The Arduous Path to Drug Approval for the Management of Prader-Willi Syndrome: A Historical Perspective and Call to Action.

Prader-Willi syndrome (PWS) is a neuroendocrine genetic disorder resulting from the loss of paternally expressed imprinted genes in chromosome 15q11-q13 [...].

Diagnosis and management of sleep disorders in Prader-Willi syndrome.

Clinical experience and a growing body of evidence suggest that sleep disturbances are common in people with Prader-Willi syndrome (PWS). PWS is a rare neuroendocrine disorder characterized by early hypotonia and feeding difficulties; developmental delays; endocrinopathies; and behavioral concerns, especially rigidity, anxiety, and behavioral outbursts. PWS is also characterized by decreased resting energy expenditure and transition to hyperphagia and obesity. We propose that, for many people with PWS, clinical diagnosis and management of sleep disorders is an unmet need. We present current information to suggest disordered sleep is a significant burden for individuals with PWS and often overlooked. While central and obstructive sleep apnea are more widely recognized in PWS, other sleep disorders have increasingly gained recognition, including hypersomnia, narcolepsy-like phenotypes, and insomnia. Sleep disorders can impact behavior, cognition, and quality of life and health for individuals with PWS. Our goal is to bring sleep disorders to the forefront of therapeutic intervention for patients with PWS. This paper presents a review of the literature and recommendations for clinical practice based on published research and our clinical experience as sleep specialists, geneticists, psychiatrists, pediatricians, otolaryngologists, and pulmonologists with extensive experience with this patient population. We recommend that management of sleep be considered an integral part of successful medical management of PWS. Further research concerning sleep problems in PWS is urgently needed to develop best practices and work toward a consensus statement for medical management to meet the needs of people with PWS. CITATION: Duis J, Pullen LC, Picone M, et al. Diagnosis and management of sleep disorders in Prader-Willi syndrome. J Clin Sleep Med. 2022;18(6):1687-1696.

Cycloid Psychosis Comorbid with Prader-Willi Syndrome: A Case Series.

Psychosis is a relatively common psychiatric phenomenon seen in patients with Prader-Willi Syndrome (PWS). However, the presentation is atypical and difficult to classify within currently defined affective or psychotic disorders. This distinct presentation may be better understood as a phenomenon called "cycloid psychosis," described as an episodic psychosis with rapid full recovery between episodes. This study retrospectively analyzed the cases of 12 patients with genetically confirmed PWS who presented to an ambulatory psychiatric center for a change in behavior consistent with psychosis. Each case was then assessed for symptoms of cycloid psychosis, bipolar disorder, depression with psychotic features, schizophrenia, and schizoaffective disorder. Out of the 12 patients, 11 (91.7%) met the currently described diagnostic criteria for cycloid psychosis. Of the 12 patients, 7 (58.3%) also met the diagnostic criteria for bipolar disorder, and 1 (8.3%) also met the diagnostic criteria for schizoaffective disorder. None of the patients met the criteria for schizophrenia or depression with psychotic features. The findings in this study suggest that cycloid psychosis and bipolar disorder may both be comorbid with PWS. Psychiatric comorbidities in patients with PWS are atypical and clinicians should be aware of conditions such as cycloid psychosis when managing this vulnerable population.

Guanfacine Extended Release for the Reduction of Aggression, Attention-Deficit/Hyperactivity Disorder Symptoms, and Self-Injurious Behavior in Prader-Willi Syndrome-A Retrospective Cohort Study.

Objective: To examine the role of Guanfacine Extended Release (GXR) in the management of behavioral disturbances in patients with Prader-Willi Syndrome (PWS). Methods: Twenty from a total of 27 individuals with genetically confirmed PWS, 6-26 years of age, with the following symptoms were identified: significant aggression/agitation, skin picking, and/or symptoms of attention-deficit/hyperactivity disorder (ADHD). Response to GXR for the above noted symptoms was categorized as improved, worsened, or unchanged, while assessing for side effects and tolerability. Results: Eleven of the 20 individuals reported skin-picking, 17 reported aggression/agitation, and 16 reported symptoms of ADHD. Nine (81.8%), 14 (82.3%), and 15 (93.7%) individuals showed an improvement in skin-picking, aggression/agitation, and ADHD, respectively, while on GXR treatment. Two patients with prior complaints of psychotic symptoms did not respond to GXR. Of note, no abnormal weight gain or significant adverse reaction was observed in this group, while on GXR. Conclusions: In this study, GXR demonstrated improvement in symptoms of skin picking, aggression/agitation, and ADHD in patients with PWS. GXR was not effective in reducing psychosis or agitation related to psychotic symptoms. Future studies are warranted to further establish the utility of GXR in PWS patients.

The ALPIM (Anxiety, Laxity, Pain, Immune, and Mood) Syndrome in Adolescents and Young Adults: A Cohort Study.

OBJECTIVE: ALPIM (anxiety, laxity, pain, immune, and mood) syndrome has been previously described in adults. The authors aimed to identify its occurrence in adolescents and confirm its existence in adults. Given the association of the disorder with somatic symptoms, separation anxiety disorder (SAD) was explored as an ALPIM comorbidity. METHODS: Medical records of patients aged 11-34 with a diagnosis of depression or anxiety (panic disorder, SAD, social anxiety or generalized anxiety disorder) seen during a 1-year period were reviewed. Data were collected on the presence of ALPIM comorbidities. Analyses were conducted to detect their co-occurrence and evaluate possible predictors of the ALPIM syndrome. RESULTS: Inclusion criteria were met by 185 patient charts. A significant association was observed between the ALPIM comorbidities with 20 study subjects (10.8%) meeting criteria for ALPIM syndrome (patients with one or more diagnoses from each ALPIM domain). Patients with SAD had increased odds of being diagnosed with ALPIM (odds ratio=7.14, 95% CI=2.48-20.54, p<0.001). Neither major depression nor generalized anxiety disorder was found to be predictive of ALPIM syndrome. There was no difference in the prevalence of ALPIM-related comorbidities between study subjects <18 years old compared with those ≥18 years old. CONCLUSIONS: These findings reestablish the association of distinct psychiatric and nonpsychiatric conditions described as the ALPIM syndrome. Furthermore, the syndrome may present during adolescence. SAD may be an independent predictive factor for the occurrence of ALPIM syndrome. Patients with individual ALPIM comorbidities should be assessed for the syndrome, especially if they have a history of SAD.

The Impact of Designated Behavioral Health Services on Resource Utilization and Quality of Care in Patients Requiring Constant Observation in a General Hospital Setting: A Quality Improvement Project.

Constant observation (CO) is a common economic burden on general hospitals. A quality improvement (QI) project focusing on behavioral health (BH) management of this population was piloted using a novel BH protocol for the proactive assessment and management of all patients requiring CO. The impact on CO-cost and length of stay (LOS) was assessed. Data on demographics, diagnoses, psychopharmacologic treatment, complications and clinical setting were collected and analyzed for all CO-patients over a 6-month period. Cost and LOS data were compared with a similar sequential group prior to project implementation. Out of the 533 patients requiring CO during the study period, 491 underwent the protocol. This QI-project resulted in a significant reduction in the average monthly CO-cost by 33.06% and a 15% reduction in LOS without any increase in complications.

A Proactive Behavioral Health Service Model to Address Use of Constant Observation in a General Hospital.

In hospitals, use of constant observation (CO) causes significant economic burden without demonstrated reduction in adverse events. A novel quality improvement (QI) project was developed to reduce use of CO by integrating proactive behavioral health management of all patients requiring CO in a general hospital. Specific nonpharmacologic and pharmacologic interventions used in this project, which included 491 patients, are discussed. Data collected were compared with data from a baseline period before project implementation. The average monthly cost of observers was reduced by 33%, and length of stay was reduced 15% without increased complications. Using QI to develop proactive and consistent involvement of a designated behavioral health team and potentially reproducible care protocols for patients requiring CO resulted in improvement in quality, reduction in cost, and enhanced behavioral health integration in the general hospital.

Obsessive-Compulsive Disorder in a 19-Year-Old Female Adolescent With Turner Syndrome.

Obsessive-compulsive disorder (OCD) in patients with Turner syndrome (TS) is an uncommon neuropsychiatric presentation that has not been well characterized in the scientific literature. Though no clear psychiatric component is syndromic to TS, the clinical manifestations of certain neuropsychiatric disorders, including mood, anxiety and eating disorders, have all been well documented in patients with TS. However, the presence of OCD in these patients has not been previously described. This report details a 19-year-old TS patient who presented with OCD since the age of 13, comorbid with several other psychiatric pathologies, including bipolar I disorder, anorexia nervosa and attention deficit hyperactivity disorder (ADHD). It will also discuss those comorbidities in relation to the patient's genetic syndrome and mention the contribution it makes to her multiple disabilities diagnosis as well as her patient-specific therapy. Patients with TS often present to treating physicians for overwhelming somatic complaints, likely resulting in poor recognition of psychiatric disorders. Thus, OCD may be significantly under-diagnosed in patients with TS and should be explored by clinicians treating this vulnerable population.

Role of Ramelteon in Reduction of As-Needed Antipsychotics in Elderly Patients with Delirium in a General Hospital Setting.

BACKGROUND AND OBJECTIVE: Abnormalities in melatonin levels have been linked to delirium. This dysregulation may be offset with the use of ramelteon, a melatonin receptor agonist. The purpose of this study was to evaluate the role of ramelteon in decreasing the need for as-needed (PRN) use of antipsychotics in elderly patients with delirium. METHODS: This was a single-center, retrospective study involving 488 patients who were placed on constant observation and received care by psychiatric service from May 2015 through October 2015. Of these patients, 125 patients were age 65 years or above, had a diagnosis of delirium, and had no standing orders for antipsychotics. These 125 patients were divided into the non-ramelteon group (who received no ramelteon and PRN antipsychotics) and the ramelteon group (who received ramelteon plus PRN antipsychotics). The use of PRN antipsychotics for agitation in each group was recorded. RESULTS: The ramelteon group had a lower incidence of PRN antipsychotic use compared to those not given ramelteon (60 vs. 80%, p value = 0.001). After adjustment for race, age, length of stay, and gender, patients in the non-ramelteon group were more likely to have been given antipsychotics compared to those in the ramelteon group (odds ratio = 4.3, p value = 0.002). CONCLUSION: Ramelteon use in elderly patients with delirium may be associated with statistically significant reduction of PRN antipsychotic use for agitation.

Pudendal nerve entrapment leading to avoidant/restrictive food intake disorder (ARFID): A case report.

Avoidant/restrictive food intake disorder (ARFID) is a diagnosis in diagnostic and statistical manual of mental disorders-5 (DSM-5) manifested by persistent failure to meet nutritional and/or energy needs. Pudendal nerve entrapment (PNE) often causes pelvic discomfort in addition to constipation and painful bowel movements. Current literature on ARFID is sparse and focuses on the pediatric and adolescent population. No association between PNE and ARFID has been described. We present a case of ARFID in an adult male with PNE resulting from subsequent scarring from testicular cancer surgery. The patient's gastrointestinal symptoms due to PNE caused significant food avoidance and restriction subsequently leading to severe malnourishment. Clinicians should be aware that distressing gastrointestinal symptoms arising from a secondary disease process such as PNE might lead to dietary restriction and food aversion. More research is needed for proper screening, detection, and treatment of ARFID. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2017; 50:84-87).

Protocol for Psychopharmacologic Management of Behavioral Health Comorbidity in Adult Patients with Diabetes and Soft Tissue Infections in a Tertiary Care Hospital Setting.

GENERAL PURPOSE: To provide information about the effect of psychiatric comorbidities on wound healing in patients with diabetes mellitus (DM). TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant should be better able to:1. Discuss the connection between DM and the development of psychiatric comorbidities.2. Identify the drugs recommended in the treatment of these psychiatric comorbidities.3. List cautions and contraindications related to the drugs discussed. ABSTRACT: In patients with diabetes mellitus type 2, psychiatric comorbidities such as depressive and anxiety disorders are 60% or more prevalent than in the general population. The severity of mental illness and the duration of diabetes have been shown to correlate with worsening glycemic control, thus impeding wound healing. A retrospective chart review was conducted in all patients with diabetes mellitus admitted to the wound service with prior or current psychiatric symptoms of anxiety, depression, or cognitive impairment. A psychopharmacologic protocol was developed based on the clinical data collected and treatment parameters used by the behavioral health consultation liaison service.

Lacosamide Induced Psychosis: Case Report, Review of Differential Diagnosis and Relevant Pharmacokinetics.

Lacosamide (LCM) is an antiepileptic medication used as an adjunctive treatment for partial seizures. Psychosis associated with LCM use is a rarely documented phenomenon, which may be difficult to detect in the context of the often complicated clinical presentation of epilepsy. We report the development of psychosis in a young woman after the use of LCM, which subsequently resolved with its discontinuation. The possible differential diagnosis and pharmacokinetic nuances are discussed. This is the first case report of LCM-induced psychosis in the United States.

A Novel Anxiety and Affective Spectrum Disorder of Mind and Body-The ALPIM (Anxiety-Laxity-Pain-Immune-Mood) Syndrome: A Preliminary Report.

The authors describe a spectrum disorder comprising a core anxiety (A) disorder and four domains: joint laxity (L), chronic pain syndromes (P), immune disorders (I), and mood disorders (M)-dubbed the ALPIM syndrome. This study examined 76 consecutive outpatients with an anxiety disorder plus at least one somatic condition from three domains. More than 80% of the patients had panic attacks, fibromyalgia, and major depressive episodes. Associations were found between joint laxity and bipolar III, headache with bipolar II, and bipolar II with chronic fatigue syndrome. Significant relationships were demonstrated within and between domains, validating ALPIM as a syndrome.