摘要:

Opipramol, a drug widely prescribed in Germany, is a tricyclic compound with no reuptake-inhibiting properties. However, it has pronounced D2-, 5-HT2-, and H1-blocking potential and high affinity to sigma receptors (sigma-1 and sigma-2). In early controlled trials, anxiolytic effects were revealed. However, those studies were performed before the concept of generalized anxiety disorder (GAD) was established. Because of the interesting receptor-binding profile and promising results of the early clinical trials, the authors performed a state-of-the-art placebo-controlled trial using alprazolam as an active control. Three hundred seven outpatients with GAD were included. After a 7-day single-blind placebo washout, patients were randomly assigned to receive either opipramol (final dose, 200 mg/day), alprazolam (2 mg/day), or placebo and were treated for 28 days. The efficacy of both active compounds was higher than the effects with placebo treatment. There were statistically significant differences (p< 0.05, according to the analysis of co-variance) in the main outcome criterion (baseline-adjusted final means of an intent-to-treat analysis of the total scores on the Hamilton Rating Scale for Anxiety) and in secondary efficacy parameters, with global improvement of 47% for placebo and significantly more for opipramol (63%) and alprazolam (64%). Regarding safety and tolerability, no substantial differences in the number of adverse events observed between treatment groups were obvious. Sedation seemed more pronounced with alprazolam treatment than with opipramol or placebo. In this trial, it was demonstrated for the first time that opipramol, a strong but nonselective sigma site ligand, possesses anxiolytic efficacy superior to placebo in the treatment of GAD.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The long-term use of the serotonin-releaser and uptake-inhibitor 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") has been associated with memory impairments and increased liability to depressive mood and anxiety attacks. It is unclear, however, whether these psychologic deviations are reflected in alterations of the underlying neurophysiologic substrate. The authors compared mood and regional cerebral blood flow (rCBF) profiles between regular polytoxic Ecstasy users and Ecstasy-naïve controls. Brain activity as indexed by rCBF was measured during cognitive activation by an attentional task using positron emission tomography and [H215O]. Mood was assessed by means of the Hamilton Rating Scale for Depression (HAM-D) and the EWL Mood Rating Scale. Statistical parametric mapping revealed that brain activity did not differ between the two groups. Both groups also performed equally on the cognitive task requiring sustained attention. However, significantly higher levels of depressiveness as determined by the HAM-D and EWL scales were found in Ecstasy-using subjects. These data indicate that, despite differences in mood, polytoxic Ecstasy users do not differ from Ecstasy-naïve controls in terms of local brain activity. Heightened depressiveness in the Ecstasy group was consistent with results from previous studies and could be related to serotonergic hypofunction resulting from repeated MDMA consumption. However, this study cannot exclude the possibility that the observed differences are preexisting rather than a result of Ecstasy use.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Naltrexone, an opiate antagonist medication, has been reported to be efficacious in the treatment of alcohol dependence when added to psychosocial treatments. Although the within-treatment efficacy of naltrexone has received primary attention, there has been little published on the outcome of individuals once the medication is discontinued. Animal studies have led to concern regarding a quick rebound to heavy drinking. This report extends the data previously reported by evaluating the outcome in alcoholic subjects during the 14 weeks after a 12-week treatment with naltrexone or placebo in conjunction with cognitive behavioral therapy. Of the 131 subjects evaluated during the treatment phase, 124 (95%) had up to 14 weeks of posttreatment drinking data available for analysis. Measures of craving and blood markers of heavy drinking were also evaluated.By the end of treatment, naltrexone demonstrated significantly greater efficacy than placebo. However, once the medication was discontinued, there was a gradual increase in relapse rates, heavy drinking days, and drinks per drinking day, and fewer days of abstinence were reported. By the end of the 14-week follow-up period, although naltrexone-treated subjects were, on average, still doing better than control subjects, the effectiveness of naltrexone was no longer statistically significant. There was no evidence that naltrexone subjects had an immediate return to heavy alcohol use as suggested in animals. These data suggest that, for a number of alcoholic subjects, continued treatment with naltrexone, or perhaps psychosocial intervention, for longer than 3 months is indicated. Future research should identify which alcohol-dependent individuals may need prolonged treatment to improve treatment success in the long term.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Although methadone maintenance is designed to stabilize opioid-dependent patients, some experience significant withdrawal in the latter part of the 24-hour interdosing interval. This study was designed to determine the mood changes that maybe associated with such withdrawal. Eighteen methadone patients, nine of whom experienced significant withdrawal, were tested over a single interdosing interval. During this time, 13 blood samples were collected to measure plasma racemic methadone concentrations, and the Profile of Mood States (POMS) was administered on 11 of these occasions. The POMS was also administered on 11 occasions over 24 hours to 10 drug-free healthy controls. In comparison with controls, methadone patients showed increased anger, depression, tension, confusion, and fatigue, as well as decreased vigor. For all scales, maximal differences from controls occurred at times of trough methadone concentration and minimal differences around the time of peak concentration. Changes in mood over the interdosing interval were more exaggerated in the nine patients who experienced significant withdrawal compared with those who did not. The composite Total Mood Disturbance (TMD) scores were calculated for each subject at each time point. The sigmoid Emaxmodel was used to relate plasma concentrations to these data and to calculate the slope factor (N). This model could be fitted for 14 of the 18 patients with a mean ± SEM slope factor of 2.2 ± 0.5. TMD score was also shown to be inversely related to the rate of decline in methadone concentration from peak to trough. These results show that significant mood changes occur in response to changes in methadone concentration, and these are more pronounced in those who experience withdrawal. The concentration-effect relationships suggest that relatively small changes in plasma concentration will result in significant mood change. Differences in the degree of mood change between those who do and do not experience significant withdrawal may be explained by variation in the rate of decline in plasma concentration from peak to trough.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The purpose of the study was to evaluate the effect of the classic antipsychotic haloperidol plus extract of ginkgo biloba (EGb) on treatment-resistant chronic schizophrenia and on blood superoxide dismutase (SOD) levels. Eighty-two patients with chronic refractory schizophrenia were studied. Forty-three patients were treated with haloperidol plus extract of ginkgo biloba (group 1), and 39 received haloperidol plus placebo (group 2). SOD levels of these patients were measured before and after treatment and were compared with SOD levels of 30 healthy volunteers. Therapeutic efficiency was equated with a change in clinical rating scores assessed by standardized measurement tools that included the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms (SANS) over this period. Patients in group 1 improved significantly as demonstrated by scores from these two assessment instruments; those in group 2 improved significantly only as shown by scores on SANS. SOD levels before treatment in all patients were significantly higher than those in healthy controls; after treatment, the SOD level decreased significantly in group 1 but not in group 2. These results suggest that EGb may enhance the efficiency of the classic antipsychotic haloperidol in patients with schizophrenia, especially on their positive symptoms, and that EGb may work through an antioxidant effect that is involved in the therapeutic mechanism in patients with chronic refractory schizophrenia.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Quetiapine fumarate ('Seroquel') is a newly introduced atypical antipsychotic with demonstrated efficacy in the treatment of positive and negative symptoms of schizophrenia. It is extensively metabolized, predominantly by cytochrome P450 3A4. Therefore, concurrent administration of drugs that induce or inhibit this enzyme may affect quetiapine pharmacokinetics. This study demonstrated that the potent cytochrome P450 enzyme-inducer phenytoin did indeed have a marked effect on the metabolism of quetiapine, resulting in a 5-fold increase in clearance when administered concomitantly to patients with DSM-IV-diagnosed schizophrenia, schizoaffective disorder, or bipolar disorder. These results indicate that dosage adjustment of quetiapine may be necessary when the two drugs are given concurrently and that caution may be required when administering other drugs that inhibit or induce cytochromes, particularly P450 3A4.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

This study was conducted to evaluate the effect of bupropion sustained-release (SR) on smoking cessation in patients with chronic posttraumatic stress disorder (PTSD). Fifteen veterans with chronic PTSD who desired to stop smoking enrolled in a 12-week double-blind evaluation of bupropion SR and placebo. Patients were randomly assigned in a 2:1 ratio to receive either bupropion SR or placebo. Bupropion SR was initiated at 150 mg daily for 3 or 4 days and increased to a final dose of 150 mg twice daily (300 mg daily total). Ten patients received bupropion SR and five received placebo. Nine of the patients who received bupropion SR were already being treated with at least one other psychotropic medication. One of the ten patients did not complete the study because of medication side effects. Eighty percent of patients receiving bupropion SR successfully stopped smoking by the end of week 2, and 6 (60%) of these 10 maintained smoking cessation at the study endpoint (week 12). At the 6-month follow-up, 40% of the patients (4 of 10) who received bupropion SR maintained smoking cessation. One (20%) of the five patients who received placebo stopped smoking and maintained smoking cessation at the 6-month follow-up. Bupropion SR was generally well-tolerated in combination with other psychotropic medications. Bupropion SR may be effective in helping patients who desire to quit smoking and who also have a concomitant anxiety disorder, such as PTSD.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Many antidepressants are known to cause adverse sexual effects. Bupropion is an antidepressant with fewer reported adverse sexual effects. Studies of sexual side effects are often confounded by psychiatric and medical conditions affecting sexual function. In this study, the effects of bupropion on subjective and objective sexual functioning were measured in healthy men. Thirteen men without psychiatric or medical illness completed a 2-week, placebo-controlled, double-blind, crossover trial of bupropion sustained-release 300 mg/day. Subjects had a 1-week washout period between trials. Sexual function was measured using a validated, self-administered questionnaire and the RigiScan, an instrument measuring nocturnal penile tumescence and rigidity. No differences were found in self-reported sexual function, number of erections, total erection time, or penile rigidity in subjects taking bupropion compared with those taking placebo or baseline. These findings support that bupropion does not have subjective adverse sexual side effects and does not affect nocturnal erections in healthy men.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

More than 50% of patients who seek psychiatric care for panic disorder have previously received prescriptions for a benzodiazepine (BZ). Research on the treatment of generalized anxiety suggests that a history of BZ exposure might decrease the efficacy and tolerability of treatment with a serotonergic anxiolytic. This study examines the effect of prior BZ treatment on the efficacy and tolerability of sertraline treatment for panic disorder. Data were pooled (N = 705) from four double-blind, placebo-controlled studies of the efficacy of sertraline for the treatment of panic. Two of the studies were 12-week fixed-dose studies with starting doses of 50 mg, whereas 2 were flexible-dose studies of 10-week duration with starting doses of 25 mg. The effect of study treatment on the frequency of panic attacks, Clinical Global Impressions (CGI) Improvement Scale, and tolerability was examined for patients with or without prior BZ treatment. The efficacy of sertraline was not affected by prior treatment with BZs. The mean endpoint reduction in panic attack frequency was identical in patients with or without prior BZ use: 79% vs. 80% (not significant). A history of good versus poor response to prior BZ treatment did not significantly influence CGI responder rates for sertraline-treated patients (67% vs. 61%, respectively). Sertraline CGI responder rates were significantly greater than placebo response, which was 47% for the good-response prior-BZ subgroup (p= 0.007), and 36% for the poor-response BZ subgroup (p= 0.013). Placebo response was lower in patients with any prior BZ use by 10% on an intent-to-treat last-observation-carried-forward analysis (p= 0.106) and by 15% on a completer analysis (p= 0.045). Prior BZ use did not influence either rates of adverse events or discontinuation rates within the first 3 weeks in patients treated with either sertraline or placebo. Sertraline is both well-tolerated and has significant efficacy in patients with panic disorder, including the subset of patients with panic disorder who have previously been treated with BZs.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID