Background Stimulant drugs are second only to cannabis as the most widely used class of illicit drug globally, accounting for 68 million past-year consumers. Dependence on amphetamines (AMPH) or methamphetamine (MA) is a growing global concern. Yet, there is no established pharmacotherapy for AMPH/MA dependence. A comprehensive assessment of the research literature on pharmacotherapy for AMPH/MA dependence may inform treatment guidelines and future research directions. Methods We systematically reviewed the peer-reviewed literature via the electronic databases PubMed, EMBASE, CINAHL and SCOPUS for randomised controlled trials reported in the English language examining a pharmacological treatment for AMPH/MA dependence or use disorder. We included all studies published to 19 June 2019. The selected studies were evaluated for design; methodology; inclusion and exclusion criteria; sample size; pharmacological and (if included) psychosocial interventions; length of follow-up and follow-up schedules; outcome variables and measures; results; overall conclusions and risk of bias. Outcome measures were any reported impact of treatment related to AMPH/MA use. Results Our search returned 43 studies that met our criteria, collectively enrolling 4065 participants and reporting on 23 individual pharmacotherapies, alone or in combination. Disparate outcomes and measures (n = 55 for the primary outcomes) across studies did not allow for meta-analyses. Some studies demonstrated mixed or weak positive signals (often in defined populations, e.g. men who have sex with men), with some variation in efficacy signals dependent on baseline frequency of AMPH/MA use. The most consistent positive findings have been demonstrated with stimulant agonist treatment (dexamphetamine and methylphenidate), naltrexone and topiramate. Less consistent benefits have been shown with the antidepressants bupropion and mirtazapine, the glutamatergic agent riluzole and the corticotropin releasing factor (CRF-1) antagonist pexacerfont; whilst in general, antidepressant medications (e.g. selective serotonin reuptake inhibitors [SSRIs], tricyclic antidepressants [TCAs]) have not been effective in reducing AMPH/MA use. Conclusions No pharmacotherapy yielded convincing results for the treatment of AMPH/MA dependence; mostly studies were underpowered and had low treatment completion rates. However, there were positive signals from several agents that warrant further investigation in larger scale studies; agonist therapies show promise. Common outcome measures should include change in use days. Future research must address the heterogeneity of AMPH/MA dependence (e.g. coexisting conditions, severity of disorder, differences between MA and AMPH dependence) and the role of psychosocial intervention.

Objectives:We quantified concomitant medication polypharmacy, pharmacokinetic and pharmacodynamic interactions, adverse effects and adherence in Australian adults on effective antiretroviral therapy.Design:Cross-sectional.Methods:Patients recruited into a nationwide cohort and assessed for prevalence and type of concomitant medication (including polypharmacy, defined as ≥5 concomitant medications), pharmacokinetic or pharmacodynamic interactions, potential concomitant medication adverse effects and concomitant medication adherence. Factors associated with concomitant medication polypharmacy and with imperfect adherence were identified using multivariable logistic regression.Results:Of 522 participants, 392 (75%) took a concomitant medication (mostly cardiovascular, nonprescription or antidepressant). Overall, 280 participants (54%) had polypharmacy of concomitant medications and/or a drug interaction or contraindication. Polypharmacy was present in 122 (23%) and independently associated with clinical trial participation, renal impairment, major comorbidity, hospital/general practice-based HIV care (versus sexual health clinic) and benzodiazepine use. Seventeen participants (3%) took at least one concomitant medication contraindicated with their antiretroviral therapy, and 237 (45%) had at least one pharmacokinetic/pharmacodynamic interaction. Concomitant medication use was significantly associated with sleep disturbance and myalgia, and polypharmacy of concomitant medications with diarrhoea, fatigue, myalgia and peripheral neuropathy. Sixty participants (12%) reported imperfect concomitant medication adherence, independently associated with requiring financial support, foregoing necessities for financial reasons, good/very good self-reported general health and at least 1 bed day for illness in the previous 12 months.Conclusion:In a resource-rich setting with universal healthcare access, the majority of this sample took a concomitant medication. Over half had at least one of concomitant medication polypharmacy, pharmacokinetic or pharmacodynamic interaction. Concomitant medication use was associated with several adverse clinical outcomes.

This pilot study provides feasibility, tolerability, proof-of-concept and preliminary evidence for clinically relevant neurocognitive improvement in cART enhancement with maraviroc in virally suppressed HAND patients. Lack of concomitant brain metabolite and biomarker change may be related to complex dynamics of brain repair.