Issues Methamphetamine or amphetamine-type stimulants are the second most frequently used illicit drug worldwide, second only to cannabis. Behavioural treatments are efficacious, but their impact is limited underscoring the need for other treatment options, notably, pharmacotherapy. Approach A review of randomised controlled trials of pharmacotherapies for methamphetamine or amphetamine-type stimulants was performed using PubMed and Google Scholar databases. Evidence for efficacy of medications is reported. Key findings Clinical trials have yielded no broadly effective pharmacotherapy. Promising signals have been observed for methylphenidate, naltrexone, bupropion and mirtazapine in subgroups of patients in reducing stimulant use (e.g. patients with less severe dependence at baseline, men who have sex with men), though none has produced an unambiguous, replicable signal of efficacy. Implications Problems in Phase II trials, including high drop-out rates, missing data and a lack of agreement on outcomes, complicate efforts to find a broadly effective pharmacotherapy for amphetamine-type stimulant disorders. Efforts to address these problems include calls for better validation of pharmacological target exposure, receptor binding and functional modulation. As well, there is a need for agreement in using findings from pre-clinical and early phases of the medication development process for selecting better pharmacotherapy candidates. Conclusion After over 20 years of efforts worldwide to develop a broadly effective medication for dependence on methamphetamine or amphetamine-type stimulants, no candidate has emerged. This highlights the need for new compounds, consistent and stringent research methods, better integration between preclinical and clinical stages of medication development, and improved collaboration between government, industry and researchers.
The majority of children in the child welfare system remain with their maltreating parents, yet little is known about their level of functioning and whether they are in need of mental health intervention. The purpose of this study was to evaluate the mental health functioning of an ethnically diverse sample of 302 maltreated children and 151 non maltreated children ages 9-12 to see if there were differences between those who remained at home, those placed in kin care, nonrelative foster care or a comparison group of children who were not maltreated. Children were evaluated on multiple measures of mental health functioning, both self report and caregiver report. Results showed that the maltreated children did not differ by placement type but did score significantly higher than the comparison children on many measures. There were substantial numbers of maltreated children scoring in the clinical range of measures in all placement types with over 60% of those remaining with birth parents being seen as functioning at a level that indicated a need for mental health intervention. While fewer comparison children had scores indicating a need for mental health care, the numbers were higher than noted in national studies. Implications of the findings are presented.
Purpose To test models linking pubertal timing, peer substance use, sexual behavior, and substance use for maltreated versus comparison adolescents. Three theoretical mechanisms were tested: 1) peer influence links early pubertal timing to later sexual behavior and substance use, 2) early maturers engage in substance use on their own and then select substance-using friends, or 3) early maturers initiate sexual behaviors which leads them to substance-using peers. Methods The data came from a longitudinal study of the effects of child maltreatment on adolescent development (303 maltreated and 151 comparison adolescents; age: 9–13 years at initial wave). Multiple-group structural equation models tested the hypotheses across three timepoints including variables of pubertal timing, perception of peer substance use, sexual behavior, and self-reported substance use. Results Early pubertal timing was associated with substance-using peers only for maltreated adolescents, indicating the mediation path from early pubertal timing through substance-using peers to subsequent adolescent substance use and sexual behavior only holds for maltreated adolescents. Mediation via sexual behavior was significant for both maltreated and comparison adolescents. This indicates that sexual behavior may be a more universal mechanism linking early maturation with risky friends regardless of adverse life experiences. Conclusions The findings are a step toward elucidating the developmental pathways from early puberty to risk behavior and identifying early experiences that may alter mediation effects.
Among the explanations for the high rates of co-occurrence between depressive symptoms and externalizing behavior is the possibility of direct causal associations between the two symptom groups. However, the mechanisms by which co-occurrence arises may not be the same across etiologically significant variables. A gender-balanced sample of 303 adolescents (ages 9–12 at the first assessment) with carefully assessed histories of maltreatment experience and 151 demographically matched nonmaltreated adolescents were assessed over the period of 1 year. Multiple-group cross-lagged panel analyses assessed the equivalence of longitudinal relations between depressive symptoms and externalizing behavior for gender/maltreatment status groups. Consistent with previous findings, the results suggest that girls, particularly maltreated girls, who exhibit early externalizing behavior are at high risk for the development of subsequent depressive symptoms.
Background Two clinical trials have shown efficacy for bupropion in treating methamphetamine (MA) dependence among those with moderate baseline MA use. However, treatment response is highly variable and it is unclear what duration of treatment is necessary to determine if maintaining the treatment course is indicated or if discontinuation or augmentation is appropriate. The present study assessed the relationship among early bupropion treatment response for moderate MA users and end-of-treatment (EOT) abstinence. These data provide estimates of the duration of treatment and the degree of responsiveness required to persist in bupropion treatment. Methods Participants with moderate baseline MA use in the bupropion condition of two randomized double-blind placebo controlled trials were included. The relationship between early treatment response and EOT outcomes was assessed with Receiver Operating Characteristic (ROC) curves. Results With thrice weekly urine drug testing, excellent predictive power was established in the first two weeks of treatment. The inability to achieve at least three MA negative samples in the first two weeks is associated with greater than 90% likelihood of treatment failure. More closely approximating clinical settings, once-weekly testing featured reliable predictive power within three weeks, suggesting that the failure to produce at least two clean samples in the first three weekly visits confers high risk of treatment failure. Discussion The findings provide preliminary evidence to guide clinical decisions for moderate MA users receiving bupropion. The results are consistent with data from the smoking cessation literature and may highlight the importance of early response in addiction treatment.
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