ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The simultaneous presentation of manic and depressive symptoms in the same patient is fairly common. The termsdysphoric, mixed,anddepressive maniahave been used as equivalents to mixed states. Pharmacotherapy is less effective in this group of patients. The aim of this study is to determine the effectiveness and safety of olanzapine as an add-on therapy in patients with bipolar disorder with a rapid cycling course during a dysphoric mania episode.Thirteen patients treated with mood stabilizers for at least 1 year and diagnosed with a mixed episode were included in an open trial. All had at least 4 episodes in the last year. Patients with organic diseases, including altered thyroid function, were excluded from the research. Patients were evaluated at inclusion and at day 28. Response was defined as a decrease of 50% in the Young Mania Rating Scale and the Hamilton Rating Scale for Depression concomitant with a Clinical Global Impression improvement of 1 or 2.All patients completed the study. The doses of olanzapine were 16.15 ± 5.82 mg/day. There was a reduction in the manic and depressive symptoms in all patients. Ten of the 13 patients were considered to have responded to the treatment according to the response definition. Adverse effects included somnolence (23.08%) and weight gain (0.81 ± 1.96 kg in women, 2.20 ± 2.28 kg in men).Our results suggest that olanzapine combined with mood stabilizers is safe and effective in the treatment of the manic and the depressive symptoms of dysphoric mania with a rapid cycling course.

ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The effects of olanzapine on the symptomatology of children with pervasive developmental disorder with emphasis on problems of communication and the safety of the drug were investigated in a 3-month open-label, open-dosage study. Participating in the study were 25 children age 6 to 16 years with a diagnosis of either autistic disorder or pervasive developmental disorder not otherwise specified. Psychometric measures included the Clinical Global Impression of Severity/Improvement, the Aberrant Behavior Checklist, and the TARGET (a checklist of five target symptoms). Communication skills were assessed during behavioral analysis of a playroom session. Safety measures included clinical chemistry variables, electrocardiography, the SimpsonAngus Neurological Rating Scale, the Barnes Akathisia Scale, and vital signs. Twenty-three children completed the study and showed significant improvement on three subscales of the Aberrant Behavior Checklist (Irritability, Hyperactivity, and Excessive Speech) and the TARGET. The final mean dose was 10.7 mg/day. Several aspects of communication were also improved after olanzapine treatment. However, only three children were considered responders in terms of the Clinical Global Impression of Severity/Improvement scores. The most important adverse events were weight gain, increased appetite, and loss of strength. Three children showed extrapyramidal symptoms that disappeared after the dose was lowered. Thus, while olanzapine was a relatively safe medication in children, its clinical relevance in children with pervasive developmental disorder may be limited.

ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Risperidone is a novel and atypical agent with a dual antagonistic effect on 5-HT2and D2receptors. Open-label reports and one controlled study suggest that risperidone addition is effective in patients with obsessive-compulsive disorder refractory to treatment with serotonin reuptake inhibitors. However, risperidone has also been implicated in the production or exacerbation of obsessive-compulsive symptoms. We report six cases (schizophrenia, five cases; psychotic depression, one case) in which risperidone was effective in the treatment of the psychotic symptoms but producedde novoobsessive-compulsive symptoms (four cases) or caused exacerbation of previous obsessive-compulsive symptoms (two cases). In all but one case, obsessive-compulsive symptoms emerged shortly after initiation of risperidone treatment with a dose above 3 mg/day. The mechanisms and risk factors for risperidone and other atypical antipsychotics to induce or exacerbate obsessive-compulsive symptoms are as yet not clear. Risperidone-induced obsessive-compulsive symptoms appear to be dose-dependent and are probably produced by serotoninergic-dopaminergic imbalance. Close monitoring of the patients receiving risperidone, especially those vulnerable to the development of obsessive-compulsive symptoms, may be of value. Gradual escalation and low final dose may be helpful.

ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Because methylphenidate is currently the most widely prescribed medication for attention-deficit/ hyperactivity disorder, several studies have used it as the active comparator medication for evaluating the efficacy of a newer stimulant, Adderall. These prior studies show Adderall to be superior to placebo and suggest it is at least as effective as the standard-release form of methylphenidate and has a longer duration of action. Although these initial studies provide useful information for clinicians treating children with attention-deficit/hyperactivity disorder, they are difficult to interpret because findings vary among studies and among the different types of measures used within each study. To provide a clearer picture of what conclusions can be drawn from these studies, we performed a meta-analysis. Data from the four available studies suggest that Adderall has a small but statistically significant advantage over the standard-release form of methylphenidate. This advantage was observed for both symptom measures and global ratings but was strongest for global ratings. The effect of Adderall was significant for clinician and parent ratings but not for teacher ratings and was significant for both fixed-dose and best-dose designs.

ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Patients with major depressive disorder remain at risk for relapse following remission and often continue to experience subthreshold symptoms. This study compared the rate of relapse of major depressive disorder and the prevalence of residual depressive symptoms during the continuation phase for patients treated with fluoxetine dose increase alone or in combination with cognitive therapy. A total of 132 outpatients with major depressive disorder who achieved remission with 8 weeks of treatment with fluoxetine 20 mg had the dose increased to 40 mg. They were randomized to receive cognitive therapy or medication management alone and were followed for up to 28 weeks for depressive relapse and change in depressive symptoms. A total of 47 (35.6%) out of 132 patients did not complete the 28-week continuation phase. Rates of discontinuation or relapse did not differ significantly between the groups. Change in residual symptoms or wellbeing as measured by Hamilton Depression Scale score or Symptom Questionnaire self-report also did not differ between groups. In this sample of outpatients in continuation phase treatment for major depressive disorder, the combination of cognitive therapy and fluoxetine 40 mg failed to yield any significant benefit in symptoms or relapse rates over fluoxetine 40 mg alone during 28 weeks of follow-up.

ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

This study was performed in elderly patients (1) to assessin vivothe degree to which CYP2D6mediated metabolism of debrisoquine at baseline determines plasma concentration to dose quotients for nortriptyline or paroxetine after 4 weeks of treatment, and (2) to compare the effects of nortriptyline and paroxetine on debrisoquine metabolism after 6 weeks of treatment.CYP2D6 activity was estimated in 66 subjects (71.4 ± 7.2 years) before initiating treatment and again after 6 weeks of treatment with either nortriptyline or paroxetine under randomized, double-blind conditions according to a standard protocol. CYP2D6 activity was estimated by the debrisoquine recovery ratio in a 6- to 8-hour urine sample collected after oral administration of 10 mg debrisoquine sulfate. Nortriptyline and paroxetine plasma concentrations were obtained weekly.Baseline debrisoquine recovery ratio values were significantly correlated with the plasma concentration to dose quotient at 4 weeks for both nortriptyline (r= −0.75,p= 0.0001, N = 29) and paroxetine (r= −0.50,p= 0.003, N = 33). Treatment with either nortriptyline or paroxetine was associated with a significant decrease in the median debrisoquine recovery ratio, reflecting inhibition of CYP2D6 metabolism. The percent decrease associated with nortriptyline was significantly smaller than that with paroxetine (p< 0.0001). None of the patients treated with nortriptyline but 19 of the 32 extensive metabolizers treated with paroxetine were converted to phenotypic poor metabolic status.Our observations of CYP2D6 inhibition are consistent within vitrodata and results obtained in younger healthy volunteers. The significant correlations between baseline debrisoquine recovery ratio and the plasma concentrations to dose quotients at 4 weeks for both nortriptyline and paroxetine are consistent with CYP2D6 playing a major role in the metabolism of both drugs. CYP2D6 inhibition by paroxetine, which effectively converted 59% of patients to phenotypic PMs, may be especially relevant for elderly patients given their generally higher concentration of paroxetine.

ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The objective of this study was to assess whether nicotine replacement therapy, administered in a real-life situation, could reduce cigarette consumption in smokers who were not prepared to quit smoking. Daily smokers of more than 20 cigarettes per day who had no intention to quit smoking in the next 6 months were recruited from the general population and randomly assigned to either a 6-month treatment of nicotine (choice among a 15-mg nicotine patch, a 4-mg nicotine gum, a 10-mg nicotine inhaler, or a combination of these, N = 265), matching placebo products (N = 269), or no intervention (N = 389). Products were sent to participants by mail. Education was limited to a booklet. Of 923 participants, 879 (95%) were followed up after 6 months. Mean baseline consumption was 30 cigarettes per day in all groups. At 6 months, cigarette consumption decreased by a median of 10 cigarettes per day in the nicotine group, 7.5 in the placebo group, and 2.5 among controls (p< 0.04 for all pair-wise comparisons). Smoking cessation rates were low (2%–4%) and did not differ significantly between groups. Quit attempts were less frequent among controls (21%) than among the nicotine (28%,p= 0.04) and placebo (27%,p= 0.08) subjects. In conclusion, nicotine replacement therapy helped smokers reduce their cigarette consumption and maintain this reduction over 6 months, but a large part of this reduction was attributable to a placebo effect. Nicotine treatment for smoking reduction had no detectable impact on smoking cessation.

ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Determination of plasma cotinine concentration is the predominant assay employed to quantify smoking and exposure to environmental tobacco smoke in epidemiological studies. However, cotinine is biotransformed into secondary metabolites. This pilot study determined plasma concentrations of cotinine, cotinine glucuronide, 3-hydroxycotinine, and 3-hydroxycotinine glucuronide. Total cotinine concentration was determined by summation of all four metabolites. The goals of this study were (1) to explore the stability and validity of total cotinine concentration as a measure of tobacco smoking and as a measure of exposure to environmental tobacco smoke in nonsmokers, (2) to explore the stability of plasma concentrations of each of the four nicotine metabolites in smokers by performing a.m. and p.m. measures, and (3) to explore the stability of indices of glucuronidation as measures of possible markers for enzymatic activity. The subject sample included 76 white volunteers (32% smokers and 68% nonsmokers). Plasma total cotinine concentration appeared to be very stable, suggesting that total cotinine concentration may be a good measure for epidemiological studies employing a single plasma sample. Moreover, plasma total cotinine concentration also reflected exposure to environmental tobacco smoke more accurately than did plasma cotinine concentration, which would have not identified 27% of passive smokers.3-Hydroxycotinine glucuronide and 3-hydroxycotinine plasma concentrations were almost as stable as cotinine concentrations. However, cotinine glucuronide and its indices of glucuronidation were unstable, suggesting that cotinine glucuronide undergoesin vivodeconjugation. New studies of total cotinine in plasma using more than two blood collections during the day are needed to definitively establish that it is a stable biomarker for epidemiological studies.

ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Olanzapine is a substrate of the cytochrome P450 enzyme (CYP) 1A2. In this study, pharmacokinetic interactions and clinical effects of adding the CYP1A2 inhibitor fluvoxamine to steady-state olanzapine was examined in patients suffering from schizophrenia. Eight patients had been treated for at least 3 months with 10 to 20 mg/day olanzapine. Fluvoxamine (100 mg/day) was added (week 0) to the olanzapine treatment and continued for 8 weeks. Concentrations of olanzapine and its metab-olite N-desmethylolanzapine and of fluvoxamine were analyzed at weeks 0, 1, 4, and 8. Addition of fluvoxamine resulted in a 12% to 112% (p< 0.01) increase of olanzapine from 31 ± SD 15 ng/mL (week 0) to 56 ± 31 ng/mL (week 8) in all patients. N-desmethylolanzapine concentrations were not significantly changed (p> 0.05). Fluvoxamine concentrations were 48 ± 26 ng/mL on week 1 and 83 ± 47 ng/mL on week 8. It is concluded that fluvoxamine affects olanzapine degradation and thus increases olanzapine concentrations. Although the combination was well tolerated in this sample and the negative symptom response appeared to be favorable in at least five patients, the combination therapy of olanzapine and fluvoxamine should be used cautiously and should be controlled by therapeutic drug monitoring to avoid olanzapine-induced side effects or intoxications.

ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID