Effect of Selective Serotonin Reuptake Inhibitors on Healthcare Utilization in Patients with Post-Traumatic Stress Disorder and Alcohol Use Disorder.

AIMS: The objective of this study is to address equivocation in estimates of selective serotonin reuptake inhibitor initiation (SSRI) effect on all-cause and alcohol-related ER visits, and medical or psychiatric admissions within 2 years of initial Post-Traumatic Stress Disorder (PTSD) diagnosis in patients with PTSD and Alcohol Use Disorder (AUD). METHODS: This study is a quasi-experimental, new-user-design cohort study of 3235 patients seen at the VA North Texas Healthcare System between January 1, 2000 and December 31, 2016. High dimensional propensity score (HDPS) techniques were used to estimate likelihood of SSRI initiation within 30 days of first PTSD diagnosis. Propensity scores were used to calculate weights for likelihood of SSRI initiation which were used to control for baseline covariates in estimations of SSRI medication effect on odds of each outcome occurring. RESULTS: Compared to those who did not receive SSRIs, patients prescribed an SSRI within 30 days showed significantly lower odds of alcohol-related ER visits (OR=0.668, 95%CI = 0.476 to 0.938, P = 0.02) and alcohol-related medical admissions (OR=0.583, 95%CI = 0.399 to 0.851, P = 0.005). LIMITATIONS: Inconsistent assessment of PTSD severity necessitated the use of HDPS models to control for baseline confounding. Our study design mimicked intent-to-treat trial design and therefore could not control for SSRI initiations after the 30-day grace period following initial PTSD diagnosis. CONCLUSIONS: SSRI initiation in patients with AUD and PTSD is associated with significantly reduced odds of alcohol-related medical hospitalization and alcohol-related ER visits within 2 years of first PTSD diagnosis. Additional studies are needed to verify these results.

Systematic review of preclinical, clinical, and post-marketing evidence of bupropion misuse potential.

Background: Bupropion is a substituted cathinone compound widely used as a first line or add-on treatment for depression, smoking cessation, and more recently in combination with naltrexone for weight loss. As abuse of synthetic cathinone compounds has received more attention in recent years, concern about the misuse potential of bupropion has grown as well. Objectives: We review bupropion pharmacology and assessments of misuse potential including preclinical evidence, human studies, and post-marketing surveillance of bupropion misuse. Methods: This review reports the results of a systematic review of publications evaluating the potential for bupropion to be misused. Publications were identified using PubMed and Medline through Ovid® as well as iterative bibliographic searches. A summary of data from informal sources of information including substance-user experience from online forum entries is included. Results: Preclinical evidence demonstrates some potential for misuse based on psychomotor, discrimination, self-administration, and conditioned place preference tasks. However, this potential is less than that of commonly misused stimulants. Studies in human populations similarly indicate that bupropion shares interoceptive effects with other stimulants, but lacks some key reinforcing effects of other stimulants. In the real-world setting, misuse of bupropion occurs, but is uncommon. Adverse effects of bupropion misuse are frequently cited as significant barriers to obtaining any desired interoceptive effect. Conclusions: While bupropion demonstrates some potential for misuse, pharmacological differences from other structurally-related stimulants limit bupropion's reinforcing effects. Without additional data indicating susceptibility of specific populations to bupropion misuse, there is no empirical data suggesting a need to modify bupropion prescribing patterns.

Systematic Review of Combined Pharmacotherapy for the Treatment of Alcohol Use Disorder in Patients Without Comorbid Conditions.

BACKGROUND: Previous reviews have examined the use of theoretically supported combinations of drugs for the treatment of alcohol use disorder. This review seeks to examine the strengths and limitations of current clinical evidence for the use of combined pharmacological interventions intended to treat alcohol use disorder. OBJECTIVES: The objective of this review was to identify combinations of pharmacological treatments for alcohol use disorder, and assess the strength of clinical evidence for these treatments. METHODS: We conducted searches using PubMed, EMBASE® through Ovid® (1974 to present), MEDLINE® through Ovid® (1946 to present), and Psychinfo® through Ovid® (1806 to present). Our primary search included the terms "alcoholism" and "drug therapy, combination". Search results were restricted to human subjects and English language. Search criteria were not restricted based on study design or patient age. Studies were evaluated for randomization, blinding, group similarity, power determination, outcome reporting, and number of patients analyzed. RESULTS: Nine hundred and eighty-four publications were initially screened for inclusion after duplicates were removed. The search identified 16 publications evaluating drug combinations for the treatment of alcohol use disorder. The majority of published trials included naltrexone combined with one of the following: gabapentin, ondansetron, acamprosate, gamma-hydroxybutyrate, sertraline, quetiapine, or escitalopram plus gamma-hydroxybutyrate. Other combinations included 5-hydroxytryptophan with carbidopa/levodopa, gamma-hydroxybutyrate with disulfiram, acamprosate with disulfiram, and mirtazapine with quetiapine. Interpretation of results across studies was limited by low statistical power, and heterogeneity of drug combinations and outcome measures. Drug combination effect sizes were comparable to those observed in single-agent trials. CONCLUSIONS: No significant benefit for the use of combinations over single agents was observed. However, benefit may be observed when combined pharmacological interventions address specific symptoms of alcohol use disorder known to be influenced by combination components, or when combinations are used in specific subpopulations in which combination components demonstrate benefit.

Plasma Insulin Level Correlation to Metabolic Parameter Shifts in Hospitalized Psychiatric Patients.

OBJECTIVE: To identify potential correlations between baseline plasma insulin level and shifts in metabolic status in psychiatric inpatients. METHODS: A population of 75 patients was identified for this single-center, retrospective study conducted at a state psychiatric hospital in Kansas City, Missouri. Patients were selected on the basis of presence of a baseline fasting plasma insulin level drawn at admission; duration of stay ≥ 12 weeks between August 1, 2013, and December 31, 2015; and presence of metabolic laboratory and weight measurements at baseline and 3 months. Total initial plasma insulin level (≥ 19 µIU/mL or < 19 µIU/mL) was compared to shifts in metabolic laboratory measurements and weight. A secondary analysis was performed to detect association between the numerical values of assessed parameters and the numerical values for plasma insulin measurements. RESULTS: The primary analysis found no correlation between plasma insulin level and changes in any metabolic parameter category at 3 (n = 75) or 6 months (n = 30) after admission. Secondary analysis found significant correlations between the numerical values of baseline total plasma insulin level and fasting plasma glucose level at baseline (r = 0.492, P < .001), 3 months (r = 0.247, P = .035), and 6 months (r = 0.723, P < .001). Secondary analysis demonstrated a significant correlation between baseline total plasma insulin level and hemoglobin A1c values at baseline (r = 0.329, P = .004), 3 months (r = 0.455, P < .001), and 6 months (r = 0.517, P = .003). CONCLUSIONS: Baseline total plasma insulin levels were strongly correlated with parameters affected directly by alterations in glucose up to 6 months after admission but were weakly correlated or not correlated with other metabolic parameters. The results do not support routine use of plasma insulin as a predictor for shifts in metabolic parameters in patients receiving antipsychotic medications.