Elucidating the mechanisms linking early pubertal timing, sexual activity, and substance use for maltreated versus nonmaltreated adolescents.

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 lead 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 time points 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.

Pharmacotherapy of amphetamine-type stimulant dependence: an update.

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 and men who have sex with men), though none has produced an unambiguous, replicable signal of efficacy. IMPLICATIONS: Problems in Phase II trials, including high dropout 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 preclinical 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.

Cigarette smoking as a target for potentiating outcomes for methamphetamine abuse treatment.

INTRODUCTION AND AIMS: Cigarette smoking occurs frequently among individuals with methamphetamine (MA) dependence. Preclinical and clinical evidence has suggested that the common co-abuse of MA and cigarettes represents a pharmacologically meaningful pattern. METHODS: The present study is a secondary analysis of a randomised, placebo-controlled trial of bupropion treatment for MA dependence (bupropion n = 36; placebo n = 37). A hierarchical logistic modelling approach assessed the efficacy of bupropion for reducing MA use separately among smokers and non-smokers. Among smokers, relations between cigarettes smoked and MA use were assessed. RESULTS: Smoking status did not affect treatment responsiveness in either the bupropion condition or the placebo condition. In the placebo condition, increased cigarette use was associated with an increased probability of MA use during the same time period. This effect was not observed in the bupropion condition. DISCUSSION AND CONCLUSIONS: Initial smoking status did not impact treatment outcomes. Among smokers, results suggest that bupropion may dissociate cigarette and MA use. The effect was modest and a precise pharmacological mechanism remains elusive. Cholinergic systems may be relevant for MA use outcomes. Future studies should continue to assess the role of smoking in MA treatment outcomes.

Integration of behavioral medicine in primary care.

The health care system in the United States is inefficient and there are many incentives for sustainable changes in the delivery of care. Incorporating behavioral medicine offers a wide range of opportunities. Within primary care settings, pain disorders, addiction, depression, and anxiety disorders are highly prevalent. Numerous chronic health conditions also require behavioral support for lifestyle change. These disorders are optimally managed through interdisciplinary collaborations that include a behavioral medicine component. This article discusses the effective integration of behavioral medicine within a primary care patient-centered medical home and describes the organizational planning and structure required for success.

Optimizing pain management through collaborations with behavioral and addiction medicine in primary care.

Chronic noncancer pain (CNCP) affects many primary care patients, and carries a large human and economic burden. In response to the widespread perception that pain is underdiagnosed and undertreated, regulatory bodies have encouraged more comprehensive services to address pain syndromes. Significant hurdles exist in treating CNCP in primary care settings, and interventional therapies and pharmacotherapy often do not provide complete symptomatic relief. This article describes a multidimensional and interdisciplinary approach to the treatment of CNCP. The utility of collaborations with behavioral and addiction medicine specialists optimizes care and advances models of patient treatment within a primary care patient-centered medical home.

Placebo-group responders in methamphetamine pharmacotherapy trials: the role of immediate establishment of abstinence.

Treatment responses of placebo groups in addiction medicine trials have important implications for research methodology and clinical practice, however studies examining placebo group responses in addiction medicine are scarce. Extant data suggest the importance of early treatment responsiveness for long-term outcomes. Among methamphetamine-(MA) dependent individuals randomized to placebo pill plus behavioral support conditions in pharmacotherapy development trials, we hypothesized that immediate abstinence would be a necessary but insufficient predictor for end-of-trial (EOT) abstinence. The study is a secondary analysis of participants (n = 184; 36% female) in the placebo condition of three randomized, placebo-controlled methamphetamine dependence pharmacotherapy trials. Receiver operating characteristic (ROC) curve analyses assessed the predictive power of initial abstinence, assessed by thrice weekly urine samples, for EOT abstinence. Sixty percent of individuals with complete abstinence in the first two weeks of treatment were abstinent at EOT, while 18% of people who failed to meet this standard were abstinent at EOT. Early response was related to retention at EOT and 12-month follow-up. Findings suggest that the inability to achieve at least three MA negative screenings in the first two weeks is associated with greater than 90% likelihood of treatment failure. A third week of screening added minimally to the prediction of EOT outcomes. The prediction of treatment failure was more precise than the prediction of treatment success. The absence of a clinical response in the first two weeks of treatment among participants in the placebo group signals high risk of treatment failure. The majority of information regarding response in the placebo group from a 12-week trial is obtained early in the trial.

A retrospective analysis of two randomized trials of bupropion for methamphetamine dependence: suggested guidelines for treatment discontinuation/augmentation.

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.

Longitudinal relations between depressive symptoms and externalizing behavior in adolescence: moderating effects of maltreatment experience and gender.

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.

Do Maltreated Children who Remain at Home Function Better than Those who Are Placed?

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, non-relative 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.