Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans.

BACKGROUND: In randomized trials, prazosin, an α1-adrenoreceptor antagonist, has been effective in alleviating nightmares associated with post-traumatic stress disorder (PTSD) in military veterans. METHODS: We recruited veterans from 13 Department of Veterans Affairs medical centers who had chronic PTSD and reported frequent nightmares. Participants were randomly assigned to receive prazosin or placebo for 26 weeks; the drug or placebo was administered in escalating divided doses over the course of 5 weeks to a daily maximum of 20 mg in men and 12 mg in women. After week 10, participants continued to receive prazosin or placebo in a double-blind fashion for an additional 16 weeks. The three primary outcome measures were the change in score from baseline to 10 weeks on the Clinician-Administered PTSD Scale (CAPS) item B2 ("recurrent distressing dreams"; scores range from 0 to 8, with higher scores indicating more frequent and more distressing dreams); the change in score from baseline to 10 weeks on the Pittsburgh Sleep Quality Index (PSQI; scores range from 0 to 21, with higher scores indicating worse sleep quality); and the Clinical Global Impression of Change (CGIC) score at 10 weeks (scores range from 1 to 7, with lower scores indicating greater improvement and a score of 4 indicating no change). RESULTS: A total of 304 participants underwent randomization; 152 were assigned to prazosin, and 152 to placebo. At 10 weeks, there were no significant differences between the prazosin group and the placebo group in the mean change from baseline in the CAPS item B2 score (between-group difference, 0.2; 95% confidence interval [CI], -0.3 to 0.8; P=0.38), in the mean change in PSQI score (between-group difference, 0.1; 95% CI, -0.9 to 1.1; P=0.80), or in the CGIC score (between-group difference, 0; 95% CI, -0.3 to 0.3; P=0.96). There were no significant differences in these measures at 26 weeks (a secondary outcome) or in other secondary outcomes. At 10 weeks, the mean difference between the prazosin group and the placebo group in the change from baseline in supine systolic blood pressure was a decrease of 6.7 mm Hg. The adverse event of new or worsening suicidal ideation occurred in 8% of the participants assigned to prazosin versus 15% of those assigned to placebo. CONCLUSIONS: In this trial involving military veterans who had chronic PTSD, prazosin did not alleviate distressing dreams or improve sleep quality. (Funded by the Department of Veterans Affairs Cooperative Studies Program; PACT ClinicalTrials.gov number, NCT00532493 .).

Does COVID-19 count?: Defining Criterion A trauma for diagnosing PTSD during a global crisis.

INTRODUCTION: The ongoing coronavirus disease 2019 (COVID-19) pandemic is a globally significant crisis with a rapid spread worldwide, high rates of illness and mortality, a high degree of uncertainty, and a disruption of daily life across the sociodemographic spectrum. The clinically relevant psychological consequences of this catastrophe will be long-lasting and far-reaching. There is an emerging body of empirical literature related to the mental health aspects of this pandemic and this body will likely expand exponentially. The COVID-19 pandemic is an example of a historic catastrophe from which we can learn much and from which the field will need to archive, interpret, and synthesize a multitude of clinical and research observations. METHODS: In this commentary, we discuss situations and contexts in which a diagnosis of posttraumatic stress disorder (PTSD) may or may not apply within the context of diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) criteria. RESULTS: Our consensus is that a COVID-related event cannot be considered traumatic unless key aspects of DSM-5's PTSD Criterion A have been established for a specific type of COVID-19 event (e.g., acute, life-threatening, and catastrophic). CONCLUSION: The application of a more liberal interpretation of Criterion A will dilute the PTSD diagnosis, increase heterogeneity, confound case-control research, and create an overall sample pool with varying degrees of risk and vulnerability factors.

Prazosin for treatment of post-traumatic stress disorder: a systematic review and meta-analysis.

BACKGROUND: Prazosin has been an accepted treatment for patients with post-traumatic stress disorder (PTSD) who experience sleep disturbances, including nightmares. Results of a recent large randomized control trial did not find benefit of prazosin vs placebo in improving such outcomes. A meta-analysis that includes this most recent trial was conducted to examine the pooled effect of prazosin vs placebo on sleep disturbances and overall PTSD symptoms in patients with PTSD. METHODS: A systematic review of the published literature on trials comparing prazosin vs placebo for improvement of overall PTSD scores, nightmares, and sleep quality was conducted. Hedges' g standardized mean differences (SMD) between prazosin and placebo were calculated for each outcome across studies. RESULTS: Six randomized placebo-controlled studies representing 429 patients were included in the analysis, including two studies with a crossover design. Results showed prazosin significantly improved overall PTSD scores (SMD = -0.31; 95% confidence intervals [CI]: -0.62, -0.01), nightmares (SMD = -0.75; 95% CI: -1.24, -0.27), and sleep quality (SMD = -0.57; 95% CI: -1.02, -0.13). In the largest trial, prazosin showed a reduction in clinical outcome measures similar to past studies, but a relatively large placebo effect size, particularly for nightmares, contributed to no treatment differences. CONCLUSIONS: Despite the results of a recent, large randomized study, pooled effect estimates show that prazosin has a statistically significant benefit on PTSD symptoms and sleep disturbances. Limitations that should be considered include heterogeneity of study design and study populations as well as the small number of studies conducted and included in this meta-analysis.

Sleep-Disordered Breathing Impact on Efficacy of Prolonged Exposure Therapy for Posttraumatic Stress Disorder.

There is growing evidence that sleep disturbances may impede the utility of existing therapeutic interventions for people with posttraumatic stress disorder (PTSD). This retrospective medical record review examined the hypothesis that sleep disturbance affects the outcome of prolonged exposure (PE) therapy for PTSD. We identified 18 combat veterans with PTSD who had completed PE therapy. There were 6 subjects who had sleep-disordered breathing, 5 of whom were documented by sleep polysomnography. All subjects in the sleep-disordered group took part in a minimum of 10 sessions; the mean number of sessions was comparable between the sleep-disordered group and the group without a sleep disorder. Posttreatment PTSD Checklist scores were significantly reduced in those without a sleep disorder (-28.25; 58.0% reduction, F(1, 11) = 59.04, p < .001), but were not reduced in those with sleep-disordered breathing (-7.17; 13.5% reduction, dIGPP = 2.25 [independent groups pretest-posttest design]). These observations supported the hypothesis that the efficacy of PE therapy is affected by sleep quality. If these findings are replicated, treatment algorithms may need to incorporate the presence or absence of sleep disorders as a factor in treatment choice.

A Protocol for the Inclusion of Minoritized Persons in Alzheimer Disease Research From the ADNI3 Diversity Taskforce.

Importance: Black or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer's Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults. Objective: To describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3. Design, Setting, and Participants: This cross-sectional study used baseline data from a longitudinal, multisite, observational study conducted from January 15, 2021, to July 12, 2022, with no follow-up. The study was conducted at 13 ADNI3 sites in the US. Participants included individuals aged 55 to 90 years without cognitive impairment and those with mild cognitive impairment or Alzheimer disease. Exposures: Efforts included (1) launch of an external advisory board, (2) changes to the study protocol, (3) updates to the digital prescreener, (4) selection and deployment of 13 community-engaged research study sites, (5) development and deployment of local and centralized outreach efforts, and (6) development of a community-science partnership board. Main Outcomes and Measures: Screening and enrollment numbers from centralized and local outreach efforts, digital advertisement metrics, and digital prescreener completion. Results: A total of 91 participants enrolled in the trial via centralized and local outreach efforts, of which 22 (24.2%) identified as Latinx and 55 (60.4%) identified as Black (median [IQR] age, 65.6 [IQR, 61.5-72.5] years; 62 women [68.1%]). This represented a 267.6% increase in the monthly rate of enrollment (before: 1.11 per month; during: 4.08 per month) of underrepresented populations. For the centralized effort, social media advertisements were run between June 1, 2021, and July 31, 2022, which resulted in 2079 completed digital prescreeners, of which 1289 met criteria for subsequent site-level screening. Local efforts were run between June 1, 2021, to July 31, 2022. A total of 151 participants underwent site-level screening (100 from local efforts, 41 from centralized efforts, 10 from other sources). Conclusions and Relevance: In this cross-sectional study of pilot inclusion efforts, a culturally informed, community-engaged approach increased the inclusion of Black and Latinx participants in an Alzheimer disease cohort study.

Improving maternal mental health: assessing the extent of screening and training about peripartum depression.

OBJECTIVE: Peripartum depression (PPD) is a common mental health complication of pregnancy and increases risk for maternal mortality and poorer outcomes for children. Despite its importance, screening rates vary across organizations and care team members. The goal of the current study was to explore the perspectives from care team members in both behavioral health and acute care settings about how they screen and refer pregnant and post pregnant women for PPD, what training around PPD is currently offered by their organization, and if they could benefit from additional PPD training. METHODS: Data were collected from an online self-report survey of care team members from behavioral health and acute care settings in the US. Questions focused on (1) when/if the care teams had a screening protocol for PPD, (2) beliefs about the efficacy of their organization's PPD screening, identification, and referral process, and (3) if their organization currently offered or needed training around the topic of PPD. RESULTS: A total of 794 care team members in behavioral health and acute care responded to the survey between December 2021 and May 2022. Nearly, all (96.7%) reported having a specific protocol for screening for PPD when they know a patient is pregnant; however, only 69.6% of respondents routinely screen regardless of symptoms being reported by the patient. While 93.3% of the sample believed their organization does a good job screening for and identifying PPD, gaps in the referral processes were described, especially in acute settings. 95.3% of the sample reported their organization currently gives training in screening, identifying, or treating PPD or in the process for establishing outpatient referrals for PPD care for care team members who have direct contact with pregnant patients; however, 96.5% also reported their organization would benefit from additional training in one or more of these areas. CONCLUSION: High rates of self-reported PPD screening and training indicate that care team members in both behavioral health and acute care are aware of the importance of maternal mental health issues. However, other research indicates that high rates of screening may not lead to improved outcomes, and there are still high rates of maternal suicide and suicidal ideation in the US. It is possible that high self-reported screening rates may indicate a false sense of security such that care team members feel the issue is addressed while problems remain. Alternatively, many respondents felt their organizations would benefit from further training, perhaps indicating an awareness of this gap. Care team members in behavioral health and acute care settings should increase collaboration to ensure high rates of screening lead to improved maternal mental health care.

Use of Predictive Analytics to Identify Unhealthy Opioid Use and Guide Intervention.

OBJECTIVE: The authors aimed to use the newly developed Opioid Risk Stratification Tool to identify individuals who may be at risk for unhealthy opioid use and to examine the impact of applying a mailing and engagement intervention to this population and their prescribers, with the goal of reducing high-risk prescribing behaviors, opioid medication use, and mortality rates. METHODS: A nonrandomized controlled study was conducted with members from two Medicaid managed care organizations. In both the intervention (N=131) and control (N=187) groups, an algorithm identified members at moderate to high risk for hazardous opioid use. Members at increased risk in the intervention group and their prescribers received a letter from the managed care organization, and members still at risk 3 months after the mailing were contacted by a care coordinator. Individuals in the control group were not contacted. Medicaid claims data were used to compare opioid use and prescribing practices between groups before and after the intervention. RESULTS: Individuals in the intervention group were less likely to have any opioid prescription postintervention compared with those in the control group (OR=0.55, p<0.001), and the intervention group had a greater reduction in the number of individuals with concurrent opioid and benzodiazepine prescriptions (OR=0.49, p=0.042). Practices such as multiple opioid prescriptions and multiple prescribers of opioids were not affected by the intervention. CONCLUSIONS: An intervention targeting individuals at risk for hazardous opioid use was associated with a reduction in some high-risk prescribing practices. Future research should determine the ideal mix of interventions to reduce as many risk factors as possible.

Ketoconazole-associated preferential increase in dopamine D2 receptor occupancy in striatum compared to pituitary in vivo: role for drug transporters?

Membrane transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are efflux pumps that remove drugs from the brain back to the peripheral blood compartment, serving as a functional component of the blood-brain barrier (BBB). We report here that coadministration of the P-gp and BCRP inhibitor ketoconazole with risperidone may preferentially increase D2 receptor occupancy in the striatum compared to pituitary. Four male patients with schizophrenia or schizoaffective disorder who had received at least 4 prior injections of the long-acting risperidone at a stable dose of 25 to 50 mg participated in this positron emission tomography study. Multiple-dose ketoconazole coadministration reduced the P-gp activity as shown by fexofenadine oral challenge. Importantly, we found a strong statistical trend in this sample of 4 subjects who consistently showed a decrease in striatal fluorine 18 (F)-fallypride binding (an indication of increased D2 receptor occupancy) after ketoconazole coadministration (P = 0.057), whereas the pituitary (a region that lies outside the BBB) F-fallypride binding did not change (P = 0.99). These observations warrant further research with selective drug transporter inhibitors. We suggest that in neuroimaging studies, the pituitary drug occupancy can serve as a useful new "positive control" to evaluate whether drug occupancy is preferentially increased in brain regions that fall inside the BBB after cotreatment with P-gp and BCRP inhibitors. This is a noteworthy study design consideration regarding the future clinical testing of novel adjunct interventions aimed at modulating membrane transporter function at the BBB, with the goal of augmenting drug access into the brain compartment, particularly in treatment-resistant psychiatric illness.

Event-related functional magnetic resonance imaging of a low dose of dexmedetomidine that impairs long-term memory.

BACKGROUND: Work suggests the amnesia from dexmedetomidine (an α2-adrenergic agonist) is caused by a failure of information to be encoded into long-term memory and that dexmedetomidine might differentially affect memory for emotionally arousing material. We investigated these issues in humans using event-related neuroimaging to reveal alterations in brain activity and subsequent memory effects associated with drug exposure. METHODS: Forty-eight healthy volunteers received a computer-controlled infusion of either placebo or low-dose dexmedetomidine (target = 0.15 ng/ml plasma) during neuroimaging while they viewed and rated 80 emotionally arousing (e.g., graphic war wound) and 80 nonarousing neutral (e.g., cup) pictures for emotional arousal content. Long-term picture memory was tested 4 days later without neuroimaging. Imaging data were analyzed for drug effects, emotional processing differences, and memory-related changes with statistical parametric mapping-8. RESULTS: Dexmedetomidine impaired overall (mean ± SEM) picture memory (placebo: 0.58 ± 0.03 vs. dexmedetomidine: 0.45 ± 0.03, P = 0.001), but did not differentially modulate memory as a function of item arousal. Arousing pictures were better remembered for both groups. Dexmedetomidine had regionally heterogeneous effects on brain activity, primarily decreasing it in the cortex and increasing it in thalamic and posterior hippocampal regions. Nevertheless, a single subsequent memory effect for item memory common to both groups was identified only in the left hippocampus/amygdala. Much of this effect was found to be larger for the placebo than dexmedetomidine group. CONCLUSION: Dexmedetomidine impaired long-term picture memory, but did not disproportionately block memory for emotionally arousing items. The memory impairment on dexmedetomidine corresponds with a weakened hippocampal subsequent memory effect.

Collaborative mental health care: A narrative review.

The Collaborative Care model is a systematic strategy for treating behavioral health conditions in primary care through the integration of care managers and psychiatric consultants. Several randomized controlled trials have demonstrated that Collaborative Care increases access to mental health care and is more effective and cost efficient than the current standard of care for treating common mental illnesses. Large healthcare systems and organizations have begun to adopt Collaborative Care initiatives and are seeing improved treatment outcomes and provider and patient satisfaction. This review discusses current research on the effectiveness and cost-efficiency of Collaborative Care. In addition, this paper discusses its ability to adapt to specific patient populations, such as geriatrics, students, substance use, and women with perinatal depression, as well as the significance of measurement-based care and mental health screening in achieving improved clinical outcomes. Current data suggests that Collaborative Care may significantly improve patient outcomes and time-to-treatment in all reviewed settings, and successfully adapts to special patient populations. Despite the high upfront implementation burden of launching a Collaborative Care model program, these costs are generally offset by long term healthcare savings.

Behavioral Health Diagnoses and Health Care Use Before and During the COVID-19 Pandemic.

OBJECTIVE: Emerging evidence has suggested a population-wide worsening of psychiatric symptoms during the COVID-19 pandemic, particularly among individuals with preexisting mental health conditions. The authors investigated whether reported behavioral health problems are being identified and treated. METHODS: This observational cohort study retrospectively compared Medicaid data of patients from the first year of the pandemic (2020) in the United States (N=1,589,111 patients) with the corresponding data from the year before (2019; N=1,715,872 patients). Outcome measures included several behavioral health diagnoses and health care utilization. RESULTS: During the pandemic period examined, the numbers of patients served, adults receiving a new diagnosis of anxiety, and children receiving a new diagnosis of depression all increased. Across all age groups, nonbehavioral health emergency department visits significantly decreased. CONCLUSIONS: These findings support reports of increases in psychiatric morbidity but do not provide evidence for increased demand for health care services.

Enhancing exposure therapy for posttraumatic stress disorder (PTSD): a randomized clinical trial of virtual reality and imaginal exposure with a cognitive enhancer.

Posttraumatic stress disorder (PTSD) is a significant public health issue. Yet, there are limited treatment options and no data to suggest which treatment will work for whom. We tested the efficacy of virtual reality exposure (VRE) or prolonged imaginal exposure (PE), augmented with D-cycloserine (DCS) for combat-related PTSD. As an exploratory aim, we examined whether brain-derived neurotrophic factor (BDNF) and fatty acid amide hydrolase (FAAH) moderated treatment response. Military personnel with PTSD (n = 192) were recruited into a multisite double-blind randomized controlled trial to receive nine weeks of VRE or PE, with DCS or placebo. Primary outcome was the improvement in symptom severity. Randomization was stratified by comorbid depression (MDD) and site. Participants in both VRE and PE showed similar meaningful clinical improvement with no difference between the treatment groups. A significant interaction (p = 0.45) suggested VRE was more effective for depressed participants (CAPS difference M = 3.51 [95% CI 1.17-5.86], p = 0.004, ES = 0.14) while PE was more effective for nondepressed participants (M = -8.87 [95% CI -11.33 to -6.40], p < 0.001, ES = -0.44). The main effect of DCS vs. placebo was not significant. Augmentation by MDD interaction (p = 0.073) suggested that depressed participants improved more on placebo (M = -8.43 [95% CI -10.98 to -5.88], p < 0.001, ES = -0.42); DCS and placebo were equally effective for nondepressed participants. There was an apparent moderating effect of BDNF Val66Met polymorphism on DCS augmentation (ES = 0.67). Met66 allele carriers improved more on DCS (ES = -0.25). FAAH 385 A carriers improved more than non-carriers (ES = 0.33), particularly those with MDD (ES = 0.62). This study provides a step toward precision therapeutics for PTSD by demonstrating that comorbid MDD and genetic markers may help guide treatment selection.ClinicalTrials.gov Identifier: NCT01352637.

Using Claims Data to Assess Treatment Quality of First-Episode Psychosis.

OBJECTIVE: Coordinated specialty care (CSC) has become the standard of care for first-episode psychosis (FEP). The gap between CSC best practices and the actual care delivered is unknown. This longitudinal study aimed to measure that gap by using a large Medicaid claims database and 10 quality indicators (QIs) reflecting aspects of CSC and to study the relationship between these QIs and future health care utilization. METHODS: Individuals with FEP were identified in a Missouri Medicaid claims database. Participants were required to have been eligible for Medicaid benefits for at least 10 months in the year prior to and the year after their first episode of psychosis and to have had no evidence of a prior psychosis diagnosis. Descriptive statistics were generated for each of the QIs, and a stratified Cox regression was used to identify predictors of subsequent health care utilization. RESULTS: Data were obtained for 6,246 participants, and follow-up lasted a mean of 4.24 years. Significant practice gaps were found in the use and monitoring of antipsychotic medications. Of those prescribed antipsychotic medication, 5% received prescriptions above recommended daily doses, 16% received two or more antipsychotics, and 20% were treated with olanzapine or clozapine. Among the QIs, lack of monitoring for smoking (hazard ratio [HR]=2.71, 95% confidence interval [CI]=2.47-2.97) and lack of integrated care delivery in treatment (HR=2.00, 95% CI=1.92-2.08) were most associated with psychiatric hospitalization. CONCLUSIONS: In most cases, treatment was far from meeting CSC recommendations, suggesting that implementation of CSC requires substantial modifications to delivery of care for individuals with FEP.

Acupuncture for combat post-traumatic stress disorder: trial development and methodological approach for a randomized controlled clinical trial.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a significant public health problem, affecting approximately 7% of the general population and 13-18% of the combat Veteran population. The first study using acupuncture for PTSD in a civilian population showed large pre- to post-treatment effects for an empirically developed verum protocol, which was equivalent to group cognitive behavior therapy and superior to a wait-list control. The primary objective of this study is to determine both clinical and biological effects of verum acupuncture for combat-related PTSD in treatment-seeking US Veterans. METHODS: This is a two-arm, parallel-group, prospective randomized placebo-controlled clinical trial. The experimental condition is verum acupuncture and the placebo control is sham (minimal) acupuncture in 1-h sessions, twice a week for 12 weeks. Ninety subjects will provide adequate power and will be allocated to group by an adaptive randomization procedure. The primary outcome is change in PTSD symptom severity from pre- to post-treatment. The secondary biological outcome is change from pre- to post-treatment in psychophysiological response, startle by electromyographic (EMG) eyeblink. Assessments will be conducted at pre-, mid-, post-, and 1-month post-treatment, blind to group allocation. Intent-to-treat analyses will be conducted. DISCUSSION: The study results will be definitive because both clinical and biological outcomes will be assessed and correlated. Issues such as the number needed for recruitment and improvement, use of sham acupuncture, choice of biological measure, and future research need will be discussed. TRIAL REGISTRATION: ClinicalTrials.gov NCT02869646 . Registered on 17 August 2016.

An analysis of fear inhibition and fear extinction in a sample of veterans with obstructive sleep apnea (OSA): Implications for co-morbidity with post-traumatic stress disorder (PTSD).

Obstructive sleep apnea (OSA) is a respiratory condition characterized by interrupted sleep due to repeated, temporary collapse of the soft tissue of the upper airway that can lead to a cascade of physiological and psychological adverse health outcomes. The most common therapeutic interventions for OSA patients include the application of continuous positive airway pressure (CPAP) which acts to keep the airway open and, as such, provides less interrupted and more restorative sleep. Improved sleep has been linked to more efficacious treatments for psychiatric conditions most notably those that include cognitive-behavioral elements, new learning, and memory consolidation. In the current study, we investigated the acquisition, inhibition, and extinction of conditioned fear in OSA patients, before and after CPAP therapy, using an established fear-potentiated startle paradigm. Patients with OSA displayed an intact ability to acquire, inhibit, and extinguish fear prior to CPAP treatment and this ability was significantly enhanced following CPAP usage. In addition, those patients with more severe OSA, as measured by apnea-hypopnea index (AHI), were more likely to show improved fear inhibition and extinction. Lastly, we observed impairments in discrimination between reinforced and nonreinforced conditioned stimuli, in the inhibition of fear, and in fear extinction in a subset of patients with OSA and co-morbid posttraumatic stress disorder (PTSD). These data suggest that evolving treatment algorithms for PTSD should address disrupted sleep problems prior to initiation of inhibition/extinction-based exposure therapies.

Dose trends for second-generation antipsychotic treatment of schizophrenia and bipolar disorder.

BACKGROUND: Antipsychotic dosing used in clinical practice can differ from dosing originally recommended in product labeling. This has been reported for olanzapine and quetiapine, where higher doses are commonly used. This may be the case for ziprasidone as well. METHOD: To characterize changes over time in dosing for the initial and subsequent prescriptions of first-line second-generation antipsychotics used during treatment episodes for outpatients with schizophrenia and bipolar disorder, the 2001-2005 Thomson MarketScan Medicaid Database (Medicaid) and the 2001-2006 MarketScan Commercial Claims and Encounters Database (Commercial) were analyzed. Dose trends were evaluated using autoregressive time-series models. RESULTS: Data were available for 49180 treatment episodes of schizophrenia (4683 Commercial and 44497 Medicaid) and 83289 treatment episodes of bipolar disorder (57961 Commercial and 25328 Medicaid). The initial prescription mean daily and overall mean daily doses of ziprasidone in schizophrenia episodes significantly increased across the Medicaid and Commercial populations, with similar trends observed for bipolar episodes. The first (May 2001) and last (December 2005) observed 3-month mean daily doses for ziprasidone were 112 mg/d and 138 mg/d for patients with schizophrenia and 93 mg/d and 113 mg/d for those with bipolar disorder in the Medicaid cohort, with similar findings for the Commercial cohort. Consistently significant trends in dose changes were not observed for the other medications, although quetiapine and olanzapine doses generally increased while aripiprazole and risperidone doses generally decreased. CONCLUSIONS: There remains a need for controlled randomized clinical trials that test fixed doses of antipsychotics to ascertain the dose-response relationship within the dose range used in contemporary clinical practice.

Implementing Patient-Reported Outcomes to Improve the Quality of Care for Weight of Patients with Schizophrenia.

"Enhancing QUality of Care In Psychosis" (EQUIP) was an eight-site clustered controlled trial of the implementation and effectiveness of patient-reported outcomes to support evidence-based practice and improve care for schizophrenia. Implementation sites chose to improve care for weight. Implementation included monitoring patient-reported outcomes using kiosks, patient and staff education, quality improvement teams, and phone care management. Qualitative and quantitative methods compared implementation and effectiveness between sites for 13 months. Eighty percent of 801 randomly selected patients were overweight. Two hundred one clinicians varied in competency. Baseline use of behavioral weight services was low. At implementation sites, patients became 2.3 times more likely to use weight services compared with control sites (95% CI, 1.5-3.6; χ2 = 14.4; p < 0.01). There was no effect on the weight gain liability of medications prescribed. Controlling for baseline, patients' final weight at control sites was 5.9 ± 2.7 kg heavier than at implementation sites (F = 4.8, p = 0.03). Patient-reported outcomes can inform implementation of evidence-based practice and improvement in outcomes.

A study of psychological pain in substance use disorder and its relationship to treatment outcome.

Substance Use Disorder (SUD) is a major public health concern affecting an estimated 22.5 million individuals in the United States. The primary aim of this study was to characterize psychological pain in a cohort of patients participating in outpatient treatment for SUD. A secondary aim was to determine the relationships between pre-treatment assessments of psychological pain, depression, anxiety and hopelessness with treatment retention time and completion rates. Data was analyzed from 289 patients enrolled in an outpatient community drug treatment clinic in Southern California, U.S. A previously determined threshold score on the Mee-Bunney Psychological Pain Assessment Scale (MBP) was utilized to group patients into high and low-moderate scoring subgroups. The higher pain group scored higher on measures of anxiety, hopelessness and depression compared to those in the low-moderate pain group. Additionally, patients scoring in the higher psychological pain group exhibited reduced retention times in treatment and more than two-fold increased odds of dropout relative to patients with lower pre-treatment levels of psychological pain. Among all assessments, the correlation between psychological pain and treatment retention time was strongest. To our knowledge, this is the first study to demonstrate that psychological pain is an important construct which correlates with relevant clinical outcomes in SUD. Furthermore, pre-treatment screening for psychological pain may help target higher-risk patients for clinical interventions aimed at improving treatment retention and completion rates.

Preferences for family involvement among veterans in treatment for schizophrenia.

OBJECTIVE: Examine preferences for family involvement in psychiatric care in a large, representative sample of veterans in treatment for schizophrenia. METHOD: Veterans with schizophrenia or schizoaffective disorder (N = 801) completed an assessment that included questions about demographic and clinical characteristics, status of family support, and preference for family involvement in their psychiatric care. Open-ended items were independently coded by two raters and categorized; Cohen's kappa was calculated for each category. RESULTS: Among the 801 participants, 496 (61.9%) indicated that they had a family member who provided them with regular support; 304 (37.9%) had no family member who provided support; and 1 did not respond. Among the 304 without support, 272 (89.4%) had a living family member. Of the 496 participants who had a supportive family member, 135 (27.2%) wanted their family member involved in their care. Of the 272 participants who did not have a supportive family member, but had living family, 57 (21.0%) wanted their family involved. Barriers to involvement included concerns about privacy and burden. Preferred method of involvement included contact with the patient's psychiatrist and education about the illness. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Preferences indicated by this large representative sample of individuals in care for schizophrenia indicate that a majority have supportive family and a substantial minority want family involved in their psychiatric care. Clinicians can address concerns about privacy and burden and deliver preferred services by phone or mail, overcoming anticipated barriers. Desire for family support groups was limited but present. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Enhanced exposure therapy for combat-related Posttraumatic Stress Disorder (PTSD): Study protocol for a randomized controlled trial.

BACKGROUND: PTSD, which has been identified in up to 23% of post-9-11 veterans, often results in a chronic, pernicious course. Thus, effective treatments are imperative. The Institute of Medicine (IOM) concluded that the only intervention for PTSD with sufficient evidence to conclude efficacy is exposure therapy. This Phase III trial compares the efficacy of exposure therapy for combat-related PTSD delivered in two different formats- via virtual reality exposure therapy (VRE) or prolonged exposure therapy (PE)- combined with D-Cycloserine (DCS), a cognitive enhancer shown to facilitate the extinction of fear. METHODS/DESIGN: Military personnel of any duty status and civilians deployed to Iraq and Afghanistan were eligible. Participants were randomly assigned to 9 sessions of exposure therapy (VRE or PE) and medication (50 mg DCS or placebo). Participants were treated at three geographically diverse sites. Participants were re-assessed at 3-months post-treatment. The co-primary hypotheses are that (1) DCS will augment response to exposure therapy (both VRE and PE) on PTSD symptoms; (2) VRE will be associated with greater improvement than PE. Genetic and psychophysiological markers will be evaluated as potential moderators and mediators of treatment outcomes as well as secondary outcomes. DISCUSSION: This study is the first to compare the relative efficacy of DCS-augmented VRE versus PE on PTSD symptoms. The design has several advantages: participants received an active, effective treatment and predictors of response to treatment included genetic and psychobiological measures. The results may directly influence the future delivery of services, and contribute to the development of a standardized treatment protocol. TRIAL REGISTRATION: NCT01352637.