Laura Bajor

The Psychopharmacology Algorithm Project at the Harvard South Shore Program: An Update on Posttraumatic Stress Disorder

Background: This project aimed to provide an organized, sequential, and evidence‐supported approach to the pharmacotherapy of posttraumatic stress disorder (PTSD), following the format of previous efforts of the Psychopharmacology Algorithm Project at the Harvard South Shore Program. Method: A comprehensive literature review was conducted to determine the best pharmacological choices for PTSD patients and to update the last published version (1999) of the algorithm. We focused on optimal pharmacological interventions to address the prominent symptoms of PTSD, with additional attention to the impact that common comorbidities have on treatment choices. Results: We found that SSRIs and SNRIs are not as effective as previously thought, and that awareness of their long‐term side effects has increased. New evidence suggests that addressing fragmented sleep and nightmares can improve symptoms (in addition to insomnia) that are frequently seen with PTSD (e.g., hyperarousal, reexperiencing). Prazosin and trazodone are emphasized at this initial step; if significant PTSD symptoms remain, an antidepressant may be tried. For PTSD‐related psychosis, an antipsychotic may be added. In resistant cases, two or three antidepressants may be used in sequence. Following that, or with partial improvement and residual symptomatology, augmentation may be tried; the best options are antipsychotics, clonidine, topiramate, and lamotrigine. Conclusion: This heuristic may be helpful in producing faster symptom resolution, fewer side effects, and increased compliance.

Off‐label use of second generation antipsychotics for post‐traumatic stress disorder in the Department of Veterans Affairs: time trends and sociodemographic, comorbidity, and regional correlates

Second generation antipsychotics (SGAs) are widely used for post‐traumatic stress disorder (PTSD), although without strong evidence base. With substantial numbers of veterans returning from Iraq/Afghanistan conflicts with PTSD, it is important to characterize the extent of SGA use and identify associated factors.

Quality of life among patients with bipolar disorder in primary care versus community mental health settings

INTRODUCTION Bipolar disorder is associated with functional impairment across a number of domains, including health-related quality of life (HRQOL). Many patients are treated exclusively in primary care (PC) settings, yet little is known how HRQOL outcomes compare between PC and community mental health (CMH) settings. This study aimed to explore the correlates of HRQOL across treatment settings using baseline data from a multisite, randomized controlled trial for adults with bipolar disorder. METHODS HRQOL was measured using the SF-12 physical (PCS) and mental (MCS) composite scale scores. Independent sample t-tests were calculated to compare differences in HRQOL between settings. Multivariate regression models then examined the effect of treatment setting on HRQOL, adjusting for covariate demographic factors, mood symptoms (Internal State Scale), hazardous drinking (AUDIT-C), and substance abuse. RESULTS A total of 384 enrolled participants completed baseline surveys. MCS and PCS scores reflected similar impairment in HRQOL across PC and CMH settings (p=0.98 and p=0.49, respectively). Depressive symptoms were associated with lower MCS scores (B=-0.68, p<0.001) while arthritis/chronic pain was strongly related to lower PCS scores (B=-5.23, p<0.001). LIMITATIONS This study lacked a formal diagnostic interview, relied on cross-sectional self-report, and sampled from a small number of sites in two states. DISCUSSION Participants reported similar impairments in both mental and physical HRQOL in PC and CMH treatment settings, emphasizing the need for integrated care for patients with bipolar disorder regardless of where they present for treatment.

Posttraumatic stress disorder, depression, and health-related quality of life in patients with bipolar disorder: Review and new data from a multi-site community clinic sample

BACKGROUND Evidence suggests that patients with bipolar disorder have an elevated risk for comorbid posttraumatic stress disorder (PTSD) compared to those without a bipolar diagnosis. Although bipolar disorder is associated with decreased health-related quality of life (HRQOL), it is unclear whether comorbid PTSD interacts to affect HRQOL. METHOD Baseline data from a multi-site study of patients with bipolar disorder were analyzed. Patient surveys ascertained clinical and demographic information, including physical and mental HRQOL based on the SF-12, mood symptoms (PHQ-9, Internal State Scale), and self-reported co-occurring conditions including PTSD. RESULTS Overall (N=384), 44.9% of patients self-reported co-occurring PTSD. Patients with PTSD had lower physical and mental HRQOL scores compared to those without PTSD (mean (SD) for those with and without PTSD, respectively): Mental Component Scale score 30.51 (8.22) and 32.86 (8.35); Physical Component Scale score 35.56 (7.77) and 37.21 (7.20). After adjusting for demographic and clinical factors including mood symptoms, multiple linear regression analyses revealed that PTSD was no longer significantly associated with physical or mental HRQOL; however, depressive symptoms were independently associated with mental HRQOL (Beta -0.63, p<0.01). CONCLUSION Depressive symptoms may explain the association between PTSD and mental HRQOL. Clinicians working with these patients will want to emphasize treatment of depression as important towards improving HRQOL for this group.

Associations between comorbid anxiety, diabetes control, and overall medical burden in patients with serious mental illness and diabetes

Objective While previous work has demonstrated elevation of both comorbid anxiety disorders and diabetes mellitus type II in individuals with serious mental illness, little is known regarding the impact of comorbid anxiety on diabetes mellitus type II outcomes in serious mental illness populations. We analyzed baseline data from patients with serious mental illness and diabetes mellitus type II to examine relationships between comorbid anxiety, glucose control as measured by hemoglobin A1c score, and overall illness burden. Methods Using baseline data from an ongoing prospective treatment study involving 157 individuals with serious mental illness and diabetes mellitus type II, we compared individuals with and without a comorbid anxiety disorder and compared hemoglobin A1c levels between these groups to assess the relationship between anxiety and management of diabetes mellitus type II. We conducted a similar analysis using cumulative number of anxiety diagnoses as a proxy for anxiety load. Finally, we searched for associations between anxiety and overall medical illness burden as measured by Charlson score. Results Anxiety disorders were seen in 33.1% (N = 52) of individuals with serious mental illness and diabetes mellitus type II and were associated with increased severity of depressive symptoms and decreased function. Hemoglobin A1c levels were not significantly different in those with or without anxiety, and having multiple anxiety disorders was not associated with differences in diabetes mellitus type II control. However, depressive symptoms were significantly associated with higher hemoglobin A1c levels. Neither comorbid anxiety nor anxiety load was significantly associated with overall medical burden. Conclusion One in three people with serious mental illness and diabetes mellitus type II had anxiety. Depressive symptoms were significantly associated with Hb1Ac levels while anxiety symptoms had no relation to hemoglobin A1c; this is consistent with previously published work. More studies are needed to better understand the relationship between depression, anxiety, and health management in people with serious mental illness and diabetes mellitus type II.

Effects of diagnostic inclusion criteria on prevalence and population characteristics in database research

OBJECTIVES Studies of serious mental illnesses that use administrative databases have employed various criteria to establish diagnoses of interest. Several studies have assessed the validity of diagnostic inclusion criteria against research diagnoses. However, no studies have examined the effect of diagnostic inclusion criteria on prevalence and population characteristics across such groups. METHODS Administrative data for 2003-2010 from the Department of Veterans Affairs were used to calculate prevalence rates and assess effects of varying the diagnostic inclusion criteria on population composition for bipolar disorder, schizophrenia, and posttraumatic stress disorder (PTSD). Specifically, for each diagnosis, mutually exclusive subpopulations were compared on the basis of the following inclusion criteria for a given diagnosis: one treatment encounter, two outpatient encounters or one inpatient encounter, and any two encounters. For bipolar disorder and schizophrenia, effects of excluding individuals who had a competing diagnosis of, respectively, schizophrenia or bipolar disorder in the prior 12 months and since 2002 were also determined. RESULTS In 2010, moving from the broadest definitions of bipolar disorder (N=120,382), schizophrenia (N=91,977), and PTSD (N=554,028) to the most restrictive definitions reduced prevalence rates by, respectively, 28.7%, 34.9%, and 25.7%, with temporal trends for 2003-2010 paralleling results in 2010. Population composition changes with changing diagnostic inclusion criteria were variable, with predominantly small odds ratios. CONCLUSIONS Population composition was relatively robust across common diagnostic inclusion criteria for each condition. Thus choice of criteria can focus on considerations of diagnostic validity and case-finding needs. Three mechanisms for the impact of diagnostic criteria on population composition in administrative data sets are discussed.

The Ascendancy of Second-Generation Antipsychotics as Frontline Antimanic Agents.

IntroductionKnowledge of the factors affecting the adoption of new medications can enhance mental health care and guide quality improvement and policy development. Food and Drug Administration indications for treating bipolar disorder with several second-generation antipsychotics (SGAs) in the 2000s represent an opportunity to identify factors that impact the spread of a then-innovative treatment through a new population. MethodsAnalysis of Department of Veterans Affairs administrative data identified the population of 170,811 veterans diagnosed with bipolar disorder from 2003 to 2010. We analyzed time trends and predictors of antimanic choice (SGA vs other) among the 40,512 outpatients with bipolar disorder who initiated their first VA outpatient antimanic prescription, using multinomial logistic regression in month-by-month analyses. We conducted classwise analyses and investigated prespecified predictors among specific agents. ResultsIn classwise analyses, SGAs supplanted lithium, valproate, and carbamazepine/oxcarbazepine as the most commonly initiated antimanics by 2007. Psychosis, but not other indices of severity, predicted SGA initiation. Demographic analyses did not identify substantial disparities in initiation of SGAs. Drug-specific analyses revealed some consideration of medical comorbidities in choosing among specific antimanic agents, although effect sizes were small. Most patients initiating an antimanic had received an antidepressant in the previous year. DiscussionSecond-generation antipsychotics quickly became the frontline antimanic treatment for bipolar disorder, although antidepressants most commonly predated antimanic prescriptions. Second-generation antipsychotics were used for a broad range of patients rather than being restricted to a severely ill subpopulation. The modest association of antimanic choice with relevant medical comorbidities suggests that continued attention to quality prescribing practices is warranted.

Patterns of initiation of second generation antipsychotics for bipolar disorder: a month-by-month analysis of provider behavior

BackgroundSeveral second generation antipsychotics (SGAs) received FDA approval for bipolar disorder in the 2000s. Although efficacious, they have been costly and may cause significant side effects. Little is known about the factors associated with prescribers’ decisions to initiate SGA prescriptions for this condition.MethodsWe gathered administrative data from the Department of Veterans Affairs on 170,713 patients with bipolar disorder between fiscal years 2003–2010. Patients without a prior history of taking SGAs were considered eligible for SGA initiation during the study (n =126,556). Generalized estimating equations identified demographic, clinical, and comorbidity variables associated with initiation of an SGA prescription on a month-by-month basis.ResultsWhile the number of patients with bipolar disorder using SGAs nearly doubled between 2003 and 2010, analyses controlling for patient characteristics and the rise in the bipolar population revealed a 1.2% annual decline in SGA initiation during this period. Most medical comorbidities were only modestly associated with overall SGA initiation, although significant differences emerged among individual SGAs. Several markers of patient severity predicted SGA initiation, including previous hospitalizations, psychotic features, and a history of other antimanic prescriptions; these severity markers became less firmly linked to SGA initiation over time. Providers in the South were somewhat more likely to initiate SGA treatment.ConclusionsThe number of veterans with bipolar disorder prescribed SGAs is rising steadily, but this increase appears primarily driven by a corresponding increase in the bipolar population. Month-by-month analyses revealed that higher illness severity predicted SGA initiation, but that this association may be weakening over time.

Off-Label Prescribing of Second-Generation Antipsychotics to Elderly Veterans with Posttraumatic Stress Disorder and Dementia

To determine whether elderly veterans with posttraumatic stress disorder (PTSD) and dementia are more likely to be prescribed second‐generation antipsychotics (SGAs) than those with PTSD alone.

A population‐based study of the comparative effectiveness of second‐generation antipsychotics vs older antimanic agents in bipolar disorder

Numerous antimanic treatments have been introduced over the past two decades, particularly second‐generation antipsychotics (SGAs). However, it is not clear whether such newer agents provide any advantage over older treatments.