Abstract: Background/Objective: Existing abbreviated Geriatric Depression Scales (GDS), derived via Classical Test Theory (CTT), often sacrifice accuracy for brevity and retain non-specific items. We aimed to develop a minimum-item GDS maintaining diagnostic performance equivalent to the full 30-item scale (GDS30) using Item Response Theory (IRT). Methods: This cross-sectional study employed rigorous 5:5 split-sample cross-validation. Participants included 6,525 older adults (aged ≥60 years) from community-based (Korean Longitudinal Study on Cognitive Aging and Dementia) and clinical settings (geropsychiatry clinic). Depression was diagnosed through standardized clinical interviews based on DSM-IV criteria. Two-parameter logistic IRT models estimated item discrimination and difficulty parameters. Sequential item reduction with DeLong tests identified the minimum number of items required to maintain GDS30-equivalent area under the curve (AUC). Results: The 10-item IRT-optimized scale (GDS10-IRT) achieved an AUC of 0.856 (95% CI: 0.809–0.895) in the validation set, showing no significant difference from GDS30 (AUC=0.883; p=0.396). Conversely, the 15-item GDS (GDS15) demonstrated significantly lower AUC than GDS30 (p< 0.001) despite having more items. GDS10-IRT achieved a 234% improvement in efficiency ratio (AUC/items) over GDS30. Notably, Item 16 ("feeling downhearted and blue"), identified as the most discriminating symptom (a=2.53), is absent from the GDS15 but included in GDS10-IRT. Conclusion: IRT-based item selection achieves GDS30-equivalent diagnostic accuracy with only 10 items, outperforming the widely used GDS15. By recovering high-discrimination items excluded by CTT, the GDS10-IRT offers a more efficient, specific screening tool for late-life depression.

Abstract: Mild Behavioral Impairment (MBI) constitutes a late-life transition state that is associated with an increased risk of cognitive impairment and dementia. Herein, we described the MBI construct and its relationship with cognitive status in Mexican-Mestizos (MM) older adults. Participants were classified according to their cognitive and behavioral statuses using tests administered to older adults and their informants. APOE_rs429358/rs7412 variants were genotyped by real-time PCR. Multivariate correlation and Principal Components Analysis (PCA) were used in statistical analysis. 246 participants were included, 13.0% had subjective cognitive decline and 30.9% mild cognitive impairment. 37% (91/246) of participants from all the cognitive spectrum met the MBI criteria; among this group, being carrier of APOEε4 was associated with two subdomains of the MBI. Subjective cognitive complaint, symptoms of depression and cognitive decline reported by the informant were associated with an increased risk for MBI (ORs in the range of 4.7-15.89). The first three components of PCA explained 68.0% of the variance of the data set, including MBI-checklist total score as a main contributor. Well-known risk factors for dementia also correlated with this PCA. MBI could be a relevant marker for cognitive decline in non-demented MM elderly people.

Abstract: Background: Comorbid obsessive-compulsive symptoms in bipolar disorder often prove highly resistant to standard treatments, with serotonergic agents carrying substantial risk of mood destabilisation. Recent interest has focused on glutamatergic modulation as an alternative pathway, inspired by the rapid effects of ketamine, though oral regimens require careful attention to pharmacokinetics for clinical success.Methods: This retrospective case report describes a 23-year-old woman with previously stabilised bipolar disorder who, following treatment discontinuation, presented with severe moral scrupulosity and compulsive reassurance-seeking refractory to mood stabilisation alone. In routine outpatient care, valproate was combined with dextromethorphan (NMDA antagonism) and piracetam (AMPA positive allosteric modulation), with subsequent addition of a mild CYP2D6 inhibitor (Deanxit). Progress was monitored through clinical interviews and standardized questionaires.Results: Dextromethorphan 30–45 mg nocte plus piracetam 600–1200 mg nocte on a background of valproate 500 mg produced only modest reduction in ruminations. Marked and sustained improvement—near-complete resolution of obsessive thoughts and reassurance-seeking, with PHQ-9 falling from 16 to 8 and GAD-7 from 19 to 7—occurred only after introduction of Deanxit 1 tablet nocte, providing CYP2D6 inhibition via melitracen.Discussion: The stepwise response pattern underscores the critical role of sustained dextromethorphan exposure in achieving therapeutic NMDA blockade sufficient to drive downstream AMPA-mediated plasticity. This observation aligns with emerging clinical experience suggesting that pharmacokinetic optimisation is essential for translating ketamine-like mechanisms into reliable oral efficacy, particularly in complex bipolar-OCD presentations where conventional options are limited.

Abstract:

Background: Interventions targeting the gut–brain axis offer potential for mitigating Subjective Cognitive Decline (SCD), a critical window for Alzheimer’s prevention. This study evaluated the effects of a novel probiotic supplement, ExoBDNF, on cognitive function, sleep, and emotional distress in adults with SCD. Methods: In this 9-week open-label study, participants received ExoBDNF supplementation. Efficacy was assessed using the SCD-Questionnaire (SCD-Q), DASS-21, PSQI, MoCA, and a computerized cognitive battery measuring inhibition (Go/No-Go), flexibility (Task Switching), and working memory. Results: Post-intervention analyses revealed significant improvements in subjective cognition (SCD-Q, p < 0.001), sleep quality (PSQI, p < 0.001), and emotional distress (DASS-21, p < 0.001). Objective cognitive performance also improved, with significant gains in MoCA scores (p = 0.047) and executive function metrics. Spearman correlation analysis indicated a significant link between cognitive and emotional changes: longitudinal reductions in SCD scores correlated with concurrent reductions in emotional distress (rho = 0.471, p = 0.009). Furthermore, higher baseline SCD scores predicted greater improvement in emotional outcomes (rho = -0.540, p = 0.002). Conclusion: ExoBDNF supplementation significantly enhanced cognitive performance, sleep quality, and emotional well-being. The findings demonstrate that improvements in subjective cognition are closely tied to alleviated emotional distress, supporting the gut–brain axis as a viable therapeutic target for early-stage cognitive decline.

Abstract: Emerging work suggests that a fully oral combination of dextromethorphan, a potent CYP2D6 inhibitor, and the AMPA-facilitator piracetam can reproduce key elements of ketamine's rapid, plasticity-enhancing action on cortico-striatal circuits. Published experience in adolescents, however, remains scarce.We report on a 15-year-old boy with autism spectrum disorder, attention-deficit/hyperactivity disorder, and long-standing, severe obsessive–compulsive disorder. Despite good adherence to sodium valproate and risperidone, he continued to exhibit near-continuous rituals, sudden aggression, and social withdrawal. An evening "stack" was introduced that paired fluoxetine 10 mg (for CYP2D6 blockade) with dextromethorphan 30 mg and, two weeks later, piracetam 600 mg. Violent outbursts and time-consuming compulsions subsided within seven days of starting dextromethorphan; school attendance, piano practice, and peer interaction resumed after the addition of piracetam. Symptom remission has been sustained for four months without dose escalation or notable adverse effects.This single case highlights the possible value of inexpensive, repurposed agents aimed at glutamatergic signalling in adolescents whose OCD proves refractory to conventional medication. Targeting synaptic plasticity during a period of heightened developmental pruning may offer a practical route to meaningful functional recovery.

Abstract: Adolescents who show both obsessive-compulsive behaviour and pronounced, labile mood present a treatment challenge: the usual recommendation of lithium, valproate or other mood stabilisers can bring metabolic and cognitive costs, yet withholding them risks an antidepressant-induced switch to mania. A 17-year-old boy illustrates an alternative course. He had childhood ADHD and long-standing checking rituals; while at boarding school overseas he developed intense rumination, wide mood swings and passive suicidal thoughts. Low-dose risperidone failed to help. Rather than add a conventional mood stabiliser, we introduced an oral glutamatergic stack aimed at reproducing ketamine-like plasticity: dextromethorphan for NMDA antagonism, piracetam to potentiate AMPA transmission and 10 mg fluoxetine nightly to slow dextromethorphan metabolism. Within weeks mood steadied, intrusive thoughts abated and function at school improved. The patient remained well without therapeutic-dose mood stabilisers. This experience suggests that carefully layered oral glutamatergic therapy may, in selected adolescents, deliver both anti-obsessional and mood-stabilising benefits while avoiding the burdens of traditional agents.

Abstract: Comorbid obsessive–compulsive symptoms in bipolar disorder remain difficult to manage because serotonin-reuptake agents can trigger mood elevation while conventional mood stabilisers seldom relieve obsessions. Rapid-acting glutamatergic interventions such as intravenous ketamine improve both mood and intrusive thinking (1,2) yet are costly and logistically demanding. We describe three consecutive adults with bipolar disorder who showed severe, mood-congruent obsessive–compulsive phenomena—including trichotillomania, onychophagia and distressing somatic ruminations—despite multiple trials of high-dose SSRIs, SNRIs, atypical antipsychotics and standard mood stabilisers. During routine outpatient care between May and November 2025 each patient began an oral ketamine-mimetic programme — the Cheung Glutamatergic Regimen — built around dextromethorphan (NMDA antagonism) whose exposure was extended with a CYP2D6 inhibitor, then augmented with piracetam (AMPA positive allosteric modulation) and, when required, L-glutamine for presynaptic glutamate replenishment. All three individuals entered sustained remission of depressive, anxious and obsessive–compulsive symptoms after the sequential addition of piracetam to the dextromethorphan base, and the gains persisted through follow-up. Treatment was generally well tolerated; transient hypomanic activation was contained by reducing dextromethorphan or its metabolic inhibitor while maintaining piracetam. These naturalistic observations suggest that a wholly oral, low-cost NMDA–AMPA modulation strategy may offer a rapid and durable option for the "bipolar-OCD" phenotype. Formal controlled studies are needed to confirm efficacy, define optimal dosing and clarify long-term safety.

Abstract: Rapid-acting antidepressant research has moved therapeutic attention from monoamines to glutamatergic neuroplasticity. Intravenous ketamine and the oral "Cheung Glutamatergic Regimen" (dextromethorphan, a CYP2D6 inhibitor, piracetam, glutamine) rely on NMDA-receptor antagonism to unleash glutamate and drive AMPA throughput, but the price is polypharmacy and demanding pharmacokinetics. I advance a counterproposal: pair methylphenidate (MPH) with the AMPA-positive allosteric modulator piracetam. Evidence indicates that MPH elicits a brief, prefrontal-selective rise in extracellular glutamate; piracetam can magnify this impulse and may recreate the "AMPA-dominant" plasticity state linked to ketamine-like efficacy.The safety of the combination is weighed against the excitotoxic risks posed by amphetamine stimulants, and clinical vignettes of executive-function recovery and "brain-fog" relief are reviewed.

Abstract: Ketamine’s ability to lift mood and spur new synapse growth has put glutamate biology at the center of modern neurotherapeutics. Yet the drug’s intravenous route, monitoring requirements, and dissociative effects make it a poor candidate for long-term prevention of Alzheimer’s disease (AD).Here we advance a testable hypothesis: an all-oral “synaptogenic stack” could mimic ketamine’s downstream benefits—namely, the rise in brain-derived neurotrophic factor (BDNF) and the activation of mTOR—while avoiding its toxicities.The stack combines three inexpensive agents that have decades of human use. First, dextromethorphan, kept in circulation with a small dose of a CYP2D6 inhibitor, provides gentle NMDA antagonism. Second, piracetam acts as a positive modulator of AMPA receptors, boosting fast excitatory transmission. Third, oral L-glutamine replenishes presynaptic glutamate stores and buffers against excitotoxic spill-over. Working in concert, these drugs should reduce extrasynaptic NMDA stress, enhance AMPA throughput, and preserve dendritic spine density in the ageing brain.If this mechanism proves sound, the regimen offers a low-cost, scalable way to delay the clinical onset of AD, particularly in people who already show prodromal biomarkers or genetic risk. Prospective trials are needed to evaluate safety, target engagement, and long-term cognitive outcomes.

Abstract: Adults with attention-deficit/hyperactivity disorder often continue to battle mental "fog," emotional lability and low drive even after guideline treatments have been optimised. Mounting evidence from mood-disorder research indicates that shifting glutamatergic traffic toward AMPA-receptor throughput can trigger rapid plastic changes, yet this principle has seldom been explored in ADHD.A 28-year-old woman who remained inattentive and anxious on atomoxetine was switched, in routine outpatient practice, to a low-dose extended-release methylphenidate formulation (18 mg) augmented with piracetam 1 200 mg daily. Within days she reported markedly sharper concentration, steadier mood and a new capacity to sustain purposeful activity without the late-day "flattening" she had experienced on stimulants alone. When piracetam was paused for three days the improvements evaporated, only to return on re-initiation, creating a clear temporal association.The observation supports the idea that a safe, inexpensive AMPA modulator can amplify the modest glutamate rise produced by methylphenidate and translate it into meaningful clinical gains. Although limited to a single case, the result invites systematic study of piracetam as an adjunct for adults whose ADHD symptoms have proven only partially responsive to standard pharmacotherapy.

Abstract: Comorbid bipolar I disorder, obsessive–compulsive disorder and attention-deficit/​hyperactivity disorder form a notoriously unstable clinical constellation. Conventional stimulants risk precipitating mania, whereas high-dose antidepressants seldom quell the mood-linked obsessions and may themselves cause switching. We detail the course of a 31-year-old man who illustrated these pitfalls. After methylphenidate produced early hypomanic signs—fragmented sleep, increased impulsive spending and heightened drive—his treatment was redirected toward a fully oral glutamatergic strategy. The regimen combined dextromethorphan for NMDA antagonism, pharmacokinetically extended by the mild, reversible CYP2D6 inhibition provided by melitracen within Deanxit, with piracetam to potentiate AMPA signalling and L-glutamine to support presynaptic glutamate balance. All adjustments were made in routine outpatient follow-up. Across three months the patient showed steady gains: depressive affect lifted, intrusive ruminations quieted and impulse control improved, while the need for methylphenidate fell from daily dosing to occasional use without loss of attentional capacity. When he later stopped dextromethorphan and piracetam on his own initiative—yet continued valproate and antipsychotic cover—both low mood and obsessive thinking re-emerged, then abated rapidly once the glutamatergic agents were reinstated. This single case suggests that a multi-target oral glutamatergic approach can stabilise mood, reduce obsessions and preserve attention in a comorbidity cluster where traditional pharmacotherapy frequently destabilises the illness. Further systematic study is warranted to confirm the safety and durability of NMDA/AMPA modulation as a non-stimulant alternative in complex bipolar-spectrum presentations.

Abstract: Older adults who live with severe obsessive–compulsive disorder (OCD) complicated by somatic anxiety rarely achieve meaningful relief on conventional serotonergic or antipsychotic regimens, and only a minority have access to intravenous ketamine, the best-validated rapid-acting glutamatergic option. We report the outpatient management of a 68-year-old man who had spent five years trapped in disabling health-related obsessions and reassurance-seeking rituals. Despite trials of mirtazapine, bupropion and several antipsychotics, his baseline burden remained high (PHQ-9 = 13).During routine follow-up, bedtime dextromethorphan 30 mg and piracetam 600 mg were added, with bupropion XL 150 mg retained to prolong dextromethorphan exposure through CYP2D6 inhibition. The patient supplied daily updates through encrypted messaging. By the fourth night he reported uninterrupted sleep, disappearance of morning restlessness and near-total quieting of intrusive health fears; residual daytime fatigue resolved after small downward adjustments of mirtazapine, risperidone and lemborexant. This experience shows that an easily deployed oral "ketamine-like" strategy—combining NMDA antagonism with AMPA potentiation—can bring about remission within days, even in a complex geriatric presentation that had resisted years of standard pharmacotherapy.

Abstract: Off-label use of glutamatergic agents is increasingly common in psychiatry, yet standardized protocols for outpatient dosing are lacking. This report describes the pharmacological management and dosing adjustments required for three patients receiving dextromethorphan (DXM) and piracetam for obsessive–compulsive disorder.Three adult women with severe OCD were treated in a routine clinical setting. Treatment history varied from naïve to treatment-resistant. All patients commenced treatment with a nighttime regimen of oral DXM and piracetam to minimize potential side effects while maintaining existing psychotropic regimens.One patient achieved full remission on a once-nightly regimen. The last two patients showed a "wearing-off" effect, that their symptoms got better quickly after they woke up but then came back in the late afternoon, which neccesitated the schedule to be changed from once a day to twice a day (b.i.d.). This change fixed the afternoon symptom breakthrough without needing to raise the dose.Experience with these cases suggests that while bedtime administration is a safe starting point for routine care, the half-life of the agents may necessitate split dosing for some individuals. The observation that simple schedule adjustments can resolve diurnal symptom fluctuation provides a practical insight for psychiatrists managing OCD with glutamatergic augmentation.

Abstract: Background/Objectives: Adults with intellectual disability (ID) experience high rates of psychiatric comorbidity but often face diagnostic challenges and treatment barriers, often leading to inappropriate psychotropic medication use. This study examined the extent to which specialised psychiatric assessment and improved diagnostic accuracy had an im-pact on medication management and clinical outcomes in adults with ID and co-occurring psychiatric disorders. Methods: This observational retrospective study ana-lysed medical records from 25 adults with ID who underwent specialised psychiatric as-sessment at a community-based service in Italy between January 2023 and January 2024. Psychopathological diagnoses were established according to Diagnostic Manu-al-Intellectual Disability 2nd version (DM-ID2) criteria, based on clinical observation and a comprehensive assessment using validated instruments. Clinical outcomes were as-sessed using a psychometric tool encompassing multiple psychopathological and behav-ioral dimensions. Data on psychotropic prescriptions and side effects were also collected. Non-parametric analyses were performed, with significance set at α=0.05. Results: The proportion of patients with a psychiatric diagnosis increased from 32% to 96% after spe-cialized assessment (p< 0.001), with notable rises in depressive (0% to 32%), bipolar (8% to 36%), anxiety (4% to 24%), and impulse control disorders (0% to 16%). First-generation an-tipsychotic prescriptions decreased (from 36% to 8%, p=0.023), while antidepressant use increased (from 12% to 52%, p=0.004). The mean number of side effects per patient de-clined from 1.6 to 0.5 (p< 0.001), particularly the elevated prolactin level, and psychomotor retardation. Significant improvements were observed in symptom intensity and frequency across multiple domains, including aggression, mood disturbances, and compulsions (p< 0.001). Conclusions: Specialised psychiatric assessment substantially improved diag-nostic accuracy, medication management, and clinical outcomes in adults with ID. The increase in psychiatric diagnoses reflects improved identification, addressing key chal-lenges in precision diagnosis for people with neurodevelopmental disorders. Evi-dence-based medication optimisation reduced inappropriate antipsychotic use and side effects. These findings support the need for specialised assessment and precision diagnosis to improve psycho-pharmacological interventions and outcomes for this vulnerable population.

Abstract: Background: Bipolar disorder secondary to traumatic brain injury (TBI) is common, mechanistically distinct, and notoriously treatment-resistant. Rapid-acting glutamatergic antidepressants such as ketamine are effective in bipolar depression but remain inaccessible to most patients.Case presentation: We describe a woman in her mid-thirties with documented right frontal atrophy after a severe violence-related subdural hematoma in 2009, subsequent onset of cyclothymic-to-bipolar illness, and recent severe depressive relapse with insomnia, auditory hallucinations, PHQ-9 = 22 and GAD-7 = 14. Conventional treatment (valproate, low-dose risperidone, lemborexant, and Deanxit [flupentixol 0.5 mg + melitracen 15 mg]) produced minimal benefit. On 5 November 2025, low-dose dextromethorphan 30 mg nightly and piracetam 600 mg nightly were added. Melitracen, a moderate CYP2D6 inhibitor, inadvertently prolonged dextromethorphan exposure, effectively replicating the pharmacokinetic principle of Auvelity® while piracetam supplied AMPA positive allosteric modulation.Results: Within four weeks the patient reported marked mood stabilization and reduced ruminations. Transient mild hypomania with moria-like inappropriate laughter emerged, prompting spontaneous reduction of dextromethorphan to 22.5 mg nightly and upward titration of piracetam to 1 200 mg, after which euthymia was restored and maintained. No dissociation or worsening psychosis occurred.Conclusions: This case provides the first clinical illustration that an ultra-low-cost, fully oral glutamatergic oral regimen (dextromethorphan + unintended CYP2D6 inhibition + piracetam) can produce ketamine-class speed and magnitude of response in secondary bipolar depression after TBI, even at dextromethorphan doses far below those in licensed combinations. The narrow therapeutic window and hypomanic overshoot highlight the heightened glutamatergic sensitivity of the post-TBI brain.

Abstract: Major depressive disorder (MDD) remains a leading cause of disability worldwide, with conventional antidepressants offering incomplete and often transient relief. Mounting ev-idence highlights disturbances in tryptophan (Trp) metabolism as a key biological axis linking inflammation, neuroplasticity, and mood regulation. Plant-derived compounds that modulate this pathway, including 5-hydroxytryptophan, isoflavones, berberine, and polyphenols, have emerged as promising candidates for integrative treatment strategies. Yet, despite encouraging preclinical and clinical findings, knowledge gaps persist re-garding long-term efficacy, mechanistic specificity, and standardized therapeutic proto-cols. This narrative review explores how plant-derived Trp modulators influence central and peripheral mechanisms relevant to depression, from serotonergic synthesis and kynurenine shunting to gut–brain–immune interactions. Evidence from animal models and randomized clinical trials is critically synthesized, with particular attention to out-comes on mood stabilization, anxiety reduction, cognitive function, and sleep regulation. Special emphasis is placed on translational potential, methodological limitations, and the need for harmonized research frameworks. Here we highlight that phytochemical inter-ventions represent a mechanistically informed and biocompatible strategy for advancing depression management. By bridging neurobiology and clinical psychiatry, these insights may pave the way for next-generation therapeutics that integrate dietary, microbio-ta-targeted, and anti-inflammatory approaches. Broader application of this research could ultimately refine personalized psychiatry, expand therapeutic horizons, and contribute to global mental health resilience.

Abstract: Intranasal esketamine has proven its worth for patients whose depression will not yield to standard medicines, yet the realities of cost and clinic-based monitoring bar many people from long-term use. The situation is especially frustrating for those who respond spectacularly to a first dose only to watch the benefits fade when they can no longer afford repeat treatments.That was the predicament of a 48-year-old office worker who, in 2023, received a single 56 mg spray of esketamine. Within hours his mood lifted and the suicidal thoughts that had haunted him for months vanished, but the HK $6,000 price tag of each session forced him to stop. Over the next two years his illness morphed into severe obsessive–compulsive disorder dominated by violent, self-directed images. Trials of flupentixol/melitracen, bupropion plus over-the-counter dextromethorphan, and other conventional combinations offered only fleeting relief.In 2025 we replaced that patchwork with a mechanistically guided, fully oral "ketamine-like" stack: dextromethorphan 120 mg/day to block NMDA receptors, fluoxetine 20–40 mg/day to slow dextromethorphan metabolism via CYP2D6 inhibition, and piracetam 1.2 g/day to boost downstream AMPA activity. A few low-dose adjuncts (risperidone, valproate, pregabalin) were retained for sleep and anxiety. Four weeks later the change was unmistakeable. Intrusive imagery that once erupted every hour now surfaced only sporadically and could be brushed aside. His PHQ-9 score fell from 17 to the 5–6 range, suicidal ideation disappeared, and he returned to full productivity at work. These gains have held steady for more than eight months at a monthly medication cost of roughly HK $400–600—less than one-tenth the expense of maintenance esketamine.The case suggests that patients who exhibit an early, dramatic response to esketamine may not need to choose between relapse and ruinous expense. A carefully constructed oral regimen that recreates ketamine's NMDA-to-AMPA plasticity cascade can deliver similar, durable results at a price most clinics and patients can manage. Systematic trials are now warranted to test whether this strategy can scale to the wider population for whom intravenous or intranasal ketamine is out of reach.

Abstract: Autism spectrum disorder (ASD) follows an unusual two-stage course of synaptic change. Infancy and early childhood are marked by an exuberant rise in dendritic spines coupled with weak pruning, a profile driven in large part by overactive mTOR signalling. By adolescence and early adulthood, the pendulum appears to swing in the opposite direction, with evidence of compensatory over-pruning and a net loss of functional connections.Against this neurodevelopmental backdrop, we reviewed longitudinal MRI findings, post-mortem histology and mechanistic pharmacology to assess a putative "Cheung glutamatergic regimen." The protocol combines dextromethorphan (an NMDA-channel blocker), a CYP2D6-inhibiting antidepressant, piracetam and the amino-acid precursor l-glutamine.Available data suggest sharply divergent risk–benefit profiles across the lifespan. In children between two and ten years of age—when synaptic numbers can exceed neurotypical levels by as much as 50 per cent—any strategy that further amplifies glutamatergic drive may heighten excitotoxic risk and worsen core autistic features; the regimen is therefore contraindicated in this window. In contrast, once puberty ushers in accelerated pruning and the possibility of synaptic depletion, carefully titrated glutamate enhancement could prove restorative. By pairing transient NMDA blockade with boosted AMPA throughput and substrate support from glutamine, the combination may help re-establish γ-band synchrony and strengthen long-range cortico-cortical connectivity often weakened in older autistic individuals.Taken together, the Cheung glutamatergic regimen may emerge as a low-cost, easily deployed option with genuine promise for post-pubertal autistic patients. Its use in younger children, however, cannot be justified on current evidence and should be strictly avoided until the early surplus of synapses has resolved.

Abstract: Sleep-onset anxiety is a transdiagnostic contributor to difficulty initiating sleep that is maintained through interconnected cognitive, physiological, and neurobiological processes. This narrative review synthesizes current evidence on mechanisms and behavioral interventions for sleep-onset anxiety, highlighting pre-sleep worry, rumination, conditioned arousal, autonomic dysregulation, and brain network alterations as key mechanisms. Evidence-based interventions are reviewed, including cognitive behavioral therapy for insomnia (CBT-I), mindfulness and acceptance-based approaches, relaxation strategies, and environmental optimization. Clinical considerations are examined for individuals with comorbid anxiety disorders, across developmental stages, and across diverse cultural contexts. Digital delivery formats are reviewed as scalable approaches to extend treatment access. Much existing evidence derives from broader insomnia populations rather than sleep-onset anxiety as a distinct construct, limiting mechanistic specificity. Future research directions include mechanistic trials integrating objective biomarkers with clinical outcomes, component optimization studies, and scalable implementation approaches. This review provides an integrative framework linking mechanisms to evidence-based interventions for sleep-onset anxiety across diverse clinical populations and settings.

Abstract: Background: Young adults with mood and anxiety disorders often remain hamstrung by "brain-fog," headaches, and other bodily complaints even after standard antidepressants or sedatives take the edge off their mood. An inexpensive OTC oral augmentation stack proposed by Cheung (2025)—dextromethorphan for NMDA blockade, low-dose fluoxetine to slow its metabolism, and piracetam to boost AMPA signalling—may reproduce ketamine's rapid neuroplastic effects without an infusion suite.Case: A 25-year-old law student arrived with severe depression (PHQ-9 = 23), generalized anxiety (GAD-7 = 15), daily tension headaches, cramping abdominal pain, episodic breathlessness, and crippling cognitive fog that had already cost her an exam. A sedative‐heavy regimen (risperidone 0.5 mg, alprazolam 0.25 mg prn, lemborexant 1.25 mg, flupentixol/melitracen 1 tablet) eased the physical distress and improved sleep, yet panic and mental slowdown roared back when the new term began.Intervention: In early September the medication plan pivoted to the Cheung Glutamatergic Regimen: fluoxetine 10 mg each morning plus dextromethorphan 30 mg and piracetam 600 mg once daily. Somatic and anxiety symptoms calmed within days, but heavy fatigue and poor concentration lingered until the DXM–piracetam pair was given twice daily.Outcome: Within a week of the dosing change the patient reported a sudden "lights-on" clarity, sustained focus, and return to full study hours. By late November her scores had fallen to PHQ-9 = 15, GAD-7 = 8; headaches and abdominal pain were rare and alprazolam use had nearly stopped.Conclusion: This report suggests that pairing oral NMDA antagonism with AMPA potentiation—especially in a morning-and-evening schedule—can quickly lift refractory cognitive and somatic symptoms where serotonergic and sedative strategies fall short. The approach merits systematic study.