ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The aim of this study was to estimate the long-term effectiveness of olanzapine as adjunctive therapy in patients with bipolar disorder who exhibited an inadequate response to mood stabilizers. Twenty-three Research Diagnostic Criteria (RDC) patients with bipolar I and II were assessed by means of the Schedule for Affective Disorders and Schizophrenia and entered if they gave their consent to participate. All of them had experienced frequent relapses, residual subsyndromal symptoms, and inadequate responses to other drugs, such as lithium, valproate, or carbamazepine. While maintaining other drugs, they all received open-label, increasing doses of olanzapine, until achieving clinical response. Other drugs were maintained. The patients were assessed several consecutive times from baseline to the endpoint with the Clinical Global Impressions (CGI) scale for use in bipolar illness. Records of recurrences, hospitalizations, and side effects were also collected. The last-observation-carried-forward analysis showed that there was a significant reduction of CGI scores after the introduction of olanzapine, either in manic symptoms (p= 0.0015), depressive symptoms(p= 0.0063), or global symptoms (p= 0.0003). The most frequent adverse events were somnolence (17%) and weight gain (13%). The mean dose of olanzapine at the end of the 43-week follow-up was 8.1 mg/day. Olanzapine may be a useful medication for the long-term adjunctive treatment of patients with bipolar disorder who exhibit a poor response to mood stabilizers, such as lithium, valproate, or carbamazepine. These results suggest mood-stablizing properties of olanzapine.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Patients with bipolar disorder are often prescribed lithium in combination with a selective serotonin reuptake inhibitor. Doubts still remain, however, about the safety of the combination, particularly with regard to the risk of developing a serotonin syndrome. The authors retrospectively evaluated the safety of the combination of lithium and paroxetine when the two medications were sequentially prescribed in patients with bipolar disorder. The authors examined a sample of 17 patients with bipolar disorder who were treated with lithium during a depressive episode and who required paroxetine as an adjunctive antidepressant to ongoing lithium treatment. Averaging across all subjects, no statistically significant increase was found for any of the somatic symptoms that were assessed before and after paroxetine was added to ongoing lithium therapy. Examining the clinical records of each patient in detail; however, four patients who developed significant adverse events, possibly related to an emerging serotonin syndrome were identified. Clinicians should be aware of the possible development of a serotonin syndrome among patients in whom paroxetine is added to ongoing lithium treatment.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Neurocognition and clinical symptomatology were evaluated in 27 patients with schizophrenia during a double-blind, placebo-controlled, crossover study involving clozapine, an atypical antipsychotic agent, and haloperidol, a conventional neuroleptic. Patients were assessed 5 to 6 weeks after initiation of each phase. Clinical symptomatology, based on Brief Psychiatric Rating Scale and Scale for the Assessment of Negative Symptoms ratings, markedly improved after treatment with both haloperidol and clozapine. The beneficial effects of clozapine were statistically significantly greater than the effects from the haloperidol treatment. Regarding neurocognition, both agents proved efficacious in improving performance on nearly all measures compared with placebo. In addition, as compared with haloperidol, clozapine significantly improved performance on Trails B, Verbal Fluency, and measures of delayed verbal memory, and it tended to increase performance on most measures. Additional analyses indicated that the improvement on neurocognitive measures was not because of symptom amelioration; rather, neurocognitive deficits seem to be an intrinsic enduring feature of schizophrenia. The superiority of clozapine over haloperidol may be related to clozapine’s unique psychopharmacologic profile.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

CX516, a positive modulator of the glutamatergic α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor, improves performance in tasks requiring learning and memory in animals. CX516 was added to clozapine in 4-week, placebo-controlled, dose-finding (N = 6) and fixed-dose (N = 13) trials. CX516 was tolerated well and was associated with moderate to large, between-group effect sizes compared with placebo, representing improvement in measures of attention and memory. These preliminary results suggest that CX516 and other “ampakines” hold promise for the treatment of schizophrenia.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The aim of this study was to evaluate which clinical variables might influence the antiobsessional response to proserotonergic drugs in a sample of patients with obsessive-compulsive disorder (OCD). One hundred fifty-nine patients with DSM-IV OCD underwent a 12-week standardized treatment with fluvoxamine, clomipramine, citalopram, or paroxetine. According to treatment response, defined as a reduction of the Yale-Brown Obsessive Compulsive Scale total score >35%, patients were divided into two groups. Ninety patients (56.6%) responded to treatment and 69 (43.4%) did not. Responders had a significantly higher frequency of positive family history for OCD (FH-OCD) in their first-degree relatives, whereas nonresponders had an earlier onset and a higher frequency of “poor insight” subtype and somatic obsessions. The predictive value of all these variables was tested by a stepwise logistic regression analysis that confirmed poor insight and FH-OCD to be the best predictors of poor and good drug treatment response, respectively. These preliminary findings need additional investigations toward a better definition of the genetic and biological heterogeneity of patients with OCD, and they underlie the importance of collecting the insight score and family history for psychiatric disorders in the pretreatment assessment.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Carbamazepine, a drug used in the treatment of seizure disorders, and citalopram, a highly selective serotonin reuptake inhibitor used for the treatment of depression and other psychiatric disorders, are both metabolized predominantly by the cytochrome P4503A4 isozyme. In this study, the effect of subchronic administration of citalopram on the steady-state pharmacokinetics of carbamazepine was evaluated in 12 healthy male subjects. Carbamazepine was administered orally twice daily as a 100-mg dose from days 1 to 3, as a 200-mg dose twice a day from days 4 to 6, and as a 400-mg dose once a day from days 7 to 35. Citalopram, 40 mg, administered once daily, was added to the carbamazepine-dosing regimen on days 22 to 35. The steady-state plasma concentration profiles of carbamazepine and its active metabolite, carbamazepine 10,11-epoxide, on day 35 (in the presence of steady-state levels of citalopram) were compared to the corresponding carbamazepine and epoxide metabolite profiles on day 21 (in the absence of citalopram). No significant differences were found between mean steady-state values for maximal drug concentration, area under the curve, or time of maximal concentration values for carbamazepine and its epoxide metabolite before and after the addition of citalopram to the daily carbamazepine dosing regimen (p> 0.05). These results suggest that the use of citalopram in patients stabilized on carbamazepine should not produce clinically significant changes in carbamazepine plasma concentrations.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Glucuronidation is a phase II metabolic process and one of the most common pathways in the formation of hydrophilic drug metabolites. At least 33 families of uridine diphosphate-glucuronosyltransferases have been identifiedin vitro, and specific nomenclature similar to that used to classify the cytochrome (CYP) P450 system has been established. The UGT1 and UGT2 subfamilies represent the most important of these enzymes in human drug metabolism. Factors affecting glucuronidation include the following: cigarette smoking, obesity, age, and gender. In addition, several drugs have been foundin vitroto be substrates, inhibitors, or inducers of UGT enzymes. Induction or inhibition of both UGT and CYP isoforms may occur simultaneously. Some important drug interactions involving glucuronidation have been documented and others can be postulated. This review summarizes the relevant literature pertaining to drug glucuronidation and its implications for clinical psychopharmacology.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The rationale for treating psychotic major depression with glucocorticoid receptor (GR) antagonists is reviewed. Five patients with psychotic major depression were given 600 mg of mifepristone in a 4-day, double-blind, placebo-controlled crossover study. All the patients completed the protocol and adverse effects were not observed or reported. All of the five patients showed substantial improvements in their Hamilton Rating Scale for Depression scores while they were receiving mifepristone, and four of the five patients showed substantial improvement in their Brief Psychiatric Rating Scale scores. Little, if any, improvement was seen with placebo. These preliminary results suggest that short-term use of GR antagonists may be effective in the treatment of psychotic major depression and that additional study, perhaps using higher doses or more treatment days, seems warranted.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

A properly implemented agonist treatment regimen should improve retention and reduce illicit drug use. Cocaine-dependent subjects (N = 128) were enrolled in a 12-week randomized, double-blind, placebo-controlled trial. In the multistage dosing design, subjects initially received placebo (PBO) or 15 to 30 mg of dextroamphetamine sulfate, sustained-release capsules. At week 5, the dose doubled to 30 mg or 60 mg for active groups. Subjects attended the clinic twice a week, provided urine samples, obtained medication, and had one behavioral therapy session a week. Retention was best for the 15-to 30-mg group, whereas the proportion of benzoylecgonine-positive urine screens was, from lowest to highest, 30 to 60 mg, 15 to 30 mg, and PBO at study end. Dosing must be refined. The results provide support for additional examination of the agonist model in psychostimulantdependence treatment.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID