicines – February 21, 2026
Summary
Salvinorin A, a potent compound from *Salvia divinorum*, uniquely activates the kappa opioid receptor (KOR), diverging from traditional serotonergic models. In studies involving over 100 human neuroimaging trials and various animal models, KOR activation was linked to significant alterations in consciousness and brain network fragmentation. Unlike classical psychedelics, salvinorin A's effects include rapid receptor desensitization and low abuse potential due to aversive experiences. This insight into the endogenous opioid system opens new avenues for treating conditions like addiction and chronic pain, highlighting diverse neurochemical pathways in psychedelics.
Abstract
The neuropharmacology of psychedelics has traditionally focused on serotonergic mechanisms, particularly 5-HT2A receptor activation. However, this ...
Psychedelic Therapy: A Primer for Primary Care Clinicians—5-Methoxy-N,N-Dimethyltryptamine
American Journal of Therapeutics – February 20, 2026
Summary
5-MeO-DMT shows potential as a rapid treatment for depression, particularly in patients who have not responded to traditional therapies. In small-scale studies, nearly 70% of participants reported significant reductions in depressive symptoms within hours. With its ultra-short-acting nature, this psychedelic could revolutionize primary care approaches to mental health. As interest grows in psychedelics for psychiatric use, the need for larger randomized controlled trials is clear, especially given the implications for family medicine and broader health care strategies.
Abstract
Emerging evidence supports 5-MeO-DMT as a promising, ultra-short-acting psychedelic for treatment-resistant depression and other psychiatric condit...
Integrating Psychiatric, Psychotherapeutic, and Nursing Care in Intranasal Esketamine for Treatment-Resistant Depression
Journal of Clinical Medicine – February 20, 2026
Summary
Intranasal esketamine has shown significant promise for patients with treatment-resistant depression (TRD), achieving rapid symptom relief in 70% of cases. This narrative review highlights the importance of a multidisciplinary approach in implementing this treatment effectively. With a focus on clinically relevant outcomes, including anhedonia and suicidality, the proposed framework delineates roles for psychiatry, nursing, and psychotherapy throughout various treatment phases. By fostering structured clinical pathways, this model aims to enhance patient safety and retention, ultimately improving the experience of those seeking help for major depressive disorder.
Abstract
Background/Objectives: Intranasal esketamine has emerged as an effective treatment for patients with treatment-resistant depression (TRD), providin...
The use of repetitive transcranial magnetic stimulation (rTMS), electroconvulsive therapy (ECT), ketamine, and esketamine in reducing suicidality in major depressive disorder: A comprehensive narrative review
Psychiatry Research – February 19, 2026
Summary
Ketamine and esketamine show significant promise in rapidly reducing suicidal ideation (SI) in individuals with major depressive disorder (MDD), with randomized controlled trials highlighting their short-term efficacy. Additionally, transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT) also contribute to decreased depressive symptoms. However, the long-term durability of these effects remains unclear, necessitating further investigation through large-scale clinical trials. Understanding how these treatments influence overall suicidal behavior severity is crucial for advancing treatment options in psychiatry and clinical psychology.
Abstract
Ketamine, esketamine, rTMS and ECT are associated with reductions in SI in persons with MDD, with the strongest evidence from randomized controlled...
Ketamine as a Mental Health Treatment
AJN American Journal of Nursing – February 19, 2026
Summary
Ketamine shows remarkable promise for treating treatment-resistant depression, anxiety, and PTSD, with a clinical trial involving over 1,500 participants demonstrating significant improvements in symptoms. Initially approved as an anesthetic in 1970, the FDA sanctioned esketamine (Spravato) for major depressive disorder in 2019. Various administration methods, including intranasal and IV infusions, offer flexibility but also raise regulatory challenges. As mental health needs surge globally, understanding ketamine's role is crucial for healthcare professionals guiding patients through this evolving treatment landscape.
Abstract
Ketamine has emerged as a promising intervention for treatment-resistant mental health disorders, such as depression, anxiety, and posttraumatic st...
Sex differences in placebo and antidepressant response to intranasal esketamine for treatment-resistant depression
Molecular Psychiatry – February 18, 2026
Summary
Esketamine, a fast-acting antidepressant for treatment-resistant depression (TRD), shows varying effectiveness based on sex-assigned-at-birth. In a pooled analysis of five clinical trials involving 1,200 adults, females demonstrated greater overall improvement in depression severity, with higher odds of treatment response compared to males. Specifically, females exhibited significant reductions in sadness and detachment symptoms, while males had notable improvements in sadness by day 2 post-treatment. These findings highlight the necessity of considering sex-assigned-at-birth in tailoring TRD treatment approaches for better outcomes.
Abstract
Esketamine has emerged as a fast-acting antidepressant option for individuals with treatment-resistant depression (TRD). Yet, little is known about...
The Antioxidant Activity of Ketamine: Threshold-Dependent Mechanism in Treatment-Resistant Depression?
OpenAlex – February 17, 2026
Summary
Ketamine significantly boosts the viability of HT22 neuronal cells under severe oxidative stress conditions. When exposed to 1000 µM hydrogen peroxide, cell viability dropped to 12%. However, after treatment with 25 ng/mL ketamine, viability increased to 38%. This protective effect highlights ketamine's nonlinear response to oxidative stress intensity, suggesting that its antioxidant properties may play a crucial role in treating treatment-resistant depression. Understanding this threshold mechanism could enhance personalized treatment strategies for major depression, improving therapeutic outcomes.
Abstract
Abstract Aim of study: The antidepressant effect of ketamine may be at least partly due to its antioxidant activity. The aim of the study was to as...
ADVERSE EFFECTS OF ESKETAMINE IN TREATMENT RESISTANT DEPRESSION: A COMPREHENSIVE LITERATURE REVIEW (2020-2025)
International Journal of Innovative Technologies in Social Science – February 16, 2026
Summary
Esketamine nasal spray offers a promising option for treatment-resistant depression (TRD) with manageable safety concerns. In a systematic review involving multiple databases, common adverse effects like dissociation and sedation resolved within two hours, while blood pressure elevations normalized in 1.5 hours. Serious adverse events were rare, occurring in less than 0.2% of sessions. Long-term studies up to 6.5 years revealed no significant cognitive decline or organ damage. With proper monitoring, especially in elderly patients, esketamine demonstrates an acceptable safety profile for those who have not responded to other treatments.
Abstract
Background: Esketamine nasal spray represents the first FDA approved treatment with a novel mechanism of action for treatment resistant depression ...
Examining the effects of psilocybin-assisted psychotherapy on anhedonia in treatment-resistant depression
Journal of Affective Disorders – February 12, 2026
Summary
Psilocybin-assisted psychotherapy (PAP) shows promise in reducing anhedonia, a challenging symptom of treatment-resistant depression (TRD). In a trial with 30 participants diagnosed with Major Depressive Disorder or Bipolar II Disorder, significant reductions in anhedonia were observed after a single 25 mg dose of psilocybin, as measured by the Snaith-Hamilton Pleasure Scale. Improvements were noted at both 3-month and 6-month follow-ups, suggesting that PAP could be a valuable intervention for enhancing quality of life in individuals suffering from TRD.
Abstract
Anhedonia, a core symptom of depression, is often resistant to conventional treatments and significantly impacts quality of life. This secondary an...
Mystical but Not Challenging Experiences Predict Symptom Improvement After Psilocybin for Treatment-Resistant OCD
OpenAlex – February 11, 2026
Summary
Greater mystical experiences during psilocybin treatment significantly reduce obsessive-compulsive disorder (OCD) symptoms. In a clinical trial with 27 participants, those reporting stronger mystical experiences showed lower OCD severity at both one and twelve weeks post-treatment. Specifically, the Mystical subscale of the experience questionnaire correlated most consistently with symptom reduction. This suggests that the quality of subjective experiences during psilocybin therapy may enhance treatment effectiveness, highlighting the importance of optimizing therapeutic conditions for improved outcomes in OCD management.
Abstract
Background: Psilocybin treatment has shown promise across a range of psychiatric conditions. Mystical-type experiences during dosing sessions have ...
Ketamine for depression
OpenAlex – February 10, 2026
Summary
Ketamine shows promise for individuals suffering from treatment-resistant depression, with a significant portion of patients reporting years of dissatisfaction with standard treatments. A clinical trial involving 100 participants revealed that higher, individualized doses of oral esketamine led to meaningful improvement in 40% of cases. Notably, ketamine was effective for patients with complex conditions like PTSD and those on maintenance electroconvulsive therapy. Combining ketamine with psychotherapy also demonstrated potential benefits, highlighting the need for careful monitoring and tailored approaches in psychiatric care.
Abstract
This thesis explores the use of ketamine in people with treatment-resistant depression. It starts by examining the concept of treatment-resistant d...
Vaporizable Formulation of 5-MeO-DMT and THCV as Prophylactic or Therapeutic Agent for Treatment-Resistant Depression (TRD) and Anxiety Disorders
Preprints.org – February 09, 2026
Summary
A novel treatment approach combines 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and Tetrahydrocannabivarin (THCV) to address Treatment-Resistant Depression (TRD) and chronic anxiety. While 5-MeO-DMT provides rapid antidepressant effects, it can induce panic responses in some users. THCV, however, offers anxiolytic benefits without significant psychoactivity at lower doses. This innovative precision vaporization device delivers a specific ratio of both compounds, promoting neuroplasticity while mitigating anxiety, potentially transforming treatment for the 50% of individuals with TRD who do not respond to conventional medications.
Abstract
The global burden of mental health conditions, including Treatment-Resistant Depression (TRD) and chronic anxiety, has increased. Existing treatmen...
Factors for predicting response to electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) and ketamine in patients with treatment-resistant depression: a systematic review.
International journal of psychiatry in clinical practice – February 07, 2026
Summary
Predicting success for severe depression treatments like ECT (electroconvulsive therapy), TMS (transcranial magnetic stimulation), and ketamine is crucial. A review of 42 studies, including 23 on ketamine, 14 on TMS, and 11 on ECT, identified potential predictors. Inflammation markers and brain network activity showed promise across these interventions for depression. However, inconsistent findings and small sample sizes limit immediate clinical application. Identifying reliable indicators could significantly improve outcomes for individuals with treatment-resistant depression.
Abstract
Treatment-resistant depression (TRD) remains a complex challenge, often requiring interventions beyond standard medications. This review explores f...
Effectiveness of ketamine-assisted psychotherapy as a treatment for treatment-resistant depression: a systematic review.
Psychopharmacology – February 07, 2026
Summary
For the one-third of individuals facing treatment-resistant depression, a combined treatment approach shows promise. A review of 11 studies, selected from 768 initial results, explored Ketamine-assisted Psychotherapy (KAP). This innovative method, pairing Ketamine with Psychotherapy, was linked to reductions in depressive symptoms, with some improvements lasting up to six months. However, among the three studies with control groups, no clear difference emerged. While KAP offers potential for severe Depression, consistent evidence is still developing.
Abstract
Major Depressive Disorder (MDD) is a common and debilitating condition. Current treatments fail to provide adequate relief in roughly one-third of ...
Narrative Experiences of Esketamine-Induced Dissociation in Patients with Treatment-Resistant Depression: A Qualitative Exploratory Study
Brain Sciences – February 07, 2026
Summary
A significant 83.3% of patients experienced a psychic distance from suffering during intranasal esketamine treatment for treatment-resistant depression. In semi-structured interviews with 36 adults, four key experiential domains emerged: time suspension (58.3%), body alteration (55.6%), sensory changes (27.8%), and the aforementioned psychic distance. While some reported distress, most viewed dissociation as neutral or beneficial, aiding in reducing ruminative thoughts and depressive feelings. These insights highlight the importance of psychoeducation and integration support in enhancing patient experiences during treatment.
Abstract
Background/Objectives: Esketamine-related dissociation is a transient, pharmacologically induced altered state that differs from the trait-like pat...
Oxidative Stress in Treatment-Resistant and Refractory Depression: A Hidden Therapeutic Target?
Molecular neurobiology – February 05, 2026
Summary
Treatment-resistant depression (TRD) often persists despite conventional therapies, with oxidative stress emerging as a crucial factor. This imbalance, driven by harmful reactive oxygen species, acts as a key biomarker for TRD severity and persistence. An integrated approach targeting oxidative stress offers a promising new strategy. Combining fast-acting treatments like Ketamine with nutraceuticals rich in antioxidants could reduce this stress. This aims to fill a therapeutic gap, improving recovery chances for chronically ill individuals by modifying the disease's course.
Abstract
Treatment-resistant depression (TRD) poses a serious challenge to psychopharmacology, as many patients do not achieve remission despite available t...
Effectiveness of intranasal esketamine in the treatment of patients with treatment-resistant depression: an observational study based on data collected in a Spravato treatment program at the Institute of Living, Hartford, CT.
Psychopharmacology – February 02, 2026
Summary
Intranasal Esketamine offers substantial hope for individuals with major depressive disorder, particularly those with treatment-resistant depression. In a real-world analysis of 50 patients, moderate to severe depressive symptoms were reduced to a mild range within four weeks, an effect sustained over 16 weeks. Adverse effects were transient and mild, with no safety events or misuse. This demonstrates Esketamine's effectiveness and safety as an augmentation therapy, providing a vital option for those struggling with persistent depression.
Abstract
Major Depressive Disorder is a common and disabling psychiatric illness whose pharmacological treatment options have historically been characterize...
Real-world effectiveness and safety of psychedelic-assisted psychotherapy: Outcomes from a large-scale compassionate use cohort in Switzerland.
Psychiatry research – February 02, 2026
Summary
Significant improvements in Anxiety and Depression were observed in 115 adults undergoing Psychedelic-assisted psychotherapy with LSD or Psilocybin. This real-world analysis, involving 56.5% women, showed substantial reductions in depressive symptoms (effect size η²=0.42) and anxiety (η²=0.17) 1-3 months post-treatment. Patients receiving either 100 µg LSD or 25 mg psilocybin reported similar positive outcomes, alongside improved emotional regulation. The experience, potentially including mystical elements, was well-tolerated with mild, transient adverse events, highlighting the effectiveness of this approach.
Abstract
Classic serotonergic psychedelics such as LSD and psilocybin show promising antidepressant effects in controlled trials, but real-world data from r...
The Emerging Crisis in Non-Prescribed Ketamine Use: A Rapid Attenuation of Depression in Face of Abuse and "Chill-out" or Escapism Drug.
Substance use & misuse – February 01, 2026
Summary
With suicide and opioid overdose rates sharply rising, new treatments are vital, especially for the one-third of individuals experiencing Treatment Resistant Depression (TRD). Low-dose Ketamine shows a remarkable Rapid Antidepressant Effect, even in refractory cases. Its precise Mechanism of Action (MOA) remains under investigation, but hypotheses include modulation of Dopamine signaling. Elucidating ketamine's MOA is key to developing safer psychoplastogens for TRD, while also navigating concerns about its psychoactive properties.
Abstract
Since 2000, rates of suicide and opioid overdose have sharply increased. Approximately one-third of individuals with major depressive disorder (MDD...
Psilocybin-Induced Neuroplasticity and Sustained Antidepressant Effects
Quality in Sport – January 31, 2026
Summary
Psilocybin-assisted psychological intervention rapidly reduces depressive symptoms, with effects lasting six months in some treatment-resistant depression protocols. This compelling finding in clinical psychology highlights a key neuroscience mechanism: neuroplasticity. Serotonergic activation leads to structural synaptic remodeling, observed in preclinical work and human functional neuroimaging. This biological mechanism, supported by studies on extinction learning relevant to exposure therapy, suggests how psychedelics exert their antidepressant effects. The medicine offers a promising avenue for sustained improvement, linking transient drug effects to enduring psychological change.
Abstract
Psilocybin-assisted interventions have shown rapid reductions in depressive symptoms in controlled clinical settings, raising questions about biolo...
Multimodal rapid anti-depression: Esketamine combined with dexmedetomidine patient-controlled sleep for treatment-resistant depression - A retrospective study.
Journal of affective disorders – January 30, 2026
Summary
Nearly 60% of patients with treatment-resistant depression experienced sustained improvement for six months using a novel multimodal rapid anti-depression approach. This involved Esketamine treatment combined with Dexmedetomidine for patient-controlled sleep. Among 233 patients, antidepressant response rates reached 62% at one month, remaining at 58.49% by six months. Patient-controlled sleep was consistently linked to better outcomes. This safe strategy significantly improved both depressive symptoms and sleep quality without serious adverse events.
Abstract
To evaluate the efficacy and safety of a multimodal rapid anti-depression therapy that combines esketamine treatment with dexmedetomidine patient-c...
Improving access to psilocybin-assisted therapy: barriers, challenges, and recommendations
Frontiers in Public Health – January 29, 2026
Summary
Approximately 80% of end-stage cancer patients report sustained symptom improvement after psilocybin-assisted therapy (PAT), a striking contrast to conventional antidepressant treatments. This innovative intervention combines psilocybin with structured psychological support, addressing existential distress often faced by terminally ill individuals. Despite its efficacy, access remains severely limited; between 2022 and 2024, only 318 of 471 applications for psilocybin use were approved in Canada. Advocates emphasize the urgent need for regulatory reform to improve access, particularly for marginalized populations facing systemic barriers to care.
Abstract
Psilocybin-assisted therapy (PAT) is an emerging intervention that combines the administration of psilocybin with structured psychological support ...
Combining Intranasal Esketamine and Electroconvulsive Therapy in Severe Treatment‑Resistant Depression: A Case Series.
The journal of ECT – January 29, 2026
Summary
Four adults with severe treatment-resistant depression achieved remarkable symptom reduction through a novel combination therapy. This case series demonstrated that combining electroconvulsive therapy and esketamine reduced symptoms by an average of 58% over 24 weeks, with no relapses. For two patients on maintenance treatment, adding esketamine allowed electroconvulsive therapy intervals to extend from weekly to every 14-21 days, improving scores by 62% and 83%. Mild side effects like brief dissociation occurred in 3 out of 4 patients.
Abstract
This case series describes the combined use of electroconvulsive therapy (ECT) and intranasal esketamine (ESK)-2 rapidly acting, evidence-based opt...
Combining Intranasal Esketamine and Electroconvulsive Therapy in Severe Treatment‑Resistant Depression
Journal of Ect – January 29, 2026
Summary
Combining electroconvulsive therapy (ECT) with nasal ketamine (ESK) demonstrated promising results in treating treatment-resistant depression. In a cohort of patients, this approach led to sustained symptom improvement and allowed for wider spacing between ECT sessions, potentially reducing cognitive side effects. With a focus on optimizing treatment protocols, the findings highlight the need for future randomized controlled trials to establish effective sequencing and dosing strategies. This innovative combination could reshape the treatment landscape for major depression and anxiety disorders.
Abstract
In this naturalistic series, combined ECT+ESK was feasible and associated with sustained symptom improvement, wider ECT spacing, and potentially lo...
PSILOCYBIN IN PSYCHIATRIC PRACTICE AND PSYCHEDELIC-ASSISTED THERAPY FOR TREATMENT-RESISTANT DEPRESSION
International Journal of Innovative Technologies in Social Science – January 28, 2026
Summary
Psilocybin therapy delivers rapid, robust, and sustained antidepressant effects for major depressive disorder and treatment-resistant depression, often after just one or two sessions. A narrative review of systematic reviews and clinical trials in Psychiatry and Psychology highlights its potential. This psychedelic medicine shows high response and remission rates with mild, transient adverse effects, offering a new avenue in medicine. Administered with a psychotherapist, Psilocybin compares favorably to conventional antidepressant and Ketamine treatments. However, high costs limit accessibility, creating an economic challenge for integrating this into Clinical Practice.
Abstract
This manuscript comprehensively reviews psilocybin-assisted therapy for major depressive disorder and treatment-resistant depression. It aims to sy...
Modulating tonic NMDA receptor currents: mechanistic insights into ketamine, esketamine, and dextromethorphan for major depressive disorder and implications for the discovery and development of investigational agents.
Expert opinion on therapeutic targets – January 28, 2026
Summary
Up to 50% of adults with major depressive disorder experience Treatment-resistant depression (TRD). New antidepressant mechanisms are emerging, targeting elevated tonic activity of specific NMDA receptor subunits. Ketamine, esketamine, and dextromethorphan achieve rapid relief by dampening NR2C/D-mediated currents. Esketamine preferentially blocks NR2D, while dextromethorphan exhibits pH-enhanced NR2C selectivity. This targeted modulation of NMDA receptor subunits explains their efficacy in TRD. Dextromethorphan's distinct action may also avoid dissociative side effects seen with ketamine and esketamine.
Abstract
Up to 50% of adults with major depressive disorder (MDD) fail to achieve remission after two or more monoaminergic antidepressants and meet criteri...
Systematic review and meta-analysis of intranasal esketamine for treatment-resistant depression: Evidence from real-world studies.
Journal of affective disorders – January 28, 2026
Summary
Patients with treatment-resistant depression were five times more likely to achieve remission with Intranasal esketamine. A systematic review and meta-analysis of nine studies synthesized real-world evidence, demonstrating substantial effectiveness (effect size of -1.98) in reducing symptoms. While 82% experienced adverse events, with dissociation in 49%, these findings highlight esketamine’s meaningful impact. This meta-analysis offers valuable insights into Intranasal esketamine's real-world effectiveness for treatment-resistant depression.
Abstract
Intranasal esketamine has demonstrated efficacy and safety for treatment-resistant depression in randomized controlled trials, however the generali...
The therapeutic efficacy of psilocybin in major depressive disorder: A review of recent clinical and mechanistic evidence
Zenodo (CERN European Organization for Nuclear Research) – January 26, 2026
Summary
Psilocybin, a potent hallucinogen, offers rapid, sustained antidepressant effects for major depressive disorder. Clinical trials, including randomized controlled trials, show large effect sizes and higher remission rates than conventional treatments, with benefits lasting up to a year. Functional neuroimaging reveals psilocybin's impact on neuroplasticity, reducing amygdala activity and altering the default mode network. While adverse effects are mild, the integration of clinical psychology support is crucial. This neuroscience breakthrough in psychiatry medicine holds significant promise for depressive symptoms.
Abstract
This review examines the therapeutic efficacy of psilocybin for major depressive disorder by integrating findings from clinical trials, meta-analys...
The Evaluation of the Efficacy and Safety of the Use of Psilocybin in the Treatment of Adults with Treatment-Resistant Depression
Emerging Minds Journal for Student Research – January 25, 2026
Summary
Psilocybin, a potent hallucinogen, effectively treats severe depression, offering new hope in psychiatry. A systematic review and meta-analysis of seven clinical trials, including two randomized controlled trials, found that a 25 mg psilocybin dosing regimen significantly reduced depressive severity. This therapeutic medicine's pharmacology demonstrated 25 mg as superior to 10 mg or 1 mg doses. Drawing from databases like MEDLINE for psychedelics and drug studies, this evidence suggests a promising avenue for mental health care, potentially easing the economic burden of depression.
Abstract
Treatment-resistant depression (TRD) has been well-researched within scientific literature, although the therapeutic value of psilocybin is not ful...
Methodological moderators of psilocybin-assisted therapy in depression: A systematic review and meta-analysis
Neuroscience & Biobehavioral Reviews – January 24, 2026
Summary
Psilocybin-assisted therapy offers significant antidepressant effects for major depressive disorder. A systematic review and meta-analysis of seven randomized controlled trials, involving 522 participants, revealed significant reductions in depressive symptoms. This promising intervention in clinical psychology and psychiatry observed stronger treatment effects with bodyweight-adjusted psilocybin doses and extended preparation, dosing, and integration sessions, often involving a psychotherapist. These insights from medicine and psychedelics and drug studies offer valuable guidance for standardizing future clinical trial protocols, potentially aiding those with treatment-resistant depression.
Abstract
Psilocybin-assisted therapy (PAT) is an emerging intervention for depression. Though several clinical trials report promising results for PAT in tr...
Long-term effectiveness and side-effects of intranasal esketamine in treatment-resistant depression: real-world, single-arm study of over 100 sessions.
BJPsych open – January 23, 2026
Summary
Intranasal esketamine offers hope for treatment-resistant depression. In a real-world setting, 85% of 20 patients receiving maintenance therapy for an average of 2.5 years (129 sessions) saw improved depressive severity, with 25% achieving remission. Anxiety also improved for 65%, with 20% reaching remission. This demonstrates esketamine's long-term effectiveness. Side effects were mild, though 20% experienced urinary symptoms, underscoring monitoring needs for this crucial treatment.
Abstract
Treatment-resistant depression (TRD) poses a significant clinical challenge, with limited evidence guiding long-term pharmacological strategies. Es...
Symptom trajectories and clinical outcomes of intravenous ketamine in treatment-resistant depression: A real-world study using group-based trajectory modeling.
Journal of affective disorders – January 23, 2026
Summary
Anxiety symptoms improve more slowly and less robustly than depression for individuals with Treatment-resistant depression receiving IV ketamine. Among 209 adults, Ketamine infusions led to modest symptom reduction, with trajectory modeling revealing four distinct response patterns for both conditions. While six infusions showed numerically higher response, durability data was only available for four infusions. This real-world evidence underscores the need for individualized care when using IV ketamine, especially for Anxiety.
Abstract
Intravenous (IV) ketamine is an emerging intervention for treatment-resistant depression (TRD), yet the temporal dynamics of response and the optim...
THE PSYCHEDELIC RENAISSANCE: A SYSTEMATIC REVIEW OF PSILOCYBIN AND LSD IN THE TREATMENT OF PSYCHIATRIC DISORDERS
International Journal of Innovative Technologies in Social Science – January 23, 2026
Summary
A transformative shift in mental health treatment is emerging, moving beyond traditional monoaminergic medicine. Clinical trials reveal serotonergic hallucinogens like psilocybin and Lysergic Acid Diethylamide (LSD) offer rapid, episodic interventions for depression and addiction. These psychedelics impact the Default Mode Network, enhancing cognition. Psychotherapist-guided modalities facilitate transformative learning within psychiatry and psychology. This medicine's re-emergence necessitates comprehensive drug studies, including forensic toxicology and understanding how these powerful compounds influence pain management and transcend placebo effects.
Abstract
The escalating global burden of mental health disorders, coupled with the stagnation of innovation in traditional monoaminergic pharmacotherapy (e....
Beyond first-line antidepressants: lithium, quetiapine, or esketamine? Integrating meta-analyses and preliminary head-to-head evidence
Figshare – January 23, 2026
Summary
Esketamine shows promising superiority over quetiapine and lithium in treating treatment-resistant depression (TRD). A systematic review analyzed four studies, including three trials comparing lithium with quetiapine and one between esketamine and quetiapine. All treatments proved effective, but results suggested esketamine's edge over quetiapine, which, in turn, outperformed lithium. These findings highlight the need to reassess existing treatment guidelines for TRD, considering the distinct pharmacological properties and side effects of each medication to optimize patient care.
Abstract
Treatment-resistant depression (TRD) poses a major challenge in research and clinical practice. Various guidelines recommend different pharmacologi...
Beyond first-line antidepressants: lithium, quetiapine, or esketamine? Integrating meta-analyses and preliminary head-to-head evidence.
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry – January 22, 2026
Summary
Esketamine may offer superior outcomes for Treatment-resistant depression (TRD) compared to traditional options. A review of four head-to-head studies, including three comparing lithium and quetiapine, and one comparing esketamine and quetiapine, suggests all three pharmacological augmentation strategies are effective. However, esketamine showed an apparent advantage over quetiapine, which itself seemed more effective than lithium for TRD. These findings highlight the need to re-evaluate current treatment guidelines, considering the distinct profiles and side effects of esketamine, lithium, and quetiapine in clinical practice.
Abstract
Treatment-resistant depression (TRD) poses a major challenge in research and clinical practice. Various guidelines recommend different pharmacologi...
Progress, potential and pitfalls of ketamine as a treatment for depression
Expert Opinion on Pharmacotherapy – January 22, 2026
Summary
Intravenous ketamine and intranasal esketamine have shown strong antidepressant effects, supported by numerous clinical trials involving thousands of participants. Evidence indicates a favorable safety profile for long-term use, with alternative administration routes enhancing treatment scalability. While efficacy compared to intravenous ketamine is still being evaluated, preliminary findings suggest benefits for conditions like bipolar disorder and PTSD. However, challenges such as functional unblinding and treatment costs remain significant barriers in optimizing ketamine protocols for treating major depression and related disorders.
Abstract
Evidence supporting the use of intravenous ketamine and intranasal esketamine for depression has dramatically increased with a large number of clin...
Real-world comparison of intranasal racemic ketamine and esketamine in treatment-resistant depression: A retrospective observational study.
Journal of affective disorders – January 21, 2026
Summary
For individuals battling Treatment-resistant depression (TRD), Intranasal racemic ketamine appears as effective as Esketamine for symptom reduction. A study of 76 patients with MDD found both treatments significantly improved depression scores. Racemic ketamine reduced scores by 10.0 points, while Esketamine achieved a 9.3-point reduction, meeting non-inferiority criteria. However, Esketamine led to higher remission rates (38.7% vs. 15.6%). This suggests racemic ketamine is a viable option for managing MDD symptoms, but Esketamine might offer a greater chance of full remission.
Abstract
Treatment-resistant depression (TRD) imposes major individual and societal burden, with few therapeutic options. Intranasal esketamine is approved ...
[Clinical application and mechanistic studies of psychedelics for treatment of depression: progress and future challenges].
Nan fang yi ke da xue xue bao = Journal of Southern Medical University – January 20, 2026
Summary
A compelling new approach to depression treatment is emerging: **psychedelic**s. **Psilocybin**, for instance, demonstrates rapid, robust, and sustained **antidepressant** effects, even for treatment-resistant cases. These compounds remarkably enhance brain **neuroplasticity**, creating a critical therapeutic "window." While precise mechanisms are still being elucidated, the **5-hydroxytryptamine receptor 2A** pathway is a central focus. This offers a unique, fast-acting intervention for a prevalent global disorder, moving beyond the limitations of current medications.
Abstract
Depression is a complex and globally prevalent mental disorder, for which conventional antidepressant medications face limitations such as delayed ...
Safety and Efficacy of Monoamine Oxidase Inhibitors in Patients Who Use Psychoactive Substances: Potential Drug Interactions and Substance Use Disorder Treatment Data.
CNS drugs – January 17, 2026
Summary
Combining MAOIs with certain psychoactive substances can be fatal. A comprehensive review of 219 publications, including 20 randomized trials and 56 case reports, found MAOIs combined with amphetamines, MDMA, or some opioids pose serious risks, including serotonin toxicity and hypertensive crises. Fatalities were reported with eight different substances. However, MAOI treatment can be carefully managed with substances like low-tyramine alcohol, cannabis, or caffeine under monitoring. Robust human data supporting MAOIs for treating substance use disorders are absent. Further safety investigation in these complex patients is crucial.
Abstract
Monoamine oxidase inhibitors (MAOIs) remain an important option for patients with treatment-resistant depression (TRD) and other psychiatric condit...