Misuse and Associated Harms of Quetiapine and Other Atypical Antipsychotics.

Recent years have seen a significant increase in the reports of atypical antipsychotic diversion, misuse and even dependency syndrome. These reports have arisen amidst a marked increase in prescribing of these agents. Much of this increase in prescribing is because of a preferential use of these medications over typical antipsychotic agents to treat schizophrenia and bipolar disorder due to perceptions of fewer extrapyramidal side effects. However, there has also been a significant increase in the off-label prescribing of these medicines to treat less well evidence-based conditions. Misuse and abuse are perhaps surprising given the putative central role of dopamine in addiction and that these agents are dopamine antagonists. However, there may be other factors such as other pharmacological effects and increasing availability driving this misuse. It is also apparent that certain patient groups appear to be more at risk. Here, we explore the evidence behind the misuse of atypical antipsychotics with a focus of quetiapine. We consider the factors that may be driving this misuse, and then, we also detail some of the adverse effects that may ensue. We end by suggesting interventions at a prescriber and systems level that may be implemented to reduce the risk of atypical antipsychotic misuse.

Exercise increases plasma THC concentrations in regular cannabis users.

BACKGROUND: The major psychoactive ingredient of cannabis, Δ(9)-tetrahydrocannabinol (THC) accumulates in fat tissue from where it slowly diffuses back into blood. THC pre-treated rats can show elevated plasma cannabinoid levels when subjected to conditions that promote fat utilization, such as fasting. Here we examine whether fasting and exercise increase plasma THC concentrations in regular cannabis users. METHODS: Fourteen regular cannabis users completed 35 min of exercise on a stationary bicycle in either a fed or overnight fasted state. Plasma cannabinoid levels were assessed prior to exercise, immediately post-exercise and 2h post-exercise. Plasma samples were also analyzed for indices of lipolysis (free fatty acids (FFA) and glycerol). RESULTS: Exercise induced a small, statistically significant increase in plasma THC levels accompanied by increased plasma FFA and glycerol levels. Exercise-induced increases in plasma THC concentrations were positively correlated with body mass index. Fasting induced a significant increase in plasma FFA levels, and a lowering of blood glucose, but did not significantly alter plasma cannabinoid levels. CONCLUSIONS: Here we demonstrate that exercise enhances plasma THC levels in regular cannabis users. The lack of a fasting effect may reflect the modest duration of fasting used which was associated with only a modest increase in fat utilization relative to exercise. Overall, these results suggest that exercise may elevate blood THC levels by releasing dormant THC from fat stores. These data suggest the interpretation of blood THC levels in roadside and workplace tests might be complicated by recent exercise.

Are cannabis users who participate in a randomized clinical trial different from other treatment seekers?

Randomized controlled trials (RCTs) provide the most convincing evidence for clinical questions concerning the efficacy of interventions. When participants in RCTs are characteristically different to those in usual clinical practice, it may be difficult to generalize findings. This study compares profiles taken from a centralized intake process for those presenting with cannabis as their main drug, which were then separated into three categories, (a) those who were offered a specialist assessment for cannabis dependence over the phone but did not attend their appointment, (b) those who presented for their initial appointment, and c) those attending and subsequently recruited into an RCT. To explore whether issues such as severity of cannabis use and co-occurring disorders acted as a barrier to attending treatment or to inclusion in an RCT, we examined basic triage information. Results indicated that there were no statistically significant differences on selected characteristics between groups, suggesting that RCT participants were representative of treatment seekers, and that the filtering that occurs between those who make phone contact with professional services and those who present to treatment are not necessarily due to presence of patient characteristics such as coexisting medical, psychological issues, or severity of their cannabis use.

A placebo-controlled trial of mirtazapine for the management of methamphetamine withdrawal.

INTRODUCTION AND AIMS: As an antidepressant with sedative and anxiolytic properties, mirtazapine may be an appropriate pharmacotherapy for methamphetamine withdrawal. This study sought to examine whether mirtazapine improves retention and alleviates methamphetamine withdrawal symptoms in an out-patient setting. DESIGN AND METHODS: An out-patient double-blind, randomised placebo-controlled trial of mirtazapine for the treatment of methamphetamine withdrawal was conducted (15 mg nocte for 2 days, 30 mg nocte for 12 days). Both groups were offered narrative therapy counselling. Measures recorded on days 0, 3, 7, 14 and 35 included: treatment retention, Amphetamine Cessation Symptoms Assessment, the Athens Insomnia Scale, the Brief Symptom Inventory, the Depression-Anxiety-Stress Scale (DASS), Severity of Dependence scale and the Opiate Treatment Index Drug Use subscale. RESULTS: Thirty-one participants were recruited (18 placebo, 13 mirtazapine) and 52% completed the 2-week medication phase. No significant differences between the mirtazapine and placebo groups in retention, or any symptom measure were observed, except greater DASS-anxiety and longer sleep duration were measured at baseline among the mirtazapine group. DISCUSSION AND CONCLUSIONS: Results suggest that mirtazapine does not facilitate retention or recruitment in out-patient methamphetamine withdrawal treatment, although recruitment may have been insufficient to identify a significant treatment effect. The potential role of narrative therapy for methamphetamine dependent patients deserves further exploration.