Lithium Treatment in the Prevention of Repeat Suicide-Related Outcomes in Veterans With Major Depression or Bipolar Disorder: A Randomized Clinical Trial.

Importance: Suicide and suicide attempts are persistent and increasing public health problems. Observational studies and meta-analyses of randomized clinical trials have suggested that lithium may prevent suicide in patients with bipolar disorder or depression. Objective: To assess whether lithium augmentation of usual care reduces the rate of repeated episodes of suicide-related events (repeated suicide attempts, interrupted attempts, hospitalizations to prevent suicide, and deaths from suicide) in participants with bipolar disorder or depression who have survived a recent event. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial assessed lithium vs placebo augmentation of usual care in veterans with bipolar disorder or depression who had survived a recent suicide-related event. Veterans at 29 VA medical centers who had an episode of suicidal behavior or an inpatient admission to prevent suicide within 6 months were screened between July 1, 2015, and March 31, 2019. Interventions: Participants were randomized to receive extended-release lithium carbonate beginning at 600 mg/d or placebo. Main Outcomes and Measures: Time to the first repeated suicide-related event, including suicide attempts, interrupted attempts, hospitalizations specifically to prevent suicide, and deaths from suicide. Results: The trial was stopped for futility after 519 veterans (mean [SD] age, 42.8 [12.4] years; 437 [84.2%] male) were randomized: 255 to lithium and 264 to placebo. Mean lithium concentrations at 3 months were 0.54 mEq/L for patients with bipolar disorder and 0.46 mEq/L for patients with major depressive disorder. No overall difference in repeated suicide-related events between treatments was found (hazard ratio, 1.10; 95% CI, 0.77-1.55). No unanticipated safety concerns were observed. A total of 127 participants (24.5%) had suicide-related outcomes: 65 in the lithium group and 62 in the placebo group. One death occurred in the lithium group and 3 in the placebo group. Conclusions and Relevance: In this randomized clinical trial, the addition of lithium to usual Veterans Affairs mental health care did not reduce the incidence of suicide-related events in veterans with major depression or bipolar disorders who experienced a recent suicide event. Therefore, simply adding lithium to existing medication regimens is unlikely to be effective for preventing a broad range of suicide-related events in patients who are actively being treated for mood disorders and substantial comorbidities. Trial Registration: ClinicalTrials.gov Identifier: NCT01928446.

The My Life, My Story Program: Sustained Impact of Veterans' Personal Narratives on Healthcare Providers 5 Years After Implementation.

Patient-centered care promotes positive patient, staff, and organizational outcomes. Communication is one critical element of patient-centered care. Establishing a patient-provider relationship in which a patient feels comfortable sharing their goals, preferences, and values is important to support patient-centered care and positive health outcomes. The My Life, My Story (MLMS) program was developed in 2013 to elicit and share Veterans' life stories with their healthcare providers. Life stories become part of the Veteran's chart so providers can access, read, and utilize as appropriate. To evaluate the program's sustained value and impact 5 years after implementation, healthcare staff were recruited to complete a short survey with closed and open-ended items. Descriptive statistics were used to analyze the quantitative survey responses and thematic analysis was used to analyze qualitative responses. Approximately 94% of staff indicated they had read MLMS notes and over 86% agreed or strongly agreed that reading the notes was a good use of their clinical time and helped them provide better treatment or care. Staff also described making more personalized decisions about the plan of treatment or care delivery after knowing the Veteran better from their story. Our findings suggest the MLMS program has been well sustained over time, and the use of patient stories in healthcare may be a valuable, practical, and sustainable tool to support the delivery of patient-centered care.

Increased Risk of Dementia Among Veterans With Bipolar Disorder or Schizophrenia Receiving Care in the VA Health System.

OBJECTIVE: The Veterans Health Administration (VHA) provides a continuum of care over the life course. Among U.S. adults, bipolar disorder and schizophrenia are associated with increased risk of dementia. To inform service planning, this study assessed the incidence of dementia among veteran VHA patients with bipolar disorder or schizophrenia, with adjustment for comorbid medical conditions. METHODS: Using data from the VHA Corporate Data Warehouse, the authors identified all veterans who received VHA care in 2004 and 2005 without a dementia diagnosis and who were alive and between ages 18 and 100 as of January 1, 2006. Individuals were categorized as having bipolar disorder, schizophrenia, or neither condition on the basis of diagnoses in 2004-2005. Among ongoing VHA users, incidence of dementia was assessed for up to 10 years (2006-2015). RESULTS: The cohort included 3,648,852 individuals. After analyses controlled for baseline comorbid general medical conditions and substance use disorders, the incidence rate ratios (IRRs) for dementia were 2.92 for those with schizophrenia and 2.26 for those with bipolar disorder, compared with VHA patients with neither condition. CONCLUSIONS: Among veterans receiving VHA care, diagnoses of bipolar disorder and schizophrenia were each associated with increased risk of receiving a new diagnosis of dementia, even when analyses controlled for baseline medical comorbidities. IRRs were elevated for patients with either condition, compared with those with neither condition, and highest for those with schizophrenia. VHA clinicians should evaluate patients for dementia when signs or symptoms of cognitive impairment are present.

Patterns of Treatment Disengagement and Personality Traits Associated With Posttraumatic Stress Disorder in Recent-Era U.S. Veterans Receiving Cognitive Processing Therapy.

Low treatment engagement is a barrier to implementation of empirically supported treatments for posttraumatic stress disorder (PTSD) among veterans. Understanding personality traits that predict dropout may help focus attempts to improve engagement. The current study included 90 veterans who served in recent conflicts in Iraq and/or Afghanistan and participated in a trial of cognitive processing therapy for PTSD. Goals were to characterize (a) personality correlates of PTSD, (b) patterns of engagement (i.e., attendance and homework completion), and (c) personality correlates of reduced engagement. Higher levels of PTSD symptoms were associated with a range of characteristics, including affective lability, r = .44 p < .001; anxiety, r = .38, p < .001; identity problems, r = .57, p < .001; intimacy problems, r = .34, p = .001; low affiliation, r = .33, p = .002; oppositionality, r = .36, p = .001; restricted expression, r = .35, p = .001; and suspiciousness, r = .50, p < .001. Notably, veterans with worse PTSD symptoms endorsed more cognitive dysregulation, r = .40, p < .001; and less insecure attachment, r = .14, p = .190, than expected. Only 52.2% of veterans completed the 12-session course of treatment and 31.0% of participants completed fewer than six sessions. Personality traits did not predict attendance or homework completion. Disengagement continues to be a significant issue in trauma-focused treatment for veterans with PTSD. Understanding veteran-level factors, such as personality traits, may be useful considerations for future research seeking to understand and improve engagement.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Patrones de desconexión del tratamiento y rasgos de personalidad asociados con el trastorno de estrés postraumático en Recientes Veteranos Estadounidenses que reciben terapia de procesamiento cognitivo DESCONEXIÓN DEL TRATAMIENTO Y PERSONALIDAD EN VETERANOS El bajo compromiso con el tratamiento es una barrera para la implementación de tratamientos con apoyo empírico para el trastorno de estrés postraumático (TEPT) entre los veteranos. Comprender los rasgos de personalidad que predicen el abandono puede ayudar a enfocar los intentos de mejorar el compromiso con el tratamiento en esta población. El estudio actual incluyó una muestra de 90 veteranos que habían servido en conflictos recientes en Irak y / o Afganistán y que estaban inscritos en el ensayo de terapia de procesamiento cognitivo para el TEPT. Los objetivos principales del estudio fueron (a) describir los correlatos de la personalidad y el TEPT de los veteranos, (b) caracterizar los patrones de compromiso (es decir, la asistencia y la finalización de la tarea), y (c) identificar los rasgos de personalidad asociados con el poco compromiso . Los niveles más altos de síntomas de TEPT se asociaron con una amplia gama de problemas de personalidad, incluida la labilidad afectiva, ansiedad, desregulación cognitiva, problemas de identidad, problemas de intimidad, baja afiliación, oposicionismo, expresión restringida y desconfianza. En particular, los veteranos con niveles más altos de síntomas de TEPT mostraron más desregulación cognitiva y menos problemas con el apego inseguro de lo esperado. Solo el 52.2% de los veteranos completaron el curso de tratamiento de 12 sesiones. Casi un tercio de los participantes (31.0%) completó menos de seis sesiones. Los rasgos de personalidad no fueron predictivos de la asistencia o la finalización de la tarea en el presente estudio. El abandono del tratamiento con apoyo empírico sigue siendo un problema importante en el tratamiento centrado en el trauma para los veteranos con TEPT. Comprender los factores a nivel de veteranos, como los rasgos de personalidad, puede ser una consideración útil para futuras investigaciones que buscan comprender y mejorar el compromiso con el tratamiento.

Randomized controlled equivalence trial comparing videoconference and in person delivery of cognitive processing therapy for PTSD.

INTRODUCTION: In an effort to improve access to and utilization of health care, the Veterans Health Administration (VHA) continues to investigate the effectiveness of video-teleconferencing (VTC) technologies for service delivery. While previous research focused on the efficacy of VTC treatment for post-traumatic stress disorder (PTSD) in Vietnam era veterans, few studies have evaluated the efficacy of this modality and treatment for the Iraq/Afghanistan era veterans. The aim of this randomized clinical trial was to evaluate equivalence between in person and VTC psychotherapy for PTSD in this newer cohort. METHODS: Veterans of the Iraq/Afghanistan conflict from two VHA hospitals in the United States were recruited and randomized to receive cognitive processing therapy (CPT) for PTSD either in person (IP) or over VTC. Clinician-administered and self-report measures were collected before, during, and after treatment. RESULTS: A trend was observed which suggested that CPT over VTC may be equivalent to the treatment delivered in person, as suggested by previous studies. Regardless of treatment, veterans who received the intervention in both conditions reported significant decreases on post-treatment measures. DISCUSSION: This study highlighted research and clinical challenges in providing services to the newest veteran generation in general as well as unique challenges with VTC. One complicating factor to the statistical power of this study was a treatment dropout rate twice the original estimate. Factors that could have influenced this high dropout rate are explored.

Fear of Losing Emotional Control Is Associated With Cognitive Processing Therapy Outcomes in U.S. Veterans of Afghanistan and Iraq.

Evidence-based treatments for posttraumatic stress disorder (PTSD) can reduce symptoms and improve veterans' psychological health. Unfortunately, many veterans leave treatment before receiving maximum benefit. Fear of emotions is related to severity of PTSD, and changes in fear of emotions are correlated with changes in PTSD symptoms. This study built upon the literature linking greater fear of emotions to PTSD severity by examining whether pretreatment fear of emotions, measured by the Affect Control Scale, was associated with completion of cognitive processing therapy (CPT) and severity of posttreatment PTSD in a sample of 89 U.S. veterans who had served in Afghanistan and Iraq. About 60% of veterans completed 10 or more therapy sessions. A logistic regression on 51 of the 89 subjects that more fear of anxiety at pretreatment was associated with decreased likelihood of completing treatment, OR = 0.93, 95% CI [0.87, 1.00]. Of those veterans who completed treatment, higher fear of anger at pretreatment was negatively related to severity of PTSD posttreatment (ß = -.29, p = .037), in a model with the other predictors. Assessing veterans for fear of anxiety and anger before CPT and teaching emotion regulation skills to those in need may reduce treatment dropout.

Using Life Stories to Connect Veterans and Providers.

The My Life, My Story patient-centered program uses veterans' personal narratives by veterans to create a strong connection between patients and providers.

Suicide attempts in veterans with bipolar disorder during treatment with lithium, divalproex, and atypical antipsychotics.

Suicide attempt rates were assessed in 1306 subjects in this 6 year retrospective study of Bipolar disorder. Participants were Veterans from 5 different Veterans Administration Hospitals who met criteria for bipolar type 1 or 2 and who had at least one prescription for lithium or divalproex or both during the study period. This study focused on the impact of atypical antipsychotics on the suicide attempt rate when used in addition to or in place of lithium or divalproex. Medication exposure was calculated using computerized pharmacy records. Suicide attempts were established through chart review including emergency room records, inpatient records, and outpatient records. There were a total of 117 suicide attempts and 2 suicide completions during the study period. Most attempts (59%) occurred when patients were on no medications. Nearly 90% of subjects spent an average of 45 months during the 6 year period on none of the aforementioned medications. The lowest percentage of suicide attempts (15%) occurred while on lithium, 21% while on divalproex and 24% while on atypical antipsychotics. When total months of exposure were taken into account, the lowest attempt rate occurred on lithium plus divalproex (6.3 attempts per 10,000 months of exposure), followed by divalproex alone (7.0 attempts/10,000 months of exposure), and lithium alone (7.7 attempts per 10,000 months of exposure). Patients on atypical antipsychotics alone had an attempt rate of 26.1 attempts per 10,000 months of exposure. In this study, lithium and divalproex provided protection against suicide attempts. Results need to be replicated in future prospective studies and clearly strategies for improving medication compliance among veterans are warranted.

A review of atypical antipsychotic medications for posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) can be a chronic and disabling illness with a limited response to antidepressant treatment, particularly in the case of combat-induced PTSD. The purpose of this study is to review randomized controlled and open-label trials of atypical antipsychotics for the treatment of PTSD. We conducted PUBMED and PILOTS database searches for clinical trials of atypical antipsychotic medications for PTSD in May 2010. Eighteen clinical trials (10 double-blind placebo-controlled, eight open-label) of atypical antipsychotics for PTSD were found and reviewed. Effect sizes of double-blind placebo-controlled trials were small, but were positive for risperidone and quetiapine. Intrusive and hypervigilance symptom subscales showed the most improvement. We concluded that atypical antipsychotic medications have a modest benefit for the treatment of PTSD. Larger randomized controlled trials are needed to clarify the potential utility of these medications in the treatment of PTSD and more rigorous examination of metabolic side effects is warranted.

Concordance of self-rated and observer-rated dysphoric symptoms in mania.

OBJECTIVES: High rates of some depressive symptoms occur in both mixed and pure manic episodes. This study examined whether manic subjects identify these depressive symptoms by self-report consistently with observer ratings, whether dysphoric symptoms are self-rated differently in mixed compared to pure manic episodes, and whether discriminative self-rated dysphoric symptom sets agree with those established by observer ratings. METHODS: Ninety-four inpatients meeting DSM-IV criteria for mania were classified as in pure or mixed episodes. Dysphoric symptoms were evaluated with the Hamilton Depression Rating Scale (HDRS) and the self-rated Carroll Depression Scale (CDS). Total scores and individual symptom scores on the two scales were compared, as were differences between the manic and mixed subtypes. Positive predictive values (PPV) of individual CDS statements for a diagnosis of a mixed bipolar episode were calculated. Those with a PPV of 0.5 or greater were summed across all subjects and the distributions within the bipolar manic and mixed groups inspected. RESULTS: Self-rated depressive symptoms were highly concordant with observer-rated depressive symptoms in mania. Differences were demonstrated between mixed and pure manic subjects based on self-report, and these differences were similar to those observed with HDRS evaluations. A group of 8 dysphoric symptoms discriminated mixed from pure manic episodes on both scales. These symptoms were depressed mood, pathological guilt, suicidal tendency, anhedonia, psychomotor agitation, psychic and somatic anxiety, and general somatic symptoms (fatigue). CONCLUSIONS: Manic patients report depressive symptoms consistently with observer ratings. Self-rated dysphoric symptoms differ significantly between mixed and pure manic episodes. Patient self-rating is another tool which may help in the diagnosis of mixed mania and the recognition of depressive symptoms during manic episodes. LIMITATIONS: The current study included patients who were evaluated during inpatient hospitalization only. The study included only subjects capable and willing to give written informed consent. Generalizability to other bipolar patients is not established.

Fear, anxiety, and the neuroimaging of PTSD.

The clinical manifestations of Posttraumatic Stress Disorder (PTSD) include both fear and anxiety symptoms. Animal studies provide significant information about the neurobiological pathways involved in fear and anxiety and are relevant to the study of PTSD. These studies are reviewed along with Rauch's proposed neurobiologic model for PTSD. Neuroimaging findings in PTSD are summarized by region. Most neuroimaging studies to date have been provocation studies which present a trauma-related stimulus and measure response.While providing information about PTSD, these complex studies were not designed to target specific emotions. Studies which can specifically elicit fear or anxiety and evaluate associated brain regions, such as the bed nucleus of the stria terminalis (BNST) may provide a clearer understanding of the biologic underpinnings of PTSD and bridge the knowledge between animal neurobiology and human studies.

Quetiapine as an adjunctive treatment for post-traumatic stress disorder: an 8-week open-label study.

This study evaluated the effectiveness of quetiapine for subjects with post-traumatic stress disorder (PTSD) who were already on a stable dose of a selective serotonin reuptake inhibitor (SSRI) but had significant PTSD symptoms. Fifteen subjects were enrolled in an 8-week open-label trial for PTSD in which quetiapine was added to an SSRI. Subjects were on a stable dose of the SSRI for at least 6 weeks before study entry and had a Clincian-Administered PTSD Scale (CAPS) score of greater than or equal to 50 at study baseline. The mean age of subjects was 49 years (eight men and seven women). The average duration of PTSD was 29 years, one-third of subjects had combat-related PTSD, and two-thirds had noncombat PTSD. The mean dose prescribed in the study was 216 mg per day. The initial median CAPS score was 80, indicating severe PTSD. The addition of a modest dose of quetiapine provided significant relief from PTSD symptoms with a 42% overall improvement in PTSD symptoms based on the CAPS and significant improvement along each dimension of symptoms: re-experiencing (Z=-3.24, P=0.0012), hyperarousal (Z=-3.30, P=0.001) and avoidance (Z=-2.13, P=0.03). Subjects rated themselves as 45% improved on average on the Davidson Trauma Scale and reported a 44% decrease in their level of disability and impairment as reflected by the Sheehan Disability Scale. Subjects with PTSD who had significant PTSD symptoms when on an SSRI benefited from the addition of quetiapine. Patients improved significantly on all three clusters of PTSD symptoms: re-experiencing, hyperarousal and avoidance.

Effectiveness and medical costs of divalproex versus lithium in the treatment of bipolar disorder: results of a naturalistic clinical trial.

OBJECTIVE: The clinical, quality of life (QOL), and medical cost outcomes of treatment with divalproex were compared with lithium in patients with bipolar I disorder over 1 year. METHODS: In a pragmatic, randomized clinical trial, 201 adults hospitalized with bipolar I manic or mixed episodes were randomized to divalproex or lithium, in addition to usual psychiatric care, and followed for 1 year. All subsequent treatment of bipolar disorder was managed by the patient's psychiatrist. Symptoms of mania and depression were evaluated at baseline and at hospital discharge. Assessments at the start of maintenance therapy and after 1, 3, 6, 9 and 12 months included manic and depressive symptoms, disability days and QOL. Medical resource use data were also collected monthly and costs were estimated using national sources. RESULTS: Divalproex-treated patients (12%) were less likely to discontinue study medications for lack of efficacy or adverse effects than lithium-treated patients (23%). No statistically significant differences between the treatment groups were observed over the 1-year maintenance phase for clinical symptoms, QOL outcomes, or disability days. Mean estimated total medical costs were USD 28,911 for the divalproex group compared with USD 30,666 for the lithium treatment group. Patients continuing mood stabilizer therapy at 3 months had slightly better health outcomes and substantially lower total medical costs than those who discontinued therapy ( USD 10,091 versus USD 34,432, respectively). CONCLUSIONS: Divalproex maintenance treatment for bipolar disorder resulted in comparable medical costs, clinical and QOL outcomes compared with lithium. Patients remaining on mood stabilizer therapy had substantially lower total medical costs and better health outcomes compared with those who discontinued therapy.

Pharmacologic treatment of posttraumatic stress disorder: a focus on antipsychotic use.

To review the literature on the pharmacologic treatment of posttraumatic stress disorder (PTSD), with a focus on reports of antipsychotic use for this illness. A MEDLINE search (1966-Oct 2002) for English only articles about pharmacologic treatment of PTSD. Antipsychotic medications are being used with some frequency for PTSD. There are few studies and scant evidence to recommend the traditional antipsychotics. There are a number of reports (mostly case reports and open trials) in which atypical antipsychotics improved sleep and decreased the frequency of nightmares and flashbacks. Some studies showed global improvement across symptom clusters. The newer atypical antipsychotics show promise for the treatment of PTSD, mainly ameliorating intrusive symptoms. The paucity of double-blind studies prevents firm conclusions, however, this class of medications may be useful particularly for refractory symptoms.

Investigation of Notch3 as a candidate gene for bipolar disorder using brain hyperintensities as an endophenotype.

The purpose of the study was to consider MRI hyperintensities as a potential endophenotype for bipolar disorder (BPD) and to investigate Notch3 (CADASIL) as a candidate gene for BPD. MRI scans were performed on 21 members of a family with a high incidence of BPD. Two-point and multipoint linkage analyses were performed and two exons of Notch3 were investigated with SSCP. Fifteen of 21 family members had MRI hyperintensities, including all bipolar patients and six family members with no affective illness. Two-point linkage analysis yielded negative results for all models. Multipoint linkage analysis yielded negative results except for Model 1a, in which a maximal LOD score was -1.24. A mutation screen of Exons 3 and 4 was negative. Notch3 does not appear to be a candidate gene for BPD in this family.