"Addicted to Euphoria": The History, Clinical Presentation, and Management of Party Drug Misuse.

Eating, drinking, sexual activity, and parenting invoke pleasure, an emotion that promotes repetition of these behaviors, are essential for survival. Euphoria, a feeling or state of intense excitement and happiness, is an amplification of pleasure, aspired to one's essential biological needs that are satisfied. People use party drugs as a shortcut to euphoria. Ecstasy (3,4-methylenedioxymethamphetamine), γ-hydroxybutyric acid, and ketamine fall under the umbrella of the term "party drugs," each with differing neuropharmacological and physiological actions. This chapter seeks to survey the history and epidemiology of party drug use; we will then discuss the pharmacological characteristics of each drug to provide a platform for understanding the difficulties that party drug users encounter through intoxication, harmful use, dependence, and withdrawal and how these should be clinically managed.

Clinical features and management of gamma-hydroxybutyrate (GHB) withdrawal: a review.

AIM: To examine the clinical course of gamma-hydroxybutyrate (GHB) withdrawal and generate management guidelines. DESIGN: Review and analysis of all published reports of GHB or GHB precursor withdrawal identified from electronic searches. FINDINGS: In total, 38 cases of GHB (n = 28) or GHB precursor (n = 10) withdrawal were identified, 36 of which were from the US. A rapidly deteriorating course into delirium (53% of cases) was typical for heavily dependent users. Symptoms were broadly similar to alcohol withdrawal but often occurred earlier in usage with delirium being associated with severe dependence as determined by more frequent ingestion. High dose benzodiazepines were effective in pharmacological management of GHB withdrawal. In benzodiazepine refractory cases withdrawal responded to other sedative agents, mainly pentobarbital or chloral hydrate. No withdrawal seizures but one death was recorded. CONCLUSIONS: GHB withdrawal is potentially life threatening and requires vigorous clinical management, preferably as an inpatient for severe cases. A management algorithm is proposed.

Is opiate detoxification unsafe in pregnancy?

Despite the widespread avoidance of detoxification in the second or third trimesters, there is no clear evidence to support the view that methadone withdrawal is harmful in pregnant opiate dependent women. We investigated the safety of methadone detoxification in pregnancy in a retrospective case series of 101 pregnant opiate dependent women who underwent a 21-day in-patient methadone withdrawal. One miscarriage occurred in the first trimester (n = 5; incidence rate ratio of 6.87 compared to population norms (95% CI = 0.16-47.3; p =.15)). No miscarriages were observed in the second trimester (n = 54; incidence rate ratio = 0 compared to population norms (95% CI = 0-3.69; p =.27). One premature delivery occurred in the third trimester (1 in 158 weeks at risk compared to 1 in 150 weeks in population norms; p =.16). Methadone detoxification treatment was not associated with any increased risk of miscarriage in the second trimester or premature delivery in the third trimester.

Increased reflection impulsivity in patients with ephedrone-induced Parkinsonism.

AIMS: To examine a syndrome of chronic manganism that occurs in drug addicts in eastern Europe who use intravenous methcathinone (ephedrone) contaminated with potassium permanganate. In many cases the basal ganglia, especially the globus pallidus and the putamen, are damaged irreversibly. Routine neuropsychological assessment has revealed no cognitive deficits, despite widespread abnormalities on brain imaging studies and severe extrapyramidal motor handicap on clinical examination. DESIGN: Case-control study. SETTING: Ephedrone patients and patients with opioid dependence were recruited from Lviv, Ukraine. PARTICIPANTS: We tested 15 patients with ephedrone-induced toxicity, 13 opiate-dependent patients who were receiving opioid replacement therapy and 18 matched healthy volunteers. MEASUREMENTS: The 'beads task', an information-gathering task to assess reflection impulsivity, was used and feedback learning, working memory and risk-taking were also assessed. FINDINGS: Opiate-dependent patients differed from controls on three of four tasks, whereas ephedrone patients differed from controls on only one task. More specifically, both patient groups were more impulsive and made more irrational choices on the beads task than controls (P < 0.001). However, ephedrone patients had no deficits in working memory (P > 0.1) or risk-taking (P > 0.1) compared with controls. Opioid-dependent patients had significantly worse working memory (P < 0.001) and were significantly more risk-prone than controls (P = 0.002). CONCLUSIONS: Ephedrone patients may have similar deficits in information-gathering and decision-making to opiate-dependent patients, with preservation of working memory and risk-taking. This may reflect specific damage to anterior cingulate- basal ganglia loops.

Harnessing clinical psychiatric data with an electronic assessment tool (OPCRIT+): the utility of symptom dimensions.

Progress in personalised psychiatry is dependent on researchers having access to systematic and accurately acquired symptom data across clinical diagnoses. We have developed a structured psychiatric assessment tool, OPCRIT+, that is being introduced into the electronic medical records system of the South London and Maudsley NHS Foundation Trust which can help to achieve this. In this report we examine the utility of the symptom data being collected with the tool. Cross-sectional mental state data from a mixed-diagnostic cohort of 876 inpatients was subjected to a principal components analysis (PCA). Six components, explaining 46% of the variance in recorded symptoms, were extracted. The components represented dimensions of mania, depression, positive symptoms, anxiety, negative symptoms and disorganization. As indicated by component scores, different clinical diagnoses demonstrated distinct symptom profiles characterized by wide-ranging levels of severity. When comparing the predictive value of symptoms against diagnosis for a variety of clinical outcome measures (e.g. 'Overactive, aggressive behaviour'), symptoms proved superior in five instances (R(2) range: 0.06-0.28) whereas diagnosis was best just once (R(2):0.25). This report demonstrates that symptom data being routinely gathered in an NHS trust, when documented on the appropriate tool, have considerable potential for onward use in a variety of clinical and research applications via representation as dimensions of psychopathology.

Patterns of adherence to oral methadone: implications for prescribers.

We investigated patterns of nonadherence to substitute treatment among patients attending an inner London community drug dependency unit and explored factors associated with nonadherence. We undertook 91 face-to-face confidential interviews with methadone-maintained patients attending community pharmacies. Thirty-eight patients (42%) had been either partial or poor adherers to their prescribed methadone regime in the past month. Multinomial logistic regression revealed that compared to full adherers, both poor adherers and partial adherers were more likely to be prescribed by unsupervised consumption. Poor adherers were also more likely to have less frequent pickups. There were seven types of nonadherent behavior detected, with dose splitting being the most prevalent (34%), followed by dose storage (28%) and missed pickups from the pharmacy (18%). We suggest that prescribers include an assessment of medication adherence at regular patient reviews as supervised consumption does not solve all adherence problems with methadone. New approaches to encouraging adherence, including a more systematic monitoring of adherence to improve the effectiveness of methadone programs, are needed.

Within-patient variability in clinical presentation of gamma-hydroxybutyrate withdrawal: a case report.

The emergence of gamma-hydroxybutyrate (GHB) dependence in the UK is described, with specific reference to a case study of serial episodes of GHB withdrawal. Symptoms are broadly similar to those for alcohol withdrawal, and rapid deterioration into delirium is common in severe dependence. This case report reflects the variability in clinical presentation of GHB withdrawal and response to treatment, even within the same patient. It is concluded that GHB withdrawal requires vigorous clinical management, preferably on an elective basis, in an inpatient setting if dependence is severe.

Lofexidine for opiate detoxification.

The evolving role for lofexidine in the treatment of opiate detoxification over the last decade is reviewed. Lofexidine is no better than methadone or clonidine in attenuating withdrawal symptom severity, although it has a more favourable side-effect profile than clonidine. In conjunction with opiate antagonists, lofexidine may facilitate accelerated withdrawal, although activity and low liability for misuse, lofexidine may be more widely acceptable to clinicians than methadone, particularly those working in out-patient, non-specialist and prison treatment settings. Further studies in these treatment settings will be particularly apposite since, apart from the studies highlighted, the evidence base for the clinical value of lofexidine is mainly to be derived from in-patient trials.

Major disruptions of sleep during treatment of the opiate withdrawal syndrome: differences between methadone and lofexidine detoxification treatments.

Sleep disturbance experienced during methadone or lofexidine opiate detoxification was investigated in 118 opiate-dependent patients receiving inpatient detoxification treatment. Sleep was assessed at four time-points during opiate detoxification using a self-report questionnaire. Maximum sleep disruption occurred at completion of detoxification and during the protracted withdrawal period, with patients in the methadone group reporting higher levels of withdrawal symptoms, lower overall sleep, longer sleep latencies and significantly longer periods of time awake than lofexidine patients. Regression analyses demonstrated a significant relationship between sleep disturbance, protracted withdrawal and retention in treatment, in addition to the major treatment benefit of reduced sleep disturbance conferred by lofexidine treatment.

The effectiveness of combined naloxone/lofexidine in opiate detoxification: results from a double-blind randomized and placebo-controlled trial.

The efficacy of lofexidine/naloxone was compared with lofexidine/placebo in a double-blind, randomized, placebo-controlled trial in 89 opiate-dependent patients. There were no significant differences between the two groups in the proportion of patients completing detoxification or in the length of stay. Patients in the active naloxone group demonstrated gradual reductions in levels of withdrawal and craving over the detoxification period. At completion of detoxification, patients who received naloxone maintained a level of withdrawal consistently lower than that in the placebo group; however, naloxone did not substantially accelerate the resolution of the withdrawal syndrome. Implications for future research are discussed.