Psychosis associated with elevated trough tacrolimus blood concentrations after combined kidney-pancreas transplant.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to G Chouinard.
Explore the source record for details and available documents.
The antidepressant mirtazapine antagonizes central presynaptic alpha2-adrenergic auto- and heteroreceptors resulting in increased central norepinephrine and serotonin activity. Histamine H2 receptors are also antagonized, as are postsynaptic serotonin 5-HT2 and 5-HT3 receptors, leading to serotonergic activity primarily via 5-HT1A receptors. Based on the case report of a patient who developed mania with higher than recommended dosage of mirtazapine, we review the literature on the atypical nature of manic symptoms with mirtazapine. Eight subjects, including those in our study, were identified as having developed mirtazapine-induced mania with atypical features, consisting of dysphoria, irritability, insomnia, psychomotor agitation and abnormal gait. Predisposing features may have included the presence of underlying brain dysfunction and certain selective serotonin reuptake inhibitor-mirtazapine combinations. Dysphoric mania with atypical features may be induced by mirtazapine, providing support for a common hypothesis such as 'central norepinephrine hyperactivity' as the basis for development of mania with mirtazapine.
Hyaliodes vitripennis (Say) is a univoltine indigenous predacious mirid. It has been reported in several orchards where IPM programmes are used. It is a generalist, and feeds on phytophagous mites in addition to other arthropods. In Quebec, a foliar application of imidacloprid, deltamethrin or lambda-cyhalothrin is used at least once per season to manage arthropod pests such as leafhoppers and leaf-eating caterpillars. Meanwhile, several applications of metiram, flusilazole, myclobutanil and mancozeb are made to control apple scab [Venturia inaequalis (Cooke) Winter]. In laboratory trials, comparison of lethal concentrations of the three insecticides against H vitripennis nymphs and adults showed no significant difference. However, when lethal concentrations were compared between two growth stages for each insecticide, a significant difference was noted between adults and nymphs treated with lambda-cyhalothrin, adults being more susceptible than nymphs. No such difference could be detected for imidacloprid or deltamethrin. When LC50 values were compared with the manufacturer's label rates, deltamethrin and imidacloprid were toxic to the nymphs and adults, and lambda-cyhalothrin was slightly toxic to the nymphs and moderately toxic to the adults. Among the fungicides evaluated in the laboratory, myclobutanil showed moderate toxicity to adults at the manufacturer's label rate. The remaining fungicides had no toxic effects to adults or nymphs, even at four times the manufacturer's label rate.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Azinphos-methyl, carbaryl, dimethoate, phosmet and phosalone were used in apple orchards to manage apple aphid, apple maggot, woolly apple aphid and leaf eating caterpillars. Among the five insecticides evaluated, dimethoate, carbaryl and azinphosmethyl were the most toxic to the nymphs and adults of Hyaliodes vitripennis (Say) from two regions. Phosalone was the least toxic. Nymphs were more resistant than the adults. While the LC50 for dimethoate was 130 ppm for nymphs, it was 3 ppm for adults from St. Jean-Baptiste-de-Rouville. There were also significant differences in the level of resistance between the two regions where the H. vitripennis were collected. At St. Alexandre the LC50 for phosalone on nymphs was 19,250 ppm whereas, at St. Jean-Baptiste-de-Rouville it was 160,000 ppm.
The efficacy and tolerability of reboxetine, a unique selective noradrenaline reuptake inhibitor, were compared with those of placebo in a 6-week, randomized, double-blind study of hospitalized patients with a DSM-III-R diagnosis of major depressive disorder. Fifty-two patients (25 in the placebo group, 27 in the reboxetine group) were included in the efficacy analysis. Sixteen (64%) of those in the placebo group and four (15%) in the reboxetine group were withdrawn during the study because of lack of efficacy. Improvement in the mean Hamilton Rating Scale for Depression (HAM-D) total score at last assessment was significantly greater in the reboxetine group than in the placebo group (p < 0.001). Similarly, the response rate to treatment, defined as > or =50% reduction in HAM-D total score, was 74% for patients who received reboxetine compared with 20% for those who received placebo (p < 0.001). A significantly greater response with reboxetine than with placebo was seen as early as day 10 of treatment (p = 0.006). The therapeutic efficacy of reboxetine was substantiated by improvement in mean scores on the Zung Self-Rating Scale and on the Clinical Global Impression Severity of Illness and Global Improvement scales. Reboxetine was well tolerated, and only one patient in each group withdrew because of adverse events. Dry mouth, insomnia, blurred vision, sweating, and constipation were recorded more frequently in the reboxetine group than in the placebo group. There was a tendency toward orthostatic changes in the systolic blood pressure, but this was not clinically significant. This study demonstrated that reboxetine is significantly more effective than placebo in the treatment of hospitalized patients with severe major depressive disorder and is well tolerated.
A randomized, double-blind, placebo-controlled, parallel-group study was conducted to evaluate the efficacy and safety of gabapentin in relieving the symptoms of panic disorder. One hundred three patients were randomly assigned to receive double-blind treatment with either gabapentin (dosed flexibly between 600 and 3,600 mg/day) or placebo for 8 weeks. No overall drug/placebo difference was observed in scores on the Panic and Agoraphobia Scale (PAS) (p = 0.606). A post hoc analysis was used to evaluate the more severely ill patients as defined by the primary outcome measure (PAS score > or = 20). In this population, the gabapentin-treated patients showed significant improvement in the PAS change score (p = 0.04). In patients with a PAS score of 20 or greater, women showed a greater response than men regardless of treatment. Adverse events were consistent with the known side effect profile of gabapentin and included somnolence, headache, and dizziness. One patient experienced a serious adverse event during the study. No deaths were reported. The results of this study suggest that gabapentin may have anxiolytic effects in more severely ill patients with panic disorder.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The authors present a new rating scale for the psychotic symptoms of schizophrenia and related psychoses. The scale links specific symptoms of psychopathology to dysfunction and overactivity of dopaminergic mechanisms underlying the processes of reward and selective attention. The Rating Scale for Psychotic Symptoms (RSPS) is a 44-item rating instrument with a seven-point severity scale for each item. Psychotic symptoms are classified into three groups: Pathological amplification of mental images (perception symptoms) (subscale 1), Distraction symptoms (including catatonia and passivity experiences) (subscale 2), and Delusions (subscale 3). A dimensional, rather than a categorical, conceptualization of psychosis is assumed. Rating is accomplished through a manual and a semi-structured interview (SSCI-RSPS). In this first of two papers, general issues about the construction of the scale and the derivation of symptom groups are discussed. Dopamine-mediated modification of cortico-striatal synapses is seen as being of critical importance in all three groups of symptoms. In this first paper, we present subscale I (perception symptoms), which includes both amplified perceptual images (illusions) and hallucinations. A total of seven illusions and 11 hallucinations are rated as individual items.
In the second paper on the Rating Scale for Psychotic Symptoms (RSPS), distraction symptoms (Subscale 2) and delusions (Subscale 3) are described. Subscale 2 includes distraction symptoms, which arise from one of two mechanisms: the symptom may arise either by loss of attentional focus (LAF) due to a competing channel of information, or by the intrusion of the competing channel into the focus of attention [attentional intrusions (AI)]. The symptom classes resulting from loss of attentional focus (LAF) include motor catatonia, negativism, and thought blocking; the attentional intrusions (AI) symptoms rated include three types of passivity experiences (Schneiderian symptoms): (1) thought insertion, (2) movements or action controlled, and (3) speech controlled by an external force. Subscale 3, consisting of delusions, is organized on the basis of content identification. Nineteen types of delusions are rated. Each item of delusional content is rated along three axes (active elaboration, persistence and active extinction) and complexity, and optionally if primary or mixed (i.e. primary with secondary elaborations). The last section of the paper includes the semi-structured interview (SCI-RSPS) for each of the items, as well as guidelines for practical application of the interview.
BACKGROUND: Recent studies have suggested clinical differences among selective serotonin reuptake inhibitors. In a 12-week randomized, multicenter, double-blind trial, the antidepressant and anxiolytic efficacy of the selective serotonin reuptake inhibitors paroxetine and fluoxetine was compared in patients with moderate to severe depression. METHODS: A total of 203 patients were randomized to fixed doses (20 mg/day) of paroxetine or fluoxetine for the first six weeks of therapy. From week 7-12, dosing could be adjusted biweekly, as required (paroxetine 20-50 mg/day, and fluoxetine 20-80 mg/day). The mean prescribed doses were paroxetine 25.5 mg/day (range 20.0-40.2 mg/day), and fluoxetine 27.5 mg/day (range 20.0-59.5 mg/day). Emergence of motor nervousness or restlessness was assessed using the ESRS scale for akathisia. RESULTS: Both active treatments demonstrated comparable antidepressant efficacy (HAM-D, CGI). Anxiolytic activity of the two drugs (COVI, STAI, HAM-D) was also comparable. However, paroxetine was found to be superior to fluoxetine on two subscore measures at week 1 of therapy (HAM-D Agitation item, p < 0.05; Psychic Anxiety item, p < 0.05), with no differences detected after week 2. The overall incidence of adverse effects was comparable in the two treatment groups. Constipation, dyspepsia, tremor, sweating and abnormal ejaculation were more common in paroxetine-treated subjects, whereas nausea and nervousness were more frequent in fluoxetine-treated patients. Weight loss was more common in the fluoxetine versus paroxetine group (11.88% versus 2.94%, respectively). ESRS scores for akathisia were low throughout the study and showed little change. LIMITATIONS: Differences observed between the two drugs in antianxiety effects were limited to two measures of anxiety among several others. DISCUSSION: The data indicate that paroxetine and fluoxetine have comparable antidepressant and anxiolytic efficacy. Paroxetine appears to produce an earlier improvement in agitation and psychic anxiety symptoms compared with fluoxetine.
1. The benzodiazepines are among the most frequently prescribed of all drugs and have been used for their anxiolytic, anticonvulsant, and sedative/hypnotic properties. Since absorption rates, volumes of distribution, and elimination rates differ greatly among the benzodiazepine derivatives, each benzodiazepine has a unique plasma concentration curve. Although the time to peak plasma levels provides a rough guide, it is not equivalent to the time to clinical onset of effect. The importance of alpha and beta half-lives in the actions of benzodiazepines is discussed. 2. The role of cytochrome P450 isozymes in the metabolism of benzodiazepines and in potential pharmacokinetic interactions between the benzodiazepines and other coadministered drugs is discussed. 3. Buspirone, an anxiolytic with minimal sedative effects, undergoes extensive metabolism, with hydroxylation and dealkylation being the major pathways. Pharmacokinetic interactions of buspirone with other coadministered drugs seem to be minimal. 4. Zopiclone and zolpidem are used primarily as hypnotics. Both are extensively metabolized; N-demethylation, N-oxidation, and decarboxylation of zopiclone occur, and zolpidem undergoes oxidation of methyl groups and hydroxylation of a position on the imidazolepyridine ring system. Zopiclone has a chiral centre, and demonstrates stereoselective pharmacokinetics. Metabolic drug-drug interactions have been reported with zopiclone and erythromycin, trimipramine, and carbamazepine. Reports to date indicate minimal interactions of zolpidem with coadministered drugs; however, it has been reported to affect the Cmax and clearance of chlorpromazepine and to decrease metabolism of the antiviral agent ritonavin. Since CYP3A4 has been reported to play an important role in metabolism of zolpidem, possible interactions with drugs which are substrates and/or inhibitors of that CYP isozyme should be considered.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Principles of benzodiazepine selection are outlined for various psychiatric indications and diverse populations (the elderly, and drug and alcohol abusers). Benzodiazepines are still among the most commonly used classes of medications, and they differ in their pharmacodynamic properties. They have varied uses as monotherapy or as adjunctive medication because of their efficacy in the treatment of conditions involving a dysfunction of the GABAergic system or where neuronal inhibition is required. In multiple therapy, benzodiazepines augment the efficacy of other drugs such as lithium in mania, antipsychotics in psychotic agitation and selective serotonin reuptake inhibitors in panic disorder. Benzodiazepines can produce dependence and tolerance in most patients; predisposed individuals are at greater risk. Short- and intermediate-beta half-life compounds carry a greater risk of rebound and withdrawal reactions, and drug dependence than long acting agents. Adverse effects include sedation, psychomotor and cognitive impairment, memory loss, potentiation of other central nervous system depressants and treatment-emergent depression. Drug potency and beta elimination half-life are reviewed and compared as pharmacokinetic variables.
Explore the source record for details and available documents.