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Biomedical subjects

G Chouinard

Publications and source records attributed to G Chouinard.

At least 37 records · Page 2Linked to original sources
PubMed1998

Phase-IV multicentre clinical study of risperidone in the treatment of outpatients with schizophrenia. The RIS-CAN-3 Study Group.

OBJECTIVE: Since most clinical trials of atypical antipsychotics have been conducted in hospitalized patients, a Phase-IV, multicentre, 8-week, open-label, flexible-dose study was performed to assess the efficacy and safety of risperidone in outpatients with schizophrenia. METHOD: Three hundred and thirty patients with a Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) diagnosis of schizophrenia were enrolled at 61 Canadian sites. Upon trial entry, the patients had their neuroleptic and antiparkinsonian drugs discontinued, and treatment with risperidone was initiated at a dose of 2 mg daily, then increased by 2 mg daily on each of the 2 following days until the initial target dose of 6 mg daily was reached on day 3. No further titration was allowed until day 14, after which the dose could be increased or decreased. RESULTS: During the stabilization phase (days 14-56), the dose was unchanged in 44% of the patients, increased in 24%, decreased in 23%, and titrated both up and down in 9% of the patients. In the efficacy-evaluable population (n = 292), treatment with risperidone produced substantial (-26.4) and significant (P = 0.0001) improvement in the total Positive and Negative Syndrome Scale (PANSS) score. At the end of the study (week 8), 85% of patients were classified as clinically improved according to an a priori definition (that is, 20% or more decrease from baseline in total PANSS score). On their last study visit, 75% of patients reported their experience with risperidone as better than their previous neuroleptic therapy. Risperidone was generally well tolerated. The adverse events reported by more than 5% of the patients were insomnia, nausea, headache, somnolence, dizziness, fatigue, anxiety, vomiting, and ejaculation disorder. Seventy-four percent of the reported treatment-related adverse events were recorded during the first 2 weeks of the trial, possibly because of the discontinuation of prior neuroleptic and antiparkinsonian drugs followed by immediate upward titration of risperidone. However, only 8.5% of adverse events were reported to have occurred during week 3, and only 0.8% of adverse events were reported for week 8. Risperidone treatment produced significant improvements over baseline in the incidence and severity of extrapyramidal symptoms (EPS). A slight but statistically significant increase in body weight was observed. CONCLUSIONS: The results of this open-label, Phase-IV trial in a large population of outpatients with schizophrenia found that risperidone was superior to the neuroleptics that patients had previously taken in terms of efficacy and severity of EPS. Our results suggest the use of risperidone at lower doses in outpatients with schizophrenia.

Adolescent↗
PubMed1997

Economic and health state utility determinations for schizophrenic patients treated with risperidone or haloperidol.

The current study uses utility analysis to assess economic and quality-of-life benefits of risperidone in patients with chronic schizophrenia. A retrospective analysis was performed on Positive and Negative Syndrome Symptoms (PANSS) data obtained from the published Canadian multicenter risperidone trial (part of the North American trial). Cluster analysis applied to endpoint PANSS scores, including all patients (N = 135), identified three clusters representing 130 patients with mild, moderate, and severe symptomatology. A narrative health state profile was written for each cluster, and 100 psychiatric nurses from Washington, DC, were asked to assign preference ratings to each one using linear analog and standard gamble (SG) methods. Mean utility values (confidence interval 95%) obtained from the SG ratings for the three health state profiles were 0.61 +/- 0.069 (mild); 0.36 +/- 0.073 (moderate); and 0.29 +/- 0.071 (severe). The mild health state (including the majority of risperidone 6 mg-treated patients) was rated by nurses to have a 0.25 +/- 0.0501 greater utility than the moderate health state (composed of the majority of haloperidol-treated patients). The results of these utility evaluations (SG) by the nurses were related to the clinical outcome for three of the six drug treatment groups (N = 65) by multiplying the percentage of patients in each of the three clusters, both at baseline and end-point, who were receiving risperidone 6 mg/day, haloperidol, or placebo, by the utility value for the health state assigned to that cluster. The gain in utility for risperidone-treated patients was 2.6 times higher (0.125) compared with haloperidol-treated patients (0.049), and 7 times higher compared with placebo (-0.021). After multiplying the gain in utility of each treatment by the remaining expected life span for men and women, it was found that risperidone-treated patients obtained more than twice as many quality-adjusted years as haloperidol patients. The incremental drug treatment cost divided by the incremental benefit of risperidone versus haloperidol was found to yield a favorable, generally accepted cost-utility ratio.

Adolescent↗
PubMed1997

The effects of risperidone on the five dimensions of schizophrenia derived by factor analysis: combined results of the North American trials.

BACKGROUND: In two double-blind trials conducted in North America, 513 patients with chronic schizophrenia received risperidone, haloperidol, or placebo. In the present study, combined data from the two trials were analyzed. METHOD: Patients were randomly assigned to receive placebo, fixed doses of risperidone (2, 6, 10, and 16 mg/day) or 20 mg/day of haloperidol for 8 weeks. Factor analysis of scores on the Positive and Negative Syndrome Scale (PANSS) produced five dimensions (negative symptoms, positive symptoms, disorganized thought, uncontrolled hostility/excitement, and anxiety/depression), similar to the five dimensions of previous factor-analytic studies of PANSS data. RESULTS: Mean changes (symptom reductions) in PANSS factor scores from baseline to treatment Weeks 6 and 8 were significantly greater in patients receiving 6-16 mg/day of risperidone than in patients receiving placebo or haloperidol. The advantages of risperidone were greatest for negative symptoms, uncontrolled hostility/excitement, and anxiety/depression. Even at the lowest dose, 2 mg/day, risperidone was significantly (p < or = .05) superior to haloperidol in reducing negative symptoms. The differences in outcomes between risperidone and haloperidol on PANSS scores were not related to extrapyramidal symptoms. CONCLUSION: Risperidone produced significantly (p < or = .05) greater improvements than haloperidol on all five dimensions. The large between-group differences on negative symptoms, hostility/excitement, and anxiety/depression suggest that risperidone and other serotonin/dopamine antagonists have qualitatively different effects from those of conventional antipsychotic agents.

Adolescent↗
PubMed1997

Moclobemide versus fluoxetine in the treatment of major depressive disorder in adults.

The objective of the present study was to compare the safety and efficacy of moclobemide versus fluoxetine in adult patients with major depressive disorder. The design of the study was a multicenter, double-blind, comparative, and randomized trial. A 1- to 2-week single-blind placebo washout phase was followed by 6 weeks of double-blind treatment with moclobemide or fluoxetine. A total of 150 patients were enrolled in the study. There were 128 patients eligible to be randomized, with 66 patients receiving moclobemide and 62 patients receiving fluoxetine. At the termination of the study, patients in the moclobemide group were receiving a mean dose of 440 mg +/- 123 mg, while the mean dose in the fluoxetine group was 35 mg +/- 8 mg. No significant treatment differences were found for any of the efficacy parameters. Headache and nausea were the most frequently reported adverse events in both treatment groups. Headache and blurred vision were reported significantly more often (P < 0.05) in the fluoxetine group, whereas significantly more dry mouth was reported (P < 0.05) in the moclobemide group. These results provide supporting evidence of the comparable efficacy of moclobemide and fluoxetine and the better tolerability of moclobemide when used in the treatment of major depressive disorder.

Adult↗
PubMed1996

Potentiation of fluoxetine by aminoglutethimide, an adrenal steroid suppressant, in obsessive-compulsive disorder resistant to SSRIs: a case report.

1. The role of serotonin in the aetiology of obsessive compulsive disorder (OCD) has been established through considerable indirect evidence (Landry and Chouinard, 1990). The strongest evidence comes from the fact that drugs known to be serotonin-selective reuptake inhibitors (SSRIs) have been found to be useful in the pharmacotherapy of OCD (Landry and Chouinard, 1990). 2. The authors investigated a new treatment approach by adding an adrenal steroid suppressant to a SSRI, fluoxetine, in the case of a severe obsessive-compulsive patient who was drug-resistant to clomipramine and SSRIs. 3. We found that the combination of aminoglutethimide 250 mg qid and fluoxetine 40 mg die significantly improved the patient's condition. Moreover, during a four and a half year period, each time we tried to decrease either fluoxetine or the steroid suppressant, the patient started to relapse, suggesting that the adrenal steroid suppressant had a potentiating effect on the SSRI.

Aminoglutethimide↗
PubMed1996

A cross-sectional study of parkinsonism and tardive dyskinesia in lithium-treated affective disordered patients.

BACKGROUND: The purpose of this study was to investigate the prevalence of extrapyramidal symptoms (EPS) and tardive dyskinesia (TD) in affective disordered patients treated with lithium and to study the association of these symptoms with medication and other factors. METHODS: This cross-sectional study was carried out in all consenting outpatients attending an affective disorders clinic in a psychiatric hospital. The study sample consisted of 130 stable outpatients: 110 with bipolar disorder, 18 with unipolar (major) depression, and 2 with atypical affective disorder. At the time of evaluation, 110 patients were receiving lithium, 37 in combination with antidepressants and 19 with neuroleptics, and 40 had a history of neuroleptic treatment during the previous 6 months. The patients were assessed with the Extrapyramidal Symptom Rating Scale (ESRS) for parkinsonism, akathisia, dystonia, and TD. The prevalence of these symptoms was calculated for all patients and by current lithium and neuroleptic intake. Multiple linear regression analysis was used to investigate the relationship between the ESRS subscale scores and gender, age, diagnosis, and medication type. RESULTS: The prevalence of tremor was 20.8%; hypokinetic parkinsonism, 7.7%; akathisia, 4.6%; dystonia, 3.8%; and TD, 9.2%. Tremor was associated with lithium and neuroleptic intake; hypokinesia was associated with neuroleptic treatment and age; and TD was associated with neuroleptic, lithium, and tricyclic intake and age. Seven of 51 patients taking lithium but without a history of neuroleptic treatment during the previous 6 months presented symptoms of TD. CONCLUSION: The combination of lithium and neuroleptics was associated with a high prevalence of EPS. The presence of TD in lithium-treated patients not treated with neuroleptics for at least 6 months is consistent with the hypothesis that lithium may exacerbate the vulnerability of affective disordered patients to dyskinesias.

Adult↗
PubMed1995

The psychotropic effects of inhibitors of steroid biosynthesis in depressed patients refractory to treatment.

Twenty patients, diagnosed as suffering from treatment-resistant major depression, were treated with one or more drugs that decrease corticosteroid biosynthesis. Nine were psychotic, 11 nonpsychotic. Seventeen completed the treatment (8 psychotic, 9 nonpsychotic); 13 responded (5 psychotic, 8 nonpsychotic; 11 responded completely (i.e., a drop in the Hamilton Depression Scale of at least 50%, to < or = 15), and 2 responded partially. The mean age of the responders (45.2 +/- 12.6 years) did not differ significantly from that of the nonresponders (48.7 +/- 12/3). Data were analyzed in the following categories; (1) the presence or absence of psychosis, (2) response or nonresponse to treatment, and (3) the drug(s) used (aminoglutethimide, ketoconazole, or a combination of either of these with metyrapone). The patients improved over time on the Hamilton Depression Scale independent of the medication used. Responders demonstrated improvement in mood, insomnia, anxiety, diurnal variation, paranoia and obsessive compulsiveness. Nonpsychotics responded better than psychotics.

Adrenal Cortex Hormones↗
PubMed1995

Double-blind parallel comparison of three dosages of sertraline and placebo in outpatients with obsessive-compulsive disorder.

BACKGROUND: Anecdotal evidence suggests patients with obsessive-compulsive disorder (OCD) are treated with selective serotonin uptake inhibitors at dosages significantly higher than those used with depressed patients. The current study examined the efficacy, safety, and optimal dosing strategy of sertraline in patients with OCD. METHODS: Three hundred twenty-four nondepressed outpatients with OCD from 11 sites followed identical protocols using a double-blind parallel design. Following 1 week of single-blind placebo, patients were randomly assigned to 12 weeks of treatment with one of three fixed dosages of sertraline (50, 100, or 200 mg/d) or placebo. RESULTS: Sertraline patients exhibited significantly greater improvement (P < .05) at end point than placebo patients on all three main efficacy measures in the 50-mg/d and 200-mg/d groups and on one measure in the 100-mg/d group. The placebo response was larger in this population of subjects with OCD than in those previously studied. Adverse experiences were common in the sertraline and placebo groups and appeared to be dose-related in the sertraline-treated patients. CONCLUSIONS: Results support the safety and efficacy of daily dosages of 50, 100, and 200 mg of sertraline in the short-term treatment of patients with OCD.

1-Naphthylamine↗
PubMed1995

A path-analytical approach to differentiate between direct and indirect drug effects on negative symptoms in schizophrenic patients. A re-evaluation of the North American risperidone study.

The hypothesis that differences in drug effects of risperidone and haloperidol on negative symptoms in schizophrenia are secondary to effects on positive, extrapyramidal, and depressive symptoms was investigated by means of an analysis of the data from the USA-Canada risperidone double-blind randomized clinical trial of 523 chronic schizophrenic patients. Regression analyses in the total sample and within treatment groups confirmed a strong relationship between changes in negative symptoms and the other variables studied (R2 = 0.50-0.51, p < 0.001). Only depressive symptoms did not contribute significantly to these results (p > 0.10). Path analysis showed that the greater mean change (p < 0.05) of negative symptoms with risperidone compared to haloperidol could not be fully explained by correlations with favourable effects on positive and extrapyramidal symptoms. The relationship between shift in extrapyramidal symptoms and shift in negative symptoms failed to reach statistical significance; however, there was a clear tendency in the expected direction in both treatment groups.

Antipsychotic Agents↗
PubMed1995

Effects of risperidone in tardive dyskinesia: an analysis of the Canadian multicenter risperidone study.

In the Canadian multicenter, double-blind clinical trial of risperidone, 135 hospitalized chronic schizophrenic patients were randomly assigned to one of six parallel treatment groups for 8 weeks: risperidone, 2, 6, 10, or 16 mg/day; haloperidol, 20 mg/day; or placebo. Risperidone (6 to 16 mg)-treated patients showed significantly (p < 0.05) lower dyskinetic scores than those receiving placebo, whereas in haloperidol- and placebo-treated patients, no significant differences for dyskinetic symptoms were noted. To explore the antidyskinetic effect of risperidone, a post hoc analysis was performed on two selected patient samples: (1) patients meeting Research Diagnosis Criteria (RDC) for tardive dyskinesia (TD) at baseline or during double-blind treatment (N = 49) and (2) patients with RDC TD and with a Clinical Global Impression (CGI) Severity of dyskinesia score > or = 5 (at least moderately severe) (N = 48). The composition of the two subsamples was found to be almost identical because all but one of the patients with RDC TD (N = 49) were members of the group with at least moderately severe TD (N = 48). Analysis of four parameters (Extrapyramidal Symptom Rating Scale-dyskinesia total score, CGI severity of dyskinesia, buccolinguomasticatory [BLM] factor score, and extremities [choreoathetoid factor] score confirmed the antidyskinetic effect that was noted in the intent-to-treat analysis, which included all patients, whether they had RDC TD or not. Results indicated that risperidone at 6 mg/day had the most beneficial effect on TD, especially on the BLM syndrome, without inducing significant parkinsonism while treating psychotic symptoms. This antidyskinetic effect was greater than with either placebo or haloperidol.

Adult↗
PubMed1995

A 1 year double-blind placebo-controlled fixed dose study of sertraline in the treatment of obsessive-compulsive disorder.

The objective of this study was to evaluate the safety and efficacy, over a 1 year treatment period, of three dose levels of sertraline and placebo in the treatment of non-depressed adult out-patients with obsessive-compulsive disorder (OCD). Following 1 week of single-blind placebo washout, patients (n = 325) from 11 sites following identical protocols were randomly assigned to 12 weeks of double-blind treatment with one of three fixed doses of sertraline (50, 100 or 200 mg) or placebo. At the end of 12 weeks, treatment responders (including placebo patients) were offered an additional 40 weeks of double-blind treatment at their assigned doses. Efficacy measures were the Yale-Brown Obsessive Compulsive Scale, the NIMH Global Obsessive Compulsive Scale, Clinical Global Impressions of Severity of Illness and Global Improvement and the Maudsley Obsessive Compulsive Inventory. Patients in the pooled sertraline group showed greater improvement than placebo-treated patients on all efficacy measures, based on the endpoint analyses. Moreover, pairwise comparisons at endpoint revealed a significant effect on all three investigator-rated scales in patients receiving 50 or 200 mg of sertraline; in the 100 mg group, there was a significant effect on the NIMH Global Obsessive Compulsive Scale only. Patients completing 3 months of sertraline treatment exhibited excellent toleration and sustained improvement during an additional 40 weeks of therapy. Results support the safety, efficacy and tolerability of daily doses of 50-200 mg of sertraline in the long-term treatment of patients with OCD.

1-Naphthylamine↗
PubMed1994

Dopamine D4 receptor variant, D4GLYCINE194, in Africans, but not in Caucasians: no association with schizophrenia.

Because antipsychotic drugs selectively block dopamine receptors and since dopamine D4 receptors are elevated sixfold in postmortem schizophrenia brain, we searched for possible abnormalities in the coding region of the genomic DNA sequence for the dopamine D4 receptor in control and schizophrenia tissues. The DNA sequence for the first 250 bases of exon 3 of this receptor was examined in the genomic DNA from 296 control individuals and 58 schizophrenics. Twenty-three out of 183 control blacks (12.6%) and 3 out of 24 (12.5%) schizophrenic blacks revealed a replacement of T by G, predicting a substitution of valine by glycine at amino acid position 194. The identical prevalence of 12.5% indicates that the variant is not associated with schizophrenia. The amino acid replacement occurs one amino acid away from a serine amino acid which is critical for the attachment of dopamine. None of the 147 Caucasians (113 controls; 34 schizophrenics) revealed this variant, termed D4GLYCINE194.

Adult↗
PubMed1994

Elevated dopa decarboxylase activity in living brain of patients with psychosis.

The hypofrontality theory of the pathogenesis of schizophrenia predicts that cortical lesions cause psychosis. During a search for abnormalities of catecholaminergic neurotransmission in patients with complex partial seizures of the mesial temporal lobe, we discovered an increase of the rate of metabolism of an exogenous dopa tracer (6-[18F]fluoro-L-dopa) in the neostriatum of a subgroup of patients with a history of psychosis. When specifically assayed for this abnormality, patients with schizophrenia revealed the same significant increase of the rate of metabolism in the striatum. The finding is consistent with the theory that a state of psychosis arises when episodic dopamine excess is superimposed on a trait of basic dopamine deficiency in the striatum. The finding is explained by the hypothesis that cortical insufficiency, a proposed pathogenetic mechanism of both disorders, causes an up-regulation of the enzymes responsible for dopa turnover in the neostriatum as well as the receptors mediating dopaminergic neurotransmission.

Adult↗
PubMed1994

CGP 25454A, a novel and selective presynaptic dopamine autoreceptor antagonist.

N-(diethylamino-ethyl)-4-chloro-5-cyano-2-methoxy-benzamide-hydrochlo rid e (CGP 25454A) is a new benzamide derivative now in clinical trials in patients with major depression. Here we describe some basic neurochemical and behavioural properties in animal experiments. In vitro, CGP 25454A increased the field-stimulated [3H]- and [14C]-overflow from rat striatal slices preloaded with [3H]dopamine and [14C]choline, indicating that CGP 25454A was able to enhance the release of both dopamine (DA) and acetylcholine (ACh). However, CGP 25454A was 12.9 times more potent in increasing, by 1/6 of the apparent maximal increase, the release of [3H]DA than that of [14C]ACh. In vivo, CGP 25454A increased [3H]spiperone binding to receptors of the D2 family in rat striatum by 90-110% (ED50: 13 mg/kg i.p.). As a similar increase in [3H]spiperone binding was found with a variety of agents which increase the synaptic concentration of endogenous DA, the effect of CGP 25454A most probably reflects an enhanced release of DA under in vivo conditions. At 30-100 mg/kg, CGP 25454A inhibited [3H]spiperone binding in the pituitary of the same animals as a result of a blockade of postsynaptic DA receptors. This dual mode of action was also apparent in terms of behavioral changes. At doses as low as 5-10 mg/kg, CGP 25454A produced a weak stimulation, suggested by a trend of increased spontaneous rearing and corroborated by a significant potentiation of the elevated rearing induced by (+)-amphetamine. By contrast, at doses of 30-100 mg/kg, it exerted clear-cut sedative and neuroleptic-like properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

A Canadian multicentre placebo-controlled study of a fixed dose of brofaromine, a reversible selective MAO-A inhibitor, in the treatment of major depression.

In a 6-week double-blind study, 220 patients with major depression (mostly outpatients) were randomly assigned to receive a fixed dose of brofaromine 150 mg daily (n = 111) or placebo (n = 109) after a 1-week single-blind placebo washout. Except for the HAM-D sleep items, brofaromine was superior to placebo on measures of depression as determined by the four methods of assessing drug efficacy: (1) psychiatric symptom rating (HAM-D 17-item less the three sleep items); (2) self-rating scale (Beck Depression Inventory); (3) Clinical Global Assessment of Efficacy; and (4) drop-out rate due to lack of efficacy. Most commonly reported adverse events with brofaromine were: headache, nausea, dizziness and sleep disturbance. Brofaromine was found to be an effective antidepressant, superior to placebo with a good tolerability profile.

Adolescent↗