A Single-Blind, Placebo Controlled Trial of Triple Beaded Mixed Amphetamine Salts in DSM-5 Adults With ADHD Assessing Effects Throughout the Day.

OBJECTIVE: To examine the effects of triple beaded mixed amphetamine salts (TB MAS) on ADHD and executive dysfunction symptoms throughout the day in adults with DSM-5 ADHD. METHOD: This was a 6 week, single-blind, placebo-lead in trial of TB MAS (12.5-37.5 mg/day); all participants received 2 weeks of single-blind placebo); one individual was a placebo responder and was discontinued. One of these 18 dropped after 1 week on 12.5 mg/day, while all others completed the trial and received 37.5 mg/day TB MAS. RESULTS: There were significant effects of TB MAS on all clinical measures, including investigator overall symptoms (AISRS); self-report overall (ASRS), time-sensitive ADHD (TASS) scores throughout the day, impairment (CGI) and executive function scores (BRIEF-A). TB MAS was generally well tolerated. CONCLUSIONS: This study extends prior findings of TB MAS to adults with DSM-5 ADHD; it further re-validates findings of efficacy of TB MAS throughout the day.

Pilot Study of Prism EFP NeuroFeedback in Adult ADHD.

OBJECTIVE: A pilot study to preliminarily examine the effects of Prism EFP NeuroFeedback (NF) in adult ADHD. METHOD: Prism EFP NF is a form of NF specifically designed to target emotional dysregulation (ED) through down regulation of amygdala activity. Prism EFP NF has been shown to improve other disorders with significant ED. Nine participants with adult ADHD received an open trial of Prism EFP NF consisting of fifteen sessions over 8 weeks; all completed at least 5 weeks of treatment with seven completing all 8 weeks. Outcomes were assessed by change in ADHD symptoms from baseline to End of Treatment. RESULTS: About two-third reduction was seen in total DSM ADHD symptom scores (primary outcome measure) with improvement observed in all other clinical measures. No significant adverse events were seen. CONCLUSION: This preliminary trial found substantial effects of Prism EFP NF on ADHD/ED symptoms and global impairment.

Updates in Pharmacologic Strategies in Adult Attention-Deficit/Hyperactivity Disorder.

Attention-deficit/hyperactivity disorder (ADHD) significantly worsens quality of life and long-term functional outcomes in adults. Individual impairments in adults with ADHD can be further contextualized within considerable costs to society at large. Food and Drug Administration (FDA) approved stimulants and nonstimulant medications can significantly improve ADHD symptoms in adults. In the past 2 decades, the United States FDA has expanded approval of pharmacotherapeutic options for adult ADHD. However, limitations still persist in available psychotropics for certain patient populations such as those with comorbid substance use or cardiovascular illness. Clinicians therefore must appreciate several ongoing investigations into medications with unique mechanisms of action. This article reviews the current FDA approved and emerging medication options while providing guidelines for pharmacologic management of adult ADHD.

Tracking Multisite Seizure Propagation Using Ictal High-Gamma Activity.

PURPOSE: Spatial patterns of long-range seizure propagation in epileptic networks have not been well characterized. Here, we use ictal high-gamma activity (HGA) as a proxy of intense neuronal population firing to map the spatial evolution of seizure recruitment. METHODS: Ictal HGA (80-150 Hz) was analyzed in 13 patients with 72 seizures recorded by stereotactic depth electrodes, using previously validated methods. Distinct spatial clusters of channels with the ictal high-gamma signature were identified, and seizure hubs were defined as stereotypically recruited nonoverlapping clusters. Clusters correlated with asynchronous seizure terminations to provide supportive evidence for independent seizure activity at these sites. The spatial overlap between seizure hubs and interictal ripples was compared. RESULTS: Ictal HGA was detected in 71% of seizures and 10% of implanted contacts, enabling tracking of contiguous and noncontiguous seizure recruitment. Multiple seizure hubs were identified in 54% of cases, including 43% of patients thought preoperatively to have unifocal epilepsy. Noncontiguous recruitment was associated with asynchronous seizure termination (odds ratio = 19.7; p = 0.029). Interictal ripples demonstrated greater spatial overlap with ictal HGA in cases with single seizure hubs compared with those with multiple hubs (100% vs. 66% per patient; p = 0.03). CONCLUSIONS: Ictal HGA may serve as a useful adjunctive biomarker to distinguish contiguous seizure spread from propagation to remote seizure sites. High-gamma sites were found to cluster in stereotyped seizure hubs rather than being broadly distributed. Multiple hubs were common even in cases that were considered unifocal.

Screening for Adult ADHD.

PURPOSE OF REVIEW: This review paper aims to update readers on the importance of screening for attention-deficit/hyperactivity disorder (ADHD) in adults and to provide a primer on how best to screen and diagnose this condition in an efficient and reliable manner. RECENT FINDINGS: The ASRS Screening Scale was updated in 2017 to reflect the changes made to identify ADHD based on the DSM-5 criteria and to reflect our understanding that adult ADHD is characterized by executive functioning deficits that are not explicitly reflected in the DSM-5 criteria. The use of the ASRS Screening Scale improves the clinician's ability to rapidly identify adult patients who require a comprehensive evaluation to diagnose ADHD and/or other comorbid psychiatric conditions. The scale has been validated for use in both the general population and in the ADHD specialty treatment population, which supports its use by both general clinicians and mental health clinicians. Identification of adult ADHD is critical due to the profound personal, familial, and societal costs associated with this condition.

Dimensional structure of posttraumatic stress disorder symptoms after cardiac arrest.

BACKGROUND: Considerable evidence suggests that posttraumatic stress disorder (PTSD) is a heterogeneous construct despite often being treated as a homogeneous diagnostic entity. PTSD in response to cardiac arrest is common and may differ from PTSD following other medical traumas. Most patients are amnesic from the cardiac event, and it is unclear if and how certain PTSD symptoms may manifest. METHODS: We examined the latent structure of PTSD symptoms in 104 consecutive cardiac arrest survivors who were admitted to Columbia University Medical Center. PTSD symptoms were assessed via the PTSD Checklist-Specific at hospital discharge. We performed a confirmatory factor analysis (CFA) to compare 4-factor dysphoria, 4-factor numbing, and 5-factor dysphoric arousal models of PTSD with our data. RESULTS: The CFA showed that each of the models had good fit. We chose the 4-factor numbing model (χ2 (113) = 151.59, p < .01, CFI = 0.94, RMSEA = 0.057, 90% CI: [0.032, 0.081]) as most representative of the data, after considering a between-factor correlation of 0.99 in the 5-factor dysphoric arousal model, and greater fit statistics than the 4-factor dysphoria model. LIMITATIONS: Certain factors were defined by only two items. Additionally, PTSD was assessed at discharge (median = 21 days); those assessed before 30 days could be displaying symptoms of acute stress disorder. CONCLUSIONS: Our findings suggest that PTSD symptoms after cardiac arrest are best represented by a 4-factor numbing model of PTSD. PTSD assessment and intervention efforts for cardiac arrest survivors should consider the underlying dimensions of PTSD.

Posttraumatic stress and depressive symptoms characterize cardiac arrest survivors' perceived recovery at hospital discharge.

OBJECTIVE: To test the hypothesis that posttraumatic stress and depressive symptoms, not cognitive or functional impairment, are associated with cardiac arrest survivors' negative recovery perceptions at hospital discharge. METHODS: Prospective observational cohort of cardiac arrest patients admitted between 9/2015-5/2017. Survival to discharge with sufficient mental status to complete a psychosocial interview was the main inclusion criterion. Perceived recovery was assessed through the question, "Do you feel that you have made a complete recovery from your arrest?" The following measures were examined as potential correlates of perceived recovery: Repeatable Battery for Assessment of Neuropsychological Status, Modified Lawton Physical Self-Maintenance Scale, Barthel Index, Modified Rankin Scale, Cerebral Performance Category, Center for Epidemiological Studies-Depression (CES-D), and PTSD Checklist-Specific (PCL-S). Logistic regression evaluated associations between perceived recovery and potential correlates of recovery. RESULTS: 64/354 patients (58% men, 48% white, mean age 52 ±â€¯17) were included. 67% (n = 43) had a negative recovery perception. There were no differences among patients' cognitive and functional domains. In individual models, patients with higher PCL-S and CES-D scores were more likely to have a negative recovery perception after adjusting for age and gender (OR: 1.2, 95% CI [1.1, 1.4], p = 0.003) and (OR: 1.1, 95% CI [1.0, 1.1], p = 0.05). CONCLUSIONS: Within one month after a cardiac arrest event, survivors' negative recovery perceptions are associated with psychological distress.

Laser ablation is effective for temporal lobe epilepsy with and without mesial temporal sclerosis if hippocampal seizure onsets are localized by stereoelectroencephalography.

OBJECTIVE: Selective laser amygdalohippocampotomy (SLAH) using magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is emerging as a treatment option for drug-resistant mesial temporal lobe epilepsy (MTLE). SLAH is less invasive than open resection, but there are limited series reporting its safety and efficacy, particularly in patients without clear evidence of mesial temporal sclerosis (MTS). METHODS: We report seizure outcomes and complications in our first 30 patients who underwent SLAH for drug-resistant MTLE between January 2013 and December 2016. We compare patients who required stereoelectroencephalography (SEEG) to confirm mesial temporal onset with those treated based on imaging evidence of MTS. RESULTS: Twelve patients with SEEG-confirmed, non-MTS MTLE and 18 patients with MRI-confirmed MTS underwent SLAH. MTS patients were older (median age 50 vs 30 years) and had longer standing epilepsy (median 40.5 vs 5.5 years) than non-MTS patients. Engel class I seizure freedom was achieved in 7 of 12 non-MTS patients (58%, 95% confidence interval [CI] 30%-86%) and 10 of 18 MTS patients (56%, 95% CI 33%-79%), with no significant difference between groups (odds ratio [OR] 1.12, 95% CI 0.26-4.91, P = .88). Length of stay was 1 day for most patients (range 0-3 days). Procedural complications were rare and without long-term sequelae. SIGNIFICANCE: We report similar rates of seizure freedom following SLAH in patients with MTS and SEEG-confirmed, non-MTS MTLE. Consistent with early literature, these rates are slightly lower than typically observed with surgical resection (60%-80%). However, SLAH is less invasive than open surgery, with shorter hospital stays and recovery, and severe procedural complications are rare. SLAH may be a reasonable first-line surgical option for patients with both MTS and SEEG confirmed, non-MTS MTLE.

Women have worse cognitive, functional, and psychiatric outcomes at hospital discharge after cardiac arrest.

AIM: To examine gender differences among cardiac arrest (CA) survivors' cognitive, functional, and psychiatric outcomes at discharge. METHODS: This is a prospective, observational cohort of 187 CA patients admitted to Columbia University Medical Center, considered for Targeted Temperature Management (TTM), and survived to hospital discharge between September 2015 and July 2017. Patients with sufficient mental status at hospital discharge to engage in the Repeatable Battery for Neuropsychological Status (RBANS), Modified Lawton Physical Self-Maintenance Scale (M-PSMS), Cerebral Performance Category Scale (CPC), Center for Epidemiological Studies Depression Scale (CES-D), and Post-Traumatic Stress Disorder Checklist - Civilian Version (PCL-C) were included. Fisher's exact, Wilcoxon Rank Sum, and regression analysis were utilized. RESULTS: 80 patients (38% women, 44% white, mean age 53 ±â€¯17 years) were included. No significant gender differences were found for age, race, Charlson Comorbidity Index, premorbid CPC or psychiatric diagnoses, arrest related variables, discharge CPC, or PCL-C scores. Women had significantly worse RBANS (64.9 vs 74.8, p = .01), M-PSMS (13.6 vs 10.6, p = .02), and CES-D (22.8 vs 14.3, p = .02) scores. These significant differences were maintained in multivariate models after adjusting for age, initial rhythm, time to return of spontaneous circulation, and TTM. CONCLUSIONS: Women have worse cognitive, functional, and psychiatric outcomes at hospital discharge after cardiac arrest than men. Identifying factors contributing to these differences is of great importance in cardiac arrest outcomes research.

Changes in Neutrophil Count After Antipsychotic Prescription Among a Retrospective Cohort of Patients With Benign Neutropenia.

BACKGROUND: There is a paucity of literature regarding the effect of antipsychotics on absolute neutrophil count (ANC) of patients with benign neutropenia (BN). We evaluated the change in ANC after atypical antipsychotic prescription (excluding clozapine) in a retrospective cohort of 22 patients with BN. METHODS/PROCEDURES: Records of all patients with BN who were prescribed antipsychotics and who had ANC measured before and during antipsychotic treatment were obtained from Bronx VA Medical Center between 2005 and 2015 (inclusive). Twenty-two patients met criteria for inclusion. Individual and group mean ANC were calculated before treatment and during treatment. A paired, two-tailed t test was performed on the group ANC means. RESULTS: The group mean pretreatment ANC was 1.24 ± 0.220 K/cmm, and the mean ANC during the time of antipsychotic prescription increased to 1.40 ± 0.230 K/cmm, with a P value of 0.0045, t value of 3.18, degrees of freedom equal to 21, and 95% confidence interval of 1.30 to 1.49 K/cmm. CONCLUSIONS: There was a statistically significant increase in ANC among our cohort during the time of antipsychotic prescription. All BN patients who were prescribed antipsychotics maintained a stable neutrophil count, with none of the 22 patients with BN in this study developing agranulocytosis during treatment. Although this study is limited by a low patient count as well as other demographic factors, these findings provide initial evidence regarding the safety of prescribing atypical antipsychotics to BN patients. Further studies are needed to replicate these findings and assess for effects of individual medications.

Clinical utility of the list sign as a predictor of non-demyelinating disorders in a multiple sclerosis (MS) practice.

OBJECTIVES: Not all patients referred for evaluation of multiple sclerosis (MS) meet criteria required for MS or related entities. Identification of markers to exclude demyelinating disease may help detect patients whose presenting symptoms are inconsistent with MS. In this study, we evaluate whether patients who present a self-prepared list of symptoms during an initial visit are less likely to have demyelinating disease and whether this action, which we term the "list sign," may help exclude demyelinating disease. METHODS: Using chart review, 300 consecutive new patients who presented for evaluation to a neurologist at a tertiary MS referral center were identified retrospectively. Patients were defined as having demyelinating disease if diagnosed with MS or a related demyelinating condition. RESULTS: Of the 233 enrolled subjects, 157 were diagnosed with demyelinating disease and 74 did not meet criteria for demyelinating disease. Fifteen (8.4%) subjects had a positive list sign, of which 1 patient had demyelinating disease. The 15 subjects described a mean of 12.07 symptoms, and 8 of these patients met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for somatic symptom disorder. The specificity and positive predictive value of the list sign for non-demyelinating disease were 0.99 (95% confidence interval (CI) 0.96-0.99) and 0.93 (95% CI 0.66-0.99), respectively. CONCLUSION: A positive list sign may be useful to exclude demyelinating disease and to guide diagnostic evaluations for other conditions. Patients with a positive list sign also have a high incidence of somatic symptom disorder.

Acute exacerbation of multiple sclerosis presenting with facial metamorphopsia and palinopsia.

We discuss the case of a patient with a known history of relapsing-remitting multiple sclerosis (MS) who presented with the isolated complaint of altered visual perception in the absence of abnormalities on ophthalmological examination. To the best of the authors' knowledge, this is the first documented case of both facial metamorphopsia and palinopsia occurring as the symptoms of demyelinating brain lesions consistent with an acute MS exacerbation. These symptoms appear to be related to active demyelination that either involved the optic radiations in the visual pathway or the visual association area in the temporo-occipital region of the left hemisphere.

Teaching "global mental health": psychiatry residency directors' attitudes and practices regarding international opportunities for psychiatry residents.

OBJECTIVE: The authors surveyed Psychiatry Residency Training Directors' (RTDs') attitudes about the role and feasibility of international rotations during residency training. METHOD: A 21-question survey was electronically distributed that explored RTDs' beliefs about the value, use, and availability of international clinical and research experiences during residency. RESULTS: Of 171 RTDs, 59 (34.5%) completed the survey; 83% of respondents rated the importance of global mental health education as 3-or-above on a scale of 1 (least important) to 5 (most important), but only 42% indicated that such opportunities were made available. The value of such opportunities was thought to lie primarily in professional development and cultural exposure, less so for enhancing core knowledge competencies. Obstacles to such opportunities included lack of accreditation, financial resources, and faculty/administrative support and supervision. CONCLUSION: RTD respondents endorsed the value of international experiences during residency, but their availability and educational impact are not fully supported.

Drug-induced leukoencephalopathy presenting as catatonia.

We discuss the case of a 35-year-old woman who presented with thought impoverishment, disorganized behavior, and echolalia. The patient's condition progressed to treatment-refractory catatonia. She was started on oral Coenzyme Q10 after magnetic resonance imaging of the brain showed findings consistent with drug-induced leukoencephalopathy (DIL). Following improvement, she acknowledged cocaine use that suggested a diagnosis of cocaine-induced leukoencephalopathy (CIL). This case report seeks to elucidate radiological and clinical features of DIL.

Sociocultural domains of depression among indigenous populations in Latin America.

Not enough research has been carried out on depression up to now in Latin America. The knowledge that has resulted from research activities in the USA or Europe offers limited generalizability to other regions of the world, including Latin America. In the Andean highlands of Ecuador, we found very high rates of moderate and severe depressive symptoms, a finding that must be interpreted within its cultural context. Somatic manifestations of depression predominated over cognitive manifestations, and higher education level was protective against depression. These findings call for an appreciation of culturally specific manifestations of depression and the social factors that influence them. These factors must be further studied in order to give them the deserved priority, allocate resources appropriately, and formulate innovative psychosocial interventions.

Somatic and cognitive domains of depression in an underserved region of Ecuador: some cultural considerations.

Not enough research efforts on depression have been carried out up to now in Latin America. The knowledge that has resulted from research activities in the United States or Europe offers limited generalizability to other regions of the world, including Latin America. In the Andean highlands of Ecuador, we found very high rates of moderate and severe depressive symptoms, a finding that must be interpreted within its cultural context. Somatic manifestations of depression predominated over cognitive manifestations, and higher education level was protective against depression. These findings call for an appreciation of culturally-specific manifestations of depression and the social factors that influence them. These factors must be further studied in order to give them the deserved priority, allocate resources appropriately, and formulate innovative psychosocial interventions.

Modafinil as an adjunctive treatment of sedation, negative symptoms, and cognition in schizophrenia: a critical review.

OBJECTIVE: Given recent reports about the off-label use of modafinil as an adjuvant for the treatment of antipsychotic-associated sedation in schizophrenia patients and the recent interest in its putative cognitive-enhancing effects in this population, we present a systematic review of available data on trials of modafinil as an adjuvant in the treatment of cognitive deficits, negative symptoms, and antipsychotic-induced fatigue, and its tolerability. DATA SOURCES: PubMed was searched for trials published in English up to January 2008 evaluating modafinil's effects on fatigue, negative symptoms, and cognition in schizophrenia with combinations of the following terms: schizophrenia, modafinil, cognition, negative symptoms, and fatigue. STUDY SELECTION: Six trials were identified: 2 randomized, prospective, double-blind placebo-controlled trials; 3 randomized, prospective, double-blind placebo-controlled crossover trials; and 1 open-label pilot study. Case series and case reports were excluded in the data analysis, except to identify potential adverse reactions to modafinil. DATA EXTRACTION: Studies were examined for number of subjects, trial duration, design, dosing, and outcomes with respect to sedation, negative symptoms, cognitive function, and tolerability. RESULTS: One of 4 reviewed studies found a significant effect of modafinil as an alerting agent for antipsychotic-induced fatigue and sedation. Neither of 2 reviewed studies found modafinil to improve negative symptoms of schizophrenia. Three of 6 reviewed studies showed that modafinil may improve short-term memory, attention, and the ability to shift mental sets. Two neuroimaging studies identified functional correlates in areas associated with working memory functions. The main adverse effect was found to be a small risk of psychosis exacerbation, which was seen in 5 of 83 patients (6.0%) in the active treatment groups as compared to 2 of 70 patients (2.9%) in the placebo groups. CONCLUSIONS: While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia. Well-powered, prospective, randomized placebo-controlled trials using the MATRICS battery concomitantly with functional outcome measures are necessary to elucidate modafinil's efficacy and effectiveness as an adjunctive treatment for sedation, negative symptoms, and cognitive deficits in schizophrenia. Hence, before prescribing modafinil to a schizophrenia patient, the possible risks and benefits of each particular case should be evaluated.