Methamphetamine (MA) abuse remains a global health challenge despite intense research interest in the development of pharmacological treatments. This review provides a summary of clinical trials and human studies on the pharmacotherapy of methamphetamine use disorder (MUD). Areas covered: We summarize published clinical trials that tested candidate medications for MUD and also conducted PubMed and Google Scholar searches to identify recently completed clinical trials using the keywords 'methamphetamine' 'addiction' 'pharmacotherapy' and 'clinical trial.' To determine the status of ongoing clinical trials targeting MUD, we also searched the ClinicalTrials.gov online database. We conclude this review with a discussion of current research gaps and future directions. Expert commentary: Clinical trials examining the potential for pharmacotherapies of MUD have largely been negative. Future studies need to address several limitations to reduce the possibility of Type II errors: small sample sizes, high dropout rates or multiple comorbidities. Additionally, new treatment targets, such as MA-induced disruptions in cognition and in the neuroimmune system, merit trials with agents that selectively modulate these processes.

Objective Several studies have suggested that bipolar disorder (BP) in adults is associated with aggressive behaviors. However, most studies have only included inpatients and have not taken possible confounding factors into consideration. The goal of this study was to compare the prevalence of aggression in subjects with BP compared to subjects with other non-BP psychopathology and healthy controls. Methods Subjects with bipolar I disorder (BP-I) and bipolar II disorder (BP-II) (n = 255), non-BP psychopathology (n = 85), and healthy controls (n = 84) were recruited. Aggression was measured using the Aggression Questionnaire (AQ). Group comparisons were adjusted for demographic and clinical differences (e.g., comorbid disorders) and multiple comparisons. The effects of the subtype of BP, current versus past episode, polarity of current episode, psychosis, the presence of irritable mania/hypomania only, and pharmacological treatment were examined. Results Subjects with BP showed significantly higher total and subscale AQ scores (raw and T-scores) when compared with subjects with non-BP psychopathology and healthy controls. Exclusion of subjects with current mood episodes and those with common comorbid disorders yielded similar results. There were no effects of BP subtype, polarity of the current episode, irritable manic/hypomanic episodes only, or current use of pharmacological treatments. Independent of the severity of BP and polarity of the episode, those in a current mood episode showed significantly higher AQ scores than those not in a current mood episode. Subjects with current psychosis showed significantly higher total AQ score, hostility, and anger than those without current psychosis. Conclusions Subjects with BP display greater rates of anger and aggressive behaviors, especially during acute and psychotic episodes. Early identification and management of these behaviors is warranted.

Objective Disruptive mood dysregulation disorder (DMDD) is a new diagnosis in the DSM-5. Youth with a family history of BD are at increased risk for BD and non-bipolar psychopathology. No studies to date have examined rates of DMDD among offspring of parents with BD. This study examines the risk for DMDD in offspring of parents with BD compared to community controls and considers rates of chronic irritability (independent of a DMDD diagnosis) across diagnoses in youth with parents with BD. Method Modified DMDD criteria were applied post hoc to 375 offspring of parents with BD and 241 offspring of community control parents aged 6–17. We calculated odds ratios using generalized linear mixed models. Additionally, we explored associations with a severe chronic irritability phenotype and various diagnoses in the high risk cohort. Results Offspring of parents with BD were more likely to meet criteria for DMDD than the offspring of community control parents (OR=8.3, 6.7% vs 0.8%), even when controlling for demographic variables and comorbid parental diagnoses (OR 5.4). They also had higher rates of chronic irritability compared to community controls (12.5% vs. 2.5%, χ 2=18.8, p<0.005). Within the offspring of parents with BD, the chronic irritability phenotype was frequently present in offspring with diagnoses of BD, depression, ADHD, and DBD. Conclusions Like other non-BD diagnoses, family history of BD increases the risk for DMDD. Severe chronic irritability and temper tantrums are the core features of DMDD and are associated with mood and behavioral disorders in youth at risk for BD.

Objectives Bipolar disorder (BP) has been associated with increased aggressive behaviors. However, all existing studies are cross-sectional and include forensic or inpatient populations and many do not take into account the effects of comorbid conditions. The goal of this study was to evaluate the longitudinal course of aggression among adult outpatients with BP compared with non-BP patients and healthy controls. Methods Subjects with bipolar I disorder (BP-I)/bipolar II disorder (BP-II) (n = 255), non-BP psychopathology (n = 85), and healthy controls (n = 84) (average 38.9 years, 78.7% female, and 84.9% Caucasian) were evaluated at intake and after two- and four-years of follow-up. Aggression was self-rated using the Aggression Questionnaire (AQ). Comparisons were adjusted for any significant demographic and clinical differences and for multiple comparisons. For subjects with BP, associations of AQ with subtype of BP, current versus past mood episodes, polarity and severity of the current episode, psychosis, and current pharmacological treatment were evaluated. Results In comparison with subjects with non-BP psychiatric disorders and healthy controls, subjects with BP showed persistently higher total and subscale AQ scores (raw and T-scores) during the four-year follow-up. There were no effects of BP subtype, severity or polarity of the current episode, psychosis, and current pharmacological treatments. Subjects in an acute mood episode showed significantly higher AQ scores than euthymic subjects. Conclusions BP, particularly during acute episodes, is associated with increased self-reported verbal and physical aggression, anger, and hostility. These results provide further evidence for the need of treatments to prevent mood recurrences and prompt treatment of acute mood episodes in subjects with BP.