Assessment of clinical outcomes in patients with post-traumatic stress disorder: analysis from the UK Medical Cannabis Registry.

BACKGROUND: The current paucity of clinical evidence limits the use of cannabis-based medicinal products (CBMPs) in post-traumatic stress disorder (PTSD). This study investigates health-related quality of life (HRQoL) changes and adverse events in patients prescribed CBMPs for PTSD. METHODS: A case-series of patients from the UK Medical Cannabis Registry was analyzed. HRQoL was assessed at 1-, 3-, and 6-months using validated patient reported outcome measures (PROMs). Adverse events were analyzed according to the Common Terminology Criteria for Adverse Events version 4.0. Statistical significance was defined as p < 0.050. RESULTS: Of 162 included patients, 88.89% (n = 144) were current/previous cannabis users. Median daily CBMP dosages were 5.00 (IQR: 0.00-70.00) mg of cannabidiol and 145.00 (IQR: 100.00-200.00) mg of Δ9-tetrahydrocannabinol. Significant improvements were observed in PTSD symptoms, sleep, and anxiety across all follow-up periods (p < 0.050). There were 220 (135.8%) adverse events reported by 33 patients (20.37%), with the majority graded mild or moderate in severity (n = 190, 117.28%). Insomnia and fatigue had the greatest incidence (n = 20, 12.35%). CONCLUSIONS: Associated improvements in HRQoL were observed in patients who initiated CBMP therapy. Adverse events analysis suggests acceptability and safety up to 6 months. This study may inform randomized placebo-controlled trials, required to confirm causality and determine optimal dosing.

The Costs and Health Benefits of Expanded Access to MDMA-assisted Therapy for Chronic and Severe PTSD in the USA: A Modeling Study.

BACKGROUND AND OBJECTIVE: Intensive psychotherapy assisted with 3,4-methylenedioxymethamphetamine (MDMA-AT) was shown in Phase 3 clinical trials to substantially reduce post-traumatic stress disorder (PTSD) symptoms compared to psychotherapy with placebo. This study estimates potential costs, health benefits, and net savings of expanding access to MDMA-AT to eligible US patients with chronic and severe PTSD. METHODS: Using a decision-analytic model, we compared the costs, deaths averted, and quality-adjusted life years (QALYs) gained of three, 10-year MDMA-AT coverage targets (25%, 50%, and 75%) compared to providing standard of care to the same number of eligible patients with chronic and severe PTSD. We used a payer perspective and discounted costs (in US$) and QALYs to 2020. We conducted one-way, scenario, and probabilistic sensitivity analyses and calculated the net monetary value of MDMA-AT using a cost-effectiveness threshold of $100,000 per QALY gained. RESULTS: Expanding access to MDMA-AT to 25-75% of eligible patients is projected to avert 43,618-106,932 deaths and gain 3.3-8.2 million QALYs. All three treatment targets are dominant or cost-saving compared to standard of care. Our sensitivity analyses found that accounting for parameter uncertainty and changes in various assumptions did not alter the main finding-MDMA-AT is dominant compared to standard of care. CONCLUSION: Expanding access to MDMA-AT to patients with chronic and severe PTSD will provide substantial health and financial benefits. The precise magnitude is uncertain and will depend on the number of eligible patients and other inputs.

Updated cost-effectiveness of MDMA-assisted therapy for the treatment of posttraumatic stress disorder in the United States: Findings from a phase 3 trial.

BACKGROUND: Severe posttraumatic stress disorder (PTSD) is a prevalent and debilitating condition in the United States. and globally. Using pooled efficacy data from six phase 2 trials, therapy using 3,4-methylenedioxymethamphetamine (MDMA) appeared cost-saving from a payer's perspective. This study updates the cost-effectiveness analysis of this novel therapy using data from a new phase 3 trial, including the incremental cost-effectiveness of the more intensive phase 3 regimen compared with the shorter phase 2 regimen. METHODS: We adapted a previously-published Markov model to portray the costs and health benefits of providing MDMA-assisted therapy (MDMA-AT) to patients with chronic, severe, or extreme PTSD in a recent phase 3 trial, compared with standard care. Inputs were based on trial results and published literature. The trial treated 90 patients with a clinician administered PTSD scale (CAPS-5) total severity score of 35 or greater at baseline, and duration of PTSD symptoms of 6 months or longer. The primary outcome was assessed 8 weeks after the final experimental session. Patients received three 90-minute preparatory psychotherapy sessions, three 8-hour active MDMA or placebo sessions, and nine 90-minute integrative psychotherapy sessions. Our model calculates the per-patient cost of MDMA-AT, net all-cause medical costs, mortality, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). We reported results from the U.S. health care payer's perspective for multiple analytic time horizons, (base-case is 30 years), and conducted extensive sensitivity analyses. Costs and QALYs were discounted by 3% annually. Costs were adjusted to 2020 U.S. dollars according to the medical component of the U.S. Bureau of Labor Statistics' Consumer Price Index (CPI). RESULTS: MDMA-AT as conducted in the phase 3 trial costs $11,537 per patient. Compared to standard of care for 1,000 patients, MDMA-AT generates discounted net health care savings of $132.9 million over 30 years, accruing 4,856 QALYs, and averting 61.4 premature deaths. MDMA-AT breaks even on cost at 3.8 years while delivering 887 QALYs. A third MDMA session generates additional medical savings and health benefits compared with a two-session regimen. Hypothetically assuming no savings in health care costs, MDMA-AT has an ICER of $2,384 per QALY gained. CONCLUSIONS: MDMA-AT provided to patients with severe or extreme chronic PTSD is cost-saving from a payer's perspective, while delivering substantial clinical benefit.

Monoamine Oxidase Inhibitors (MAOIs) in Psychiatric Practice: How to Use them Safely and Effectively.

Monoamine oxidase inhibitors (MAOIs) were among the first licensed pharmacological treatments for patients with depression but over time have fallen out of mainstream clinical use. This has led to a loss of clinician training opportunities and reduced availability of MAOIs for prescribing. This article provides a concise and practical overview of how to use MAOIs safely and effectively in psychiatric practice. We consider the history of MAOIs, why they are not used more frequently, their mechanisms of action, availability, indications and efficacy, general tolerability, withdrawal symptoms, and safety considerations (including hypertensive reactions and serotonin syndrome). Practical advice is given in terms of dietary restrictions, interactions with other medications (both prescribed and non-prescribed), and how prescribers can stop and switch MAOIs, both within the drug class and outside of it. We also provide advice on choice of MAOI and treatment sequencing. Lastly, we consider emerging directions and potential additional indications.

Serious shortcomings in assessment and treatment of asylum seekers' mental health needs.

BACKGROUND: The prevalence of psychological complaints is known to be very high in populations of asylum seekers. Despite this, data on the health care system's ability to adequately meet these high-risk populations' mental health needs are scarce. This article investigates how well the German outpatient health care system is able to detect and adequately treat them. METHODS: To this end, we combined data from a cross-sectional survey with billing data from the local social welfare office from the year 2015. Using descriptive statistics, the data of the cross-sectional study are used to quantify the psychological health care needs of asylum seekers while the secondary data analysis indicates the actual access to and extent of psychological treatment. RESULTS: In the cross-sectional study, 54% of patients were screened positive for symptoms of depression, 41% for symptoms of anxiety disorder and 18% for symptoms of Posttraumatic Stress Disorder. In total, 59% were screened positive for at least one of these three disorders. However, when contrasting these screening-based prevalences with the prevalences based on data from the health care system, a mismatch becomes apparent: According to the social welfare office's billing data, only 2.6% of asylum seekers received the diagnosis of depression, 1.4% were diagnosed with anxiety disorder and 2.9% with Posttraumatic Stress Disorder (PTSD). In combination, 4.9% were diagnosed with at least one of these three disorders. Overall, less than one tenth of asylum seekers with symptoms of depression, anxiety or PTSD received the corresponding diagnosis by the health care system. Among those who were diagnosed, about 45% received no treatment at all, while 38% were treated with drugs alone. Only 1% of all patients received psychotherapy. CONCLUSIONS: Psychological complaints are very common among asylum seekers, yet only a small proportion of this population receives the corresponding diagnoses and treatment. While various factors can contribute to these shortcomings, there is an urgent need to systematically address this deficit and introduce measures to improve mental health care for this high-risk population.

Integrating Unified Medical Language System and Kleinberg's Burst Detection Algorithm into Research Topics of Medications for Post-Traumatic Stress Disorder.

BACKGROUND: The treatment of post-traumatic stress disorder (PTSD) has long been a challenge because the symptoms of PTSD are multifaceted. PTSD is primarily treated with psychotherapy and medication, or a combination of psychotherapy and medication. The present study was designed to analyze the literature on medications for PTSD and explore high-frequency common drugs and low-frequency burst drugs by burst detection algorithm combined with Unified Medical Language System (UMLS) and provide references for developing new drugs for PTSD. METHODS: Publications related to medications for PTSD from 2010 to 2019 were identified through PubMed, Web of Science Core Collection, and BIOSIS Previews. SemRep and SemRep semantic result processing system were performed to extract the set of drug concepts with therapeutic relationship according to the semantic relationship of UMLS. Kleinberg's burst detection algorithm was applied to calculate the burst weight index of drug concepts by a Java-based program. These concepts were sorted according to the frequency and the burst weight index. RESULTS: Four hundred and fifty-nine treatment-related drug concepts were extracted. The drug with the highest burst weight index was "Psilocybine", a hallucinogen, which was more likely to be a hotspot for the pharmacotherapy of PTSD. The highest frequency concept was "prazosin", which was more likely to be the focus of research in the medications for PTSD. CONCLUSION: The present study assessed the medication-related literature on PTSD treatment, providing a framework of burst words detection-based method, a baseline of information for future research and the new attempt for the discovery of textual knowledge. The bibliometric analysis based on the burst detection algorithm combined with UMLS has shown certain feasibility in amplifying the microscopic changes of a specific research direction in a field, it can also be used in other aspects of disease and to explore the trends of various disciplines.

The cost-effectiveness of MDMA-assisted psychotherapy for the treatment of chronic, treatment-resistant PTSD.

BACKGROUND: Chronic posttraumatic stress disorder (PTSD) is a disabling condition that generates considerable morbidity, mortality, and both medical and indirect social costs. Treatment options are limited. A novel therapy using 3,4-methylenedioxymethamphetamine (MDMA) has shown efficacy in six phase 2 trials. Its cost-effectiveness is unknown. METHODS AND FINDINGS: To assess the cost-effectiveness of MDMA-assisted psychotherapy (MAP) from the health care payer's perspective, we constructed a decision-analytic Markov model to portray the costs and health benefits of treating patients with chronic, severe, or extreme, treatment-resistant PTSD with MAP. In six double-blind phase 2 trials, MAP consisted of a mean of 2.5 90-minute trauma-focused psychotherapy sessions before two 8-hour sessions with MDMA (mean dose of 125 mg), followed by a mean of 3.5 integration sessions for each active session. The control group received an inactive placebo or 25-40 mg. of MDMA, and otherwise followed the same regimen. Our model calculates net medical costs, mortality, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Efficacy was based on the pooled results of six randomized controlled phase 2 trials with 105 subjects; and a four-year follow-up of 19 subjects. Other inputs were based on published literature and on assumptions when data were unavailable. We modeled results over a 30-year analytic horizon and conducted extensive sensitivity analyses. Our model calculates expected medical costs, mortality, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio. Future costs and QALYs were discounted at 3% per year. For 1,000 individuals, MAP generates discounted net savings of $103.2 million over 30 years while accruing 5,553 discounted QALYs, compared to continued standard of care. MAP breaks even on cost at 3.1 years while delivering 918 QALYs. Making the conservative assumption that benefits cease after one year, MAP would accrue net costs of $7.6 million while generating 288 QALYS, or $26,427 per QALY gained. CONCLUSION: MAP provided to patients with severe or extreme, chronic PTSD appears to be cost-saving while delivering substantial clinical benefit. Third-party payers are likely to save money within three years by covering this form of therapy.

Cost-effectiveness of psychological treatments for post-traumatic stress disorder in adults.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a severe and disabling condition that may lead to functional impairment and reduced productivity. Psychological interventions have been shown to be effective in its management. The objective of this study was to assess the cost-effectiveness of a range of interventions for adults with PTSD. METHODS: A decision-analytic model was constructed to compare costs and quality-adjusted life-years (QALYs) of 10 interventions and no treatment for adults with PTSD, from the perspective of the National Health Service and personal social services in England. Effectiveness data were derived from a systematic review and network meta-analysis. Other model input parameters were based on published sources, supplemented by expert opinion. RESULTS: Eye movement desensitisation and reprocessing (EMDR) appeared to be the most cost-effective intervention for adults with PTSD (with a probability of 0.34 amongst the 11 evaluated options at a cost-effectiveness threshold of £20,000/QALY), followed by combined somatic/cognitive therapies, self-help with support, psychoeducation, selective serotonin reuptake inhibitors (SSRIs), trauma-focused cognitive behavioural therapy (TF-CBT), self-help without support, non-TF-CBT and combined TF-CBT/SSRIs. Counselling appeared to be less cost-effective than no treatment. TF-CBT had the largest evidence base. CONCLUSIONS: A number of interventions appear to be cost-effective for the management of PTSD in adults. EMDR appears to be the most cost-effective amongst them. TF-CBT has the largest evidence base. There remains a need for well-conducted studies that examine the long-term clinical and cost-effectiveness of a range of treatments for adults with PTSD.

Development of a Practice Tool for Primary Care Providers: Medication Management of Posttraumatic Stress Disorder in Veterans with Mild Traumatic Brain Injury.

Posttraumatic stress disorder (PTSD) and comorbid mild traumatic brain injury (mTBI) are highly prevalent in veterans who served in Iraq [Operation Iraqi Freedom/Operation New Dawn] and Afghanistan [Operation Enduring Freedom]. Complicated psychotropic medications are used for treatment of PTSD and comorbid mTBI symptoms lead to polypharmacy related complications. Primary care providers (PCPs) working in Community Based Outpatient Clinics (CBOCs) are usually burdened with the responsibility of managing this complicated medication regimen or relevant side effects. The PCPs do not feel equipped to provide this complicated psychopharmacological management. Thus, there is a need for a comprehensive yet concise tool for the medication management of PTSD in veterans with comorbid mTBI. (1) To conduct focus groups of interdisciplinary team of experts and other stake holders to assess need, (2) To carefully review current VA/Department of Defense practice guideline to identify content, (3) To develop an evidence based, user friendly, and concise pocket guide for the PCP's. Content was identified by review of current guidelines and available literature and was finalized after input from stakeholders, multidisciplinary team of experts, and review of qualitative data from focus groups/interviews of clinicians working in remote CBOCs. The pocket tool was formatted and designed by multimedia service. A pocket guide in the form of a bi-fold, 4″ × 5.5″ laminated card was developed. One thousand hard copies were distributed in the local VA medical center. This product is available online for download at the South-Central Mental Illness Research, Education, and Clinical Center website ( https://www.mirecc.va.gov/VISN16/ptsd-and-mtbi-pocket-card.asp ). This pocket card provides PCPs an easy to carry and user-friendly clinical decision-making tool to effectively treat veterans with PTSD and comorbid mTBI.

A systematic review of network meta-analyses for pharmacological treatment of common mental disorders.

QUESTION: Network meta-analyses (NMAs) of treatment efficacy across different pharmacological treatments help inform clinical decision-making, but their methodological quality may vary a lot depending also on the quality of the included primary studies. We therefore conducted a systematic review of NMAs of pharmacological treatment for common mental disorders in order to assess the methodological quality of these NMAs, and to relate study characteristics to the rankings of efficacy and tolerability. STUDY SELECTION AND ANALYSIS: We searched three databases for NMAs of pharmacological treatment used in major depression, generalised anxiety disorder (GAD), social anxiety disorder (SAD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD) and specific phobia.Studies were appraised using the International Society for Pharmacoeconomics and Outcomes Research checklist of good research practices for indirect-treatment-comparison and network-meta-analysis studies. FINDINGS: Twenty NMAs were eligible for inclusion. The number of randomised controlled trials per NMA ranged from 11 to 234, and included between 801 to more than 26 000 participants. Overall, antidepressants were found to be efficacious and tolerable agents for several disorders based on rankings (45%) or statistical significance (55%). The majority of NMAs in this review adhered to guidelines by including a network diagram (70%), assessing consistency (75%), making use of a random effects model (75%), providing information on the model used to fit the data (75%) and adjusting for covariates (75%). CONCLUSIONS: The 20 NMAs of depression and anxiety disorders, PTSD and/or OCD included in this review demonstrate some methodological strengths in comparison with the larger body of published NMAs for medical disorders, support current treatment guidelines and help inform clinical decision-making.

Cost-Effectiveness of Telemedicine-Based Collaborative Care for Posttraumatic Stress Disorder.

OBJECTIVE: The study examined the cost-effectiveness of a telemedicine-based collaborative care model designed to increase rural veterans' engagement in evidence-based treatments for posttraumatic stress disorder (PTSD). METHODS: The Telemedicine Outreach for PTSD (TOP) study used a pragmatic randomized effectiveness trial to examine effects of PTSD care teams located at Veterans Affairs medical centers and supporting primary care providers in satellite clinics. Teams included a nurse care manager, pharmacist, psychologist, and psychiatrist. Effectiveness was estimated with quality-adjusted life years (QALYs) derived from the Short Form Health Survey for Veterans and Quality of Well-Being (QWB) scale. Intervention and health care costs were collected to evaluate the cost-effectiveness of the intervention. RESULTS: The sample (N=265) included mostly rural, unemployed, middle-aged men with a military service-connected disability for PTSD randomly assigned to TOP or usual care. Only minor improvements in QWB QALYs were found. The TOP intervention was relatively expensive, with costs totaling $2,029 per patient per year. Intervention costs were not offset by reductions in health care utilization costs, resulting in an incremental cost-effectiveness ratio of $185,565 per QALY (interquartile range $57,675 to $395,743). CONCLUSIONS: Because of the upfront training costs and the resource-intensive nature of this intervention, associated expenses were high. Although PTSD-specific effectiveness measures were significantly improved, these changes did not translate to QALYs in the main analysis. However, analyses focusing on patient subgroups with comorbid mental disorders indicated greater QALY improvement for TOP at lower cost.

Psychotropic Medication Use among Medicare Beneficiaries Following Traumatic Brain Injury.

OBJECTIVES: To characterize psychotropic medication use before and after traumatic brain injury (TBI) hospitalization among older adults. A secondary objective is to determine how receipt of indicated pharmacologic treatment for anxiety and post-traumatic stress disorder (PTSD) differs following TBI. DESIGN: Retrospective cohort. SETTING: United States. PARTICIPANTS: Medicare beneficiaries aged ≥65 years hospitalized with TBI between 2006 and 2010 with continuous drug coverage for 12 months before and after TBI (N = 60,276). MEASUREMENTS: We obtained monthly psychotropic medication use by drug class and specific drugs from Medicare Part D drug event files.ICD-9 codes were used to define anxiety (300.0x) and PTSD (309.81). RESULTS: Average monthly prevalence of psychotropic medication use among all patients hospitalized for TBI was 44.8%; antidepressants constituted 73%. Prevalence of psychotropic medication use increased from 2006 to 2010. Following TBI, psychotropic medication use increased slightly (OR: 1.05; 95% CI: 1.03, 1.06.) Tricyclic antidepressant use decreased post-TBI (OR: 0.76; 95% CI: 0.73, 0.79) whereas use of the sedating antidepressants mirtazapine (OR: 1.31; 95% CI: 1.25, 1.37) and trazadone (OR: 1.11; 95% CI: 1.06, 1.17) increased. Antipsychotic (OR: 1.15; 95% CI: 1.12, 1.19) use also increased post-TBI. Beneficiaries newly diagnosed with anxiety (OR: 0.42; 95% CI: 0.36, 0.48) and/or PTSD (OR: 0.39; 95% CI: 0.18, 0.84) post-TBI were less likely to receive indicated pharmacologic treatment. CONCLUSIONS: Older adults hospitalized with TBI have a high prevalence of psychotropic medication use yet are less likely to receive indicated pharmacological treatment for newly diagnosed anxiety and PTSD following TBI.

Sedative-Hypnotic Use Among Older Adults Participating in Anxiety Research.

Older adults are prescribed sedative-hypnotic medications at higher rates than younger adults. These are not recommended for older adults due to risk of sedation, cognitive impairment, and falls. Severe generalized anxiety disorder (GAD) is a possibly appropriate use of these medications in older people, but little is available on use of sedative-hypnotic medications among older adults with GAD. This study examined the frequency and predictors of sedative-hypnotic medication use among older adults screening positive for anxiety. 25.88% ( n = 125) of participants reported taking sedative-hypnotics over the past 3 months; 16.36% ( n = 79) reported taking benzodiazepines, and 12.22% ( n = 59) reported taking hypnotic sleep medications. Depressive symptoms were more strongly associated with sedative-hypnotic use than insomnia or worry. Major depressive disorder and posttraumatic stress disorder, but not GAD, predicted sedative-hypnotic use. Other medications and treatments are more appropriate and efficacious for depression, anxiety, and insomnia in this population.

Opioid Overdose: Risk Assessment and Mitigation in Outpatient Treatment.

The present clinical case discussion focuses on a patient with comorbid substance use disorder (SUD) and chronic pain, who experienced an overdose of heroin. The case illustrates the complex array of risk factors that contribute to overdose risk, discusses the use of naloxone, and highlights the need for further risk mitigation interventions in patients at risk for overdose.

Cannabis for posttraumatic stress disorder: A neurobiological approach to treatment.

The endocannabinoid system is intricately involved in regulation of the neurobiological processes, which underlie the symptomatology of posttraumatic stress disorder (PTSD). This article discusses the neurobiological underpinnings of PTSD and the use of cannabis for treating PTSD in the New Mexico Medical Cannabis Program.

Use of antidepressant medication after road traffic injury.

OBJECTIVES: Mental ill health after road traffic injury is common, as is the use of antidepressant medication after injury. Little is known about antidepressant use by injured people prior to their injury. The aim of this study is to describe the nature and extent of antidepressant use before and after road traffic injury. METHODS: Victorian residents who claimed Transport Accident Commission (TAC) compensation for a non-catastrophic injury that occurred between 2010 and 2012 and provided consent for Pharmaceutical Benefits Scheme (PBS) linkage were included (n=734). PBS records dating from 12 months prior through to 12 months post injury were provided by the Department of Human Services (Canberra). PBS and TAC claims data were linked. RESULTS: Among participants, 12% used antidepressants before injury (84.4D efined Daily Doses/1000 person-days) and 17% used antidepressants after injury (114.1DDD/1000p-d). Only 7.7% of the injured cohort commenced antidepressant treatment post injury. Thus, of all post-injury antidepressant use, 45% could potentially be related to the incident injury, with the remaining 55% most probably a continuation of pre-injury use. Pre-injury use was more common among women (109.4 vs. 54.6 DDD/1000p-d, p<0.0001), and those with whiplash injury (119.3 vs. 73.1, p=0.03). Cyclists and motorcyclists were less likely to use antidepressants pre-injury than car drivers (18.3 vs. 16.9 vs. 109.3, respectively; p<0.001). CONCLUSIONS: Less than half of post-injury antidepressant use could potentially be attributable to the incident injury. These results highlight the importance of obtaining information on pre-injury health status before interpreting post-injury health service use to be an outcome of the injury in question.