Does Suicide Risk Screening Improve the Identification of Primary Care Patients Who Will Attempt Suicide Versus Depression Screening Alone?

OBJECTIVE: The effectiveness of suicide risk screening relative to depression screening alone among primary care patients has not been tested rigorously. This study compared the performance of multiple depression screening methods (Patient Health Questionnaire [PHQ]-2, PHQ-8, and PHQ-9) and multiple suicide risk screening methods (PHQ-9 item 9 and suicide-focused screening of "thoughts of killing yourself" during the entire lifespan, within the past month, and within the past week) in a convenience sample of primary care patients. METHODS: A total of 2,744 patients (military personnel, family members, and retirees) from six military primary care clinics completed the PHQ-9 and screening for suicidal ideation (SI) during routine clinic visits. Follow-up phone interviews were conducted for one year post-baseline to assess the incidence of suicide attempts, the study's primary outcome. Sensitivity, specificity, accuracy, and F1 statistics were calculated for each screening method for identifying patients who attempted suicide. RESULTS: More than 65% of patients who screened positive for SI also screened positive for depression on the PHQ-9. Depression screening with the PHQ-9 correctly identified more patients who attempted suicide during follow-up than the PHQ-2, past week SI, and past month SI. The PHQ-9 correctly identified more patients who attempted suicide within 3 months than lifetime SI, but lifetime SI correctly identified more patients who attempted suicide within 6 and 12 months. CONCLUSION: Depression screening with the PHQ-9 was the most effective strategy for identifying patients who attempted suicide in the near term. Universal suicide risk screening is unlikely to meaningfully improve identification of higher-risk patients beyond PHQ-9 depression screening.

Rapid intensification of suicide risk preceding suicidal behavior among primary care patients.

BACKGROUND: Approximately half of those who attempt suicide report experiencing suicidal ideation and suicidal planning in advance; others deny these experiences. Some researchers have hypothesized that rapid intensification is due to past suicidal ideation and/or behaviors that are "mentally shelved" but remain available for rapid access later. METHOD: To evaluate this hypothesis, we examined (a) temporal sequencing of suicidal ideation, suicidal planning, and suicidal behavior, and (b) speed of emergence of suicidal behavior in a prospective cohort study of 2744 primary care patients. RESULTS: Of 52 patients reporting suicidal behavior during follow-up, 20 (38.5%) reported suicidal ideation and planning prior to their suicidal behavior, 23 (44.2%) reported suicidal ideation but not planning, and nine (17.3%) denied both suicidal ideation and planning. Over half (n = 30, 57.7%) reported the onset of suicidal ideation and/or planning on the same day as or after their suicidal behavior (i.e., rapid intensification). Rapid intensification was not associated with increased likelihood of reporting recent or past suicidal ideation, planning, or behaviors, suggesting rapid intensification does not depend on prior experience with suicidal ideation and/or behaviors. CONCLUSION: Detecting primary care patients at risk for this form of suicidal behavior may be limited even with universal suicide risk screening.

Development of antidrug antibodies against adalimumab maps to variation within the HLA-DR peptide-binding groove.

Targeted biologic therapies can elicit an undesirable host immune response characterized by the development of antidrug antibodies (ADA), an important cause of treatment failure. The most widely used biologic across immune-mediated diseases is adalimumab, a tumor necrosis factor inhibitor. This study aimed to identify genetic variants that contribute to the development of ADA against adalimumab, thereby influencing treatment failure. In patients with psoriasis on their first course of adalimumab, in whom serum ADA had been evaluated 6-36 months after starting treatment, we observed a genome-wide association with ADA against adalimumab within the major histocompatibility complex (MHC). The association signal mapped to the presence of tryptophan at position 9 and lysine at position 71 of the HLA-DR peptide-binding groove, with both residues conferring protection against ADA. Underscoring their clinical relevance, these residues were also protective against treatment failure. Our findings highlight antigenic peptide presentation via MHC class II as a critical mechanism in the development of ADA against biologic therapies and downstream treatment response.

Scores on the suicide cognitions scale-revised (SCS-R) predict future suicide attempts among primary care patients denying suicide ideation and prior attempts.

BACKGROUND: Approximately half of patients who attempt or die by suicide screened negative for suicidal ideation during their most recent medical visit. Maladaptive beliefs and schemas can increase cognitive vulnerability to suicidal behavior, even among patients without recent or past suicidal thoughts and behaviors. Assessing these beliefs could improve the detection of patients who will engage in suicidal behavior after screening negative for elevated suicide risk. METHODS: Primary care patients who completed the Patient Health Questionnaire-9 and the Suicide Cognitions Scale-Revised (SCS-R) during routine clinic visits and denied suicidal ideation at baseline (N = 2417) were included in the study sample. Suicidal behaviors during the 12 months after baseline were assessed. Logistic regression analyses examined the association of baseline SCS-R scores with later suicidal behavior. RESULTS: In both univariate and multivariate analyses, SCS-R total scores were associated with significantly increased risk of suicidal behavior within 90, 180, and 365 days post-baseline. Results were unchanged when patients who reported prior suicidal behavior were excluded (N = 2178). In item-level analyses, all 16 SCS-R items significantly differentiated patients with and without follow-up suicidal behavior. LIMITATIONS: Study limitations included missing follow-up data, restriction of sample to U.S. military medical beneficiaries, and inability to assess representativeness of the sample relative to the full primary care population. CONCLUSIONS: SCS-R scores are elevated among patients who attempt suicide after denying both suicidal ideation and prior suicide attempts, suggesting the scale may reflect enduring suicide risk. The SCS-R could enhance suicide risk screening and assessment.

Suicide Risk Among Hospitalized Versus Discharged Deliberate Self-Harm Patients: Generalized Random Forest Analysis Using a Large Claims Data Set.

INTRODUCTION: Suicide rates are extremely high among emergency department patients seen for deliberate self-harm. Inpatient hospitalization is often recommended for these patients, but evidence on the suicide prevention impacts of hospitalization is scarce. Confounding by indication and challenges to implementing randomized designs are barriers to advances in this field. METHODS: Investigators used 2009-2012 statewide data on 57,312 self-harm emergency department patients from California, linked to mortality records. Naive 12-month and 30-day suicide risks were estimated among patients who were hospitalized versus those who were discharged. Then, generalized random forest methods were applied to estimate the average treatment impacts of hospitalization on suicide, conditioning on observable covariates. Associations were calculated separately for sex- and age-specific subgroups. Analyses were conducted in February 2019-August 2021. RESULTS: In naive analyses, suicide risk was significantly higher in hospitalized than in discharged patients in each subgroup. In 12-month models accounting for the observed covariates through generalized random forest methods, hospitalized male patients had 5.4 more suicides per 1,000 patients (95% CI=3.0, 7.8), hospitalized patients aged 10-29 years had 2.4 more suicides per 1,000 (95% CI=1.1, 3.6), and those aged ≥50 years had 5.8 more suicides per 1,000 (95% CI=0.5, 11.2) than corresponding discharged patients. Hospitalization was not significantly associated with suicide among female patients or patients aged 30-49 years in generalized random forest analyses. Patterns were similar in 30-day generalized random forest models. CONCLUSIONS: Emergency department personnel intend to hospitalize self-harm patients with high suicide risk; this study suggests that this goal is largely realized. Analyses that control for confounding by observable covariates did not find clear evidence that hospitalization reduces suicide risk and could not rule out the possibility of iatrogenic effects.

Psychometric evaluation of the Suicide Cognitions Scale-Revised (SCS-R).

The measurement of self-reported suicide risk can be complicated in medical settings due to patient apprehension about the potential consequences of self-disclosure. The Suicide Cognitions Scale (SCS) was designed to assess suicide risk by measuring a range of suicidogenic cognitions (e.g., hopelessness, perceived burdensomeness) collectively referred to as the suicidal belief system. The SCS's concurrent, known groups, and prospective validity for suicidal thoughts and behaviors have previously been supported. The present study examined the factor structure, known-groups, and concurrent validity of a revised, 16-item version of the SCS (SCS-R), which removed two items that explicitly used the word "suicide" and changed item scoring from a 1-5 to 0-4 scale, thereby improving the interpretation of scores. In a sample of 2,690 primary care patients presenting for routine medical care at one of six US military clinics, results of bifactor analysis supported the scale's unidimensionality. The SCS-R significantly differentiated participants with a history of suicide attempts and was significantly correlated with frequency of thoughts about death and self-harm during the previous 2 weeks. Results align with earlier research and provide psychometric support for the SCS-R.

Improving Suicide Risk Screening to Identify the Highest Risk Patients: Results From the PRImary Care Screening Methods (PRISM) Study.

PURPOSE: Over 95% of patients who screen positive on the Patient Health Questionnaire-9 (PHQ-9) suicide risk item do not attempt or die by suicide, which could lead to unnecessary treatment and/or misallocation of limited resources. The present study seeks to determine if suicide risk screening can be meaningfully improved to identify the highest-risk patients. METHODS: Patients eligible to receive medical treatment from the US Department of Defense medical system were recruited from 6 military primary care clinics located at 5 military installations around the United States. Patients completed self-report measures including the PHQ-9 and 16 items from the Suicide Cognitions Scale (SCS) during routine primary care clinic visits. Postbaseline suicidal behaviors (suicide attempts, interrupted attempts, and aborted attempts) were assessed by evaluators who were blind to screening results using the Self-Injurious Thoughts and Behaviors Interview. RESULTS: Among 2,744 patients, 13 (0.5%) engaged in suicidal behavior in the 30 days after screening and 28 (1.0%) displayed suicidal behavior in the 90 days after screening. Multiple SCS items differentiated patients with suicidal behavior less than 30 days after screening positive for suicide risk. Augmenting the PHQ-9 suicide risk item with SCS items improved the identification of patients who were most likely to have suicidal behavior within a month of screening positive without sacrificing sensitivity. CONCLUSION: Among primary care patients who screen positive for suicide risk on the PHQ-9, SCS items improved screening efficiency by identifying those patients who are most likely to engage in suicidal behavior within the next 30 days.

The Effect of Propofol on a Forced Swim Test in Mice at 24 Hours.

BACKGROUND: There are few rapidly acting treatments for acute suicidality or treatment-resistant depression. Propofol (2,6-diisopropylphenol) is an intravenous anesthetic agent used in outpatient settings. It is a gamma-aminobutyric acid type A agonist and has affinity at the N-methyl-D-aspartate receptor. Elevation in mood and sociality in humans has been observed following propofol-induced anesthesia. Other authors reported an open-label study of repeated dosing of propofol in treatment-resistant depression in which several patients experienced sustained improvement. Recently, we reported that in a rodent model of despair, a forced swim test, 45 minutes after administration of 50 mg/kg propofol, immobility time was significantly reduced. OBJECTIVE: The objective of the experiment was to determine whether the antidepressant-like effects of a single dose of propofol in mice are sustained for 24 hours. METHODS: The time spent immobile during a forced swim test 24 hours after intraperitoneal administration of a single dose of propofol 50 mg/kg or 0.9% saline was evaluated in 24 adult male mice (C57/BL6). Immobility time was quantified and evaluated with a custom video analysis software program. RESULTS: Propofol-treated mice were immobile for a mean (SEM) time of 115 (13) seconds, whereas saline-treated mice were immobile for a mean (SEM) time of 94 (14) seconds. A 2-tailed unpaired t test found no significant difference between the treatment groups (t = 1.07, df = 22; P = 0.30). CONCLUSIONS: Twenty-four hours after intraperitoneal administration, the effect of propofol on immobility time was not statistically significantly different from vehicle. However, given our previous report of at least a short-term benefit of propofol on struggling time in the forced swim time and an encouraging pilot study in humans with treatment-resistant depression, further evaluation of propofol's antidepressant potential may be warranted.

Welfare Checks and Therapeutic Risk Management.

In clinical practice, welfare checks have become a fairly common aspect of suicide prevention. At the same time, the medical literature provides almost no guidance to inform clinicians under what circumstances welfare checks should be requested, how best to go about placing those requests, or how to document decision-making related to this important subject. Literature searches spanning both PubMed and Google Scholar failed to yield any applicable results. Performed correctly, welfare checks have the potential to be life-saving interventions for persons in suicidal crises. Performed incorrectly, welfare checks may become an overly defensive practice that damages therapeutic relationships, violates patients' rights, and consumes important and limited community resources. The need for thoughtful guidance to assist clinicians in navigating these difficult clinical scenarios is long overdue. This column, the second in a 2-part series, offers an approach to welfare checks informed by the tenets of therapeutic risk management.

Implementing an Emergency Department Telephone Follow-Up Program for Suicidal Patients: Successes and Challenges.

BACKGROUND: Many emergency department (ED) patients are at risk of suicide, and the ED is a key setting for suicide prevention. Although ED interventions are associated with reduced suicide attempts and societal costs, most EDs do not have follow-up programs. This pilot investigated the feasibility and implementation process of a statewide program. METHODS: This multicenter prospective pilot program included all patients evaluated for suicidal behavior in, and discharged home from, participating EDs across Colorado. Suicidal ED patients were offered crisis hotline follow-up calls that focused on continued support and connection to outpatient care. Data collection at EDs focused on implementation issues and referral and participation rates; the crisis line collected patient information and call statistics. RESULTS: From July 1, 2015, to October 31, 2017, the program expanded to 15 EDs covering almost a quarter of ED visits in a large, high-burden state. Some sites achieved 100% referral rates, suggesting that referral became routine, and the mean referral rate was 76%. High referral rates were associated with an ED champion, record system enhancements, repeated training, and regular communication. Of 5,620 visits with referral, 2,737 resulted in participation (48.7%). Although the program was free for patients, half declined it. The call center made 15,414 calls, ultimately reaching all but 9.8% of participants. Few participants reported repeat ED visits or suicide attempts. CONCLUSION: This project demonstrated the feasibility of using a state crisis hotline to provide postdischarge follow-up for suicidal ED patients. Continued investigation into sustainable implementation and outcomes of such programs is warranted.

Welfare Checks for Suicide Risk Management: Risks and Benefits.

In clinical practice, welfare checks have become a fairly common aspect of suicide prevention. At the same time, there is almost no guidance in the medical literature to inform clinicians under what circumstances welfare checks should be requested, how best to go about placing those requests, or how to document decision-making around this important subject. Literature searches spanning both PubMed and Google Scholar fail to yield any applicable results. Performed correctly, welfare checks have the potential to be life-saving interventions for persons in suicidal crises. Performed incorrectly, the welfare check may become an overly defensive practice that damages therapeutic relationships, violates patients' rights, and consumes important and limited community resources. The need for thoughtful guidance to assist clinicians in navigating these difficult clinical scenarios is long overdue. This article, the first in a 2-part series, will describe welfare checks and explore their potential risks and benefits.

Screening and Intervention for Suicide Prevention: A Cost-Effectiveness Analysis of the ED-SAFE Interventions.

OBJECTIVE: Suicide screening followed by an intervention may identify suicidal individuals and prevent recurring self-harm, but few cost-effectiveness studies have been conducted. This study sought to determine whether the increased costs of implementing screening and intervention in hospital emergency departments (EDs) are justified by improvements in patient outcomes (decreased attempts and deaths by suicide). METHODS: The Emergency Department Safety Assessment and Follow-up Evaluation (ED-SAFE) study recruited participants in eight U.S. EDs between August 2010 and November 2013. The eight sites sequentially implemented two interventions: universal screening added to treatment as usual and universal screening plus a telephone-based intervention delivered over 12 months post-ED visit. This study calculated incremental cost-effectiveness ratios and cost-effectiveness acceptability curves to evaluate screening and suicide outcome measures and costs for the two interventions relative to treatment as usual. Costs were calculated from the provider perspective (e.g., wage and salary data and rental costs for hospital space) per patient and per site. RESULTS: Average per-patient costs to a participating ED of universal screening plus intervention were $1,063 per month, approximately $500 more than universal screening added to treatment as usual. Universal screening plus intervention was more effective in preventing suicides compared with universal screening added to treatment as usual and treatment as usual alone. CONCLUSIONS: Although the choice of universal screening plus intervention depends on the value placed on the outcome by decision makers, results suggest that implementing such suicide prevention measures can lead to significant cost savings.

The PRImary care Screening Methods (PRISM) study: Rationale and design considerations.

BACKGROUND: Primary care is the most frequently visited clinic type immediately prior to suicidal behavior, with nearly half of suicide decedents visiting a primary care provider within a month of their death. Data supporting the efficacy of suicide risk screening in this setting is lacking, however. Improved suicide risk screening in primary care could lead to earlier intervention and treatment. PURPOSE: The PRImary care Screening Methods (PRISM) study is designed to develop and evaluate the efficacy of an alert algorithm that can be used by military primary care providers to accurately identify high-risk patients, to improve the identification of high-risk patients who deny suicidal thoughts, and to quantify patient subgroups who are more likely to be missed by existing screening methods (i.e., false negatives). METHODS: The rationale of the PRISM study is discussed, along with ethical and design considerations related to the conduct of suicide prevention research. The PRISM study enrolled 2690 patients from six primary care clinics across the U.S. Patients were enrolled during routine visits to a primary care clinic, and completed a battery of self-report scales in clinic waiting rooms. Follow-up phone interviews are conducted 1, 6, and 12 months after enrollment. The primary outcome is suicide attempt. CONCLUSIONS: PRISM is the first study to prospectively examine multiple suicide risk screening methods in "real-world" military primary care clinics. Ethical and design issues were considered to ensure that human participants, especially suicidal patients, were adequately protected while minimizing the potential confounding effect of risk management protocols.

The Effect of Acutely Administered Propofol on Forced Swim Test Outcomes in Mice.

Objective: Propofol (2,6-diisopropylphenol) is a gamma-aminobutyric acid type A agonist intravenous anesthetic agent used in outpatient settings. Based on anecdotal reports of improved mood in humans following propofol-induced anesthesia, the impact of acute propofol treatment alone or in combination with subchronic fluoxetine dosing was tested on forced swim test (FST) performance. Design: Seventy-two adult male mice (C57/BL6, CRL-provided) were pretreated daily with saline or fluoxetine (20 mg/kg, intraperitoneally) (21 days for cohort 1; 24 days for cohort 2). At 24 hours after the last pretreatment injection, the mice received saline or propofol (35 or 50 mg/kg, intraperitoneally). Then, 45 minutes later, the mice underwent a five-minute FST. Immobility time was quantified and evaluated with a custom video-analysis software program. Results: A one-way analysis of variance indicated statistically significant effects of propofol on immobility time in cohorts 1 and 2. A comparison performed using Dunnett's method revealed that propofol 50 mg/kg (p < 0.05) but not 35 mg/kg (p = not significant) reduced immobility time as compared with in the saline-saline control group (difference between means of 38.42 and 16.46 seconds, respectively). Conclusion: In comparison with saline, propofol significantly decreased immobility time during the FST, which models depression and resilience to stress. Our preclinical results are consistent with a small open-label study of propofol used in treatment-resistant depression recently reported by Mickey BJ, White AT, Arp AM, et al (2018). Further investigation of propofol regarding its potential antidepressant effects seems warranted.

Genome-wide meta-analysis implicates mediators of hair follicle development and morphogenesis in risk for severe acne.

Acne vulgaris is a highly heritable common, chronic inflammatory disease of the skin for which five genetic risk loci have so far been identified. Here, we perform a genome-wide association study of 3823 cases and 16,144 controls followed by meta-analysis with summary statistics from a previous study, with a total sample size of 26,722. We identify 20 independent association signals at 15 risk loci, 12 of which have not been previously implicated in the disease. Likely causal variants disrupt the coding region of WNT10A and a P63 transcription factor binding site in SEMA4B. Risk alleles at the 1q25 locus are associated with increased expression of LAMC2, in which biallelic loss-of-function mutations cause the blistering skin disease epidermolysis bullosa. These findings indicate that variation affecting the structure and maintenance of the skin, in particular the pilosebaceous unit, is a critical aspect of the genetic predisposition to severe acne.

Predictive utility of an emergency department decision support tool in patients with active suicidal ideation.

Emergency department (ED) clinicians routinely decide the disposition of patients with suicidal ideation, with potential consequences for patient safety, liability, and system costs and resources. An expert consensus panel recently created a 6-item decision support tool for patients with passive or active suicidal ideation. Individuals scoring a 0 (exhibiting none of the tool's 6 items) are considered "lower risk" and suitable for discharge, while those with non-0 scores are considered "elevated risk" and should receive further evaluation. The current study tested the predictive utility of this tool using existing data from the Emergency Department Safety Assessment and Follow-up Evaluation. ED patients with active suicide ideation (n = 1368) were followed for 12 months after an index visit using telephone assessment and medical chart review. About 1 in 5 patients had attempted suicide during follow-up. Because of the frequency of serious warning signs and risk factors in this population, only three patients met tool criteria for "lower risk" at baseline. The tool had perfect sensitivity, but exceptionally low specificity, in predicting suicidal behavior within 6 weeks and 12 months. In logistic regression analyses, several tool items were significantly associated with suicidal behavior within 6 weeks (suicide plan, past attempt) and 12 months (suicide plan, past attempt, suicide intent, significant mental health condition, irritability/agitation/aggression). Although the tool did not perform well as a binary instrument among those with active suicidal ideation, having a suicide plan identified almost all attempters while suicide plan and past attempt identified over four-fifths of near-term attempts. (PsycINFO Database Record

Modeling the Cost-Effectiveness of Interventions to Reduce Suicide Risk Among Hospital Emergency Department Patients.

OBJECTIVE: This study estimated the expected cost-effectiveness and population impact of outpatient interventions to reduce suicide risk among patients presenting to general hospital emergency departments (EDs), compared with usual care. Several such interventions have been found efficacious, but none is yet widespread, and the cost-effectiveness of population-based implementation is unknown. METHODS: Modeled cost-effectiveness analysis compared three ED-initiated suicide prevention interventions previously found to be efficacious-follow-up via postcards or caring letters, follow-up via telephone outreach, and suicide-focused cognitive-behavioral therapy (CBT)-with usual care. Primary outcomes were treatment costs, suicides, and life-years saved, evaluated over the year after the index ED visit. RESULTS: Compared with usual care, adding postcards improved outcomes and reduced costs. Adding telephone outreach and suicide-focused CBT, respectively, improved outcomes at a mean incremental cost of $4,300 and $18,800 per life-year saved, respectively. Monte Carlo simulation (1,000 repetitions) revealed the chance of incremental cost-effectiveness to be a certainty for all three interventions, assuming societal willingness to pay ≥$50,000 per life-year. These main findings were robust to various sensitivity analyses, including conservative assumptions about effect size and incremental costs. Population impact was limited by low sensitivity of detecting ED patients' suicide risk, and health care delivery inefficiencies. CONCLUSIONS: The highly favorable cost-effectiveness found for each outpatient intervention provides a strong basis for widespread implementation of any or all of the interventions. The estimated population benefits of doing so would be enhanced by increasing the sensitivity of suicide risk detection among individuals presenting to general hospital EDs.

Suicide and High Altitude: An Integrative Review.

Reno, Elaine, Talia L. Brown, Marian E. Betz, Michael H. Allen, Lilian Hoffecker, Jeremy Reitinger, Robert Roach, and Benjamin Honigman. Suicide and high altitude: an integrative review. High Alt Med Biol 19:99-108, 2018. INTRODUCTION: Suicide rates are greater at high altitudes, and multiple mechanisms have been suggested for this relationship, including hypoxia, differences in population density, characteristics of suicide victims, and firearms ownership and access. To better understand these potential mechanisms, studies evaluating the associations between high altitude and suicide were examined. METHODS: A literature review of published studies on high altitude and suicide was conducted in Medline, Embase, Web of Science, the Cochrane Database of Systematic Reviews, and the Cochrane CENTRAL database. We extracted and analyzed all studies that met the inclusion criteria, excluding foreign language studies and letters. Most of the measurements and results were synthesized using modified Letts' criteria. RESULTS: Searches using an extensive list of keywords returned 470 articles, but only 6 met the inclusion criteria. The studies' samples ranged in size from 8871 to 596,704, while studies which did not document sample size reported suicide rates. In five of the studies selected, individuals living at high altitudes were at greater risk of suicide. Four studies used aggregated data at a county or state level to analyze variables, such as age, gender, race, socioeconomic factors, and firearms access. All the studies found that high altitude was independently associated with suicide. One study found that many individual characteristics of those who committed suicide were different at high altitudes than low altitude, including a lack of access or barriers to mental healthcare. Depression exacerbated by hypoxia was hypothesized as a possible biologic mechanism in three studies. CONCLUSION: These research studies published since 2009 support an association between high altitude and suicide rates at the state or county level, but do not provide sufficient data to estimate the effect of high altitude on an individuals' suicide risk. Although the impact of hypoxia on mood and depression has been hypothesized to be a contributing cause, many other individual factors likely play more important roles.

Efficacy of lurasidone in the treatment of agitation: A post hoc analysis of five short-term studies in acutely ill patients with schizophrenia.

OBJECTIVE: This post hoc analysis evaluated the effect of lurasidone on agitation in acutely ill patients with schizophrenia. METHOD: Patient-level data were pooled from five 6-week, randomized, double-blind, placebo-controlled studies of fixed-dose, once-daily, oral lurasidone (40, 80, 120, or 160 mg/d). Agitation was assessed with the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) score, utilizing a mixed model for repeated measurement analysis. RESULTS: In patients with higher levels of agitation at baseline (PANSS-EC score≥14; n=773), lurasidone was associated with significantly greater improvement in least-squares (LS) mean PANSS-EC scores versus placebo at Day 3/4 (-1.6 vs -1.0; p<0.05), Day 7 (-2.3 vs -1.6; p<0.05), and at Week 6 endpoint (-5.5 vs -3.8; p<0.001; effect size=0.43). In patients with lower agitation at baseline (PANSS-EC score<14; n=754), LS mean PANSS-EC score change was significantly greater for lurasidone compared with placebo at Day 7 (-0.8 vs -0.1; p<0. 01) through Week 6 endpoint (-1.9 vs -0.9; p<0.001; effect size=0.31). Higher doses of lurasidone were notably more effective than lower doses in patients with more severe agitation at study baseline. CONCLUSION: In this pooled analysis of 5 short-term studies, lurasidone provided early and sustained reduction in agitation, assessed using the PANSS-EC score, in patients with an acute exacerbation of schizophrenia. Higher doses of lurasidone were particularly effective in patients with more severe agitation at study baseline. Overall, these results suggest that lurasidone may be a useful treatment option for patients exhibiting agitation associated with acute psychotic symptoms of schizophrenia. ClinicalTrials.gov Identifiers: NCT00088634 (Study D1050196); NCT00549718 (Study D1050229), NCT00615433 (Study D1050231); NCT00790192 (Study D1050233). Study D1050006 was completed prior to the requirement to register trials.