A dozen studies have been published showing that opiate antagonists suppress alcohol drinking in animals, and two independent placebo-controlled, double-blind clinical trials of naltrexone found this agent was associated with decreased alcohol craving and consumption in alcohol-dependent patients. Nalmefene is a newer opiate antagonist that has a number of potential advantages over naltrexone in the treatment of alcoholism, including no dose-dependent association with liver toxicity and more effective binding to central opiate receptors. Consequently, a double-blind pilot study was conducted to gather preliminary data on the safety and efficacy of nalmefene for reducing alcohol consumption in alcohol-dependent subjects. Twenty-one alcohol-dependent subjects meeting admission criteria were randomly assigned to 12 weeks of double-blind treatment with 40 mg nalmefene, 10 mg nalmefene, or placebo, resulting in 7 patients/treatment group. Nalmefene was well tolerated, with no serious adverse drug reactions. The 40 mg group had a significantly lower rate of relapse (p < or = 0.05), and a greater increase in the number of abstinent days/week (p < or = 0.09), than the other treatment groups. A significant decrease in the number of drinks/drinking day was noted for both nalmefene groups (p < or = 0.04), but not for placebo. These results were supported by parallel decreases in ALT. These pilot data provide preliminary support for the hypotheses that nalmefene can be safely given to alcoholics, and that nalmefene may have a role in reducing alcohol consumption and preventing relapse, particularly at the 40 mg level. A full-scale study is underway to confirm these preliminary findings.

SY N OP S I S A study was conducted on 66 psychiatric inpatients who took major tranquilizers for periods of four to 16 years. The frequency of signs of Parkinsonism and the effects of orphenadrine on these were studied in a double-blind crossover method. Sixty-one per cent of the patients showed signs of Parkinsonism. Female patients and those with organic brain pathology more frequently exhibited Parkinsonism (although the difference was not statistically significant). No correlation was found between duration of treatment and extrapyramidal effects. Of the 40 patients who developed Parkinsonism, 25 responded favourably to orphenadrine, while six (15%) had more marked manifestations on orphenadrine than on placebo.Although phenothiazines have been widely used in psychiatry for approximately 20 years, there is relatively little information concerning many aspects of their chronic administration. The recognition of persistent orofacial dyskinesia as a syndrome connected with prolonged treatment with these drugs raises the possibility of irreversible toxic effects on the brain, particularly the extrapyramidal system (Korczyn, 1972). There have been suggestions that the Parkinsonism effects, frequently observed with these drugs, might become irreversible after prolonged treatment (McGeer et al., 1961) or, conversely, disappear (Cahan andParish, 1960;Mandell and Oliver, 1961). The ideal way to answer this question-that is, to follow up patients maintained on the same dosage of neuroleptic drugs for several years-is not practical, and available information in the literature deals almost exclusively with the effects of relatively short periods of treatment. We have tried to approach the problem by measuring the extrapyramidal side-effects in patients treated with antipsychotic drugs for long periods, and correlating these manifestations with various parameters. In addition we have measured the protection offered by 1 Present address: Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv, Israel. (Accepted 21 April 1976.) orphenadrine against the extrapyramidal manifestations. It has been claimed that with prolonged treatment in Parkinson's disease orphenadrine loses efficacy (Strang, 1965), but there is no information concerning the effects of prolonged treatment in drug-induced Parkinsonism. METHODSThe population under study consisted of 66 psychiatric patients. These were among the 228 patients in seven long-stay wards at Goodmayes Hospital, Ilford, Essex. The rest of the patients in these wards had not been on major tranquillizers at the time of examination, or the dosage was not kept constant for any length of time before initiation of the study. The drugs used were chlorpromazine, thioridazine, trifluoperazine, fluphenazine, and haloperidol. The most common diagnosis was schizophrenia, either simple or paranoid.The patients were examined carefully neurologically, and special attention was given to the following signs and symptoms: hypokinesia, rigidity, trem...

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e20548 Background: This study assessed the safety and efficacy of Aprepitant, a neurokinin 1 receptor antagonist, in the management of DCINV associated with HCT. Methods: Pilot phase I-II RCT, adult patients undergoing ablative HCT. Eligibility Criteria: Presence of DCINV (>1 episode of vomiting/24 hrs or >25 mm on nausea visual analogue scale (VAS) on day 2–14 post- HCT). Control arm: ondansetron + metoclopramide. Aprepitant arm: Same regimen + aprepitant 125 mg on d1 and 80 mg d2–3. Controls with DCINV persisting >72 hours were crossed to treatment arm. Safety endpoints: Primary: myeloid engraftment (ANC>500/μL by d15.) Secondary: platelet engraftment (plts >20,000/μL by d21.) Efficacy endpoints: Primary: no episodes of emesis. Secondary: VAS reduction ≥ 25 mm Results: 12 pts, ages 23–62 yrs, were randomized, 9 to treatment arm. Two of 3 controls crossed over. The study was interrupted prior to completion of accrual to control arm. Results are summarized as median ± SD in the table below. Treatment arm showed no delay in granulocyte and platelet engraftment, less emesis, and little difference in VAS compared to control. No patients in either group developed unexpected grade III-IV toxicities, including VOD or IPS. Conclusions: The use of aprepitant for control of DCINV after myeloablative HCT decreased the frequency of DCINV and had no adverse effect on granulocyte and platelet engraftment. This pilot study supports the safety and efficacy of aprepitant for DCINV in the setting of HCT. [Table: see text] [Table: see text]