Gambling disorder (GD) is associated with a higher prevalence of adverse childhood experiences (ACEs). Whether this applies to groups such as U.S. veterans, who already have elevated ACEs, is not known. In this pilot study, we extracted ACEs from the charts of a random sample (n = 19) male veterans in residential GD treatment and compared them to those from a general veteran sample (n =154, 30 females, 124 males). The GD group had an elevated prevalence (79% vs. 37%) of three or more ACEs and a lower prevalence (5% vs. 49%) of one or fewer ACEs. Within groups with elevated ACEs, higher ACE load may still confer a higher risk of adult GD.

In this brief report, the authors evaluate the effects of a possible association between different bupropion formulations and treatment-emergent insomnia in veterans with major depressive disorder prescribed bupropion based on provider discretion.

Gandotra, Kamal MD; Chen, Peijun MD; Konicki, P. Eric MD; Strohl, Kingman P. MD Author Information

Electronic health records (EHRs) linked to extensive biorepositories and supplemented with lifestyle, behavioral, and environmental exposure data, have enormous potential to contribute to genomic discovery, a necessary step in the pathway towards translational or precision medicine. A major bottleneck in incorporating EHRs into genomic studies is the extraction of research-grade variables for analysis, particularly when gold-standard measurements are not available or accessible. Here we develop algorithms for age-related macular degeneration (AMD), a common cause of blindness among the elderly, and controls free of AMD. These computable phenotypes were developed using billing codes (ICD-9-CM and ICD-10-CM) and Current Procedural Terminology (CPT) codes and evaluated in two study sites of the Veterans Affairs Million Veteran Program: Louis Stokes Cleveland VA Medical Center and the Providence VA Medical Center. After establishing a high overall positive and negative predictive values (93% and 95%, respectively) through manual chart review, the candidate algorithm was deployed in the full VA MVP dataset of >500,000 participants. The algorithm was then optimized in a data cube using a variety of approaches including adjusting inclusion age thresholds by examining previously-reported genetic associations for CFH (rs10801555, a proxy for rs1061170) and ARMS2 (rs10490924). The algorithm with the smallest p-values for the known genetic associations was selected for downstream and on-going AMD genomic discovery efforts. This two-phase approach to developing research-grade case/control variables for AMD genomic studies capitalizes on established genetic associations resulting in high precision and optimized sample sizes, an approach that can be applied to other large-scale biobanks linked to EHRs for precision medicine research.

To the Editors: L iterature suggests behavioral disinhibition includes motor, instinctual, emotional, cognitive, and perceptual aspects. The clinical signs and symptoms of this pathology are indistinguishable from the signs and symptoms that comprise the criteria for the diagnosis of mania in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. These include symptoms such as irritability, hyperactivity, pressured speech, decreased need for sleep, distractibility, hypersexuality, hyperphagia, aggressive outbursts, euphoria or elation, grandiosity, racing thoughts, and perceptual abnormalities such as hallucinations and paranoid ideation. The incidence of drug-associated behavioral disinhibition varies significantly and cannot be quantified precisely, as most descriptions arise predominately from case reports rather than clinical trials. Adverse effects are seldom the target of clinical studies, although they are nowmonitoredmoremeticulously in controlled trials. The incidence is contingent upon the sample studied but tends to be elevated in patients with preexisting poor impulse control. Alcohol amplifies the disinhibiting effect of benzodiazepines. Disinhibition has been reported after treatment with tricyclic antidepressants, and reports are now appearing that describe disinhibition in patientswhohave been treatedwith selective serotonin (5-hydroxytryptamine [5-HT]) reuptake inhibitors. Disinhibition is uncommon with antipsychotics and benzodiazepine anticonvulsants but few case reports have emerged. The prior case reports of behavioral disinhibition illustrate patients treated with high doses of high-potency benzodiazepines, such as alprazolam, flunitrazepam, and triazolam, especially when they are administered intravenously or intranasally. To the best of our knowledge, this is the first case of disinhibition syndrome that occurred in the context of low-dose clonazepam therapy for treatment of rapid eye movement (REM) sleep behavior disorder (RBD).

Free AccessDepressionEffective Treatment of Insomnia With Mirtazapine Attenuates Concomitant Suicidal Ideation Kamal Gandotra, MD, Peijun Chen, MD, PhD, MPH, George E. Jaskiw, MD, P. Eric Konicki, MD, Kingman P. Strohl, MD Kamal Gandotra, MD Address correspondence to: Kamal Gandotra, MD; Psychiatry Service, Louis Stokes VA Medical Center, Cleveland, OH(216) 791-3800 ext. 5601 E-mail Address: [email protected] Psychiatry Service, Louis Stokes VA Medical Center, Cleveland, Ohio Division of Pulmonary, Critical Care and Sleep Medicine, Louis Stokes VA Medical Center, Cleveland, Ohio Department of Psychiatry, Case Western Reserve University, Cleveland, Ohio , Peijun Chen, MD, PhD, MPH Psychiatry Service, Louis Stokes VA Medical Center, Cleveland, Ohio Department of Psychiatry, Case Western Reserve University, Cleveland, Ohio , George E. Jaskiw, MD Psychiatry Service, Louis Stokes VA Medical Center, Cleveland, Ohio Department of Psychiatry, Case Western Reserve University, Cleveland, Ohio , P. Eric Konicki, MD Psychiatry Service, Louis Stokes VA Medical Center, Cleveland, Ohio Department of Psychiatry, Case Western Reserve University, Cleveland, Ohio , Kingman P. Strohl, MD Division of Pulmonary, Critical Care and Sleep Medicine, Louis Stokes VA Medical Center, Cleveland, Ohio Division of Pulmonary, Critical Care and Sleep Medicine, University Hospitals, Case Western Reserve University, Cleveland, Ohio Published Online:May 15, 2018https://doi.org/10.5664/jcsm.7142Cited by:5SectionsPDF ShareShare onFacebookTwitterLinkedInRedditEmail ToolsAdd to favoritesDownload CitationsTrack Citations AboutINTRODUCTIONAlthough chronic insomnia is an established risk factor for suicidal ideation in depressive disorders,1–3 the therapeutic benefit of targeting insomnia per se in such patients remains understudied. We report an initial case and a series of patients in whom treatment of insomnia with mirtazapine proved highly therapeutic.A 60-year-old man presented with a 5-year history of distress due to nonrestorative sleep despite having adequate sleep time and good environmental sleep conditions. His Clinically Useful Depression Outcome Scale (CUDOS)4 score (50/64) indicated severe depression. After 3 weeks of treatment with low-dose mirtazapine (7.5 mg at bedtime), his CUDOS score (11/64) declined into the minimal depression range, whereas suicidal ideation and insomnia symptoms resolved. He attributed his improvement in mood primarily to regaining restorative sleep.We then administered mirtazapine (7.5–30 mg at bedtime) on a clinical basis primarily to treat insomnia in patients who (1) were referred to the mental health clinic for significant depressive symptoms, (2) met International Classification of Diseases, 10th Revision criteria for insomnia, and (3) endorsed subjective suicidal ideation. The subsequent chart review was approved by the Institutional Review Board.A total of 28 male patients (age 40–75 years) were started on mirtazapine. In six patients, mirtazapine was discontinued because of side effects (somnolence in four; tinnitus in one; dermatitis in one). However, significant improvement (n = 15) or complete resolution (n = 7) of both insomnia and suicidal ideation was achieved in the remaining 22 patients. For the group as a whole, the change in CUDOS score (mean ± standard deviation of the mean: baseline 42.39 ± 7.07; 4 to 6 weeks 19.5 ± 3.06; 6 to 8 weeks 16.89 ± 2.59) was significant by repeated-measures analysis of variance (F34,2 = 65.7, P < .0001).DISCUSSIONBoth in the index patient and most patients in the case series, insomnia, depressive symptoms, and suicidal ideation resolved in parallel during treatment with mirtazapine at bedtime in the low-dose range (7.5 mg, n = 2; 15 mg, n = 18; 30 mg, n = 2). The pivotal original studies supported an FDA-approved antidepressant indication for mirtazapine 15–45 mg/d. While the drug is commonly used off-label at lower doses (7.5 to 15 mg at bedtime) primarily for a soporific effect, antidepressant effects at doses of 7.5 mg/d have been reported.5,6 One possibility is that our data merely confirm the established antidepressant actions of mirtazapine. However, the relationship between depression, suicidal ideation, and insomnia is complex. Insomnia often precedes the onset of depression and constitutes a powerful independent risk factor for development of depression, suicidality, executive impairment, and impulsive behavior.7–9 We postulate that at least in some patients, targeting and effectively treating insomnia may lead to secondary resolution of concomitant suicidal ideation and other depressive symptoms. Our report underscores the importance of recognizing and treating insomnia in patients with depression and suicidal ideation. When insomnia is present concomitantly with suicidal ideation, antidepressant selection should be guided at least in part by the goal of providing restorative sleep.DISCLOSURE STATEMENTAll authors have seen and approved the manuscript. Work for this study was performed at the Louis Stokes VA Medical Center. The views expressed in this letter do not necessarily represent the views of the Department of Veterans Affairs or of the US Federal Government. The authors report no conflicts of interest.CITATIONGandotra K, Chen P, Jaskiw GE, Konicki PE, Strohl KP. Effective treatment of insomnia with mirtazapine attenuates concomitant suicidal ideation. J Clin Sleep Med. 2018;14(5):901–902.REFERENCES1 Bjorngaard JH, Bjerkeset O, Romundstad P, Gunnell DSleeping problems and suicide in 75,000 Norwegian adults: a 20 year follow-up of the HUNT I study. Sleep; 2011;349:1155-1159, 21886352. CrossrefGoogle Scholar2 Chellappa SL, Araujo JFSleep disorders and suicidal ideation in patients with depressive disorder. Psychiatry Res; 2007;1532:131-136, 17658614. CrossrefGoogle Scholar3 Bernert RA, Joiner TE, Cukrowicz KC, Schmidt NB, Krakow BSuicidality and sleep disturbances. Sleep; 2005;289:1135-1141, 16268383. CrossrefGoogle Scholar4 Zimmerman M, Chelminski I, McGlinchey JB, Posternak MAA clinically useful depression outcome scale. Compr. Psychiatry; 2008;492:131-140. Google Scholar5 Matreja PS, Badyal DK, Deswal RS, Sharma AEfficacy and safety of add on low-dose mirtazapine in depression. Indian J Pharmacol; 2012;442:173-177, 22529470. CrossrefGoogle Scholar6 Uguz FLow-dose mirtazapine in treatment of major depression developed following severe nausea and vomiting during pregnancy: two cases. Gen Hosp Psychiatry; 2014;361:125.e125-e126. CrossrefGoogle Scholar7 de Jonge P, Mangano D, Whooley MADifferential association of cognitive and somatic depressive symptoms with heart rate variability in patients with stable coronary heart disease: findings from the Heart and Soul Study. Psychosom Med; 2007;698:735-739, 17942844. CrossrefGoogle Scholar8 Krakow B, Ribeiro JD, Ulibarri VA, Krakow J, Joiner TESleep disturbances and suicidal ideation in sleep medical center patients. J Affect Dis; 2011;1311-3:422-427, 21211850. CrossrefGoogle Scholar9 McCall WV, Black CGThe link between suicide and insomnia: theoretical mechanisms. Curr Psychiatry Rep; 2013;159:389, 23949486. CrossrefGoogle Scholar Previous article FiguresReferencesRelatedDetailsCited by Cross talk mechanism of disturbed sleep patterns in neurological and psychological disordersSahu M, Tripathi R, Jha N, Jha S, Ambasta R and Kumar P Neuroscience & Biobehavioral Reviews, 10.1016/j.neubiorev.2022.104767, Vol. 140, , (104767), Online publication date: 1-Sep-2022. Davis M Mirtazapine and Depressions NeuroPsychopharmacotherapy, 10.1007/978-3-030-62059-2_102, (1281-1309), . When Night Falls FastFernandes S, Zuckerman E, Miranda R and Baroni A Child and Adolescent Psychiatric Clinics of North America, 10.1016/j.chc.2020.08.009, , Online publication date: 1-Oct-2020. Davis M Mirtazapine and Depressions NeuroPsychopharmacotherapy, 10.1007/978-3-319-56015-1_102-1, (1-29), . Drug treatment strategies for insomnia in patients with post-traumatic stress disorderAkinnusi M and El Solh A Expert Opinion on Pharmacotherapy, 10.1080/14656566.2019.1574745, Vol. 20, No. 6, (691-699), Online publication date: 13-Apr-2019. Volume 14 • Issue 05 • May 15, 2018ISSN (print): 1550-9389ISSN (online): 1550-9397Frequency: Monthly Metrics History Submitted for publicationFebruary 19, 2018Submitted in final revised formFebruary 19, 2018Accepted for publicationMarch 1, 2018Published onlineMay 15, 2018 Information© 2018 American Academy of Sleep MedicinePDF download

Background In an effort to prevent opioid overdose mortality among Veterans, Department of Veterans Affairs (VA) facilities began implementing opioid overdose education and naloxone distribution (OEND) in 2013 and a national program began in 2014. VA is the first national health care system to implement OEND. The goal of this study is to examine patient perceptions of OEND training and naloxone kits. Methods Four focus groups were conducted between December 2014 and February 2015 with 21 patients trained in OEND. Participants were recruited from a VA residential facility in California with a substance use disorder treatment program (mandatory OEND training) and a homeless program (optional OEND training). Data were analyzed using matrices and open and closed coding approaches to identify participants’ perspectives on OEND training including benefits, concerns, differing opinions, and suggestions for improvement. Results Veterans thought OEND training was interesting, novel, and empowering, and that naloxone kits will save lives. Some veterans expressed concern about using syringes in the kits. A few patients who never used opioids were not interested in receiving kits. Veterans had differing opinions about legal and liability issues, whether naloxone kits might contribute to relapse, and whether and how to involve family in training. Some veterans expressed uncertainty about the effects of naloxone. Suggested improvements included active learning approaches, enhanced training materials, and increased advertisement. Conclusions OEND training was generally well received among study participants, including those with no indication for a naloxone kit. Patients described a need for OEND and believed it could save lives. Patient feedback on OEND training benefits, concerns, opinions, and suggestions provides important insights to inform future OEND training programs both within VA and in other health care settings. Training is critical to maximizing the potential for OEND to save lives, and this study includes specific suggestions for improving the effectiveness and acceptability of training.

OBJECTIVE:Clozapine is underutilized in the management of treatment-resistant schizophrenia. To understand contributing factors, we analyzed the frequency and causes of clozapine discontinuations that occurred over a 15-year period in a clinical setting.METHOD:Data were extracted from computerized records and from mandatory termination reports for discontinuation events 1993-2007. The reasons for termination were analyzed.RESULTS:Over half of the patients (n = 183/320; 57%) had at least one discontinuation (median time 609 days). The two most common causes for discontinuation were non-adherence (35%) and side-effects (28%). Hematological side-effects accounted for 45% of all side-effect associated discontinuations; most such patients remained eligible for clozapine treatment, and a significant fraction remained on clozapine after rechallenge. Central nervous system side-effects accounted for 35% of side-effect induced discontinuations. General factors significantly associated with discontinuation were African American race, older age at initiation of clozapine and less improvement in psychiatric symptoms.CONCLUSION:In addition to anticipating and addressing causes of non-adherence, psychiatrists should consider clozapine rechallenge in eligible patients and implement measures to mitigate clozapine-associated sedation, seizures, and other side-effects. Future studies should particularly address why African American and older patients may be more likely to discontinue clozapine.

Back to table of contents Previous article Next article Frontline ReportsFull AccessIncorporating Clinical Monitoring Into Electronic Orders for AntipsychoticsJennifer Roche-Desilets, Pharm.D., Matthew A. Fuller, Pharm.D., and P. Eric Konicki, M.D.Jennifer Roche-DesiletsSearch for more papers by this author, Pharm.D., Matthew A. FullerSearch for more papers by this author, Pharm.D., and P. Eric KonickiSearch for more papers by this author, M.D.Published Online:1 Apr 2004https://doi.org/10.1176/appi.ps.55.4.455AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Postmarketing surveillance of atypical antipsychotics has revealed that, in addition to the commonly reported side effect of weight gain, these medications have potentially serious metabolic side effects—specifically, altered glucose metabolism and elevated serum lipids. In addition, case reports have linked these agents with diabetic ketoacidosis (DKA), which has resulted in a number of deaths.Although the mechanism by which atypical antipsychotics affect lipids and glucose regulation is unclear, the clinical effects have been well documented. Diabetes, weight gain, and elevated serum lipids are associated with an increased risk of cardiovascular disease, even among persons with relatively small serum lipid elevations. Psychiatric patients, particularly those with schizophrenia, have a greater risk of cardiovascular disease than the general population as a result of the higher prevalence of diabetes and cigarette smoking among persons with schizophrenia. In light of the risks associated with use of atypical antipsychotics, many have advocated for routine monitoring of weight, glucose, and lipids as the standard of care.After an internal audit of rates of routine monitoring for patients taking atypical antipsychotics that revealed very poor current performance, the psychiatry service of the Louis Stokes Veterans Affairs Medical Center (VAMC) recommended that all patients who are given atypical antipsychotics be monitored for weight gain, elevation of serum lipids, and glucose dysregulation. Routine monitoring was introduced in September 2003.Guidelines for monitoring these agents were developed by a multidisciplinary group that considered case reports, the results of prospective and retrospective studies, and guidelines published by the American Diabetes Association (ADA) and the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (the National Cholesterol Education Program, or NCEP). The frequencies of weight and lipid monitoring are based on NCEP guidelines. Glucose monitoring is more frequent than recommended in the ADA guidelines on the grounds that reported cases of DKA have occurred more often during the first three months of therapy. Because of the difficulty of obtaining fasting glucose measurements in the outpatient veteran population, hemoglobin A1c was selected as an indicator of glucose regulation. Because hemoglobin A1c is a measure of glucose irreversibly bound to hemoglobin over the 120-day life of a red blood cell, it is not affected by daily fluctuations, and fasting is not required. Fasting blood glucose would be a suitable substitute in settings in which fasting can be assured.Under the monitoring schedule used at the medical center, height and weight are measured at baseline, and weight is measured at every visit (a minimum of every six months). Serum lipids are measured at baseline and every six months. Hemoglobin A1c is measured at baseline, after one month, after three months, and then every six months.To maximize the number of patients who were monitored, a method of ordering weight measurements and laboratory tests was developed and tied to prescription order entry, which is done electronically at the VAMC. The intervention consists of an electronic order menu designed for the computerized patient record system (CPRS), which is the software used by the VAMC for all electronic medical records. When a prescriber attempts to order an atypical antipsychotic a pop-up box appears. The box contains a list of buttons containing the names of the drugs. When the drug and dosage have been selected, the box prompts the prescriber to enter baseline height and weight (the CPRS automatically calculates body mass index) and to use check boxes to select required laboratory tests. The check boxes are linked to the laboratory order menu, and the necessary blood draw is immediately ordered. If the prescriber is renewing an order, the baseline measurements that have already been collected will be displayed at the top of the box, and check boxes will appear below so that the prescriber can order follow-up laboratory tests.The utility of this intervention will be measured by comparing rates of metabolic monitoring of patients receiving atypical antipsychotics before and after the implementation of the intervention. Through data collection from CPRS, we will be able to follow-up in a meaningful way to further demonstrate the utility of direct physician computer order entry. In addition, we expect that increased monitoring will result in earlier detection of diabetes and dyslipidemia, earlier intervention, and improved health outcomes.All authors are affiliated with the psychiatry service of Louis Stokes Veterans Affairs Medical Center, 10701 East Boulevard, Cleveland, Ohio 44106 (e-mail, jennifer. [email protected]). Dr. Konicki and Dr. Fuller are also with the department of psychiatry at Case Western University Medical School in Cleveland. FiguresReferencesCited byDetailsCited byNone Volume 55Issue 4 April 2004Pages 455-455 Metrics PDF download History Published online 1 April 2004 Published in print 1 April 2004

BACKGROUND:Weight gain is a common side effect of clozapine treatment and may expose patients to obesity-associated health risks. We proposed that concomitant treatment with an appetite suppressant such as phenylpropanolamine (PPA) would lead to a decrease in appetite and therefore loss of weight.METHOD:This was a 12-week, double-blind, randomized, placebo-controlled trial of PPA, 75 mg/day, in outpatients with treatment-refractory schizophrenia (DSM-IV) who were stable on clozapine treatment for at least 4 months and had gained > 10% of their baseline body weight since starting clozapine. Patients were evaluated for adverse effects and weighed weekly. A Positive and Negative Syndrome Scale (PANSS) assessment, a short dietary quiz, and blood indices were completed monthly.RESULTS:Sixteen patients were equally randomly assigned to receive PPA or placebo. The groups did not differ in mean age, baseline weight, dose of clozapine, baseline PANSS scores, or the percent of weight gained since the start of clozapine. There was no significant effect of treatment on weight (t = 0.219, df = 10, p = .831). There was no significant change in either the total PANSS scores (t = -0.755, df = 10, p = .468), the positive or negative symptom cluster scores, or any of the remaining variables.CONCLUSION:Phenylpropanolamine 75 mg/day was well tolerated but was not effective in reversing established weight gain associated with clozapine treatment in stable outpatients with schizophrenia.

Increased sulcal widening in the prefrontal cortex of patients with schizophrenia may be associated with a poor treatment response to clozapine. To further evaluate this, we examined data from patients treated with clozapine in our center. Patients with the greatest degree of improvement (n=26) and those with no improvement (n=10) were compared. Computerized tomography (CT) scans were rated blindly on a visual scale of prefrontal sulcal widening. Patients with the greatest degree of functional improvement had significantly less prefrontal sulcal widening than those whose symptoms remained unchanged. There was no relationship between clozapine response and general sulcal widening. These data support the link between the superior therapeutic efficacy of clozapine and the integrity of the prefrontal cortex.

We previously reported significant differences in force control (FC) function between schizophrenics treated with typical antipsychotic drugs (APD) and those treated with clozapine. Clozapine treatment was associated with an attenuation of the capacity for fine motor control. We now report that a test–retest study with 41 treatment-refractory patients confirms our earlier finding; the FC deficit is due primarily to clozapine treatment. An additional comparison was made with 10 patients who were administered the FC test repeatedly through the initial clozapine titration interval of 6–8weeks. The results suggest that two distinct clozapine effects can be distinguished, an initial transient stage characterized by `drowsiness' and a subsequent stage with dose-dependent emerging myoclonic features.