Impulsiveness as a predictor of topiramate response for cocaine use disorder.

BACKGROUND/OBJECTIVES: Topiramate has been studied in the treatment of substance use disorders and is often used off-label in the treatment of other disorders with impaired impulse control. We sought to determine whether impulsiveness could predict topiramate treatment response in individuals with cocaine use disorder (CUD). METHODS: In a post-hoc analysis of a 12-week, double-blind, randomized, placebo-controlled trial of topiramate for CUD, we examined the relationship between response to treatment and participants' baseline score on the Barrett Impulsiveness Scale (BIS-11). During the original trial, topiramate was titrated up to 300 mg/day over 6 weeks and maintained for 6 weeks. All participants received weekly cognitive behavioral therapy. RESULTS: Individuals with total BIS-11 scores above the median had 11.2% more cocaine-free days with topiramate versus placebo (Bonferroni corrected p = 0.047). Individuals with first-order factor scores above the median in self-control (Bonferroni corrected p = 0.020) and at or below the median in attention (Bonferroni corrected p = 0.022), and second-order factor scores at or below the median in attentional (Bonferroni corrected p = 0.024) and motor impulsiveness (Bonferroni corrected p = 0.046) were all associated with a greater improvement with topiramate. DISCUSSION/CONCLUSION: The results indicate an association between higher within-group impulsiveness and response to topiramate for CUD. The subscore findings may suggest a complex interaction between effectiveness and known cognitive side effects. The finding that trait impulsiveness is associated with treatment response is a promising discovery that may help guide treatment for CUD. SCIENTIFIC SIGNIFICANCE: This analysis suggests a possible endophenotype based on impulsiveness that can predict treatment response to topiramate. (Am J Addict 2019;XX:1-6).

Epidemiology of pediatric buprenorphine and methadone exposures reported to the poison centers.

BACKGROUND: Buprenorphine prescriptions have increased dramatically within the United States, whereas methadone continues to be used widely. We investigated the trends and characteristics of buprenorphine and methadone exposures in the pediatric population. METHODS: We identified pediatric exposures to buprenorphine and methadone using the National Poison Data System from 2013 to 2016. We descriptively assessed characteristics of the exposures. Trends in exposures were evaluated using generalized linear mixed models. RESULTS: Pediatric buprenorphine exposures increased from 2013 (1097) to 2016 (1226) while methadone calls decreased (486 to 396). After adjusting for the random effects of the geographical region, the mean number of pediatric buprenorphine exposures (per 100,000 pediatric population) increased from 1.3 to 1.5 (P = .05). Conversely, the mean number of methadone exposures decreased from 0.6 to 0.4 (P = .03). Children aged ≤3 years constituted the highest percentage of both exposures. Unintentional exposures accounted for most of the buprenorphine (86.9%) and methadone (62.4%) exposures. Major clinical effects were demonstrated in 2.3% of buprenorphine exposures and were more frequent with methadone (13%). West Virginia and Maryland demonstrated the highest incidence of buprenorphine and methadone exposures, respectively. CONCLUSIONS: Pediatric buprenorphine exposures increased but demonstrated less severe effects compared to methadone exposures, which decreased during the study period.

Women and Addiction: An Update.

Gender-related alcohol and drug abuse problems are related not only to biological differences, but also to social and environmental factors, which can influence the clinical presentation, consequences of use, and treatment approaches. Women are becoming the fastest-growing population of substance abusers in the United States. Given that women experience a more rapid progression of their addiction than men, it is important that we understand and address the differences to help develop prevention and treatment programs that are tailored for women, incorporating trauma assessment and management, identification and intervention for medical and psychiatric comorbidities, financial independence, pregnancy, and child care.

A Review of Alprazolam Use, Misuse, and Withdrawal.

: Alprazolam is one of the most widely prescribed benzodiazepines for the treatment of generalized anxiety disorder and panic disorder. Its clinical use has been a point of contention as most addiction specialists consider it to be highly addictive, given its unique psychodynamic properties which limit its clinical usefulness, whereas many primary care physicians continue to prescribe it for longer periods than recommended. Clinical research data has not fully shed light on its "abuse liability," yet it is one of the most frequently prescribed benzodiazepines. "Abuse liability" is the degree to which a psychoactive drug has properties that facilitate people misusing it, or becoming addicted to it, and is commonly used in the literature. We have replaced it in our manuscript with "misuse liability" as it reflects a more updated terminology consistent with the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). In this paper, we have reviewed alprazolam's indications for use, its effect on pregnant women, misuse liability, withdrawal syndrome, pharmacodynamic properties, and suggest better clinical prescription practice of alprazolam by presenting an indepth theory of its clinical effects with use and withdrawal.

Trends and characteristics of naloxone therapy reported to US poison centers.

BACKGROUND AND AIMS: In the United States, access to naloxone has been expanded as a measure to address growing opioid overdose mortality. The study aimed to describe the national trends in naloxone use as reported to the US poison centers (PCs). METHODS: The National Poison Data System (NPDS) was queried for cases reporting naloxone therapy from 1 January 2001 to 31 December 2016. Demographic and clinical characteristics were assessed descriptively. Trends in naloxone reports were evaluated by using generalized linear mixed models that were adjusted for age, gender and random effects of the geographical census region. Cumulative incidence rates (CIR) of naloxone reports at the state- and national-level were calculated. RESULTS: There were 304 249 cases reporting naloxone therapy during the study period. The frequency of naloxone reports increased from 9498 in 2000 to 26 826 in 2016. The proportion of cases where naloxone was used prior to PC recommendation increased from 59.8% in 2000 to 81.5% in 2016. The mean number of NPDS naloxone reports per 100 000 human exposures increased from 9.6 [95% confidence interval (CI) = 6.4-14.2] to 31.7 (95% CI = 21.4-46.9, P < 0.001). Among the cases, 52.4% were female and the most frequent age group was 20-39 years (39.1%). The principal reason for a toxic exposure resulting in a naloxone report was suspected suicide (55.0%). Life-threatening symptoms were seen in one-fifth of the cases, with 53.9% cases being admitted to critical care units. Opioids (59.7% cases), were the most commonly reported exposure agents, with hydrocodone being most frequently reported. The national CIR of naloxone reports to the US PCs was 6.3 cases per 100 000 population, with West Virginia demonstrating the highest incidence. CONCLUSIONS: Analysis of calls to the United States poison centers indicates an increasing trend of naloxone use from 2000 to 2016.

Women and Addiction.

Gender-related alcohol and drug abuse problems are related not only to biological differences, but also to social and environmental factors, which can influence the clinical presentation, consequences of use, and treatment approaches. Women are becoming the fastest-growing population of substance abusers in the United States. Given that women experience a more rapid progression of their addiction than men, it is important that we understand and address the differences to help develop prevention and treatment programs that are tailored for women, incorporating trauma assessment and management, identification and intervention for medical and psychiatric comorbidities, financial independence, pregnancy, and child care.