Buprenorphine for the treatment of posttraumatic stress disorder.

BACKGROUND AND OBJECTIVES: The core pharmacological treatment of Post-Traumatic Stress Disorder (PTSD) is selective serotonin reuptake inhibitors (SSRIs), although remission is only around 30% with them. Many patients will self-treat with opioids and due to the opiate system involvement in dysphoric mood and anxiety/stress responses, it is likely that antagonism of the kappa opioid receptor (KOR) system represents a potential target for treatment of PTSD. The aim of this study is to compare response of PTSD symptoms when antagonizing KOR via buprenorphine/naloxone compared to SSRIs or opioid therapy. METHODS: A retrospective chart review of patients in the MEDVAMC between June 1, 2010 and June 30, 2016 was conducted. Inclusion criteria included patients with a documented diagnosis of PTSD with at least two documented PTSD scores (either PCLC or PC-PTSD). Exclusion criteria included patients not prescribed one of the study medications (ie, buprenorphine, SSRI, or opiate for chronic pain), and patients not on the study medication for at least 30 days. RESULTS: Buprenorphine patients exhibited the lowest final average PTSD score (2.47) and the largest change from baseline (-24.0%) compared to opioids (-16.1%) or SSRIs (1.16%). The average buprenorphine dose was 23.3 mg/day, and the average length of therapy was 860 days. CONCLUSIONS: Buprenorphine may help decrease PTSD symptoms more than SSRIs or opioids alone. Prospective studies are needed to determine whether these effects are reproducible. SCIENTIFIC SIGNIFICANCE: Pharmacotherapy advancements in PTSD treatment have been limited and the kappa opioid receptor system presents a new target that warrants further research. (Am J Addict 2019;XX:1-6).

A Systematic Review of Practice Guidelines and Recommendations for Discontinuation of Cholinesterase Inhibitors in Dementia.

Cholinesterase inhibitors (ChEIs) are the primary pharmacological treatment for symptom management of Alzheimer disease (AD), but they carry known risks during long-term use, and do not guarantee clinical effects over time. The balance of risks and benefits may warrant discontinuation at different points during the disease course. Indeed, although there is limited scientific study of deprescribing ChEIs, clinicians routinely face practical decisions about whether to continue or stop medications. This review examined published practice recommendations for discontinuation of ChEIs in AD. To characterize the scientific basis for recommendations, we first summarized randomized controlled trials of ChEI discontinuation. We then identified practice guidelines by professional societies and in textbooks and classified them according to 1) whether they made a recommendation about discontinuation, 2) what the recommendation was, and 3) the proposed grounds for discontinuation. There was no consensus in guidelines and textbooks about discontinuation. Most recommended individualized discontinuation decisions, but there was essentially no agreement about what findings or situations would warrant discontinuation, or even about what domains to consider in this process. The only relevant domain identified by most guidelines and textbooks was a lack of response or a loss of effectiveness, both of which can be difficult to ascertain in the course of a progressive condition. Well-designed, long-term studies of discontinuation have not been conducted; such evidence is needed to provide a scientific basis for practice guidelines. It seems reasonable to apply an individualized approach to discontinuation while engaging patients and families in treatment decisions. .

Impact of Lithium on Suicidality in the Veteran Population.

Background: Lithium has known antisuicidal properties making it an important agent to study in veterans with psychiatric conditions, a population at high risk for suicide. Methods: A single-site, retrospective chart review was conducted at a US Department of Veterans Affairs (VA) teaching hospital. Patients taking lithium for at least 6 months were identified using the VA Lithium Lab Monitoring Dashboard. The primary and secondary objectives were to evaluate the change in number of suicide attempts and suicidal ideation from 3 months prior to lithium initiation to 3 months after a 6-month duration of lithium. Results: The review included 98 patients; 47 (47.9%) received concomitant psychotherapy, 50 (51.0%) were taking an antipsychotic, and 29 (29.6%) an additional mood stabilizer. During the 6-month intervention period, 75 (76.5%) patients had a lithium level drawn and 28 were in the therapeutic range. Of the 98 patients, hospitalization for suicide attempt decreased from 4.1% before lithium use to 0% after lithium use for 6 months (P = .045). Hospitalization for suicidal ideation also decreased from 13.3% before lithium use to 1.0% after lithium use for 6 months (P = .0004). Conclusions: We observed a statistically significant reduction in hospitalization for suicide attempts and suicidal ideation in veterans prescribed lithium following nonfatal suicide behavior and suicidal ideation.

History of Suicide Attempt and Clozapine Treatment in Veterans With Schizophrenia or Schizoaffective Disorder.

Objective: To evaluate whether a history of suicide attempt increases the odds of receiving clozapine treatment in veterans with schizophrenia or schizoaffective disorder.Methods: Electronic health record data were obtained for veterans with schizophrenia or schizoaffective disorder treated at any US Veterans Affairs Medical Center between January 1, 2000, and January 31, 2021 (N = 134,692). Logistic regression (adjusted and unadjusted) was applied to estimate odds ratios (ORs) for clozapine treatment in suicide attempters relative to nonattempters.Results: 3,407 patients had a documented history of suicide attempt, while 6,867 patients had received clozapine treatment. Also, 9.4% (n = 321) of suicide attempters versus 5.0% (n = 6546) of nonattempters had received clozapine treatment. The odds of being treated with clozapine was approximately 2-fold in patients with a history of suicide attempt in unadjusted (OR = 1.98, 95% CI, 1.76-2.22) and adjusted (OR = 1.91, 95% CI, 1.67-2.15) analyses.Conclusions: Despite the higher odds of clozapine treatment in suicide attempters with schizophrenia or schizoaffective disorder, clozapine was underutilized in the current sample of veterans. Concerted efforts should be made to expand the use of clozapine in patients with schizophrenia or schizoaffective disorder, especially those with a history of suicide attempt.

Case Report: Concurrent Clonidine Abuse and Opioid Use Disorder.

Clonidine is a centrally acting alpha-2 selective adrenergic receptor agonist used to treat hypertension and to control or prevent withdrawal in patients with opioid and alcohol use disorders. Case reports describe abuse of clonidine alone or in combination with benzodiazepines, methadone, codeine, or heroin. Clonidine reportedly boosts and extends the opioid-related euphoria and reduces the amount of psychoactive drug needed. In this case report, we describe clonidine abuse and withdrawal management in an elderly patient with concurrent opioid use disorder. The usage of clonidine in the treatment of opioid detoxification remains controversial. Clonidine abuse is underestimated and requires more attention among health-care providers who concurrently prescribe clonidine and opioids. With the opioid epidemic becoming increasingly prevalent, physicians and other health-care providers must be vigilant in their opioid prescribing as well as concurrent prescribing of other psychoactive pharmacologic agents.

Veteran adherence to oral versus injectable AUD medication treatment.

INTRODUCTION: AUD medication treatment has been shown to improve outcomes compared with placebo when confined to per-protocol analysis. The same outcomes, however, have not always been maintained in intent-to-treat analysis, thus suggesting adherence may have a significant impact on efficacy outcomes. There is conflicting evidence present in the literature comparing adherence to oral versus injectable AUD pharmacotherapy and a paucity of information in the veteran population on risk factors for low adherence. METHODS: The primary end point of this retrospective chart review was to determine whether adherence rates differ between oral and injectable AUD treatments in veterans during the first year of treatment (at 3, 6, 9, and 12 months) using the portion of days covered model. Secondary end points were to determine differing characteristics between patients with high versus low adherence and compare alcohol-related readmission rates and discontinuation rates between groups. RESULTS: Adherence to injectable extended-release (XR) naltrexone was significantly higher than oral naltrexone at all time points and was significantly higher than disulfiram at 3, 6, and 9 months, but it was not significantly different from acamprosate at any time point. At months 9 and 12, acamprosate had significantly higher adherence compared with oral naltrexone. Patients with higher adherence were seen more frequently in the mental health clinic and had previously tried more AUD medications. The discontinuation rates and alcohol-related admission rates were not significantly different between groups at 1 year. DISCUSSION: XR naltrexone may improve adherence rates compared with oral naltrexone or disulfiram, but not acamprosate based on these outcomes. Patients may have increased adherence if they are seen more often in clinic and have trialed more AUD medications.

History of Suicide Attempts and COVID-19 Infection in Veterans with Schizophrenia or Schizoaffective Disorder: Moderating Effects of Age and Body Mass Index.

INTRODUCTION: Relative to the general population, patients with schizophrenia or schizoaffective disorder have higher rates of suicide attempts and mortality from COVID-19 infection. Therefore, determining whether a history of suicide attempt is associated with COVID-19 in patients with schizophrenia or schizoaffective disorder has implications for COVID-19 vulnerability stratification in this patient population. METHODS: We carried out cross-sectional analyses of electronic health records of veterans with a diagnosis of schizophrenia or schizoaffective disorder that received treatment at any United States Veterans Affairs Medical Center between January 1, 2020, and January 31, 2021. We used logistic regression to estimate unadjusted and adjusted (including age, sex, race, marital status, body mass index (BMI), and a medical comorbidity score) odds ratios (ORs) for COVID-19 positivity in suicide attempters relative to nonattempters. RESULTS: A total of 101,032 veterans (mean age 56.67 ± 13.13 years; males 91,715 [90.8%]) were included in the analyses. There were 2,703 (2.7%) suicide attempters and 719 (0.7%) patients were positive for COVID-19. The association between history of suicide attempt and COVID-19 positivity was modified by age and BMI, such that the relationship was only significant in patients younger than 59 years, and in obese (BMI ≥30) patients (adjusted OR 3.42, 95% CI 2.02-5.79 and OR 2.85, 95% CI 1.65-4.94, respectively). CONCLUSIONS: Higher rates of COVID-19 in young or obese suicide attempters with a diagnosis of schizophrenia or schizoaffective disorder might be due to the elevated risk for the infection in this subgroup of patients.

Hallucinogen Persisting Perception Disorder and Risk of Suicide.

A 30-year-old male patient developed a hallucinogen persisting perception disorder (HPPD) after smoking cannabis laced with phencyclidine (PCP) or lysergic acid diethylamide (LSD) 10 years prior to hospital admission. Clinically, he reported seeing vivid, saturated colors and caricature-like objects. The patient described perceiving objects or people in motion as moving faster than normal. He reported living in a dream-like state and feeling numb and detached from other people and his surroundings. Upon pharmacotherapy initiation, facility transfer, and subsequent discharge from an acute psychiatry unit, he ultimately committed suicide. Although hallucinogen abuse is common in the United States, this case suggests that HPPD maybe significantly underdiagnosed and undertreated. In some cases, this oversight may perpetuate years of unnecessary patient suffering and can ultimately lead to severe depression and suicide.

Targeting treatment-resistant depression.

Only 50% of depressed patients achieve remission of symptoms after 2 trials of antidepressants. Therefore one half of patients are considered treatment resistant. Studies have shown that with each failed antidepressant, chances of remission continue to decline. Untreated depressive symptoms lead to impaired social and occupational function, decline of physical health, suicidal thoughts, and increased health care utilization. Clinicians recognize there is an urgent need to find an efficacious treatment, but it becomes more difficult to decide on an appropriate therapy once a patient has failed 2 to 3 trials of antidepressants. An evidence-based review was performed to assess the efficacy and safety of several different antidepressant strategies to help the clinician decide which may be beneficial for specific patients.