ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Fluoxetine is effective in treating obsessive-compulsive disorder (OCD). Nonetheless, a substantial number of patients do not respond or have only partial improvement. Data generated by a multicenter, placebo-controlled, fixed-dose trial of fluoxetine were reanalyzed to identify characteristics of responders. Multiple regression methods were used to evaluate the relationship between therapeutic response and baseline measures such as severity of symptoms, type of symptoms (obsessions, compulsions, depression), course of illness, previous treatment, age of onset, and other demographic factors (age, race, and sex). Fluoxetine was more effective than placebo on all outcome measures. A 60-mg dosage was associated with a greater drop in Yale-Brown Obsessive-Compulsive Scale total score and a greater drop in Compulsion items than a 20-mg dosage. Response rates and overall improvement were greatest for patients with a history of remissions, with no previous drug treatment or with only prior behavior therapy, with more severe OCD (especially with greater interference and distress from obsessions), or with either low or high Hamilton Rating Scale for Depression scores. This study did not detect any associations between response and current age, age of OCD onset, gender, and race. None of the demographic or clinical factors evaluated was found to be related to improvement in the placebo group. (J Clin Psychopharmacol 1998; 18:185-192)

ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Selective serotonin reuptake inhibitors may be associated with new adverse events after abrupt discontinuation.Hypothesizing that the long half-life of fluoxetine would be protective, this study analyzed the effects of abrupt fluoxetine discontinuation during a randomized, double-blind, placebo-controlled study of depression maintenance treatment. After 12 weeks of fluoxetine treatment (20 mg/day), 395 responders were abruptly randomized to placebo (N = 96) or to continued fluoxetine (N = 299). Patients were seen at weeks 1, 2, 4, and 6 after randomization. Reports of new or worsened adverse events were similar for both groups at each visit after randomization. Patient discontinuations related to adverse events were also similar in both groups. Mild, self-limited lightheadedness or dizziness occurred in a small percentage of patients who discontinued fluoxetine treatment but was of little clinical significance. No cluster of symptoms suggestive of a discontinuation syndrome was observed. Abrupt discontinuation of fluoxetine treatment was well tolerated and did not seem to be associated with significant clinical risk. Fluoxetine may offer a potential safety advantage over shorter-acting agents with respect to treatment interruption and/or discontinuation and may be a better choice for those patients who are likely to miss doses because of travel or forgetfulness. (J Clin Psychopharmacol 1998;18:193-197)

ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

0.05). The extent of inhibition of CYP2D6 and CYP1A2 by paroxetine and fluvoxamine, respectively, displayed a positive correlation with baseline enzyme activity (p < 0.05). In addition, a negative association was found between the plasma paroxetine concentration and the CYP2D6 activity after paroxetine treatment (r = -0.47, p < 0.05). These data indicate that paroxetine and fluvoxamine treatment with minimum clinically effective doses significantly inhibit CYP2D6 and CYP1A2, respectively. The extent of inhibition of CYP2D6 by paroxetine and of CYP1A2 by fluvoxamine is dependent in part on the baseline enzyme activity. The interindividual variability in CYP2D6 inhibition by paroxetine can also be explained by variability in plasma paroxetine concentration. Most patients treated with fluvoxamine (50-100 mg/day) will reach population minimums for CYP1A2 activity. These results have potential implications for interindividual variability in the risk for drug-drug interactions mediated by CYP2D6 and CYP1A2 as well as for the disposition of 17 beta-estradiol and environmental procarcinogens. (J Clin Psychopharmacol 1998;18:198-207)

ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

There is considerable evidence that adding selective serotonin reuptake inhibitor (SSRI) antidepressants to antipsychotic treatment improves negative symptoms of schizophrenia.This augmentation effect may be due to "nonspecific" antidepressant action or be specifically related to action on the serotonergic system. This study examined the serotonergic specificity of SSRI augmentation by comparing an SSRI antidepressant with a comparably effective antidepressant acting via the noradrenergic system. Consenting patients having chronic schizophrenia with prominent negative symptoms were studied. Either fluvoxamine or maprotiline was added to their regular antipsychotic treatment in a double-blind manner for 6 weeks. Patients were assessed using the Brief Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms, the Scale for the Assessment of Positive Symptoms, the Montgomery-Asberg Depression Rating Scale (MADRS), and the Neurological Rating Scale for Extrapyramidal Side Effects. Twenty-five patients completed the study. Negative symptoms improved significantly in the fluvoxamine group, but not in the maprotiline group. MADRS scores, which were low, did not change significantly in either group. Positive symptoms were not affected by either treatment. It is concluded that the mechanism by which fluvoxamine augmentation improves negative symptoms involves the serotonergic system and is distinct from its antidepressant action. (J Clin Psychopharmacol 1998;18:208-211)

ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Effects of venlafaxine, an antidepressant acting by selective serotonin and norepinephrine reuptake inhibition with a potency ratio of 5:1, were assessed in a standardized, actual driving test, a battery of psychomotor tests (Critical Flicker/Fusion Frequency, Critical Tracking, Divided Attention), and a 45-minute vigilance test (Mackworth Clock). Thirty-seven healthy volunteers, 22 of whom completed the study, received venlafaxine in fixed (37.5 mg twice a day) and incremental (37.5-75 mg twice a day) doses as well as mianserin (10-20 mg three times a day) and placebo according to a 4-period (15 days each), double-blind, crossover design. Testing occurred on days 1 and 7 and after dose increments, on days 8 and 15. Plasma concentrations of venlafaxine and its active metabolite were measured on test days for confirming compliance. Venlafaxine had no significant effect on the primary driving parameter (standard deviation of lateral position) and failed to impair psychomotor performance. Mianserin profoundly and consistently impaired driving and psychomotor performance. However, both drugs significantly impaired vigilance performance. Maximal effects occurred on day 1 with mianserin and similarly on day 7 with venlafaxine in both series. The increment in venlafaxine's dose on day 8 did not increase this effect. The drug's selectively impairing effect on vigilance is shared by other "serotonergic" anxiolytics and antidepressants, suggesting that interference with 5-HT transmission reduces arousal in particularly monotonous tasks or environments. This study concludes that venlafaxine does not generally affect driving ability and should be safe for use by patients who drive. (J Clin Psychopharmacol 1998;18:212-221)

ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

50% reduction of baseline Hamilton score) and the pretreatment values of biochemical variables was examined. Responders had a lower pretreatment platelet 5-HT (530 +/- 36 vs. 664 +/- 50 ng/109platelets, p < 0.03; N = 44 and 39, respectively). Patients with a platelet 5-HT concentration above 800 ng/109platelets had a lower response rate than those below this value (p < 0.003). This difference was maximal in the subgroup of patients treated with 5-HT uptake inhibitors (N = 49). In this subgroup, the response rates of patients with 5-HT concentrations below and above the cutoff point were, respectively, 70% and 17% (p < 0.001). A pretreatment platelet 5-HT value above 800 ng/109platelets had a predictive value for a negative response of 92%. These results suggest the presence of biochemical differences in the peripheral serotonergic system between melancholic and non-melancholic patients. The inverse relationship between the pretreatment platelet 5-HT content and clinical response may be useful in the investigation of the relationship between the 5-HT system and antidepressant response. (J Clin Psychopharmacol 1998;18:222-230)

ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Sibutramine is a serotonin and norepinephrine reuptake inhibitor that has shown efficacy as a weight loss and weight maintenance agent.Because of the abuse liability and physical dependence potential of amphetamines and related antiobesity agents, this study evaluated the abuse potential of sibutramine and compared it with that of dextroamphetamine and placebo in recreational stimulant users. Thirty-one male recreational stimulant users participated in this single-site, Latin square crossover study that compared the effects of two doses of sibutramine (20 mg and 30 mg) to dextroamphetamine (20 mg and 30 mg) and placebo, using a series of validated subjective scales or questionnaires. For scales measuring stimulation and euphoria, there was a greater mean response for dextroamphetamine 30 mg versus 20 mg, with both doses having a significantly greater stimulant and euphoric effect than placebo at the majority of time points (p < 0.05); responses for both doses of sibutramine were statistically indistinguishable from placebo at all time points. Responses to "street value" and "most enjoyed study session" questions confirmed that sibutramine lacks abuse potential; mean cash value estimates of street value were significantly greater for both dextroamphetamine doses than for placebo or either sibutramine doses (p < 0.05), and the rank order of session enjoyment placed both doses of sibutramine last. Together with the relatively late Tmaxof the active metabolites (3-4 hours), this short-term, single-dose study provides strong evidence that sibutramine does not have the potential for abuse that is characteristic of amphetamines and that it is indistinguishable from placebo in abuse potential. (J Clin Psychopharmacol 1998;18:231-236)

ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

0.05) in plasma lithium concentrations during any phase of the study. The results of this study demonstrated that OTC doses of naproxen sodium and acetaminophen did not increase plasma lithium concentrations in these volunteers when taken for short periods of time. (J Clin Psychopharmacol 1998;18:237-240)

ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Although recognized for their sedative properties, benzodiazepines are also known to impair sustained and selective attention.Flumazenil at low doses may act to antagonize benzodiazepine-induced effects. This study examined whether low doses of flumazenil would improve event-related brain potential (ERP) indicators of selective attention and induce feelings of activation and anxiety in healthy men. Data from 11 men (24-30 years) who received intravenous flumazenil (0.2 mg, plus 0.3 mg 30 minutes later) and placebo were analyzed according to a double-blind crossover design. ERPs were recorded while subjects performed an auditory selective attention task. Mismatch negativity (MMN), processing negativity (PN), and the P3 component were extracted from the ERP as markers of preattentive mismatch processing, selective attention, and stimulus processing within working memory, respectively. Counting accuracy and performance on a letter cancellation test were used as behavioral indicators of attention. Mood was assessed by an adjective checklist and the State-Trait Anxiety Inventory. Flumazenil significantly increased PN over frontocortical areas, indicating improved selective attention (p < 0.05). Increases in the P3 amplitude and MMN after drug treatment remained nonsignificant. Subjects felt more activated and extraverted after flumazenil treatment than after placebo (p < 0.05). Anxiety was not increased. The findings of this study confirm the concept that flumazenil administered at a low dose in humans exerts effects opposite to those of benzodiazepines. (J Clin Psychopharmacol 1998;18:241-247)

ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID