Transitioning insomnia patients from zolpidem to lemborexant: A multicenter, open-label study evaluating a next-dose transition approach to insomnia pharmacotherapy.

Objective: Few clinical studies have assessed real-world abrupt transitioning between insomnia medications. This study assessed strategies for directly transitioning patients from zolpidem tartrate (ZOL) immediate/extended release to the dual orexin receptor antagonist, lemborexant (LEM). Methods: This randomized, open-label, multicenter study (Study 312; E2006-A001-312) enrolled 53 adults age ≥18 years with insomnia disorder and ≥1-month history of intermittent (3-4 nights/week) or frequent (≥5 nights/week) ZOL use. Subjects recorded their ZOL use in a 3-week Pretreatment Phase, followed by a 2-week Treatment Phase (TRT; Titration) during which ZOL was discontinued. Intermittent ZOL users transitioned to LEM 5 mg (LEM5), Cohort 1, and frequent ZOL users were randomized 1:1 to LEM5, Cohort 2A, or LEM 10 mg (LEM10), Cohort 2B. One dose adjustment was permitted during the TRT. Subjects completing the TRT could continue LEM in the 12-week Extension Phase (EXT). The primary outcome was proportion of subjects who successfully transitioned and remained on LEM at the end of the TRT. Results: Most subjects (43 [81.1 %]) successfully transitioned to LEM (9 [90 %], 17 [81.0 %], and 17 [77.3 %] in Cohorts 1, 2A, and 2B, respectively). By the end of the EXT, 66.7 % in Cohort 1 and 60.0 % in Cohort 2A up-titrated to LEM10, whereas 41.2 % in Cohort 2B down-titrated to LEM5; 61.0 % were receiving LEM10 at study end. At the end of the TRT, more subjects taking LEM reported that it helped them return to sleep after waking, compared with those taking ZOL (71.7 % vs. 49.1 %). There were no important differences between treatments regarding how subjects reported feeling as they fell asleep. Most of the treatment-emergent adverse events with LEM were mild in severity. Conclusions: Most subjects transitioned successfully to LEM from ZOL (intermittent or frequent use). LEM was well tolerated.

Considerations when selecting an antidepressant: a narrative review for primary care providers treating adults with depression.

Major depressive disorder (MDD) is a debilitating mental disorder that can be treated with a number of different antidepressant therapies, each with its own unique prescribing considerations. Complicating the selection of an appropriate antidepressant for adults with MDD is the heterogeneity of clinical profiles and depression subtypes. Additionally, patient comorbidities, preferences, and likelihood of adhering to treatment must all be considered when selecting an appropriate therapy. With the majority of prescriptions being written by primary care practitioners, it is appropriate to review the unique characteristics of all available antidepressants, including safety considerations. Prior to initiating antidepressant treatment and when patients do not respond adequately to initial therapy and/or exhibit any hypomanic or manic symptoms, bipolar disorder must be ruled out, and evaluation for psychiatric comorbidities must be considered as well. Patients with an inadequate response may then require a treatment switch to another drug with a different mechanism of action, combination, or augmentation strategy. In this narrative review, we propose that careful selection of the most appropriate antidepressant for adult patients with MDD based on their clinical profile and comorbidities is vital for initial treatment selection.Strategies must be considered for addressing partial and inadequate responses as well to help patients achieve full remission and sustained functional recovery. This review also highlights data for MDD clinical outcomes for which gaps in the literature have been identified, including the effects of antidepressants on functional outcomes, sleep disturbances, emotional and cognitive blunting, anxiety, and residual symptoms of depression.

Major depressive disorder (MDD) is a leading cause of disability worldwide and can affect each patient differently. Antidepressants play a critical role in treatment; however, with multiple antidepressant options available, it is important that providers select the best fit for each patient. Rather than use a "one size fits all" approach, it is important to consider each patient's symptoms, medical and psychiatric comorbidities, as well as their treatment preferences. A clear summary of each antidepressant's distinctive characteristics is essential for providers to select antidepressants to best match each patient's needs.This narrative review aims to discuss the latest information on available antidepressants, including their risks and benefits and how they impact symptoms of MDD such as sleep disturbances, anxiety, emotional blunting, and changes in cognition, as well as different treatment goals, such as the ability to function in everyday life. This information can guide clinical practice recommendations and further enable shared decision-making between the provider and patient, incorporating individual treatment needs and preferences.In addition, many patients do not reach their treatment goals with the first antidepressant or may continue to have symptoms of depression after treatment. This review discusses strategies to increase the likelihood of symptom improvement and creates awareness of patient-specific considerations.Overall, careful, personalized selection of antidepressant treatment is critical for finding the right balance of maximized antidepressant effect with minimized side effects, leading to the best possibility for patients to tolerate the medication and ultimately helping patients reach their treatment goals.

Practical Advice for Primary Care Clinicians on the Safe and Effective Use of Vortioxetine for Patients with Major Depressive Disorder (MDD).

Primary care clinicians have a vital role to play in the diagnosis and management of patients with major depressive disorder (MDD). This includes screening for MDD as well as identifying other possible psychiatric disorders including bipolar disorder and/or other comorbidities. Once MDD is confirmed, partnering with patients in the shared decision-making process while considering different treatment options and best management of MDD over the course of their illness is recommended. Vortioxetine has been approved for the treatment of adults with MDD since 2013, and subsequent US label updates indicate that vortioxetine may be particularly beneficial for specific populations of patients with MDD, including those with treatment-emergent sexual dysfunction and patients experiencing certain cognitive symptoms. Given these recent label updates, this prescribing guide for vortioxetine aims to provide clear and practical guidance for primary care clinicians on the safe and effective use of vortioxetine for the treatment of MDD, including how to identify appropriate patients for treatment.

A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of AR19, a Manipulation-Resistant Formulation of Amphetamine Sulfate, in Adults With Attention-Deficit/Hyperactivity Disorder.

Objective: To assess the efficacy and safety of AR19 in the treatment of attention-deficit/hyperactivity disorder (ADHD) diagnosed by DSM-5 criteria in adults from 18 through 55 years of age. AR19 is a pellets-in-capsule, immediate-release amphetamine sulfate investigational formulation with physical and chemical barriers designed to resist manipulation to deter snorting, smoking, and intravenous injection.Methods: This randomized, double-blind, placebo-controlled, fixed-dose, forced titration, multicenter trial investigated the safety and efficacy of AR19 from September 2018 to April 2019. Study participants were randomized and titrated to 20 mg or 40 mg AR19 daily or placebo. Study medication was dosed once in the morning and again 4 to 6 hours later for a period of 5 weeks. The primary efficacy measure was the total score on the Adult ADHD Investigator Symptom Rating Scale (AISRS).Results: Participants (N = 320) were randomized and received at least 1 dose of study medication. Demographics and baseline characteristics were similar across treatment groups. The least squares mean treatment differences versus placebo (97.5% CI) were -7.2 (-11.3 to -3.1) for the AR19 20-mg group and -7.3 (-11.4 to -3.2) for the AR19 40-mg group (each P < .001). The most common treatment-emergent adverse events occurring in participants in the AR19 treatment groups were insomnia, dry mouth, decreased appetite, palpitations, headache, and tachycardia and are consistent with the known safety profile of amphetamine sulfate.Conclusions: AR19 demonstrated efficacy on all endpoints and was generally well tolerated, supporting the efficacy and safety of AR19 20 mg and 40 mg in adults with ADHD.Trial Registration: ClinicalTrials.gov Identifier: NCT03659929.

The Rapid Mood Screener (RMS): a novel and pragmatic screener for bipolar I disorder.

OBJECTIVE: Depressive episodes and symptoms of bipolar I disorder are commonly misdiagnosed as major depressive disorder (MDD) in primary care. The novel and pragmatic Rapid Mood Screener (RMS) was developed to screen for manic symptoms and bipolar I disorder features (e.g. age of depression onset) to address this unmet clinical need. METHODS: A targeted literature search was conducted to select concepts thought to differentiate bipolar I from MDD and screener tool items were drafted. Items were tested and refined in cognitive debriefing interviews with individuals with self-reported bipolar I or MDD (n = 12). An observational study was conducted to evaluate predictive validity. Participants with clinical interview-confirmed bipolar I or MDD diagnoses (n = 139) completed a draft 10-item screening tool and other questionnaires. Data were analyzed to identify the smallest possible subset of items with optimized sensitivity and specificity. RESULTS: Adults with confirmed bipolar I (n = 67) or MDD (n = 72) participated in the observational study. Ten draft screening tool items were reduced to 6 final RMS items based on the item-level analysis. When 4 or more items of the RMS were endorsed ("yes"), sensitivity was 0.88 and specificity was 0.80; positive and negative predictive values were 0.80 and 0.88, respectively. These properties were an improvement over the Mood Disorder Questionnaire in the same analysis sample while using 60% fewer items. CONCLUSION: The pragmatic 6-item RMS differentiates bipolar I disorder from MDD in patients with depressive symptoms, providing real-world guidance to primary care practitioners on whether a more comprehensive assessment for bipolar I disorder is warranted.

Systematic Review: Nonmedical Use of Prescription Stimulants: Risk Factors, Outcomes, and Risk Reduction Strategies.

OBJECTIVE: To review all literature on the nonmedical use (NMU) and diversion of prescription stimulants to better understand the characteristics, risk factors, and outcomes of NMU and to review risk-reduction strategies. METHOD: We systematically searched PubMed, PsycINFO, and SCOPUS from inception to May 2018 for studies containing empirical data about NMU and diversion of prescription stimulants. Additional references identified by the authors were also assessed for inclusion. RESULTS: A total of 111 studies met inclusion criteria. NMU and diversion of stimulants are highly prevalent; self-reported rates among population samples range from 2.1% to 58.7% and from 0.7% to 80.0%, respectively. A variety of terms are used to describe NMU, and most studies have examined college students. Although most NMU is oral, non-oral NMU also occurs. The majority of NMU is associated with no, or minor, medical effects; however, adverse medical outcomes, including death, occur in some individuals, particularly when administered by non-oral routes. Although academic and occupational performance enhancement are the most commonly cited motivations, there is little evidence that academic performance is improved by NMU in individuals without attention-deficit/hyperactivity disorder. CONCLUSION: NMU of stimulants is a significant public health problem, especially in college students, but variations in the terms used to describe NMU and inconsistencies in the available data limit a better understanding of this problem. Further research is needed to develop methods to detect NMU, identify individuals at greatest risk, study routes of administration, and devise educational and other interventions to help reduce occurrence of NMU. Colleges should consider including NMU in academic integrity policies.

Addressing Diagnosis and Treatment Gaps in Adults With Attention-Deficit/Hyperactivity Disorder.

Attention-deficit/hyperactivity disorder (ADHD) was originally defined in children but is now recognized to persist into adulthood for some patients. Despite this recognition, adult ADHD remains underdiagnosed. This narrative review describes the negative impact of ADHD across multiple functional domains, diagnostic guidelines for adult ADHD and its clinical features, the importance of screening tools and clinical interviews to help evaluate adults for ADHD, and adult ADHD treatment options. Diagnostic guidelines for ADHD now incorporate adult-specific symptoms and behavioral manifestations, which may aid in diagnosing adult ADHD. However, diagnosis of ADHD is complicated by symptom overlap between ADHD and psychiatric disorders that might be comorbid with ADHD. Screening tools, such as the Adult ADHD Self-Report Screening Scale for DSM-5, can identify adults requiring evaluation for ADHD. However, clinical interviews and longitudinal family histories provide critical information that diagnoses ADHD and differentiates ADHD from psychiatric comorbidities. Various pharmacologic and nonpharmacologic treatments are available for adults diagnosed with ADHD. First-line pharmacologic treatment of ADHD usually consists of treatment with a psychostimulant, and a variety of short-acting and long-acting formulations are available for use in adults. When developing a treatment plan for adults with ADHD, it is important to recognize that the demands of adult life, both at work and at home, necessitate symptom control throughout the entire day and into the evening and indicate that a long-acting medication formulation is often preferable. Furthermore, there are important safety concerns, including the potential for drug dependence and serious cardiovascular events, which must be considered before prescribing stimulants.​.

Tactics to improve adherence in depressed primary care patients.

Follow the case of Mr K, a 28-year-old patient who becomes intentionally nonadherent to his antidepressant due to adverse effects. Mr K's symptoms at follow-up suggest that the clinician should consider alternative diagnoses besides major depressive disorder. Reassessment may require additional screening tools and collateral information from patients' family members or friends. Regardless of diagnosis, medication adherence is important. By changing the way that questions are phrased and spending a few extra minutes explaining instructions for successful treatment, clinicians may be able to improve adherence.

Diagnosing binge eating disorder in a primary care setting.

Binge eating disorder (BED), now recognized as a distinct eating disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, is the most prevalent eating disorder. Although nearly half of individuals with BED are obese, BED also occurs in nonobese individuals. Despite the relatively high percentage of weight loss treatment-seeking individuals meeting BED criteria, primary care physicians may not be familiar with or have ever diagnosed BED. Many providers may also have difficulty distinguishing BED as a contributory factor in obesity. This review differentiates BED from other causes of obesity by describing how obese individuals with BED differ from obese individuals without BED and from nonobese individuals with BED in areas including psychopathology, behavior, genetics, physiology, quality of life and productivity. The ways in which health-care providers can identify individuals who may have BED are also highlighted so the proper course of treatment is pursued. Overall, obese individuals with BED demonstrate a number of key characteristics that differentiate them from obese individuals without eating disorders, including increased impulsivity in response to food stimuli with loss of control over eating, resulting in the consumption of more calories. They also experience significant guilt and other negative emotions following a meal. In addition, individuals with BED patients have more psychiatric comorbidity, display more psychopathology, exhibit longer binge durations, consume more meals as snacks during the day and have less dietary restraint compared with individuals with BED who are not obese. However, the differences between individuals with BED who are obese versus not obese are not as prominent. Taken together, the evidence appears to support the conclusion that BED is a unique and treatable neurobehavioral disorder associated with distinct behavioral and psychological profiles and distinct medical and functional outcomes, and that it is not merely a subtype of obesity.

Discontinuity in the transition from pediatric to adult health care for patients with attention-deficit/hyperactivity disorder.

BACKGROUND: Although attention-deficit/hyperactivity disorder (ADHD) is a chronic disorder, treatment declines dramatically in adolescence and into early adulthood. This premature termination of care is likely compounded by the difficulty many patients have switching from a pediatric to an adult provider. OBJECTIVE: To review, from the adult primary care provider perspective, the barriers to continuity of care and their implications for patients with ADHD who transition from pediatric to adult health care. DESIGN: Literature review. APPROACH: Relevant articles were identified by searches of the PubMed and EMBASE databases and by reviewing the reference lists of articles obtained from these searches. RESULTS: Health care transition for adolescents and young adults with ADHD remains a crucial area of research. The current literature reveals a number of barriers to the continuity of care, including disparities and inadequacies in ADHD education in primary care and internal medicine residencies, prohibitive prescribing practices with respect to stimulants, inadequate clinic staffing, lack of support in the college health care system, inadequate health insurance coverage, and failure to conduct transitional planning. Without improved continuity of care and adherence to medication, adolescents and young adults with ADHD are at greater risk of academic, social, and vocational difficulties, as well as behavioral problems, including substance abuse, unsafe driving, and criminal activity. CONCLUSION: If we are to adequately address the health care needs of adolescents and young adults with ADHD, we need to educate primary care providers and support additional research.

Distinguishing symptoms of ADHD from other psychiatric disorders in the adult primary care setting.

Attention-deficit/hyperactivity disorder (ADHD) is frequently misdiagnosed or undiagnosed in adults. Owing to the relatively recent recognition of adult ADHD as a valid mental disorder and its overlapping symptomatology with other conditions, primary care physicians often fail to screen for ADHD in patients who present with inattention, impulsivity, and hyperactivity. A substantial proportion of adults with ADHD also have psychiatric comorbidities. Physicians need to recognize the ways in which ADHD symptoms are expressed in adults and distinguish them from symptoms of other disorders, including mood, anxiety, and substance abuse disorders.

The effect of pain on outcomes in a trial of duloxetine treatment of major depressive disorder.

BACKGROUND: Patients with major depressive disorder (MDD) frequently report one or more pain symptoms. To explore the relationship between improvement in pain symptoms and MDD treatment outcomes, we conducted a secondary analysis of an approximately 12-week, open label trial of duloxetine in MDD. The primary objective was to test the hypothesis that a greater reduction in pain was associated with a higher probability of MDD remission. METHODS: Adults with DSM-IV MDD were enrolled in the study if they had a Hamilton Depression Scale (HAMD-17) total score of 15 or more and a Clinical Global Impression of Severity (CGI-S) score of 4 or more. The duloxetine dose of patients could be titrated on the basis of the degree of response within the range from 60 to 120 mg given QD, with 90 mg QD as an intermediate dose. Remission of major depressive disorder was defined as a HAMD-17 total score of < or = 7. Core emotional symptoms of depression were determined by the HAMD-17 Maier subscale. Pain was assessed using a 100 mm visual analog scale (VAS) of overall pain severity over the last week (0 = no pain, 100 = pain as severe as I can imagine). For the primary analysis, mean change in VAS overall pain score over time was compared between remitters and non-remitters at endpoint using a mixed model repeated measures approach. RESULTS: Two hundred forty nine patients were included in the analysis. A greater reduction in pain was associated with a significantly higher probability of remission of MDD, after accounting for changes in the core emotional symptoms. Greater pain reduction was associated with significant improvement in MDD core emotional symptoms. A greater improvement in pain was also associated with improvements in patient and clinician-rated global assessments. CONCLUSIONS: The effective treatment of pain symptoms in patients with major depressive disorder was associated with higher remission rates. The results underscore the importance of effectively treating painful symptoms associated with depression.

Attention-deficit/hyperactivity disorder in adults: a survey of current practice in psychiatry and primary care.

BACKGROUND: Recognition and treatment of attention-deficit/hyperactivity disorder (ADHD) in adults in psychiatry and primary care have faced many obstacles. METHODS: Review by 50 psychiatrists and 50 primary care practitioners (PCPs) of 537 and 317 medical records, respectively, of adults diagnosed as having ADHD. Information on other psychiatric disorders, time of onset of ADHD, source of referral, use of referrals for diagnosis, ADHD treatment, and use of drug holidays was recorded. RESULTS: Forty-five percent of the patient records reviewed by psychiatrists and 65% reviewed by PCPs indicated previous diagnoses of ADHD. Only 25% of the adults with ADHD had been first diagnosed as having the disorder in childhood or adolescence. A diagnosis of ADHD was the initial cause for referral in 80% of psychiatric patients and 60% of PCP patients. Most patients with previously diagnosed and undiagnosed ADHD were self-referred. Among patients who had not received a prior diagnosis, 56% complained about ADHD symptoms to other health professionals without being diagnosed; PCPs were the least aggressive in diagnosing ADHD. In psychiatric and PCP settings, there was a statistical difference in the use of pharmacotherapy (91% vs 78%, respectively) and the proportion of patients taking drug holidays (24% vs 17%, respectively); most drug holidays were initiated by the patient (57%). Stimulants were the treatment of choice for adult ADHD (84% treated with stimulants). CONCLUSION: Data contained within this medical record review suggest that adult ADHD is a substantial source of morbidity in both psychiatric and PCP settings.