This case of a 10-year-old girl herein presented is one of the earliest to report safe and effective use of cariprazine, a metabolic-friendly agent, targeting the behavioral facets in ASD. This might open new treatment venues in such complicated clinical scenarios.
Eugeroics are a distinct, yet heterogeneous group of psychotropic agents that differ from classical stimulants, are less activating, of less abuse potential, sorely clinically underutilized, and have an attractive pharmacological portfolio speaking to the idea of pluripotent molecules of an expanded therapeutic potential. Herein, authors would touch briefly on the current available literature on eugeroics as germane to psychiatric practice whilst examining the extant evidence.
Background:Traumatic brain injury (TBI) is associated with a range of neuropsychiatric sequelae, including secondary psychotic disorders. Delusional syndromes are a prominent and clinically significant manifestation, often classified as Psychotic Disorder Due to Another Medical Condition.1,2. Methods:This narrative synthesis reviews case series, cohort studies, retrospective analyses, and conceptual literature published between 1998 and 2025, focusing on epidemiology, clinical features, pathophysiology, diagnosis, and psychopharmacologic management of post-TBI delusional syndromes. Results:Delusions-commonly persecutory or misidentification types-frequently emerge after a latency of months to years and are more prevalent than schizophrenia-like presentations.1,2,6 Risk factors include moderate-to-severe injury, frontal or temporal lesions (particularly right-sided), post-traumatic epilepsy, and genetic vulnerability.3-6 Compared to primary psychotic disorders, negative symptoms are typically less prominent, though cognitive impairment is nearly universal.6,7,12 Low-dose atypical antipsychotics demonstrate favorable response rates, but tolerability concerns-including sedation, extrapyramidal symptoms, and seizure risk-necessitate cautious use.8,9 Adjunctive anticonvulsants may be beneficial, particularly in patients with comorbid epilepsy.10,15. Conclusions:Post-TBI delusional syndromes highlight the role of structural brain injury in the development of psychosis. Careful diagnostic evaluation and individualized, low-dose psychopharmacologic strategies are essential. Further research is needed to guide evidence-based treatment in this population.
Aims:To compare the efficacy and safety of electroconvulsive therapy (ECT) and ketamine infusion (KET-IFU) in routine care for patients with bipolar I or II depression (BPD). Methods:Electronic medical records of patients who received ECT and/or KET-IFU were used to identify patients with BPD who received both ECT and KET-IFU treatments. The change in the 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-16-SR) total score was used as an efficacy outcome. Self-reported side effects and Montreal Cognitive Assessment (MoCA) were used as safety measures. Results:Six patients with BPD received both ECT and KET-IFU treatments. All patients received ECT first. Five patients received KET-IFU due to subjective memory concerns from ECT although their MoCA scores were within normal range. One patient with multiple previous ECT series received two KET-IFU series followed by an ECT series. Four patients responded to acute ECT treatments well with ⩾ 50% improvement in QIDS-16-SR total scores. Two of them also responded to KET-IFU well with ⩾ 50% improvement but the onset of antidepressant effect differed. One patient did not respond to ECT or KET-IFU. The patient who had two series of KET-IFU responded well during the first KET-IFU series but had limited benefit from the second KET-IFU series. No patient discontinued KET-IFU due to an adverse event. Conclusion:Most patients responded to ECT well and half of them had similar benefit from KET-IFU as from ECT. Randomized, head-to-head comparison studies of ECT versus KET-IFU in BPD are warranted to confirm or refute these findings.
Background:Approximately 30% of patients treated for major depressive disorder develop treatment-resistant depression (TRD). The STAR*D study demonstrated remission rates decline progressively with each antidepressant failure (37%, 31%, 14%, and 13%, respectively). A single-day individualized dosing regimen of GH001 (synthetic mebufotenin for inhalation) produced rapid, large improvements in depressive symptoms versus placebo in patients with TRD in a Phase 2b trial (least-squares mean difference, -15.5; effect size, -2.0; 57.5% remission at Day 8 versus 0% placebo). The current post hoc analysis examines whether GH001 efficacy varies by number of prior lifetime antidepressant treatment failures. Methods:This analysis included all 40 patients who received GH001 in the double-blind part of a Phase 2b trial. Spearman rank correlations between number of prior lifetime antidepressant failures and change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) scores were calculated at Day 8 and among 6-month open-label extension completers. Remission rates (MADRS ⩽10) were examined by subgroup (2, 3, 4, or ⩾5 prior lifetime failures). Results:No meaningful correlation was observed between prior lifetime treatment failures and MADRS improvement at Day 8 (r = -0.13; P = 0.44) or 6-month OLE completers (r = -0.10; P = 0.60). Remission rates at Day 8 likewise were similar across subgroups (range, 53.9%-63.6%) and were maintained at end of treatment visit/Month 6 (range, 61.5%-85.7%). Secondary endpoints were not associated with treatment history. Conclusions:The efficacy of GH001 in patients with TRD appears largely independent of number of prior lifetime antidepressant treatments, and further research in patients with extensive treatment histories will be conducted in subsequent development stages.
Introduction:This study examines how inpatients with catatonia responded when treated with or without antipsychotic medications. It employs two metrics to account for both the catatonic symptoms and the more traditionally psychotic symptoms. Length of stay is a secondary metric. Methods:The primary investigator retrospectively collected data on 164 patients diagnosed with catatonia on an academic inpatient service from July 2018 through September 2023. The treatments of these patients were separated into two distinct categories: Group A (n = 81) received antipsychotic medication with benzodiazepines and/or electroconvulsive therapy, and Group B (n = 83) received benzodiazepines and/or electroconvulsive therapy without antipsychotics. Scores on admission from the Bush Francis Catatonia Rating Scale and positive symptom subscale from the Positive and Negative Syndrome Scale were collected and compared with scores at discharge. ANOVA analysis was used to compare outcomes. Results:The antipsychotic-treated group demonstrated significantly higher Bush Francis Catatonia Rating Scale scores (p < 0.0001) and positive scale of the Positive and Negative Syndrome Scale scores (p < 0.0001) at discharge than the group receiving only benzodiazepines and/or electroconvulsive therapy. Patients hospitalized multiple times and treated under both conditions were used as their own controls. Bush Francis Catatonia Rating Scale scores (p < 0.0001) and positive scale of the Positive and Negative Syndrome Scale scores (p < 0.0001) were higher at discharge when antipsychotics were added to treatment. Conclusion:Patients treated without antipsychotics showed greater improvement in both their traditional catatonic symptoms and in their psychotic symptoms.
This case of a 10-year-old girl herein presented is one of the earliest to report safe and effective use of cariprazine, a metabolic-friendly agent, targeting the behavioral facets in ASD. This might open new treatment venues in such complicated clinical scenarios.
Escitalopram-induced dystonia is a rare but clinically important occurrence. Clinicians should have a high index of suspicion in order to intervene early and improve symptoms.
The American medical landscape is currently defined by a profound paradox. While the ongoing opioid crisis, characterized by a rise in synthetic illicit opioids continues to ravage communities, our primary pharmacological defense for both opioid use disorder (OUD) and chronic pain management remains underutilized in the very training programs designed to produce "experts" in the field. Pain medicine fellowship training frequently emphasizes the technical mastery of interventional procedures and non-opioid pharmacologic strategies. While these approaches are critically important, education in medication-assisted treatment (MAT), particularly the use of buprenorphine for OUD and complex chronic pain, often receives limited attention. The transition from the restrictive "X-waiver" era to the current regulatory environment was intended to expand and democratize access to buprenorphine treatment. However, legislative change alone cannot substitute for structured clinical education. Removing regulatory barriers does little to improve access if clinicians lack the knowledge, confidence, and training necessary to prescribe and manage these medications effectively. As the opioid crisis persists, it is critical that buprenorphine education be standardized as a core competency within pain medicine fellowship programs. Future pain specialists should be as comfortable initiating and managing buprenorphine therapy as they are performing advanced interventional procedures such as spinal cord stimulation. Strengthening training in this area will better equip pain physicians to address both chronic pain and opioid use disorder within an evolving and increasingly complex public health landscape.
Eugeroics are a distinct, yet heterogeneous group of psychotropic agents that differ from classical stimulants, are less activating, of less abuse potential, sorely clinically underutilized, and have an attractive pharmacological portfolio speaking to the idea of pluripotent molecules of an expanded therapeutic potential. Herein, authors would touch briefly on the current available literature on eugeroics as germane to psychiatric practice whilst examining the extant evidence.
Background:Antipsychotic medications are associated with increased cardiovascular morbidity and mortality in patients with serious mental illness (SMI). Clozapine-induced myocarditis and cardiomyopathy are well established; however, emerging pharmacovigilance and observational data suggest that cardiotoxic risk extends beyond clozapine to other antipsychotic agents. Methods:We conducted a narrative review of the literature (2000-2026), including pharmacovigilance databases (VigiBase, FAERS), cohort studies, case series, and consensus guidelines. Emphasis was placed on epidemiology, mechanisms, comparative risk, clinical presentation, diagnosis, and practical management strategies relevant to psychiatric practice. Results:Clozapine demonstrates the highest risk of myocarditis (estimated incidence 0.3-3%), typically within the first 4-8 weeks of treatment. Pharmacovigilance data consistently identify secondary signals for quetiapine and olanzapine, with weaker but present associations for risperidone, aripiprazole, and other agents. Proposed mechanisms include hypersensitivity myocarditis, inflammatory cytokine activation, oxidative stress, and mitochondrial dysfunction. Early recognition through symptom monitoring and selective biomarker use significantly improves outcomes. Conclusions:Cardiotoxicity associated with antipsychotics is not limited to clozapine. Psychiatrists should adopt a risk-stratified approach incorporating cautious titration, early symptom recognition, and targeted monitoring. Greater awareness and multidisciplinary collaboration are essential to optimize both psychiatric and cardiovascular outcomes.
We report the case of a 27-year-old male who developed elevated liver enzymes during treatment with low-dose mirtazapine for insomnia. Liver function normalized after discontinuation of the drug, supporting a probable drug-induced liver injury (DILI). This case highlights the need for hepatic monitoring during mirtazapine therapy, even at low doses and in asymptomatic patients.
Adolescent bipolar disorder (BD) is frequently accompanied by persistent sleep disturbances and depressive episodes that are resistant to standard treatments. Conventional antidepressants carry a risk of inducing mania or rapid cycling, particularly in younger patients. Agomelatine, a melatonergic agonist and selective serotonergic antagonist, addresses both circadian dysregulation and depressive symptoms through a unique mechanism that does not increase synaptic serotonin, thereby potentially minimizing the risk of mood switch. Despite its efficacy in adults, its use in adolescent BD remains largely unexplored. We present three cases of adolescents (ages 16-17) with bipolar depression and chronic insomnia in whom agomelatine (25-50 mg nightly) was added adjunctively to existing mood stabilizer or atypical antipsychotic regimens. Clinical outcomes were assessed using the Hamilton Depression Rating Scale (HDRS), Pittsburgh Sleep Quality Index (PSQI), and Young Mania Rating Scale (YMRS) over a 24-week follow-up period. All three patients demonstrated clinically meaningful improvements in both sleep quality and depressive symptomatology within the first 4-6 weeks, without manic switching or hepatic adverse effects. One patient successfully discontinued sedative-hypnotic use following sleep normalization. These cases suggest that adjunctive agomelatine may offer a dual benefit of sleep regulation and mood stabilization in adolescent BD, representing a promising alternative in patients who have failed or cannot tolerate conventional antidepressants. Controlled clinical trials are warranted to confirm these preliminary findings.
Background:Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder associated with persistent functional impairment across the lifespan. Although several pharmacological treatments are available, their clinical utility is often limited by tolerability concerns, heterogeneous efficacy, and limited long-term safety data. Centanafadine, a novel triple monoamine reuptake inhibitor targeting norepinephrine, dopamine, and serotonin transporters, has emerged as a potential non-stimulant treatment for ADHD; however, its efficacy and safety have not been systematically quantified. Objective:To systematically review and quantitatively synthesize randomized controlled trials (RCTs evaluating the efficacy and safety of centanafadine compared with placebo in individuals with ADHD. Methods:PubMed, Embase, Scopus, and ClinicalTrials.gov were searched from inception to the most recent available date. Placebo-controlled RCTs enrolling participants with a formal ADHD diagnosis were included. Primary efficacy outcomes were changes in ADHD symptom severity assessed using validated rating scales and pooled as standardized mean differences (Hedges' g). Secondary efficacy outcomes included clinician-rated global severity assessed using the Clinical Global Impressions-Severity (CGI-S) scale. Safety outcomes included the incidence of any adverse event. Random-effects meta-analyses using restricted maximum-likelihood estimation with Hartung-Knapp adjustment were performed. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. Results:Five RCTs (n = 1,968) showed that centanafadine significantly reduced ADHD symptom severity versus placebo (Hedges' g = -0.37, 95% CI -0.68 to -0.05; p = 0.032). Four RCTs (n = 1,683) demonstrated significant improvement in CGI-S scores (mean difference = -0.26, 95% CI -0.31 to -0.21; p = 0.0006; I2 = 0%). Safety analyses of six RCTs (n = 2,287) showed a numerically higher but non-significant risk of adverse events (risk ratio = 1.29, 95% CI 0.97 to 1.71). Conclusions:Centanafadine provides statistically significant and clinically meaningful improvement in ADHD symptoms with generally acceptable tolerability, supporting its role as a non-stimulant treatment option. Further long-term and comparative trials are warranted.
Major Depressive Disorder (MDD) represents the classically described episodic depression, with varying degrees of severity and recurrence. With a lifetime prevalence close to 20%, the condition represents a leading cause of disability worldwide. Pharmacotherapy is an option for initial treatment, especially in cases of higher severity. As over half of patients will not experience remission after first antidepressant trial, it is essential for clinicians to understand the vast number of medications available and their unique characteristics. This review provides a comprehensive clinical update on evidence-based pharmacotherapies for MDD, including both established and novel treatment options. Traditional monoaminergic antidepressants remain as important options with comparable efficacy but often distinct side-effect profile. Augmentation strategies are often employed with partial treatment response and are available with a wide range of mechanisms and unique clinical nuances. Fast-acting agents are now a reality in practice, including neuroactive steroids for postpartum depression and agents that target glutamatergic pathways. Relevant aspects for clinical practice are provided for over forty different medications, presenting dose ranges, adverse effects, monitoring requirements, and important patient characteristics to consider when prescribing. We also highlight concepts important for successful pharmacotherapy such as accurate diagnosis and treatment resistance. With the expanding therapeutic arsenal for MDD, ongoing comparative-effectiveness and real-world studies will be crucial for transforming today’s advances into accurately personalized care.
Objective:Inflammation has been proposed as a possible mechanism and treatment target for posttraumatic stress disorder (PTSD), but traditional methods for measuring it are performed infrequently in clinical practice. The present study sought to determine if widely available complete blood count (CBC)-derived indices of inflammation predicted treatment response to Glecaprevir/Pibrentasvir (GLE/PIB), a potential inflammation modulator, in patients with PTSD. Methods:We performed a secondary analysis of an uncontrolled trial of GLE/PIB in 10 patients with PTSD. Nearest CBC lab tests were taken from the Veterans Affairs electronic health record, and six CBC-derived indices of inflammation were calculated and Z-standardized. The effect of the indices on PTSD symptoms following GLE/PIB treatment, as measured by the Clinician Administered PTSD Scale for DSM-5 (CAPS), was determined through multiple linear regression. Results:Four of the six indices of inflammation tested had statistically significant associations with post-treatment CAPS scores at an α = 0.05 significance level. Regression coefficients for the statistically significant findings ranged from -19.56 (95% CI: -28.99, -10.14) to -14.24 (95% CI: -25.51, -2.98), indicating lower post-treatment CAPS scores in patients with greater inflammatory indices. Conclusions:CBC-derived indices of inflammation may be an efficient and widely available biomarker for predicting treatment response in medications targeting potential inflammatory mechanisms of PTSD.
Abrupt discontinuation of clozapine can result in serious and potentially life-threatening psychiatric and physical complications, including psychotic rebound, increased risk of suicide, catatonia, cholinergic rebound, and autonomic instability. Although exceedingly rare, the literature contains case reports describing seizures following abrupt clozapine withdrawal. We report and discuss an additional case of this phenomenon. A 45-year-old man with a diagnosis of paranoid schizophrenia, treated with clozapine 300 mg/day for at least 20 years, abruptly discontinued the medication. Two weeks later, he experienced two generalized tonic-clonic seizures. No alternative medical cause was identified, and the temporal association suggests clozapine withdrawal as the precipitating factor. This case highlights the importance of preventing abrupt clozapine discontinuation. In clinical situations where abrupt discontinuation is unavoidable, it should be performed in a hospital setting. When feasible, gradual tapering is recommended to minimize withdrawal-related complications.
Background:Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics that can cause significant functional impairment. Deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, has been evaluated in randomized controlled trials (RCTs) for tic reduction; however, individual studies have reported mixed results across clinical outcomes. We conducted a systematic review and meta-analysis to assess the efficacy and safety of deutetrabenazine compared with placebo in patients with Tourette syndrome. Methods:A comprehensive literature search of PubMed, Embase, Scopus, and ClinicalTrials.gov was performed to identify randomized controlled trials evaluating deutetrabenazine versus placebo in Tourette syndrome up to October 2025. Primary outcomes included changes in Yale Global Tic Severity Scale (YGTSS), Tourette Syndrome-Clinical Global Impression (TS-CGI), Tourette Syndrome-Patient Global Impression of Improvement (TS-PGII), and Children and Adolescents-Gilles de la Tourette Syndrome Quality of Life (C&A-GTS-QOL). Secondary outcomes included depressive symptoms assessed by the Children's Depression Inventory-2 (Parent Version) and the incidence of adverse events. Random-effects meta-analyses using restricted maximum likelihood estimation were conducted, with risk of bias assessed using the Cochrane Risk of Bias 2.0 tool. Results:Three RCTs comprising 297 participants were included. Deutetrabenazine was associated with a statistically significant reduction in tic severity compared with placebo as measured by YGTSS (MD = -0.61; 95% CI: -1.15 to -0.07; p = 0.039), with no observed heterogeneity (I2 = 0%). No statistically significant differences were observed for TS-CGI, TS-PGII, C&A-GTS-QOL, or depressive symptoms. The risk of adverse events did not differ significantly between deutetrabenazine and placebo (RR = 1.18; 95% CI: 0.62 to 2.26; p = 0.39). Conclusions:Deutetrabenazine demonstrates a modest but statistically significant reduction in tic severity in patients with Tourette syndrome, with a favorable safety profile. However, improvements in tic severity did not translate into significant benefits in global clinical impression, quality of life, or depressive symptoms. These findings support the role of deutetrabenazine as a potential adjunctive treatment for selected patients, while underscoring the importance of multimodal management strategies and further long-term studies.
Background:Tramadol is a widely used analgesic with a unique dual mechanism of action, combining weak μ-opioid receptor agonism with inhibition of norepinephrine and serotonin reuptake. It is frequently prescribed for various acute and chronic pain conditions. Evaluating prescribing trends can provide valuable insight into clinical practice patterns and inform institutional pain management strategies and policy development. Objective:To assess tramadol prescribing patterns over a one-year period in a university-based health system and compare them to overall opioid prescribing. Methods:A retrospective review was conducted using electronic medical record (EMR) data from January 1, 2024, to December 31, 2024. The number of tramadol prescriptions was quantified quarterly and compared to the total number of opioid prescriptions (including tramadol) during the same period. No identifiable patient information was collected. Results:A total of 17,660 tramadol prescriptions were written in 2024. Quarterly breakdowns were: Q1 - 4,347; Q2 - 4,382; Q3 - 4,369; Q4 - 4,562. Overall, tramadol prescriptions accounted for 25.9% of the 68,212 total opioid prescriptions written during the year. Conclusion:Tramadol constituted over one-quarter of all opioid prescriptions in this academic medical center. Prescribing remained stable across all quarters, with a slight increase observed in Q4. These findings highlight tramadol's significant role in opioid prescribing practices for acute and chronic pain management.
