Goldstone Psychiatry & Neuromodulation Center
Psychiatry & Neuromodulation Center
The week’s most clinically relevant research on TMS, ketamine, esketamine, ECT, DBS, and psychedelic-assisted therapy, read and annotated for practicing clinicians and patients considering treatment.
Curated by Gibson Anugwom, MD · Interventional and Adult Psychiatrist
Medical disclaimer: this brief is provided for educational purposes and summarizes emerging research. It does not constitute medical advice or endorsement of any investigational treatment. Treatment decisions should be made through an individualized evaluation with a qualified clinician. Request a consultation at Goldstone.
Issue · October 16, 2026
October 12 — Peer-reviewed systematic review and meta-analysis: Augmentation strategies for intravenous ketamine in treatment-resistant depression
Seven randomized trials involving 346 adults examined pharmacological or psychological strategies added to IV ketamine. The exploratory pooled analysis found no significant additional antidepressant benefit over control conditions; CBT and automated self-association training showed preliminary maintenance signals, but each was supported by only one study.
Sustaining ketamine response remains a central clinical challenge. These findings argue against presenting medication add-ons or ketamine-integrated psychotherapy as established methods for prolonging benefit, while identifying structured psychological approaches as worthwhile research priorities.
Evidence certainty was low. Small trials, different interventions, and heterogeneous outcome timing mean the pooled null result does not establish that every augmentation strategy is ineffective.
October 12 — Peer-reviewed mechanistic study: Excitation-Inhibition Balance and Fronto-Limbic Connectivity Distinguish TMS Treatment Outcomes in Refractory Depression
Investigators combined TMS-EEG with computational brain-network modeling in 90 patients receiving iTBS for treatment-resistant depression. Responders showed changes consistent with greater inhibitory control after treatment; a pretreatment pattern of opposing subgenual-cingulate and left-DLPFC dynamics also distinguished responders from nonresponders.
This challenges the shorthand that antidepressant iTBS works merely by “exciting an underactive prefrontal cortex.” It links treatment response to local excitation–inhibition balance and broader circuit dynamics, offering candidate physiological markers for future personalization.
Synaptic and circuit properties were inferred through modeling, not directly measured. These associations require independent validation and do not establish a clinically usable response test or justify changing routine targeting or dosing.
October 11 — Peer-reviewed living systematic review and meta-analysis; all included trials MAPS-sponsored: A living systematic review, meta-analysis, and open data resource of trials of MDMA-assisted therapy for PTSD
Across six randomized trials involving 286 participants, MDMA-assisted therapy produced greater short-term PTSD symptom improvement than control conditions, with a pooled standardized effect of approximately 0.71. Response and remission were also more frequent, but the authors rated the overall evidence as low certainty using GRADE.
The review pairs a meaningful efficacy signal with an appropriately conservative assessment of confidence. Its open database also provides a transparent resource for tracking how conclusions change as additional trials become available.
All trials shared one sponsor. Expectancy, functional unblinding, concerns about study conduct, and incomplete safety characterization are not adequately captured by conventional risk-of-bias tools; longer-term controlled evidence remains necessary.
Curated by Gibson Anugwom, MD · Interventional and Adult Psychiatrist · Clinical Director, Goldstone Psychiatry & Neuromodulation Center
Educational content only. This brief summarizes emerging research and does not constitute medical advice or endorsement of investigational treatments. Treatment decisions require individualized clinical evaluation.
Issue · October 9, 2026
This was a modest week for new clinical evidence. The most useful developments involved a practical TMS-targeting method, TMS-EEG biomarkers, ECT-related brain-network changes, and a cautious ketamine suicidality analysis. No comparably substantive new DBS, psychedelic-treatment outcome, Spravato-specific, regulatory, or guideline update cleared the bar for inclusion.
October 3 — Peer-reviewed methodological report: A Standard Coil Placement for Reliable TMS of the Frontoparietal Depression Network
Researchers developed the “F5–AF7 method,” positioning the coil over the F5 EEG landmark with its handle oriented toward AF7. In electric-field simulations involving 20 healthy participants and 20 patients with depression, this placement covered the frontoparietal depression network more selectively than standard Beam F3 positioning. PubMed
This offers a low-cost, reproducible alternative between routine scalp-based targeting and individualized MRI or connectivity-guided neuronavigation. It could be especially useful for clinics seeking more network-informed targeting without adding imaging infrastructure.
This was computational method development—not a clinical treatment trial—and therefore does not show higher response or remission rates. Targeting was also sensitive to coil-rotation errors, making accurate orientation important.
October 3 — Systematic review and meta-analysis: TMS-Evoked Cortical Reactivity Signatures as Biomarkers of Depression
Across 21 studies involving 1,025 patients with major depression and 517 healthy controls, negative TMS-evoked potentials—particularly the N100—were larger in depression and associated with greater symptom severity. Treatment-related reductions in these signals correlated with remission, while preliminary evidence suggested that baseline measures might predict response. PubMed
TMS-EEG could eventually help distinguish whether stimulation is engaging the intended circuitry, track physiological change during treatment, or support individualized dosing and treatment selection.
The contributing studies varied in stimulation site, treatment, EEG processing, medication status, and artifact control. The apparently large predictive effect came from limited evidence and is not sufficient to justify routine clinical TMS-EEG testing.
October 2 — Longitudinal resting-state fMRI study: ECT Shifting Brain Dynamics Toward More Adaptive and Integrated States in TRD
Researchers compared 72 patients with TRD with 63 healthy controls; 52 patients completed post-ECT imaging. After ECT, clinical improvement was accompanied by greater occupancy of default-mode/frontoparietal and highly integrated whole-brain states, while some subcortical-dominant abnormalities persisted. pubmed.ncbi.nlm.nih.gov
The findings support a compensatory model of ECT: recovery may occur because the brain gains access to more adaptive and coordinated functional states—not because every pretreatment abnormality disappears. This could refine future studies of target engagement and relapse vulnerability.
This was an uncontrolled imaging study with attrition, concurrent clinical treatment, and no untreated TRD comparison. Neurotransmitter associations were inferred from normative receptor maps rather than directly measured in these patients.
October 2 — Secondary analysis of an open-label clinical trial: Repeated Ketamine Infusions, Suicidal Ideation, and Plasma Biomarkers
Outpatients with TRD received four intravenous ketamine infusions at 0.5 mg/kg over two weeks. Suicide-related items on the MADRS and QIDS-SR improved modestly, but the Columbia Suicide Severity Rating Scale change was nonsignificant; nominal associations involving citric and kynurenic acid did not survive correction for multiple testing. PubMed
This appropriately tempers claims that improvement on a single depression-scale item establishes a robust antisuicidal effect. It also provides another useful negative biomarker result: neither metabolite is ready to guide ketamine selection or monitoring.
The study was small, open-label, lacked a comparator, and enrolled outpatients with relatively low baseline suicidality. It cannot establish suicide prevention or substitute for comprehensive risk assessment and acute safety interventions.
Curated by Gibson Anugwom, MD · Interventional and Adult Psychiatrist · Clinical Director, Goldstone Psychiatry & Neuromodulation Center
Dr. Anugwom is passionate about innovation, neuroscience, and translating emerging psychiatric research into thoughtful, evidence-based clinical care. His interests include treatment-resistant depression, TMS, ketamine and esketamine, ECT, and evolving neuromodulation therapies.
This brief is provided for educational purposes and summarizes emerging research. It does not constitute medical advice or endorsement of any investigational treatment. Findings should be interpreted in the context of the complete study and an individualized clinical evaluation.
Issue · October 2, 2026
This was a relatively quiet week for new clinical-outcome data. The strongest publication was a large connectomic analysis of DBS for treatment-resistant depression, accompanied by two useful evidence syntheses. No new TMS, ECT, ketamine/esketamine, or psychedelic efficacy trial published during this window cleared the bar for inclusion.
October 1 — Multicohort retrospective study: Connectomic Determinants of Subcallosal Cingulate Deep Brain Stimulation for Depression
This is one of the largest circuit-level analyses of SCC-DBS for depression. It helps explain why earlier trials using broadly similar anatomical targets produced inconsistent outcomes: electrodes placed in the same region may engage meaningfully different white-matter pathways.
This was a retrospective association across heterogeneous cohorts, targeting methods, and stimulation settings—not a randomized comparison of connectomic versus conventional targeting. DBS remains invasive and investigational for depression.
September 29 — Substantive expert analysis; not a new trial: Rapid Antidepressants and Suicide Risk: What Do We Really Know?
The authors distinguish improvement in suicidal thoughts from prevention of attempts or deaths. Ketamine has placebo-controlled evidence for rapidly reducing suicidal ideation; the ASPIRE trials showed rapid depressive-symptom improvement with esketamine but no significant advantage on clinician-rated suicidality, while ECT’s association with fewer attempts and deaths comes largely from observational data. Psychiatric Times
This is an important corrective to overly broad claims that ketamine, Spravato, or ECT “prevents suicide.” These interventions may be valuable components of acute stabilization, but none should replace hospitalization when indicated, lethal-means mitigation, safety planning, monitoring, and longitudinal treatment.
This is a narrative evidence review rather than a systematic review. Suicide deaths are uncommon and ethically difficult to study prospectively, so uncertainty does not demonstrate absence of benefit.
October 1 — Peer-reviewed narrative review:Brain Stimulation Therapeutic Interventions in Neuropsychiatry: A Cambrian Explosion
Sackeim and George survey the rapid expansion of invasive and noninvasive brain-stimulation technologies using electrical, magnetic, acoustic, and other forms of energy, emphasizing advances in targeting, stimulation parameters, and adaptive treatment approaches. neuropsychiatry
The review provides a useful framework for viewing TMS, ECT, DBS, VNS, temporal-interference stimulation, and emerging technologies as variations on circuit engagement—not isolated treatments. It also highlights the field’s movement toward individualized targets and state-dependent or closed-loop dosing.
This is a field-level synthesis, not comparative evidence that newer or more technologically complex approaches outperform established treatments. Many precision and closed-loop strategies remain experimental.
This brief is provided for educational purposes and summarizes emerging research. It does not constitute medical advice or endorsement of any investigational treatment. Findings should be interpreted in the context of the complete study and an individualized clinical evaluation.
Issue · September 25, 2026
This was an active but methodologically mixed week. The most notable publications addressed accelerated TMS dosing, treatment-related brain-network changes, ECT cognition and anesthesia, ketamine biomarkers, and psilocybin in bipolar II depression. No major new DBS, Spravato-specific, regulatory, or guideline development cleared the bar for inclusion.
September 19 — Retrospective cohort: Accelerated bilateral iTBS for PTSD and depression following mild traumatic brain injury
This single-site study evaluated 64 treatment courses in 55 adults with PTSD, depression, and predominantly mild traumatic brain injury. Patients received 20 bilateral DLPFC iTBS sessions daily for four days—80 sessions total—and showed improvement across depression, PTSD, anxiety, and perceived-stress measures; 85.9% completed the intended course, with no treatment-emergent adverse events documented.
The study suggests that very compressed bilateral treatment may be operationally feasible, even in a clinically complex population. The delayed improvement reported after treatment also cautions against judging accelerated-TMS outcomes immediately after the final session.
This was an uncontrolled, retrospective study with a small sample, incomplete follow-up, and reliance on routine documentation for adverse events. It does not establish that 80 sessions are necessary, superior to a lower dose, or safe enough for routine adoption.
September 19 — Observational 7-Tesla fMRI study: Accelerated TMS and subgenual cingulate–default mode network coupling
Twenty-two patients with depression received 24,000 left-DLPFC pulses over two weeks. Following treatment, functional connectivity decreased between the subgenual anterior cingulate cortex and the bilateral precuneus and left frontal pole, although these connectivity changes were not associated with improvement in depression severity.
The findings support the idea that accelerated TMS engages broader depression-related networks rather than acting only at the cortical stimulation site. They may help refine future targeting and target-engagement biomarkers.
This was a small, uncontrolled mechanistic study. Because network changes did not correlate with antidepressant improvement, the findings should not be interpreted as validating a clinical response biomarker or a particular targeting method.
September 20 — Systematic review and meta-analysis: Subjective and objective memory effects after ECT for depressive disorders
Across 12 studies involving 837 participants, subjective memory ratings improved after ECT even while delayed recall and autobiographical memory declined during the first month. Beyond one month, immediate and delayed recall improved, but autobiographical-memory impairment remained detectable in the pooled results.
Asking only whether a patient “feels” cognitively better may miss important autobiographical-memory effects. Counseling and monitoring should distinguish subjective memory, verbal learning, delayed recall, and autobiographical memory rather than treating cognition as a single outcome.
There was substantial heterogeneity in ECT techniques, cognitive measures, follow-up intervals, and study quality. Pooled study-level relationships cannot predict what an individual patient will experience.
September 19 — Retrospective analysis of 5,148 ECT sessions: Effect of ECT anesthetics on reorientation time
After adjustment for clinical and treatment variables, propofol was associated with reorientation approximately 6.2 minutes faster than S-ketamine; combined propofol and S-ketamine shortened reorientation by approximately 1.5 minutes. Etomidate and thiopental did not differ significantly from S-ketamine.
A six-minute difference can affect patient experience and recovery-unit workflow across a high-volume ECT service. Anesthetic selection may be one modifiable component of postictal cognitive recovery.
This was not a randomized comparison and remains vulnerable to confounding by indication. Reorientation time is not equivalent to long-term cognitive safety, seizure adequacy, or antidepressant effectiveness, so the findings do not establish propofol as universally preferable.
September 21 — Systematic review and meta-analysis: Modulation of GABA and glutamate by ketamine in depression
Eleven magnetic-resonance-spectroscopy studies were included. The pooled evidence did not demonstrate significant ketamine-related changes in GABA, glutamate, or combined glutamate/glutamine concentrations, with substantial variation in brain regions, scanning times, dosing, and acquisition methods.
This is a useful negative result. The commonly cited model of ketamine producing a measurable glutamate surge or correcting excitation–inhibition balance has not yet translated into a reliable human MRS biomarker that can guide treatment selection or monitor response.
Static MRS metabolite concentrations do not directly measure synaptic excitation or inhibition. The null pooled result may reflect inconsistent methods and poorly timed measurements rather than the absence of meaningful neurochemical effects.
September 21 — Open-label, dose-escalation pilot study: Psilocybin-assisted therapy for bipolar II depression
Fourteen participants received 10 mg of psilocybin with structured psychotherapy, followed by 25 mg when symptoms persisted. Depression scores improved, but three participants experienced clinically notable psychiatric events—including suicidal ideation or hypomania—that resolved with additional support.
Bipolar-spectrum patients are routinely excluded from psychedelic trials because of concerns about mania, psychosis, and destabilization. This study provides preliminary prospective data while also demonstrating why careful screening, structured support, and longitudinal monitoring remain essential.
The sample was extremely small, uncontrolled, and used adapted bipolar II diagnostic criteria. Expectancy, psychotherapy, regression to the mean, and selective enrollment prevent conclusions about efficacy or routine safety.
This brief is provided for educational purposes and summarizes emerging research. It does not constitute medical advice or endorsement of any investigational treatment. Findings should be interpreted in the context of the complete study and an individualized clinical evaluation.
Issue · September 18, 2026
This was a neuromodulation-heavy week, with several findings that temper enthusiasm for increasingly complex stimulation protocols. No comparably strong new ketamine, esketamine, ECT, DBS, or psychedelic-treatment outcome study warranted inclusion.
September 16 — Randomized, placebo-controlled trial: Connectivity- and frequency-individualized accelerated iTBS in TRD
This is an important counterweight to recent positive targeting studies. Increasing personalization with resting-state fMRI and EEG does not automatically improve outcomes, and these expensive additions should not yet be presented as established requirements for effective TMS.
The trial was small, had relatively muted improvement across all groups, and did not include a standard active TMS protocol as a comparator. It does not establish that accelerated iTBS or connectivity-based targeting is ineffective more broadly.
September 11 — Double-blind, randomized, sham-controlled trial: Efficacy of tDCS-primed iTBS in major depressive disorder
Seventy-six medication-free patients received 20 sessions of active or sham cathodal tDCS immediately before left-DLPFC iTBS. Both groups had response rates exceeding 70%, but active tDCS priming provided no additional antidepressant benefit.
More stimulation is not necessarily better. The result argues against adding tDCS to routine iTBS without stronger evidence and reinforces the need to test protocol complexity against simpler active treatments.
Participants were not treatment resistant, and the high response in both groups may have created a ceiling effect. Different tDCS intensity, timing, montage, or patient selection could produce different results.
September 12 — Multisite cross-sectional synthesis: TMS-EEG correlate of suicidal ideation in depression
Investigators pooled 299 adults with depression across five academic centers. A more negative left-DLPFC N100 response was associated with greater suicidal-ideation severity independently of overall depression severity, age, sex, and study site.
The finding supports the possibility that suicidality has a measurable inhibitory-circuit signature rather than simply tracking global depression severity. Eventually, TMS-EEG could help study target engagement or anti-suicidal mechanisms.
This was a cross-sectional association—not a prospective suicide-risk test or treatment-response biomarker. It should not replace clinical suicide-risk assessment, and validation with sham-controlled measurement is needed.
September 16 — Prospective, open-label multicenter cohort: Two-year VNS outcomes in higher-grade TRD
Nineteen patients with severe, highly resistant depression received implanted VNS, with 16 completing 24 months. Mean MADRS scores declined 48% by month 24, suicidality improved, and 87.5% met response criteria at some point during follow-up; no serious safety concern emerged.
The delayed, sustained trajectory is consistent with VNS functioning as a long-term treatment rather than a rapid antidepressant intervention. This supports evaluating it with longitudinal outcomes rather than short acute-trial endpoints.
The sample was extremely small and lacked a control group. The 87.5% figure represents cumulative response at any point—not necessarily the proportion remaining in response at month 24—and concurrent treatments may have contributed.
September 16 — Systematic review and meta-analysis: Safety of temporal-interference stimulation in humans
Across 24 studies involving 853 participants, investigators found no reported serious adverse events. Active stimulation increased tingling, while other adverse effects were generally mild and transient.
Temporal-interference stimulation is being developed to reach deeper brain structures noninvasively, potentially occupying a space between conventional electrical stimulation and implanted DBS. A consolidated human safety assessment is an important early step.
The evidence involved short exposures, small studies, and conservative parameters of approximately 2 kHz and no more than 2 mA per channel. This review establishes neither psychiatric efficacy nor the safety of stronger, repeated, or long-term treatment.
Educational content only. This brief summarizes emerging research and does not constitute medical advice or endorsement of an investigational treatment. Findings should be interpreted in the context of the complete study and individualized clinical evaluation.
Issue · September 11, 2026
A meaningful but evidence-mixed week: two major psychedelic-development updates rely on sponsor-reported data, alongside useful peer-reviewed ECT, deep-TMS, and ketamine studies. No substantive new DBS or Spravato-specific development cleared the bar.
September 9 · Company-sponsored Phase 3 topline report, open-label and not peer reviewed · COMP005 52-week results
COMP005 initially randomized 258 patients with TRD to COMP360 psilocybin 25 mg or placebo. Among the approximately 70% entering its open-label extension, an additional 25-mg dose was followed by 40%–45% response and approximately 30% remission during the ensuing six weeks; previously active-treated participants who were redosed averaged a 13-point MADRS reduction from original baseline at week 52.
The emerging clinical model is intermittent retreatment rather than assuming one psychedelic session produces permanent remission. These data may help define realistic maintenance and clinic-capacity requirements if COMP360 is approved.
The 26–52-week phase was uncontrolled and selectively included study completers. Retreatment timing was not randomized, and all findings remain sponsor-reported topline results without peer-reviewed patient-level analyses.
September 8 · Regulatory development, company-sponsored announcement · DT120 Breakthrough Therapy designation
The designation followed the company’s 149-participant Phase 3 Emerge trial, in which a single supervised 100-µg dose of orally disintegrating lysergide reportedly produced an 8.1-point placebo-adjusted MADRS advantage at week six, with benefit maintained through week 12.
This is a concrete regulatory signal that pharmaceutical LSD has moved beyond exploratory psychedelic research toward possible review as an MDD treatment. Breakthrough status can facilitate development and FDA interaction.
Breakthrough designation is neither approval nor confirmation of efficacy. Full Phase 3 results remain unpublished, psychedelic trials are highly vulnerable to functional unblinding, and the designation announcement supplied no new detailed safety data.
September 8 · Single-center observational cohort · ECT for catatonia in autistic and non-autistic patients
Among 110 patients—43 autistic and 67 non-autistic—at least 50% improvement on the Bush-Francis scale occurred in approximately 77% of both groups. Autistic patients, particularly those with intellectual disability, had substantially longer maintenance courses; self-injury prevalence among autistic patients fell from 42.9% to 17.1%.
The study supports sustained access to continuation/maintenance ECT for autistic catatonia rather than interpreting a prolonged course as treatment failure. The improvement in severe self-injury is particularly clinically relevant.
Treatment was neither randomized nor blinded, follow-up duration differed, and clinician-rated outcomes may be affected by ascertainment bias. The 100% CGI-I response reported in the autistic subgroup should not be generalized beyond this specialized center.
September 10 · Randomized, sham-controlled trial · High-frequency deep rTMS for depression
Eighty patients with moderate-to-severe depression received 20 active or sham deep-rTMS sessions over four weeks. Active treatment produced significantly greater HAMD-17 improvement; higher baseline fasting triglycerides were associated with greater improvement, particularly in the active group.
The randomized efficacy result supports conventional four-week high-frequency deep-TMS treatment. The metabolic association is hypothesis-generating evidence that systemic biology might eventually help stratify neuromodulation response.
This was a small biomarker analysis without external validation; triglycerides correlate with numerous demographic, metabolic, and medication variables. It should not currently influence TMS selection or counseling.
September 6 · Multicenter open-label mechanistic study · Bio-K ketamine metabolomics study
Sixty-nine adults with TRD received three IV racemic-ketamine infusions; MADRS decreased from 27.8 to 11.1 and 54% met the study’s remission criterion. Ketamine altered multiple metabolic pathways, but no metabolite change correlated with symptom improvement after correction for multiple testing.
This is a useful negative result: ketamine clearly produces broad mitochondrial, neurotransmitter, and neuroendocrine changes, but these should not yet be marketed as validated response biomarkers.
The study was open-label, lacked placebo controls, and examined a modest sample across hundreds of metabolites. The findings demonstrate exposure-related correlates, not causal mechanisms or a clinically usable test.
Issue · September 4, 2026
This was a genuinely quiet week. Only one new publication cleared the bar; I found no comparably substantive ECT, ketamine/esketamine, DBS, psychedelic, or regulatory development released since August 28.
September 2 · Secondary analysis of a double-blind, sham-controlled trial · Neurophysiological signatures of Stanford Neuromodulation Therapy in treatment-resistant depression
In 24 TMS-naive patients with TRD, five days of individualized, high-dose accelerated iTBS progressively reduced TMS-evoked cortical excitability at the stimulated left-DLPFC site, becoming significant by day three. Estimated medial-prefrontal/subgenual-ACC activity also decreased, while higher baseline sgACC activity was associated with greater symptom improvement in the active-treatment group.
The findings support the possibility of using TMS-EEG to verify target engagement and, eventually, tailor accelerated-TMS dosing—potentially identifying who is likely to respond or when sufficient stimulation has been delivered. They also complicate the simplistic idea that left-DLPFC iTBS works merely by “increasing excitability.”
This was a small, single-center mechanistic analysis—only 12 patients received active treatment. The sgACC signal was source-estimated rather than directly measured, and the clinical correlation was exploratory. It does not yet justify routine TMS-EEG monitoring or protocol changes without independent prospective validation.
Issue · August 28, 2026
A selective week: one meaningful TMS-targeting trial, an important VNS reassessment, and two practically relevant ketamine/esketamine publications. I found no comparably strong new ECT, DBS, or psychedelic efficacy trial worth adding.
August 26 · Randomized, double-blind, sham-controlled trial · Individualized TMS targeting based on DLPFC–pgACC connectivity
Among 68 patients with MDD, investigators targeted each patient’s left-DLPFC location showing the strongest negative functional connectivity with the pregenual ACC. HAMD-17 scores declined by 64.3% with active individualized iTBS versus 41.4% with sham.
This expands connectivity-guided targeting beyond the usual subgenual-ACC model and provides prospective evidence that the pgACC may be another clinically useful circuit anchor. It strengthens the broader argument that functional connectivity—not simply scalp coordinates—can influence antidepressant outcomes.
This was a small, single-center trial, and the 90° coil-tilt sham may not reproduce active stimulation’s sensory experience. The unusually large sham improvement and lack of comparison with Beam F3 or another active targeting method mean it does not establish that resting-state fMRI targeting is necessary for routine practice.
August 26 · Peer-reviewed trial synthesis, industry involvement · The RECOVER Trial of Vagus Nerve Stimulation in Markedly Treatment-Resistant Depression
This review summarizes the 493-patient, 12-month triple-blind RECOVER trial. The prespecified MADRS-based primary outcome did not separate active from sham VNS, but several secondary symptom, functioning, quality-of-life, and composite outcomes favored active stimulation; more than 80% of patients benefiting at 12 months retained benefit through months 18 and 24.
VNS may produce slow, durable, multidimensional improvement in profoundly resistant illness rather than rapid remission. The study also illustrates why conventional short-term symptom endpoints may inadequately evaluate treatments whose benefit accumulates over many months.
The negative primary endpoint remains decisive and cannot be neutralized by favorable secondary analyses. Multiplicity, post hoc outcome emphasis, concomitant treatment-as-usual, and participation by LivaNova employees require conservative interpretation.
August 26 · Retrospective observational cohort · Real-World Effectiveness and Safety of Esketamine Nasal Spray in TRD
Electronic-record data compared 82 patients receiving esketamine plus oral antidepressants with 87 receiving venlafaxine-based therapy. After propensity matching, PHQ-9 scores favored esketamine by 1.02 points at three months and 1.94 points at six months; 44.3% of continuing esketamine patients met response criteria at six months, but none met the study’s remission criterion.
This is a useful counterweight to dramatic clinic-marketing claims. In routine, complex TRD populations, esketamine may confer incremental benefit that becomes clearer over months, while many patients remain substantially symptomatic.
Treatment was not randomized, baseline severity and prior failures differed, attrition was substantial, and analyses of patients who continued treatment are vulnerable to survivor bias. The findings cannot establish comparative efficacy against venlafaxine.
August 26 · Expert teaching article; not a guideline or new trial · The Prescriber’s Guide to Oral Ketamine for Major Depressive Illness
The article provides an extensive protocol for oral racemic ketamine, including patient selection, slow-sipping administration, dosing, monitoring, maintenance, drug interactions, and caregiver-supervised home treatment. Its central argument is that slowly administered oral ketamine can offer a low-cost option where IV ketamine or esketamine is inaccessible.
It is one of the most operationally detailed oral-ketamine discussions available and highlights how administration rate may influence peak exposure and acute tolerability. It is especially relevant to access questions in resource-constrained settings.
Several recommendations—including very limited contraindications, reduced monitoring, urgent administration without routine pretreatment testing, and domiciliary use—rest substantially on the author’s experience and heterogeneous low-level evidence. They should not be treated as a US practice standard, and concerns about diversion, cumulative urinary toxicity, substance-use risk, liability, and inconsistent compounded-product exposure remain.
Issue · August 21, 2026
This was a relatively quiet week for ECT and device-based neuromodulation, but there were meaningful developments in ketamine safety, psychedelic implementation, and DBS. I also included one important TMS-targeting trial published just before this week’s window.
August 17 · Systematic review · Long-term safety outcomes of ketamine and esketamine in TRD
Across 32 studies—including 11 randomized trials—with follow-up ranging from three months to nine years, investigators found no consistent evidence of cumulative organ toxicity, persistent cognitive dysfunction, or treatment-induced addiction. Dissociation and sedation generally remained transient.
This supports carefully monitored maintenance treatment rather than limiting ketamine or Spravato solely because of theoretical cumulative toxicity. It is particularly relevant when counseling patients considering prolonged treatment.
Safety assessment varied considerably among studies, and controlled long-term data remain limited. Absence of observed addiction or organ injury is not proof of zero risk—especially for higher-frequency, compounded, oral, or unsupervised ketamine regimens.
August 19 · Prospective observational cohort · Safety and Mental Health Outcomes of Oregon State-Regulated Psilocybin Services
This study followed 346 adults treated at 24 licensed Oregon centers. Mean PHQ-9 scores declined from 9.3 at baseline to 4.2 at one month and 5.2 at three months. Four participants—1.2%, all psychedelic-naive—experienced serious behavioral reactions requiring medical attention; no serious medical reactions were reported.
This begins to answer whether psilocybin outcomes observed in highly controlled trials translate into community practice. It also shows that preparation, supervised administration, integration, and longitudinal adverse-event tracking are substantive parts of the intervention—not optional accessories.
This was uncontrolled and self-selected, psychiatric diagnoses were not established, baseline symptoms were relatively mild, and the sample was disproportionately White, highly educated, and affluent. The symptom improvement cannot be attributed causally to psilocybin.
August 18 · Expert editorial · The expansion of psychedelic-assisted therapy: The case for caution over acceleration
The analysis argues that psychedelic effect sizes are inflated partly by functional unblinding and unusually poor outcomes in control groups. It notes that effect estimates shrink when psilocybin is compared with active treatments or when analyses attempt to equalize unblinding.
For interpreting psychedelic trials, the central question should increasingly be: Compared with what, and was blinding remotely credible? This is especially important before presenting psychedelic-assisted therapy as superior to established antidepressants or interventional treatments.
This is a narrative editorial, not a new systematic review, and takes an intentionally skeptical position. Still, its critique of expectancy, control selection, and therapist-treatment confounding is methodologically sound.
August 19 · Substantive analysis/trial update · Can Deep Brain Stimulation Finally Deliver for Depression? and the TRANSCEND trial record
The ongoing Abbott-sponsored TRANSCEND study plans to enroll approximately 100 adults with severe TRD and compares active bilateral subcallosal-cingulate white-matter DBS with sham stimulation under double-blind conditions for 12 months.
Unlike uncontrolled DBS series, this design can directly test efficacy while allowing enough time for the gradual recovery trajectory often reported with SCC stimulation. The field’s underlying wager is that improved white-matter/network targeting and a longer blinded period can overcome the limitations of the earlier negative multicenter trial.
There are no efficacy results yet. DBS remains invasive and investigational for depression, and the study is device-industry sponsored.
August 12 · Randomized, double-blind trial · Individualized Connectivity-Guided Versus Conventional Targeting of Accelerated Theta-Burst Stimulation
Individualized subgenual-cingulate connectivity-guided targeting produced greater early antidepressant improvement than conventional 5-cm targeting during accelerated iTBS.
This adds prospective evidence that where high-dose accelerated TMS is delivered may materially influence outcomes. It supports the depression-circuit model rather than treating every left-DLPFC location as interchangeable.
The comparator was the relatively imprecise 5-cm rule—not Beam F3 or modern MRI-guided anatomical targeting—so the study does not establish that individualized resting-state fMRI is necessary for routine TMS practice. Replication in larger, multicenter samples is needed.
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Medical disclaimer: this page is provided for educational purposes and summarizes emerging research. It does not constitute medical advice or endorsement of any investigational treatment, and it is not a substitute for an individualized evaluation with a qualified clinician. If you are in crisis, call or text 988 (Suicide & Crisis Lifeline) or go to your nearest emergency room.
Curated by Gibson Anugwom, MD · Interventional and Adult Psychiatrist · Clinical Director, Goldstone Psychiatry & Neuromodulation Center
Dr. Gibson is passionate about advancing interventional psychiatry at the intersection of neuroscience, innovation, and clinical practice. His interests include treatment-resistant depression, TMS, ketamine and esketamine, ECT, and other evolving neuromodulation therapies. Through The Interventional Psychiatry Brief, he critically examines emerging research and translates it into clear, evidence-based insights for clinicians, patients, and others interested in what matters now—and what may shape the future of psychiatric care.
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