The treatment of negative symptoms: a clinical and methodological study.

The primary objective of this study was to evaluate the efficacy, safety and tolerability of remoxipride (controlled release) versus haloperidol in patients with negative symptoms. The study comprised a multicentre, randomised, double-blind, parallel-group clinical trial. Two hundred and five patients were randomised to either remoxipride or haloperidol. Patients eligible for this study were aged 18-65 years, met the DSM-III-R diagnosis for chronic schizophrenia and the Positive and Negative Symptoms Scale (PANSS) criteria for predominant negative symptoms. There was a statistically significant reduction in the PANSS scores of at least 20% from baseline to last rating for 39 remoxipride (49.4%) and 45 haloperidol (47.6%) treated patients. There were no statistical differences found between the two treatment groups with respect to improvement of negative symptoms and adverse events. The PANSS data suggest that both remoxipride and haloperidol improve the cluster of negative symptoms concerned with social functioning. In addition, the design of the study provides a methodology that is appropriate to the study of primary negative symptoms in schizophrenia.

A further examination of the time-dependent effects of oxazepam and lorazepam on implicit and explicit memory.

Until recently, research indicated that all benzodiazepines impair explicit memory, while only lorazepam impairs priming. Stewart and associates provided preliminary data which indicated that both oxazepam and lorazepam may impair implicit memory, but in a time-dependent fashion. The present study was designed to replicate Stewart et al.'s findings after overcoming several limitations of the original study. Thirty subjects were administered an acute dose of lorazepam (2 mg), oxazepam (30 mg) or a placebo and were tested with an implicit (word-stem completion) test and an explicit (cued recall) test. However, subjects were only tested at 170 min post-drug (close to oxazepam's theoretical peak concentration) to rule out the possible "explicit memory contamination" explanation of the Stewart et al. implicit memory findings. Consistent with previous research, both drugs impaired explicit memory relative to placebo. Also, both lorazepam and oxazepam impaired priming performance, supporting the "time-dependence" interpretation of the Stewart et al. findings. The results also indicate that episodic memory is impaired by both benzodiazepines in a time-dependent fashion even when the research methodology used involves everyday memory demands.

An examination of differences in the time course of oxazepam's effects on implicit vs explicit memory.

The present study was designed to examine the effects of oxazepam on implicit vs explicit memory processes, as a function of this drug's time course. The effects of oxazepam (30 mg) or placebo on directly comparable tests of implicit memory (word stem completion) and explicit memory (cued recall) were examined at three time points: 100 min post-drug administration (prior to the theoretical peak plasma concentration of oxazepam; i.e.'pre-peak' condition), 170 min post-drug (close to theoretical peak; i.e. 'peak' condition) or 240 min post-drug (following theoretical peak: i.e. 'post-peak' condition). Sixty healthy volunteers were randomly assigned to either the drug condition or the placebo condition in a double-blind design and were tested on both memory tests at one of the three time points. In the 'pre-peak' condition, oxazepam impaired cued recall performance relative to placebo but did not impair priming. In the 'peak' condition, oxazepam impaired performance on both memory tasks. In the 'post-peak' condition, cued recall performance in the oxazepam group remained significantly impaired relative to placebo. However, oxazepam-induced impairments in priming were only marginal, suggesting that oxazepam-induced impairments in implicit memory processes begin to wane following theoretical peak drug concentrations. The fact that oxazepam-induced priming impairments were significant only when the word stem completion task was administered close to peak plasma concentrations, supports the hypothesis that benzodiazepines exert time-dependent effects on implicit memory processes. The results also support the theoretical distinction between implicit and explicit memory processes, since the directly comparable implicit and explicit tasks showed different impairment curves over time.

Effects of oxazepam and lorazepam on implicit and explicit memory: evidence for possible influences of time course.

The effects of oxazepam (30 mg), lorazepam (2 mg), and placebo on implicit and explicit memory were studied in two testing cycles, 100 and 170 min after drug administration. Thirty healthy volunteers were randomly assigned to one of three groups (placebo, oxazepam, or lorazepam) in a double-blind, independent groups design. Drug groups were equivalent prior to drug administration on a variety of cognitive measures. Following drug administration, both oxazepam and lorazepam equally impaired performance on a cued-recall explicit memory task relative to placebo, at both testing cycles. Relative to placebo, lorazepam markedly impaired priming on a word-stem completion implicit memory task, at both testing cycles. Consistent with previous work, oxazepam failed to produce impairments in priming on the word-stem completion task at 100 min post-drug administration. However, oxazepam was found significantly to impair priming on this latter task relative to placebo, at close to theoretical peak plasma concentration (i.e., 170 min post-drug administration). Explanations for the observed detrimental effect of oxazepam on implicit memory task performance are considered, including: possible time-dependent effects related to the relative rate of absorption of these two benzodiazepines (BZs); and potential contamination of the implicit memory task by explicit memory strategies during the second testing cycle.

Clozapine in the treatment of refractory schizophrenia: Canadian policies and clinical guidelines.

Clozapine is an atypical neuroleptic agent that has recently become available in Canada with potential clinical efficacy in the treatment of refractory schizophrenia, and in patients with schizophrenia neurologically intolerant to conventional neuroleptics. Although it causes few extra-pyramidal symptoms, the drug has a number of other adverse effects including a risk of agranulocytosis in one to two percent of all patients. Because of this, the use of the drug is permitted only if the white blood count is monitored weekly. The monitoring system, outlined in this article, requires a coordinated effort between clinical staff, pharmacy, laboratory and the Clozaril Support and Assistance Network. Clinical guidelines are proposed, detailing the indications and contraindications for treatment and the pharmacokinetics, dosing, adverse effects, and drug interactions with clozapine. In addition, the economics, government policies and implications for future research are considered. Although there are administrative and clinical difficulties associated with its use, clozapine represents an advance in therapeutic research. Patients and family members will be inquiring about the drug and may deserve a trial. This article aims to inform Canadian mental health professionals about the safe and beneficial use of clozapine.