An evidence-based approach to psychopharmacology for posttraumatic stress disorder (PTSD) - 2022 update.

Algorithms for posttraumatic stress disorder were published by this team in 1999 and 2011. Developments since then warrant revision. New studies and review articles from January 2011 to November 2021 were identified via PubMed and analyzed for evidence supporting changes. Following consideration of variations required by special patient populations, treatment of sleep impairments remains as the first recommended step. Nightmares and non-nightmare disturbed awakenings are best addressed with the anti-adrenergic agent prazosin, with doxazosin and clonidine as alternatives. First choices for difficulty initiating sleep include hydroxyzine and trazodone. If significant non-sleep PTSD symptoms remain, an SSRI should be tried, followed by a second SSRI or venlafaxine as a third step. Second generation antipsychotics can be considered, particularly for SSRI augmentation when PTSD-associated psychotic symptoms are present, with the caveat that positive evidence is limited and side effects are considerable. Anti-adrenergic agents can also be considered for general PTSD symptoms if not already tried, though evidence for daytime use lags that available for sleep. Regarding other pharmacological and procedural options, e.g., transcranial magnetic stimulation, cannabinoids, ketamine, psychedelics, and stellate ganglion block, evidence does not yet support firm inclusion in the algorithm. An interactive version of this work can be found at www.psychopharm.mobi.

The Relationship of Transcranial Magnetic Stimulation With Sleep and Plasticity.

Neuroplasticity is an area of expanding interest in psychiatry. Plasticity and metaplasticity are processes contributing to the scaling up and down of neuronal connections, and they are involved with changes in learning, memory, mood, and sleep. Effective mood treatments, including repetitive transcranial magnetic stimulation (rTMS), are reputed to work via changes in neuronal circuitry. This article explores the interrelatedness of sleep, plasticity, and rTMS treatment. A PubMed-based literature review was conducted to identify all available studies examining the relationship of rTMS, plasticity, and sleep. Key words used in this search included "TMS," "transcranial magnetic stimulation," "plasticity," "metaplasticity," "sleep," and "insomnia." Depressed mood tends to be associated with impaired neural plasticity, while antidepressant treatments can augment neural plasticity. rTMS impacts plasticity, yielding long-lasting effects, with differing impacts on the waking and sleeping brain. Higher quality sleep promotes plasticity and learning. Reports on the sleep impact of high-frequency and low-frequency rTMS are mixed. The efficacy of rTMS may rely on brain plasticity manipulation, enhanced via the stimulation of neural circuits. Total sleep time and sleep continuity are sleep qualities that are likely necessary but insufficient for the homeostatic plasticity driven by slow-wave sleep. Understanding the relationship between sleep and rTMS treatment is likely critical to enhancing outcomes.

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

OBJECTIVES: 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. METHODS: A historical cohort design investigated the nationwide population of outpatients with bipolar disorder treated in the Department of Veterans Affairs who were newly initiated on an antimanic agent between 2003 and 2010 (N=27 727). The primary outcome was likelihood of all-cause hospitalization during the year after initiation, controlling for numerous demographic, clinical, and treatment characteristics. Potential correlates of effect were explored by investigating time to initiation of a second antimanic agent or antidepressant. RESULTS: After control for covariates, those initiated on lithium or valproate monotherapy, compared to those beginning SGA monotherapy, were significantly less likely to be hospitalized, had a longer time to hospitalization, and had fewer hospitalizations in the subsequent year. Those on combination treatment had a significantly higher likelihood of hospitalization, although they also had a longer time to addition of an additional antimanic agent or antidepressant. CONCLUSIONS: The present analysis of a large and unselected nationwide population provides important complementary data to that from controlled trials. Although various mechanisms may be responsible for the results, the data support the utilization of lithium or valproate, rather than SGAs, as the initial antimanic treatment in bipolar disorder. A large-scale, prospective, randomized, pragmatic clinical trial comparing the initiation of SGA monotherapy to that of lithium or valproate monotherapy is a logical next step.

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.

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.

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.