The dual orexin receptor antagonist lemborexant (LEM) is approved in multiple countries including the United States, Japan, Canada, and Australia for insomnia treatment in adults. In phase 3 study E2006-G000-303 (Study 303; SUNRISE-2; NCT02952820), LEM provided significant benefit vs placebo (PBO) on subjective sleep outcomes over 6 months and was well tolerated. This post hoc analysis evaluated the effect of LEM on sleep outcome measures and insomnia severity as assessed by the Insomnia Severity Index (ISI) over 6 months in subjects with a lifetime history of depression (DepHx subgroup). We performed this analysis as insomnia in DepHx subjects could be a residual symptom of unresolved depression, and therefore, these subjects may respond differently to insomnia treatment.

Study 303 was a randomized, double-blind, 12 months global study in adults (≥18 years) with DSM-5 insomnia disorder. For 6 months (Treatment Period 1), subjects were randomized to PBO or LEM (5 mg [LEM5]; 10 mg [LEM10]). For the next 6 months (Treatment Period 2; not reported), PBO subjects were rerandomized to LEM and LEM subjects continued their original dose. The inclusion criteria allowed for participation of subjects with a lifetime DepHx, concomitant antidepressant medication use and/or mild depression (maximum Beck Depression Inventory II score of 19). Subjects had a baseline ISI total score (ISI-ts) ≥15.

The Full Analysis Set comprised 949 subjects, including 112 subjects in the DepHx subgroup (PBO, n = 34; LEM5, n = 39; LEM10, n = 39). Baseline median subjective sleep onset latency (sSOL; minutes) was 52.9, 57.1, and 70.7 for PBO, LEM5, and LEM10, respectively. At 6 months, greater median decreases from baseline in sSOL were observed with LEM5 (−21.7) and LEM10 (−40.1) vs PBO (−12.9). Baseline mean subjective sleep efficiency (sSE; %) was 62.2, 59.2, and 62.4 for PBO, LEM5, and LEM10, respectively. At 6 months, greater mean (SD) increases from baseline in sSE were observed with LEM5 (17.2 [18.3]) and LEM10 (20.9 [19.0]) vs PBO (14.9 [15.4]). Baseline mean subjective wake after sleep onset (sWASO; minutes) was 123.7, 151.0, and 132.6 for PBO, LEM5, and LEM10, respectively. At 6 months, greater mean (SD) decreases from baseline in sWASO were observed with LEM5 (−52.7 [69.2]) and LEM10 (−68.8 [81.9]) vs PBO (−46.7 [69.4]). Mean baseline ISI-ts were 18.6, 19.9, and 19.0 PBO, LEM5, and LEM10, respectively. At 6 months, greater mean (SD) decreases from baseline in ISI-ts were observed with LEM5 (−9.1 [6.8]) and LEM10 (−10.0 [5.9]) vs PBO (−7.9 [5.6]). Treatment-emergent adverse event rates in the DepHx subgroup were similar to those in the overall study population.

At 6 months, LEM improved patient-reported sleep outcomes and reduced patient-reported insomnia severity in subjects with DepHx. These results suggest that LEM may be a therapeutic option for patients with insomnia and DepHx.

Eisai, Inc.

Hyponatremia is an electrolyte disorder that can be caused by multiple factors, among which the syndrome of inappropriate antidiuretic hormone secretion (SIAHS) is one of the most frequent causes. Selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressant drugs in all age groups for efficacy, safety, and adverse effects, although they can cause serious and undesirable side effects.

Report of a series of cases of patients with SIAHS secondary to the use of SSRIs.

We report 21 cases of patients between 52 and 76 years of age, of both sexes, undergoing treatment for depressive disorder with SSRI antidepressants and anxiolytics, concomitant with other clinical treatments (ACEI, thiazides, and carbamazepine). Biochemical laboratory and electrocardiogram studies were performed prior to the start of treatment.

In the first weeks (mean = 2.5) after starting psychopharmacological treatment, hyponatremia (mean = 126 mEq/L) was recorded in 9 symptomatic patients, and Inadequate Antidiuretic Hormone Secretion Syndrome (SIAHS) was diagnosed with referral to Nephrology and Endocrinology. The SSRI was withdrawn, achieving normalization of the biochemical values (plasma and urinary sodium, plasma, and urinary osmolarity), psychotherapy was reinforced until the rotation of another antidepressant. The mean time of suspension of the antidepressant was 7.1 days, the time of disappearance of symptoms after the suspension was 4.3 days and the normalization of biochemical values was 21.68 days. Only one case was severe and 5 required hospitalization.

In the cases presented, the SSRI antidepressants were associated with hyponatremia caused by the syndrome of inappropriate antidiuretic hormone secretion. This adverse event was more significant in elderly patients and in those treated with other drugs that cause the disease, such as antineoplastic, diuretic, and antiepileptic drugs, due to synergism between the causative mechanisms.

No funding

The behavioral variant of frontotemporal dementia presents clinical specificities and difficulties for its early diagnosis in the initial stages due to the overlap of symptoms with other psychiatric pathologies. The delay in diagnosis places the subject in a state of vulnerability because the treatment will not be adequate and the alteration in the psycho-functional capacity can expose him to risks.

The objective of this research was to describe the importance at the forensic and health level of the neuropsychological evaluation of social cognition in people with behavioral variant frontotemporal dementia and to correlate the results with the clinical manifestations of the patients.

Forty-five patients with behavioral variant frontotemporal dementia were studied with social cognition tests (Reading the Mind in the Eyes and Faux Pas Tests) and staged with standardized scales (CDR [Clinical Dementia Rating], GDS [Global Deterioration Scale], and the FTD-FRS [Frontotemporal Dementia Rating Scale]). The results were analyzed with descriptive and inferential statistical tests and the current ethical-legal requirements were met (requirement of informed consent, reservation of the identity of the participants, compliance with the GCP-Good clinical practice-, ANMAT provision 6677/10 and adherence to the Ethical Principles derived from the Declaration of Helsinki).

We found a significant prevalence of alterations in social cognition tests, mainly in Faux Pas Test, from the initial stages of the disease, which were correlated with the clinical stage of the patient.

The behavioral variant of frontotemporal dementia is a condition with significant diagnostic complexity in its initial stages that affects decision-making, the type of treatment to be instituted and presents the consequences for the subject and their environment. Early detection with a deep assessment of social tools will provide clinical tools for pharmacological treatment, as well as to know the capacity and safeguard the rights of the subject and implement the necessary support measures. It was confirmed that the alterations in the social cognition tests were correlated with the clinical stage in the FTD-FRS scale and high implication in the results of the Faux Pas Test mainly, and secondarily in the Reading the Mind in the Eyes Test.

No funding

A number of intrinsic (age, gender, physical comorbidities, genetic factors, and ethnicity), and extrinsic factors (diet, concomitant medications, alcohol use, and smoking) influence an individual’s response to psychotropic medications. Data suggest that ethnicity may affect medication efficacy, tolerability, and safety through different pharmacokinetics and pharmacodynamics. Asians have been found to have a high frequency of reduced function of CYP2D6 allele (CYP2D6*10), which contributes to the slower metabolism of some medications compared to other ethnic groups. The previous study has shown East Asians appear to have a clinically relevant decrease in clozapine clearance compared with Caucasians. This review will explore the magnitude of the impact of ethnicity, especially the East Asian population on psychotropic medications such as atypical antipsychotics.

To understand the efficacy, safety, and tolerability of atypical antipsychotics in East Asian ethnicity. To emphasize the importance of ethnicity in clinical practice while offering/prescribing atypical antipsychotic medications.

Several previous studies reported the diverse response to the antipsychotics among different ethnicities secondary to differences in pharmacokinetics and pharmacodynamics. One study revealed White Europeans may require higher doses of therapeutic antipsychotics than Asians and Hispanics. Aripiprazole in Asians had a relatively higher rate of akathesia, and a significantly increased risk of tremor compared to placebo. A significantly increased risk of weight gain and fasting total cholesterol from olanzapine were observed in Japanese patients. Olanzapine was also associated with somnolence and dizziness. Quetiapine XR was associated with a significant increase risk of somnolence and dizziness in Chinese patients.

It is indicated from previous studies antipsychotics respond in various ways in different ethnicity in terms of metabolism, clearance, and adverse effects. Further research could be beneficial on what is clinically most effective dosing of different antipsychotics among different populations including East Asians.

No funding

No funding

No funding

Deutetrabenazine is FDA-approved for the treatment of tardive dyskinesia (TD) in adults. In two 12-week pivotal trials (ARM-TD/AIM-TD), deutetrabenazine significantly improved Abnormal Involuntary Movement Scale (AIMS) scores and was well-tolerated. This post hoc analysis examined the efficacy and safety of long-term deutetrabenazine treatment in TD patients with comorbid psychiatric illness, including schizophrenia/schizoaffective disorder and mood disorders (bipolar/depression/other).

Patients who completed ARM-TD or AIM-TD enrolled in the 3-year, open-label extension (OLE) study. Deutetrabenazine was titrated based on dyskinesia control and tolerability. Change from baseline in total motor AIMS score, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and adverse events (AEs) were analyzed in subgroups by comorbid psychiatric illness.

A total of 337 patients in the OLE study were included in the analysis: 205 patients with schizophrenia/schizoaffective disorder (mean age, 55 years; 50% male; 6.4 years since diagnosis; 92% taking DRA) and 131 patients with mood disorders (mean age, 60 years; 35% male; 4.6 years since diagnosis; 50% taking DRA). At week 145, mean ± SE dose was 40.4 ± 1.1 mg/day for schizophrenia/schizoaffective disorder (n = 88) and 38.5 ± 1.2 mg/day for mood disorders (n = 72). Mean ± SE change from baseline in AIMS score at week 145 was −6.3 ± 0.49 and −7.1 ± 0.58, 56% and 72% achieved PGIC treatment success, and 66% and 82% achieved CGIC treatment success in schizophrenia/schizoaffective disorder and mood disorder patients, respectively. Overall AE incidence (exposure-adjusted incidence rates [incidence/patient-years]) was low: any, 1.02 and 1.71; serious, 0.10 and 0.12; leading to discontinuation, 0.07 and 0.05).

Long-term deutetrabenazine treatment provided clinically meaningful improvements in TD-related movements, with a favorable safety profile, regardless of underlying comorbid psychiatric illness.

Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel

Tardive dyskinesia (TD) is an involuntary movement disorder that can result from exposure to dopamine-receptor antagonists (DRAs). Deutetrabenazine demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores in the 12-week pivotal trials (ARM-TD/AIM-TD). This post hoc analysis assessed the long-term efficacy and safety of deutetrabenazine by baseline DRA use.

Patients who completed ARM-TD or AIM-TD enrolled in the 3-year, open-label extension (OLE) study, with deutetrabenazine dose titrated based on dyskinesia control and tolerability. Change from baseline in total motor AIMS score, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and adverse event (AE) rates were analyzed in subgroups by baseline DRA use.

Of 337 patients in the OLE study, 254 were taking DRAs at baseline (mean age, 56 years; 48% male; 6.0 years since diagnosis) and 83 were not (mean age, 60 years; 31% male; 4.9 years since diagnosis). Mean ± SE dose at week 145 was 39.9 ± 1.0 mg/day in patients taking DRAs (n = 108) and 38.5 ± 1.5 mg/day in patients not taking DRAs (n = 53). At week 145, mean ± SE change from baseline in AIMS score was −6.1 ± 0.43 and −7.5 ± 0.71; 64% and 62% achieved PGIC treatment success; and 69% and 81% achieved CGIC treatment success, respectively. Overall AE incidence was low (exposure-adjusted incidence rates [incidence/patient-years]: any, 1.08 and 1.97; serious, 0.10 and 0.12; leading to discontinuation, 0.06 and 0.05).

This analysis suggests that deutetrabenazine for long-term treatment of TD is beneficial, with a favorable safety profile, regardless of concomitant DRA use.

Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality. Hyperlipidemia and vascular subinflammation play critical roles in the pathogenesis of atherosclerosis. Patients with Major Depressive Disorder (MDD) are at higher risk for ASCVD and current antidepressant therapies may carry ASCVD risks. REL-1017 is a novel NMDAR channel blocker which showed rapid, robust, and sustained antidepressant effects, currently in Phase 3 clinical trials for MDD.

We analyzed total cholesterol (TC), triglycerides (TG), Proprotein Convertase Subtilisin/Kexin 9 (PCSK9), and high-sensitivity C-reactive protein (hs-CRP) from patients enrolled in a Phase-2, multicenter, randomized, double-blind, placebo-controlled, 7-day, 3-arm trial to assess safety, tolerability, pharmacokinetics, and efficacy of REL-1017. Patients were randomized in a 1:1:1 ratio to either placebo, REL-1017 25 mg QD, or REL-1017 50 mg QD. TC, TG, PCSK9, and hs-CRP levels were measured in patients at baseline, day 7 and day 14, 7 days after treatment discontinuation. 6 out of 21 (28% of patients), 6 out of 16 (37%), and 1 out of 19 (5%), were under statin therapy in the placebo, REL-1017 25 and 50 mg groups, respectively.

At baseline, day 7, day 14 TC levels (mg/dL) were 117.8 ± 30.8, 124.7 ± 34.1, 114.2 ± 18.1; 123.7 ± 59.3, 119.0 ± 28.1, 115.1 ± 14.8; 113.9 ± 22.9, 118.6 ± 29.5, 115.8 ± 25.5 for placebo (n = 21), REL-1017 25 mg (n = 16) and REL-1017 50 mg (n = 19), respectively. Considering the subgroup not on statins, TC levels were 127.5 ± 28.6, 134.2 ± 35.0, 117.8 ± 14.8; 131.0 ± 71.7, 121.1 ± 32.9, 118.6 ± 15.4; 115.5 ± 22.1, 121.4 ± 27.1, 119.0 ± 21.9 for placebo (n = 15, 72% of patients), REL-1017 25 mg (n = 10, 63%) and REL-1017 50 mg (n = 18, 95%), respectively. TG were 57.0 ± 25.6, 55.7 ± 20.0, 58.0 ± 34.1; 62.7 ± 52.1, 56.0 ± 31.0, 59.5 ± 32.6; 48.5 ± 25.3, 50.2 ± 18.4, 55.1 ± 21.9 for placebo (n = 21), REL-1017 25 mg (n = 16) and REL-1017 50 mg (n = 19), respectively. Considering the group not on statins, TG were 52.9 ± 27.6, 55.7 ± 23.1, 51.3 ± 26.8; 70.6 ± 63.3, 57.6 ± 38.9, 65.2 ± 38.9; 47.4 ± 25.4, 48.9 ± 17.9, 52.6 ± 19.5 for placebo (n = 15), REL-1017 25 mg (n = 10), and REL-1017 50 mg (n = 18), respectively. Levels of PCSK9, a key player of LDL cholesterol levels, significantly (P < .05) increased from baseline to day 7 and did not further change by day 14 for placebo, with similar results for REL-1017 25 or 50 mg groups, suggesting fluctuations unrelated to treatment. A total of 30% of the patients had hs-CRP plasma levels higher than 2 mg/L, thus potentially associated with a higher incidence of CV events. However, 7 days of treatment with REL-1017 did not alter hs-CRP plasma levels, neither at 25 mg/day nor at 50 mg/day. In summary, REL-1017 of 25 or 50 mg for 7 days did not affect TC, TG, PCSK9 and hs-CRP levels.

A 7-day treatment course with REL-1017 did not significantly alter TC, TG, PCSK9, or hs-CRP, suggesting the absence of detrimental effects on ASCVD risk. These data should be confirmed in longer and larger trials.

Relmada Therapeutics, Inc.

No funding

Deviant cognitive control performance is implicated in Attention-Deficit-Hyperactivity-Disorder (ADHD). It is also conjectured to be a potential diagnoser and differentiator between the Inattentive and Hyperactive-Impulsive ADHD types. Reliable measures have not been established due to the variation in published results.

We performed a systematic review and meta-analysis of the literature published up to May 2021 with data on electrophysiological correlates, that is, EEG correlates of cognitive control monitoring (error-related negativity, ERN; error positivity, Pe; correct-response negativity, CRN) in ADHD patients and the efficiency of EEG recordings in differentiating between ADHD types. Multiple databases including PubMed, Scopus, Google Scholar, bioRxiv, and medRxiv were searched for eligible literature. Meta-Analyses were performed through statistical tools provided by the open-source metafor package and separately using the Hedge’s g standardized mean differences.

Meta-Analyses were performed on a shortlisted set of 125 studies involving 7248 participants. To avoid extraneous variables, the sex ratio was maintained at 50:50, and the age groups of participants were equally varied between early teenagers (12-15 years), late teenagers (15-18 years), young adults (21-25), and middle-aged adults (29-37). The ADHD-afflicted group showed reduced ERN (Hedge’s g = −0.58 [CIs: −0.76, −0.35]) and reduced Pe (Hedge’s g = −0.65 [CIs: −0.79, −0.44). The Hyperactive-Impulsive ADHD types (2574/7248 participants) showed an increased CRN (Hedge’s g = 0.68 [CIs: 0.71, 0.29]), while the Inattentive ADHD Types (4674/7248 participants) showed a slightly reduced CRN (Hedge’s g = −0.25 [CIs: −0.31, −0.28]. The prevalence of counted task errors was higher in the teenagers’ group (12-18 years) than the adults’ group (21-37 years).

Results suggest that EEG Pattern Markers (especially Pe and CRN) can act as strong differentiators/diagnosers between the Hyperactive-Impulsive and Inattentive ADHD types. In further development, deep learning classifiers can be built for ADHD types using EEG Markers as Features and statistical values as weights.

Pranjali Awasthi is a 14-year-old researcher working on the overlap of neuroimaging and machine learning at the Neural Dynamics of Control Lab, FIU. She is an avid speaker on topics of AI Awareness and Ethics. Here is a recent feature by the Analytics India Magazine: https://analyticsindiamag.com/how-this-15-year-old-created-a-research-career-in-machine-learning.

New York Institute of Technology MRGA Committee

All current antipsychotics have direct dopamine (DA) D2 receptor activity, which is associated with problems such as dysphoria, EPS, or prolactin elevation. Muscarinic receptor agonists have shown antipsychotic-like activity across preclinical models and clinical trials. This poster reviews preclinical evidence as to how muscarinic receptor agonists, such as the M1/M4 preferring agonist xanomeline, might have clinically relevant antipsychotic effects.

Highlight the novel mechanisms through which muscarinic receptor agonists are associated with antipsychotic effects without having any direct dopaminergic D2 receptor activity.

The muscarinic receptor family is composed of 5 G protein-coupled receptors (GPCRs). One of the leading hypotheses explaining the antipsychotic activity of muscarinic receptor agonists is preclinical studies of muscarinic receptor modulation of those DA circuits associated with psychosis. Both M1 and M4 receptors are expressed in DA neural circuits implicated in psychosis, and provide unique regulation of these circuits. Xanomeline has both functional M1 and M4 receptor agonist activity, and shows robust antipsychotic-like effects in several animal models that require the presence of functional M1 and M4 receptors. M4 receptors are autoreceptors on cholinergic neurons that regulate DA circuits in two locations: ventral tegmental area (VTA) and nucleus accumbens (NAc). Cholinergic-rich neurons from the hindbrain at the VTA, where they release acetylcholine (ACh) into DA-rich synaptic spaces. M4 autoreceptors are present on these neurons, and their activation reduces ACh release and lowers ambient synaptic ACh concentrations, leading to reduced DA cell firing. Cholinergic interneurons residing in the NAc also express M4 autoreceptors. These ACh interneurons regulate ACh release with M4 activation also turning off ACh release. Therefore, M4 receptors serve as DA regulators at VTA and NAc, both key sites for dopamine’s role in psychotic processes. M1 receptors regulate DA circuits in a different, “top down” manner. M1 receptors are found on cortical inhibitory interneurons. When activated, inhibitory drive onto excitatory output neurons is enhanced, which leads to reduced excitatory tone to VTA DA neurons.

Over the last 25 years, a growing body of evidence has shown potential for muscarinic receptor agonists to become a new class of medicines with potent antipsychotic activity. Preclinical data at micro-and macro-circuit levels suggest that the M1 and M4 receptor subtypes are most relevant in the regulation of DA circuits. The antipsychotic effects of muscarinic agonists effects may arise from influencing these key muscarinic receptor subtypes that are integral to the regulation of DA neural circuits. In summary, there has been great progress in understanding the potential for muscarinic receptor agonists for the treatment of psychosis.

Karuna Therapeutics

As a result of COVID-19, patients and clinicians rapidly shifted to telehealth. An observational survey study, Real-World Tele-Health Evaluation of Tardive Dyskinesia (TD) Symptoms Communication/Observation Procedure Evaluation in Outpatient Clinical Settings (TeleSCOPE), was conducted to better understand how this shift affected the evaluation of drug-induced movement disorders (DIMDs), including TD.

Twenty-minute online quantitative surveys were conducted with neurology and psychiatry specialists (physicians and advanced practice providers) who met the following criteria: ≥3 years of practice with ≥70% of time spent in a clinic; prescribed a vesicular monoamine transporter 2 (VMAT2) inhibitor or benztropine for DIMD at least once in the past 6 months; and conducted telehealth visits with ≥15% of their patients from December 2020 to January 2021.

Respondents included 277 clinicians (neurology = 109, psychiatry = 168). Telehealth visits increased after COVID-19, with significantly greater increases in psychiatry vs neurology: phone (38% vs 21%); video (49% vs 42%). Across both specialties, top drivers/prompts for further DIMD evaluation were as follows: mention of tics or movements by family members or others (86%); trouble with gait, falls, walking, or standing (82%); difficulty swallowing or eating (74%); and difficulty writing, using phone, computer (71%). However, in the 6 months prior to June 2021, virtual evaluation, diagnosis, and monitoring of patients were challenging. For both specialties, many at-risk patients (ie, taking a dopamine receptor blocking agent) were not evaluated for DIMDs via video-based visits (psychiatry = 45%, neurology = 70%) or phone-only visits (psychiatry = 76%, neurology = 91%). Clinicians listed evaluation of gait/falls/walking/standing as the most challenging aspect of virtual assessment for phone-only visits (psychiatry = 53%, neurology = 57%) and video-based visits (psychiatry = 26%, neurology = 31%). Additional challenges included limited access to computers, insufficient training for clinicians and staff, and greater difficulty obtaining reimbursements (especially for complex telehealth visits). Patients without a participating caregiver, along with lower functioning patients, were at the highest risk of a missed DIMD diagnosis.

During the COVID-19 pandemic, telehealth significantly reduced clinicians’ ability or willingness to evaluate, diagnose, and monitor DIMDs. Clinicians stated multiple factors increased the risk of a missed or incorrect diagnosis. Challenges to optimal telehealth effectiveness included lack of patient access to computers, need for more clinician/staff training, lack of awareness of coverage, need for sufficient fee reimbursement. In-person evaluation continues to be the gold standard for assessing and treating DIMDs. However, if telehealth is necessary, the use of specific questions and directions is recommended for better communication and more accurate assessments.

Neurocrine Biosciences, Inc.

The current study involved decades of research and a Systematic Literature Review.

Six hundred and seventy-two former prisoners were interviewed, shortly upon release from incarceration. Multiple variables experienced while incarcerated were reviewed. Animal models around overcrowding and sustained levels of stress were also considered. The neurological underpinnings and relatedness to the concept of hypervigilance, thought to be an effective survival technique and PTSD were comprehensively researched. Hypervigilance is a well-regarded survival technique that is likened to the marine in a forward foxhole who hears a twig snap in the middle of the night and responds directly and decisively. The loading placed on the neuronal pathways and related brain regions is seen as a precursor to PTSD and otherwise burdensome to the overstimulated nervous system attempting to maintain an emotional equilibrium.

A particular area of inquiry was around the presence of early parental/adult absence, recognized as a precursor to Complex PTSD (see World Health Organization ICD 11). But not delineated in DSM 5 (American Psychiatric Association). Significant rates of PTSD symptoms were identified in individuals experiencing early developmental trauma. All subjects met the criteria for Subthreshold PTSD at a minimum, and others (193) Posttraumatic Stress Disorder. Complex PTSD was descriptive of the findings of 179 of 193 subjects diagnosed with PTSD. These findings suggest that preexisting subthreshold Complex PTSD prior to incarceration predicts the development of Complex PTSD while incarcerated.

The social cost of American Corrections incubates PTSD and subthreshold PTSD, releasing to society individuals more at risk to themselves and society than prior to the Correctional experience is incalculable. A philosophical reconsideration of the American Correctional experience at this time is long overdue. This philosophy is grounded on the concepts of Incapacitation; Punishment and Deterrence, v the European model generally of Rehabilitation and Reintegration.

No funding

No funding

Delusions, such as belief in conspiracy theories (CT), exist on a continuum representing clinical and subclinical populations. Some individuals are more susceptible to CT belief. Social media has allowed conspiracy theories to spread relatively unchecked. We report a previously healthy male hospitalized for delusions and reckless behavior. We analyze potential risk factors affecting this patient.

A 54-year-old Caucasian male presents with worsening persecutory and grandiose delusions over the past 6 months. An active participant in conspiracy theory-related online forums, he believes he has sensitive information regarding the Federal Bureau of Investigation. He endorses delusions of surveillance and tracking by family members, citing these concerns prompted him to rely on public transportation and prepaid cell phones, and even trespassing on U.S. Navy property. On evaluation, the patient prompts the team to review his collection of classified evidence claiming government involvement in a global sex trafficking operation. When challenged, the patient becomes argumentative, citing social media sources. He shows no evidence of overt depression, mania, or post-traumatic stress. The patient’s level of functioning is reduced but not markedly impaired and he maintains employment. CBC, CMP, noncontrast head CT, CXR, and EKG are unremarkable. Cannabinoids are found on UTOX. He has a Positive and Negative Syndrome Scale score of 23/49 (positive), 10/49 (negative), and 31/112 (General Psychopathology), and Brown Assessment of Beliefs Scale score of 19/24.

Conspiracy theories (CT) are the result of an altered perception of reality. Belief in CT correlates with negative social, health, and civic outcomes, including increased tolerance to violent and antisocial behavior. Magical thinking, trait Machiavellianism, narcissistic traits, and primary psychopathy have been shown to be significant positive predictors of belief in CT. Individuals with maladaptive perception/attribution styles may also develop cognitive distortions. Finally, intuitive thinking, as opposed to analytical thinking, is associated with CT beliefs. Social or political crises may incite elevated emotional responses, causing increased popularity of CT during times of major social or political change. Identifying these traits may be useful for clinicians providing interventions for patients with CT ideation. This patient’s presentation with delusions and nonimpaired functioning may be explained by deficits in objective reasoning as a result of maladaptive cognitive and affective response mechanisms, rather than psychotic illness.

Conspiracy theories are generated as a consequence of social and political discontent and can result in a clinically significant impact on mental health and well-being. Patients with narcissistic traits and primary psychopathy are more likely to demonstrate impaired judgment related to CT.

No funding

Subdural hematoma (SDH) is a diagnosis characterized by a wide array of symptoms. In the absence of apparent neurological deficits, behavioral abnormalities alone make SDH a difficult diagnosis. Chronic subdural hematoma presents with alteration in sensorium, raised intracranial pressure, and motor weakness. Depending on the degree of cerebral compression and location, convulsions or personality changes can also be seen. Common psychiatric manifestation with CSDH is a cognitive impairment which may mimic delirium or dementia. We report a case of an elderly male with no prior psychiatric history who developed insidious psychotic symptoms.

Patient is an 83-year-old male with no prior psychiatric history brought in by police for making suicidal and homicidal threats to family members with increasingly aggressive behavior. He later endorsed a 3-week history of depression symptomatology related to a recent motor vehicle accident. Prior history of chronic myeloid leukemia, hypertension, and hypercholesterolemia with an unremarkable family and social history. On evaluation, the patient was uncooperative, irritable, and verbally aggressive. Laboratory testing, EKG, and MMSE were performed and grossly normal. Noncontrast head CT demonstrated bilateral chronic subdural hematomas. The patient refused neurology consult and proposed interventions but was compliant with risperidone 0.5 mg twice daily. His delusions and aggressive behavior improved drastically and was discharged.

Chronic Subdural Hematoma (CSDH) is amongst the most common neurosurgical conditions in the United States with an incidence of 10 per 100,000 annually. Risk factors for CSDH include age, male gender, trauma, coagulopathy, chronic alcoholism, vascular malformations, and metastatic tumors. Noncontrast head CT is diagnostic for CSDH, but MRI should be considered in acute ischemia, infection, or dural-based neoplasms. The DSM-5 criteria for Psychotic Disorder Due to Another Medical Condition include prominent delusions that are the direct pathophysiological consequence of another medical condition and cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. The diversity in symptoms is correlated with increased ICP caused primarily by the ruptured bridging veins. Traditional management of CSDH has been trephination, however, nonsurgical options are available including high-dose corticosteroids to inhibit the formation of new blood vessels thereby reducing mortality. Recurrence is possible and may constitute surgical obliteration of the subdural space.

Chronic subdural hematoma should be considered in the differential diagnosis of new-onset psychosis, particularly in patients with other risk factors. A thorough history and physical are vital to ascertain this diagnosis and noncontrast head imaging is confirmatory. Management varies based on the etiology of the CSDH.

No funding

The COVID-19 pandemic has greatly affected how physicians, including child and adolescent psychiatrists, practice. A major shift came in the form of telehealth, in which patients attend clinic appointments online.

The objective of this study was to identify the advantages and disadvantages of the telepsychiatry care delivery system and to devise future strategies to resolve drawbacks to improve patient and caregiver satisfaction.

A proposal was approved by the University of Missouri-Columbia Internal Review Board to conduct this study. One hundred patients were randomly selected for the study questionnaires. To understand patient satisfaction with telehealth and work toward improvements, this study conducted comparative survey research with 50 patients seen virtually and 50 patients seen in-person. Identical survey questions were filled out by patients and their respective guardians. The survey’s first question asked which setting was preferred during the COVID-19 crisis and was followed by free-response questions prompting responses about what they liked and disliked about telehealth and in-person visits.

Of the 50 patients seen virtually, 72% indicated a preference for telehealth, 14% preferred in-person, and 14% had no preference. These patients stated they preferred telehealth because it was convenient, required no travel and required fewer absences from school or work. A total of 28% of patients listed safety from exposure to COVID-19 as a reason they liked telehealth. Over half of these patients reported no complaints with telehealth, the most common issue according to patients seen virtually was internet connectivity and technology problems. A total of 64% of in-person patients reported a preference for in-person visits during the COVID-19 crisis. Similar to virtual patients, convenience was the most popular advantage of telehealth and personal connection was the most common disadvantage. The second most common complaint regarding telehealth and the highest reported advantage of in-person visits is the element of personal connection. A total of 16% of patients seen virtually and 24% of patients seen in-person reported more accurate assessment advantage of in-person care. These patients listed concerns about body language, vital signs, and other physical symptoms.

With telehealth as a seemingly permanent aspect of medicine, the field of psychiatry must adapt. Expansion of broadband and increasing affordability of high-speed internet connection are practical solutions to technological issues with telehealth. For patients preferring to be seen virtually, a recommendation can be made to have at least the first visit in-person to establish a personal relationship. Vital signs can be checked at home with proper training. Telepsychiatry is likely to continue to be a part of our care delivery system. To that end, we must be vigilant and develop better strategies to improve the quality of patient care and patient satisfaction.

No funding

Lamotrigine is an antiepileptic drug of the phenyltriazine class with inhibitory effects on voltage-sensitive sodium channels, leading to an inhibition in the release of glutamate and resulting in a general inhibitory effect on cortical neuronal function. Lamotrigine is also a weak dihydrofolate reductase inhibitor. The drug is approved by the U.S. Food and Drug Administration for maintenance treatment of bipolar type I disorder in adults. There have been reports of hematologic adverse effects with lamotrigine therapy. This case report describes a 16-year-old female who developed profound anemia while on lamotrigine therapy.

Ms. X was a 16-year-old African-American female with sickle cell trait and mood disorder referred by the Division of Youth Services (DYS). Her medication regimen included lamotrigine 200 mg in the morning, aripiprazole 5 mg in the morning, and mixed amphetamine salts extended-release 30 mg in the morning. While at DYS, she developed fatigue and headaches with exertion. Her blood work detected a very low hemoglobin level of 3.1 g/dL and a very low hematocrit of 10.9%. Her MCV, MCH, and MCHC were within the normal range. The remainder of her blood count and other labs were within normal limits. The patient’s blood pressure was 105/70 mm Hg and her pulse was 109. The patient was sent to the local emergency room immediately; upon hospital admission, she received 4 units of packed red blood cells via transfusion.

After a blood transfusion, the patient’s hemoglobin level improved to 9.7 g/dL. The patient’s symptoms had improved significantly; her headaches and fatigue with exertion were gone. It was suspected that her profound anemia was induced by lamotrigine. She was discharged from the hospital with instructions to stop lamotrigine and visit a hematology specialist. Several weeks later, she underwent a hematologic evaluation, including a bone marrow biopsy and genetic testing, which were unremarkable. Her hemoglobin level remained stable.

The patient’s anemia resolved after the discontinuation of lamotrigine. The patient was followed for 1 year with blood work performed every few months. Her hemoglobin level did not drop further and in fact slowly increased to 13.9 g/dL spontaneously over the next year. In the literature, there have been reports of blood dyscrasias that may or may not be associated with hypersensitivity syndrome in patients who take lamotrigine. Considering hematologic adverse effects, it may be prudent to consider a baseline blood count before starting lamotrigine and repeat this test 3 to 6 months after initiation. It remains unclear whether lamotrigine use with a background of sickle cell trait in this patient put her at an increased risk of profound anemia. Further studies are required to explore the effects of this commonly used medicine.

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How can psychiatrists best provide care in complex, sometimes overwhelming disasters? COVID-19 strained every aspect of health care to the breaking point, from finances to pharmaceutical supply lines. We can expect more challenges to prescribing in the future, as shown by recent hurricanes in Puerto Rico, fires in California, and ice storms in Texas. When medications become scarce or inaccessible, then clinicians need to make difficult prescribing decisions. We suggest that a culture of deprescribing, a systematic approach to reducing or simplifying medications, could be applied to a wide variety of crises. Deprescribing is defined as the planned reduction of medications to improve patient health or to reduce side effects (see deprescribing.org). It has been used to reduce polypharmacy in geriatric and other complex populations. It provides evidence-based guidance for phasing out many classes of medications. It is part of the larger program to reduce waste in health care and to make pharmacy more rational. Disasters and resource scarcity, however, require a different approach. In contrast to routine care focused on individual patients, crisis standards of care (CSC) shift the clinical focus to the community. Instead of deprescribing guidelines for individual clinicians, CSC deprescribing would be national policies addressing shortages of important medications. We did a scoping review looking for studies of deprescribing in a crisis.

We extracted 1340 references in Google Scholar 2016 to 2021 using (deprescribing) AND (disaster OR crisis OR climate OR pandemic OR supply lines). A scan of texts found 160 references matching our criteria, and only 19 of them addressed deprescribing as a strategy to strengthen health systems or providers in an emergency. Most of those were related to scarce supplies during COVID, and a few addressed the carbon impact of medications. We also reviewed related literatures on medication supply chain vulnerabilities, WHO Essential Medicines, and healthcare rationing.

Deprescribing gained attention during the COVID pandemic, responding to both disrupted supply lines and improving patient safety. Writers concerned with climate change support deprescribing to reduce the carbon impact of medications. Deprescribing as crisis policy could help streamline national stockpiles, supply chains, and manufacturing. Education could make deprescribing second nature for clinicians, potentially decreasing stress and increasing flexibility in future emergencies. Barriers to deprescribing generally include cultural inertia, industry lobbyists, education, and malpractice fears. In a crisis, deprescribing guidelines could provide clinicians with confidence and flexibility while conserving scarce resources. Research is needed to evaluate deprescribing guidelines for crises, especially ensuring equity in how they reduce polypharmacy and save money.

No funding