The population of patients with major depressive disorder (MDD) and suicidal ideation (SI) or behaviors/attempts (SA) is not well characterized. Electronic health records (EHR) may contain useful data elements that are unavailable in other routinely used population-level databases like insurance claims. For example, the Patient Health Questionnaire (PHQ)-9 is a disease severity metric in this population which may influence treatment choices and hence, outcomes. This study sought to describe the treatments, depression severity, and health resource utilization among this population prior to, during, and following a suicide-related event.

Adult patients enrolled in an integrated delivery network with a diagnosis code indicating MDD and without a diagnosis for bipolar or related disorders, dementia, intellectual disability, schizophrenia or other non-mood psychotic disorders between 10/31/2015 and 9/30/2019 were selected from the Optum de-identified EHR database. Only patients with a diagnosis code for SI or probable SA (SI/SA) between 10/31/2016 and 9/3/2019 and healthcare activity ≥12 months prior to their 1st observed SI/SA diagnosis were included. MDD-related treatments and PHQ-9 scores (obtained from physician notes using natural language processing) were described during 3 periods: the 1st SI/SA health care encounter (index period), 12 months before (pre-period), and 6 months after (follow-up period). For those with multiple PHQ-9 scores during a period, the latest one was used. All-cause and MDD-related healthcare utilization were assessed during follow-up period.

A total of 71,161 patients with MDD and SI/SA were included in the analysis; mean (SD) age was 39 years (16 years); 55% were female. Antidepressants were prescribed for 31.3% during the pre-period and 41.2% during the index period. The use of psychotherapy was 9.5% during the pre-period and 18.7% during the index period. In the subgroup with data at 6 months (N=40,261), 43.4% and 20.5% received an antidepressant prescription and psychotherapy, respectively. During follow-up, the percent with ≥1 all-cause (MDD-related) hospitalization, observation stay and ED visit were: 11.8% (7.0%), 5.0% (2.1%), and 33.1% (11.1%). More than half (61.0) had ≥1 outpatient visit, and about 1/3 (33.4%) had ≥1 MDD-related outpatient visit. Very few patients had PHQ-9 scores recorded: pre-period 4.4% (mean [SD] 13.0 [7.5]); index period 1.3% (mean [SD] 17.0 [7.2]); and follow-up period 7.6% (mean [SD] 12.1 [7.5]).

This study documents a high level of health care resource utilization among those with MDD and suicidal thoughts and behaviors. Only a small proportion had documented PHQ-9 scores. Given that sizable proportions did not receive any antidepressant therapy or psychotherapy, even after suicidality was noted in their medical record, continued efforts in screening and treatment intensification are warranted for this vulnerable population.

Janssen Scientific Affairs, LLC

To describe characteristics of veterans with MDD and the different treatment regimens received during the first observed and treated major depressive episode (MDE).

A retrospective study was performed using the Veterans Health Administration (VHA) database from 4/1/2015 to 2/28/2019 (study period), supplemented with Medicare Part A/B/D data from 4/1/2015 to 12/31/2017. Adult veterans with ≥1 MDD diagnosis in the VHA database between 10/1/2015 and 2/28/2017 (index date) were included if they received ≥1 line of therapy (LOT) within a complete MDE. An MDE was considered as starting on the date of the first observed MDD diagnosis preceded by ≥6 months depression-free period (i.e. a period without an MDD diagnosis or antidepressant (AD) use); an MDE was considered as ended on the date of the last MDD diagnosis or the end of the medication supply of the last AD/augmentation medication, whichever came last and then followed by ≥6 months depression-free period. An MDE was required to begin and end during the study period. A LOT was defined as ≥1 AD at adequate dose and duration (≥6 weeks of continuous therapy with no gaps longer than 14 days) with or without an augmenting medication. Patients were required to have VA benefit enrollment for ≥6 months before (baseline) and ≥24 months after index (follow-up). Patient baseline demographic and clinical characteristics as well as the number and type of LOTs (up to the first six LOTs) received during the first observed and treated MDE were evaluated.

Overall, 40,240 veterans with MDD were identified (mean ± standard deviation [SD] age: 50.9±16.3 years).The majority were male (83.9%), White (63.4%), and non-Hispanic (88.6%); 60.1% were unemployed or retired at some point during the study period. The most commonly observed baseline comorbidities included hypertension (27.5%), hyperlipidemia (20.8%), post-traumatic stress disorder (17.5%), and diabetes (14.8%). During the first observed and treated MDE (mean ± SD duration: 14.7 ± 8.6 months), patients received a mean of 1.6±1.0 LOTs, with 36.5% and 14.6% of patients receiving ≥2 and ≥3 LOTs, respectively; 0.8% of patients received ≥6 LOTs. The most commonly observed therapies were SSRI monotherapy (58.9%) followed by SNRI monotherapy (8.8%) in LOT1; SSRI monotherapy followed by AD augmented with anticonvulsants in LOT2 (SSRI monotherapy: 48.7%; AD augmentation with anticonvulsants:12.1%) and LOT3 (SSRI monotherapy: 43.5%; AD augmentation with anticonvulsants:15.0%).

This study used an episodic approach to evaluate the current standard of care among veterans with MDD. During the first observed and treated MDE, about one in seven veterans received ≥3 LOTs, suggesting presence of treatment-resistant MDD. Monotherapy with SSRIs or SNRIs and combination therapies of AD with anticonvulsants were the most common therapies in the first three LOTs.

Janssen Scientific Affairs, LLC

The purpose of this case study is to review the clinical presentation and medical workup of a young adult male presenting with acute behavior changes in the setting of undiagnosed ornithine transcarbamylase deficiency (OTCD)

This case study involves a 19-year-old male with a psychiatric history of depression and one previous suicide attempt, who presented to a large midwestern university hospital emergency department after being found by police naked in a neighbor’s yard. He displayed manic signs and symptoms, including euphoria, lack of sleep for five days, and attempting to purchase a new car and three large screen TVs. Family reported the patient uncharacteristically announced three weeks earlier that he was vegetarian and stopped eating his frequent customary cheeseburgers. Due to increased anxiety and inability to sleep, the patient received lorazepam 2 mg in the emergency department. Upon transfer to the psychiatric unit, therapy was initiated with aripiprazole 5 mg daily and valproate 1000 mg nightly on Day 1 of treatment. The patient refused medications on hospital Day 2, then received this combination again on Day 3. The next morning, the patient complained of lethargy, headache, nausea, and vomiting.

The patient’s ammonia level was found to be 204 micromol/L with ALT and AST of 714 and 647 IU/L respectively. Tests for infectious hepatitis were negative. Medical consultation recommended discontinuation of current medications, vigorous hydration, and further work up. On further investigation, the patient was found to have low plasma citrulline level of 8 micromol/L, undetectable plasma arginine, and high urinary orotic acid. The laboratory data showed a biochemical phenotype consistent with a diagnosis of partial OTCD, an X-linked urea cycle disorder resulting in toxic hyperammonemia. The patient was treated with a low protein diet modification as well as a combination of sodium benzoate and sodium phenylbutyrate to reduce serum ammonia concentration. With treatment the patient’s laboratory values normalized, and mental status improved.

In conclusion, partial ornithine transcarbamylase deficiency may manifest with psychiatric symptoms in early adulthood. In young patients with elevated ammonia and mental status change, OTCD is an important diagnosis to consider, as it is the most common inherited cause of hyperammonemia.

Restraint and seclusion were considered a form of treatment but consistently has led to physical and mental injuries to staff and patients. De-escalation has been viewed as a safer option. Understanding which intervention yields decreased injuries, aggression and violence will guide policy and inform practice.

To identify which intervention leads to decreased physical and psychological injury to patients and staff.

The frequency of physical injuries to patients and staff from aggressive patients; frequency of psychological injuries to patients and staff from violent, aggressive incidents; frequency of violence, agitation and aggression; competence of staff at managing aggression and violence were evaluated.

Fourteen studies were included in this review. There are many forms of de-escalation. Studies where techniques were taught to staff, the intervention was effective in decreasing injury in approximately half the studies. De-escalation techniques taught to patients decreased injury in 100% of the studies included in this review.

Consensus on which intervention works best could not be reached, nor is there overwhelming evidence for a particular type of de-escalation better suited for decreasing aggression and violence. Caution should be exercised when choosing a de-escalation technique for implementation in institutions due to lack of regulating agencies that inform practice and standards. In addition, the literature lacks best practices for de-escalation techniques backed by evidence. Restraint and seclusion should be used as a last resort due to inherent risk associated with the intervention.

The impact of pandemic events such as the coronavirus (COVID-19) pandemic led to an economic crisis worldwide as well as an increase of mental health problems. In the United States, the gaps in the mental health care system struggle to meet the needs of vulnerable populations and have caused a major public health problem. We aim to increase the awareness of health care professionals, psychiatrists, and policy makers regarding failures and gaps in the mental health care system and suggest new ideas to overcome the growing burden of mental disorders.

We utilized data from PubMed, Science Direct, Cochrane, Embase and Clinicaltrials.gov databases to analyze available information on the US mental health system. We included any relevant articles addressing the prevalence of mental diseases, disparities and the gaps for an accessible and affordable mental health system, as well as the psychological impact of COVID-19 pandemic.

‘COVID-19’, ‘Coronavirus’, ‘SARS-CoV-2’, ‘mental health’, ‘Health, Mental’ were used.

Following scoping review of several studies we noticed that while prevalence of mental health problems in the US varies between states and socio-demographic groups, it is among the top 10 causes of premature death and disability in adults. We noticed that mental health problems are currently one of the costliest public health issues in the healthcare system. Tracking Poll from one of the studies in our scoping review suggested that financial inequities are magnified by the COVID-19 pandemic and that psychological distress was substantially larger among respondents with lower income (33%), Hispanics (28%) and Blacks (26%). Furthermore, in another poll 62% of US population are shown to be anxious due to COVID-19. We observed that the prevalence of reported symptoms of psychological distress among US adults increased when compared to 2018. Common barriers such as failure of accessibility, insufficient funding, insufficient psychiatric beds, limited insurance access and economic burden, clinician shortages, fragmented care, insufficient mental health care policies and insufficient education and awareness about mental illness become more prominent during the COVID-19 pandemic era.

The impact of COVID-19 on mental health is alarming, which affects public health and has made the health care system more vulnerable. Pandemic events not only cause acute negative impact, they also result in long-lasting health problems, isolation and stigma. The COVID-19 pandemic threatens the mental health of the population and its long-term consequences can lead to a secondary pandemic. The outcomes of the COVID-19 pandemic on mental health emphasize the need for policies and strategies to support and strengthen a concerted effort to address its burden on the US mental health care system. In addition, it magnifies the need for high quality and well-funded research for future pandemics.

Chorea is defined as a hyperactive movement disorder associated with involuntary, quick, and unpredictable muscle contractions of the limbs, face, and trunk. The unpredictable nature of these movements includes variation in speed, timing, and direction of movement. A wide variety of medications, medical conditions and illicit drugs have been associated with movement disorders. Examples include a multitude of antipsychotic induced movement disorders and dyskinesia related to dopaminergic agents, like levodopa and metoclopramide. Dyskinesias have been associated with psycho-stimulant use, such as methylphenidate. However, most cases reported were associated with large doses or chronic use. Aside from dyskinesia, methylphenidate is known to be associated with tic disorder, tremor, and muscle spasm. However, this case reported is unlike any of the above described and involved the development of chorea after only 2 days of moderate doses of methylphenidate, in a patient on chronic methadone maintenance treatment, with successful arrest of symptoms following discontinuation of the methylphenidate.

A 47-year-old female was admitted to our hospital after presenting to the emergency department with 1 week of violent flailing movements. The ballistic flailing movements started acutely after 2 days of initiating methylphenidate in addition to her chronic methadone treatment and 2-week period of initiation of paroxetine. Lab work showed normal CBC, CMP, CRP, CK, and TSH. Urine drug screen, CT angiography of the head, and Huntington’s disease testing were all unremarkable, suggesting a decreased likelihood of illicit drugs, traumatic brain injury, or Huntington’s disease etiologies. Confirmation of the diagnosis was made as the chorea symptoms abruptly resolved upon discontinuation of methylphenidate and administration of intravenous Benadryl. The patient has been on methadone alone for 11 months and methylphenidate alone 2 years back with no involuntary movements or any similar presentation that shows the possibility of drug interaction through cytochrome P450 metabolism between Methylphenidate and methadone.

We are presenting a rare case report that adds on to the scarce literature on methylphenidate-induced chorea. It also challenges the consulting psychiatrists to broaden their differential diagnosis for acute onset of choreiform movement disorders. This unique case intrigues the thought process to consider the interaction of methylphenidate in the presence of cytochrome P450 2D6 and 3A4 inhibitors like methadone.

This review discusses the potential negative consequences of untreated insomnia in correctional settings.

A literature review was conducted on the association between insomnia and negative health outcomes, the best practices for treating insomnia with and without medications, and common practices that prohibit the treatment of insomnia in correctional settings.

Untreated insomnia was associated with increased psychiatric distress, increased risk for suicide, and increased all-cause mortality. Common practices in many correctional institutions impose restrictions on treating insomnia. These practices lead to an increased likelihood for negative health outcomes, including suicide and an increase in all-cause death.

Practices that prohibit the treatment of sleep in correctional settings increase the risk of death by suicide and other adverse health outcomes. The practices are often put in place due to pressure from the security staff who have trouble controlling the black-market trade of prescribed medications and other contraband within jails and prisons. Healthcare professionals in the correctional setting must advocate for the importance of treating sleep problems in jails and prisons and work with security staff on ways to overcome the problems of pill diversion and the trade of contraband in order to provide quality healthcare to this protected population.

Coordinated specialty care (CSC) is widely accepted as an evidence-based treatment for first episode psychosis (FEP). The NAVIGATE intervention from the Recovery After an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP) study is a CSC intervention which offers a suite of evidence-based treatments shown to improve engagement and clinical outcomes, especially in those with shorter duration of untreated psychosis (DUP). Coincident with the publication of this study, legislation was passed by the United States Congress in 2014–15 to fund CSC for FEP via a Substance Abuse and Mental Health Services Administration (SAMHSA) block grant set-aside for each state. In Michigan (MI) the management of this grant was delegated to Network180, the community mental health authority in Kent County, with the goal of making CSC more widely available to the 10 million people in MI. Limited research describes the outcomes of implementation of CSC into community practices with no published accounts evaluating the use of the NAVIGATE intervention in a naturalistic setting. We describe the outcomes of NAVIGATE implementation in the state of MI.

In 2014, 3 centers in MI were selected and trained to provide NAVIGATE CSC for FEP. In 2016 a 4th center was added, and 2 existing centers were expanded to provide additional access to NAVIGATE. Inclusion: age 18–31, served in 1 of 4 FEP centers in MI. Data collection began in 2015 for basic demographics, global illness (CGI q3 mo), hospital/ED use and work/school (SURF q3 mo) and was expanded in 2016 to include further demographics, diagnosis, DUP, vital signs; and in 2018 for clinical symptoms with the modified Colorado Symptom Inventory (mCSI q6 mo), reported via an online portal. This analysis used data until 12/31/19. Mixed effects models adjusted by age, sex and race were used to account for correlated data within patients.

N=283 had useable demographic information and were included in the analysis. Age at enrollment was 21.6 ± 3.0 yrs; 74.2% male; 53.4% Caucasian, 34.6% African American; 12.9 ± 1.7 yrs of education (N=195). 18 mo retention was 67% with no difference by sex or race. CGI scores decreased 20% from baseline (BL) to 18 mo (BL=3.5, N=134; 15–18 mo=2.8, N=60). Service utilization via the SURF was measured at BL (N=172) and 18 mo (N=72): psychiatric hospitalizations occurred in 37% at BL and 6% at 18 mo (p<0.01); ER visits occurred in 40% at BL and 13% at 18 mo (p<0.01). 44% were working or in school at BL and 68% at 18 mo (p<0.01). 21% were on antipsychotics (AP) at BL (N=178) and 85% at 18 mo (N=13) with 8% and 54% on long acting injectable-AP at BL and 18 mo, respectively. Limitations include missing data and lack of a control group.

The implementation of the NAVIGATE CSC program for FEP in MI resulted in meaningful clinical improvement for enrollees. Further support could make this evidence-based intervention available to more people with FEP.

Supported by funds from the SAMHSA Medicaid State Block Grant set-aside awarded to Network180 (Achtyes, Kempema). The funders had no role in the design of the study, the analysis or the decision to publish the results.

The purpose of this work was to determine the extent to which a multiparametric magnetic resonance imaging (MRI) approach to patients with dementia and/or traumatic brain injury (TBI) can help to determine the most likely diagnosis and the prognosis of these patients.

Volumetric brain MRI alone is recognized as a useful imaging tool to differentiate behavioral variant frontotemporal dementia (bvFTD) from the more common Alzheimer’s disease (AD). Our objective is to create a protocol that will provide additional non-standard, objective imaging data that can be utilized clinically to distinguish common and uncommon forms of dementia and TBI. As patients with these diseases are increasingly presenting to clinical practice, our ability to combine multiple parameters within the standard 30-minute or 45-minute (pre- and post-contrast) MRI exams has high potential to affect current and future clinical practice.

All MRI studies were performed on 1.5 T MRI GE 450w or GE HDx imagers. All patients were seen clinically in outpatient practices. All techniques are FDA approved. The 30 minute protocol utilized T2w FSE 3 mm, 2.5 mm SWAN, 3D T1 sagittal 1.2 mm, DWI 5 mm, 3D FLAIR 1.2 mm, 2.5 mm SWAN (susceptibility sensitive), 3D T1 sagittal 1.2 mm, arterial spin labeling perfusion, posterior cingulate single voxel PRESS MR spectroscopy and NeuroQuant automated volumetric analysis and LesionQuant automated lesion detection and measurement. The 45-minute TBI protocol added diffusion tensor imaging, MR spectroscopy (MRS) of normal appearing frontal white matter and 3D gadolinium enhanced technique.

The combination of multiparametric data together with standard imaging and clinical information allowed radiologic interpretation that was able to focus on 1–2 specific diagnoses and to indicate those patients in which a combination of pathologies was most likely. Neurologists, gerontologists, neuropsychologists and psychiatric specialists used these data and our summary conclusions to develop more specific diagnoses, treatments and prognoses.

Readily available MRI techniques can be added to standard imaging to markedly improve the usefulness of the radiologic opinion in cases of subjective cognitive insufficiency, clinical mild cognitive insufficiency, behavioral pathologies, dementia and post-traumatic brain syndromes.

There is a plethora of drugs available to psychiatrists for treatment of mental illness, which can vary in efficacy, tolerability, metabolic pathways and drug-drug interactions. Psychotropics are the second most commonly listed therapeutic class mentioned in the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling. Pharmacogenomic (PGx) assays are increasingly used in psychiatry to help select safe and appropriate medication for a variety of mental illnesses. Our commercial laboratory offers PGx expert consultations by PharmDs and PhDs to clinician-users. Our database contains valuable information regarding the treatment of a diverse and challenging population.

Genomind offers a PGx assay currently measuring variants of 24 genes relevant for selection of drugs with a mental illness indication. Since 2012 we have analyzed > 250,000 DNA samples. Between 10/18 - 8/20 6,401 reports received a consult. The data contained herein are derived from those consults. Consultants record information on prior meds, reason for failure or intolerability, potential risk-associated or useful drugs based on the genetic variants. Consultants only recommend specific drugs and doses consistent with a published PGx guideline.

The 5 most commonly discussed genes were SLC6A4, MTHFR, CACNA1C, COMT and BDNF. The 3 most commonly discussed drugs were fluoxetine, lithium and duloxetine. The most common reasons for drug failure were inefficacy and drug induced “agitation, irritability and/or anxiety”. SSRIs were the most common class of discontinued drug; sertraline, escitalopram and fluoxetine were the three most commonly reported discontinuations and were also the 3 most likely to be associated with “no improvement”. Aripiprazole was the most commonly reported discontinued atypical antipsychotic. The providers rated 94% of consultations as extremely or very helpful at the time of consult. An independent validation survey of 128 providers confirmed these ratings, with 96% reporting a rating of “very helpful” or “extremely helpful”. In addition, 94% reported that these consults were superior to PGx consults provided through other laboratories. Patient characteristics captured during consults via a Clinical Global Impressions-Severity (CGI-S) scale revealed that the majority of patients were moderately (54%) or markedly ill (23%). The most frequent symptoms reported were depression, anxiety, insomnia and inattentiveness.

The large variety of psychotropic drugs available to providers, and their highly variable response rates, tolerability, capacity for drug-drug interactions and metabolic pathways present a challenge for even expert psychopharmacologists. Consultation with experts in PGx provides additional useful information that may improve outcomes and decrease healthcare resource utilization. This database may provide future opportunities for machine learning algorithms to further inform implications of included gene variants.

Genomind, Inc.

Depression is an important cause of disability in the United States (US). The care experience of major depressive disorder (MDD) is highly variable and has only been documented to a limited degree. This study examines the prevalence incidence and treatment patterns for MDD in the US general population.

In this longitudinal study 2 interview waves were conducted between 2002 and 2015. The initial wave (W1) was carried out with 12,218 individuals from the general population in 8 US states with participants aged 18 years or older. In the second wave (W2) 10,931 of the initial participants agreed to be interviewed again 3 years later; the analyses were carried out for individuals who participated in both interviews (N=10,931). Diagnosis of MDD was confirmed according to Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria.

The 3-year incidence of MDD was 3.4% (95% CI 3.1%–3.7%). The prevalence of MDD was 5.1% (95% CI 4.7%–5.5%) and 4.2% (95% CI 3.8%–4.6%) in W1 and W2, respectively. The percentages of participants who achieved partial and complete remission were 4.4% (95% CI 4.0%–4.8%) and 3.9% (95% CI 3.5%–4.3%) in W1 compared with 7.9% (95% CI 7.4%–8.4%) and 4.4% (95% CI 4.0%–4.8%) in W2, respectively. The prevalence of MDD was 13.4% and 16.5% in W1 and W2, respectively, when including participants with MDD partial and complete remission episodes. 61.9% of participants with an MDD diagnosis in W1 had at least one associated comorbidity. 41.8% of participants with an MDD diagnosis at W1 still reported significant depressive symptoms at W2. 19.9% of participants in partial remission and 5.5% of participants in complete remission in W1 did not achieve remission in W2. 52.2% and 42.9% of participants with MDD were treated with an antidepressant (AD) in W1 and W2, respectively; selective serotonin reuptake inhibitors (SSRIs) were the most commonly prescribed (34.7% in W1 vs 28.3% in W2). ADs were mainly prescribed by primary care physicians (45.7%) followed by psychiatrists (31.4%), neurologists (2.5%), and other specialties (7.9%). The average duration of treatment was 36.9 (SE 2.4) months. More than one-third of AD users in W1 expressed dissatisfaction with their AD treatment which translated into changes in types of antidepressant in W2.

Depression affects a sizable part of the general population in the US with a prevalence of MDD at 13.4%–16.5%; yet MDD remains largely undertreated as shown by the finding that only about half (52%) of individuals in this study who met the diagnostic criteria for MDD were treated with an antidepressant (SSRI being the most common treatment). In addition, more than a quarter of patients with MDD in this study did not achieve remission after initial treatment underscoring the challenges in successful antidepressant treatment of MDD.

Takeda Pharmaceuticals U.S.A. Inc. and Lundbeck LLC

Although mania is the hallmark symptom of bipolar I disorder (BD-I), most patients initially present for treatment with depressive symptoms. Misdiagnosis of BD-I as major depressive disorder (MDD) is common, potentially resulting in poor outcomes and inappropriate antidepressant monotherapy treatment. Screening patients with depressive symptoms is a practical strategy to help healthcare providers (HCPs) identify when additional assessment for BD-I is warranted. The new 6-item Rapid Mood Screener (RMS) is a pragmatic patient-reported BD-I screening tool that relies on easily understood terminology to screen for manic symptoms and other BD-I features in <2 minutes. The RMS was validated in an observational study in patients with clinically confirmed BD-I (n=67) or MDD (n=72). When 4 or more items were endorsed (“yes”), the sensitivity of the RMS for identifying patients with BP-I was 0.88 and specificity was 0.80; positive and negative predictive values were 0.80 and 0.88, respectively. To more thoroughly understand screening tool use among HCPs, a 10-minute survey was conducted.

A nationwide sample of HCPs (N=200) was selected using multiple HCP panels; HCPs were asked to describe their opinions/current use of screening tools, assess the RMS, and evaluate the RMS versus the widely recognized Mood Disorder Questionnaire (MDQ). Results were reported by grouped specialties (primary care physicians, general nurse practitioners [NPs]/physician assistants [PAs], psychiatrists, and psychiatric NPs/PAs). Included HCPs were in practice <30 years, spent at least 75% of their time in clinical practice, saw at least 10 patients with depression per month, and diagnosed MDD or BD in at least 1 patient per month. Findings were reported using descriptive statistics; statistical significance was reported at the 95% confidence interval.

Among HCPs, 82% used a tool to screen for MDD, while 32% used a tool for BD. Screening tool attributes considered to be of the greatest value included sensitivity (68%), easy to answer questions (66%), specificity (65%), confidence in results (64%), and practicality (62%). Of HCPs familiar with screening tools, 70% thought the RMS was at least somewhat better than other screening tools. Most HCPs were aware of the MDQ (85%), but only 29% reported current use. Most HCPs (81%) preferred the RMS to the MDQ, and the RMS significantly outperformed the MDQ across valued attributes; 76% reported that they were likely to use the RMS to screen new patients with depressive symptoms. A total of 84% said the RMS would have a positive impact on their practice, with 46% saying they would screen more patients for bipolar disorder.

The RMS was viewed positively by HCPs who participated in a brief survey. A large percentage of respondents preferred the RMS over the MDQ and indicated that they would use it in their practice. Collectively, responses indicated that the RMS is likely to have a positive impact on screening behavior.

AbbVie Inc.

Cariprazine, a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist, is approved for the treatment of schizophrenia and for depressive, manic, or mixed episodes associated with bipolar I disorder. Previous post hoc analyses have demonstrated that cariprazine was effective versus placebo for improving cognitive symptoms in patients with schizophrenia or bipolar depression. This post hoc analysis evaluated the effects of cariprazine on cognitive symptoms in patients with acute manic or mixed bipolar episodes.

Data from 3 phase II/III, randomized, double-blind, placebo-controlled studies in patients with manic or mixed episodes associated with bipolar I disorder (NCT00488618, NCT01058096, NCT01058668) were pooled and analyzed. Patients were randomized to placebo or flexibly dosed cariprazine (3-12 mg/d, 3-6 mg/d, or 6-12 mg/d [1 study only]) for 3 weeks of double-blind treatment; all dose groups were combined for the pooled analysis. Cognitive symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) Cognitive subscale (sum of PANSS items P2, N5, N7, G10, G11); a score of 15 or greater at baseline indicated the presence of cognitive symptoms. Mean changes from baseline to week 3 in PANSS cognitive subscale/item scores and Young Mania Rating Scale (YMRS) total score were evaluated in the overall intent-to-treat (ITT) population and in the subgroup of patients with baseline cognitive symptoms. A mixed-effects model for repeated measures (MMRM) was used to impute missing values.

Of the 1012 patients in the ITT population, 174 (placebo=71; cariprazine=103) had a PANSS Cognitive subscale score of 15 or greater at baseline. At week 3, the cariprazine group demonstrated significantly greater mean improvement than the placebo group on PANSS cognitive subscale scores in both the ITT population (−2.2 vs −1.3; P<.0001) and the subgroup with baseline cognitive symptoms (−4.0 vs −1.9; P=.0002). In patients with baseline cognitive symptoms, improvement was significantly greater for cariprazine- versus placebo-treated patients on YMRS total score (−16.7 vs −8.2; P<.0001) and the individual PANSS cognitive subscale items of conceptual disorganization (−1.1 vs −0.5; P=.0004), difficulty in abstract thinking (−0.8 vs −0.3; P=.0044), stereotyped thinking (−0.3 vs −0.1; P=.0350), and poor attention (−1.1 vs −0.6; P=.0043).

In patients with manic or mixed episodes associated with bipolar I disorder, cariprazine versus placebo was effective in improving cognitive symptoms in the overall patient population as well as in patients with baseline cognitive symptoms. In addition, cariprazine versus placebo also demonstrated efficacy in improving manic symptoms in patients with baseline cognitive symptoms. These results suggest that cariprazine may provide benefits for the treatment of cognitive symptoms in patients with bipolar I mania.

AbbVie Inc.

The Montgomery-Åsberg Depression Rating Scale (MADRS) is commonly used for the assessment of depressive symptom changes in patients with major depressive disorder (MDD) or bipolar depression. Categories of depression severity that correspond to ranges of MADRS total score have been previously reported in patients with MDD, but it appears that MADRS severity ranges have not been reported for patients with bipolar I disorder. The objective of this study was to evaluate MADRS total score ranges that correspond with different grades of depression severity in patients with bipolar I depression.

Data were pooled from 3 randomized, double-blind, placebo-controlled, 6- or 8-week trials of cariprazine in patients with bipolar I depression. MADRS severity ranges were evaluated using an anchor-based approach with the clinician-rated, 7-category Clinical Global Impression-Severity (CGI-S) scale. CGI-S has previously been used to determine severity thresholds in MDD. Correlations between MADRS total score and CGI-S score were assessed in the pooled dataset at week 6; placebo and active treatment arms were pooled together. Youden index from receiver operating characteristic (ROC) curves was used to determine the optimal threshold for MADRS total score corresponding to each CGI-S severity level.

The pooled dataset included 1523 patients with bipolar depression. Mean CGI-S scores were highly correlated with mean MADRS total scores at week 6 (r=.87; P<.0001), with MADRS total scores increasing with CGI-S severity. Using the ROC curves, MADRS total score ranges corresponding to each CGI-S severity category were estimated as follows: score of 0-6 for “normal, not at all ill”, 7-12 for “borderline mentally ill”, 13-18 for “mildly ill”, 19-23 for “moderately ill”, 24-36 for “markedly ill”, 37-39 for “severely ill”, and 40 or greater for “extremely ill”. Area under the curve (AUC) values for these cutoffs ranged from 0.930 to 0.997, representing outstanding sensitivity and specificity.

Utilizing data from 3 recent clinical trials of subjects with bipolar depression, we were able to identify MADRS severity thresholds. These empirical findings may help clinicians to understand and contextualize MADRS results from bipolar clinical research and apply to their patients in practice.

AbbVie Inc.