ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

5% from the baseline total Yale-Brown Obsessive-Compulsive Scale score, as measured in two successive assessments, and a worsening of global clinical condition as measured by the CGI scale. The main result of the study was borne out from the survival analysis. There were no significant differences in the cumulative proportion of patients from each group of treatment who did not worsen during the 102 days of observation. This preliminary result, which needs to be confirmed in larger samples, suggests that long-term maintenance therapy for obsessive-compulsive disorder might be provided with lower dosages of the antiobsessional drug, with clear advantages for tolerability and compliance. (J Clin Psychopharmacol 1997;17:4-10).

ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We sought to determine whether fluvoxamine and fluoxetine, two different antidepressants with in vitro selectivity for the serotonin uptake transporter also demonstrated similar selectivity in vivo.To accomplish this, we measured cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and homovanillic acid (HVA) before and after 6 weeks of treatment with these two drugs.Twenty-four subjects who had major depression according to DSM-III-R criteria gave written, informed consent for the collection of CSF during a double-blind comparative treatment trial of fluvoxamine (50-150 mg/day) and fluoxetine (20-80 mg/day). The symptoms of subjects were assessed clinically on a weekly basis throughout the treatment trial. CSF samples were obtained after a 7- to 14-day washout period before treatment and again at the end of treatment. CSF samples were analyzed for 5-HIAA, HVA, and MHPG using high-pressure liquid chromatography coupled to electrochemical detection.Fluvoxamine-and fluoxetine-treated patients did not differ in clinical outcome or in the CSF concentrations of monoamine metabolite levels before or after treatment. Therefore, the CSF data were pooled. Drug treatment, overall, was associated with significant decreases in 5-HIAA and MHPG and a trend toward a reduction in HVA levels. Levels of 5-HIAA, MHPG, and HVA were reduced by 57%, 48%, and 17%, respectively. In addition, the magnitude of the decreases in 5-HIAA and MHPG appeared to be correlated (r = 0.83) across the subjects, although a Spearman rank correlation indicated that outlying values had an undue effect on this relationship. These results suggest that treatment with selective serotonin reuptake inhibitors, which are selective for serotonin uptake in vitro, does not show a similarly selective effect on serotonin in vivo during treatment of patients. (J Clin Psychopharmacol 1997;17:11-14).

ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Cardiovascular adverse effects are amongst the most serious observed with antidepressant drugs and are often due to effects on cardiac conduction and refractoriness.However, such electrophysiologic effects may not be evident when using conventional electrocardiographic measures. Forty patients with major depressive disorder (according to DSM-III-R criteria) were enrolled in a 6-week double-blind parallel group study of fluoxetine (N = 20) or doxepin (N = 20). Cardiac conduction (QRS duration) and repolarization (corrected QT interval, QT (c)), were measured using signal-averaged electrocardiograms and 12-lead electrocardiogram at baseline and after 2, 4, and 6 weeks of treatment.Patients taking doxepin (mean daily dosage at 6 weeks 169 +/-42 mg) were similar to those taking fluoxetine (37 +/- 18 mg) for demographic variables and improvement in depression scores but volunteered more side effects (p = 0.011), especially dry mouth (p <0.001) and dizziness/lightheadedness (p = 0.005). After 6 weeks, doxepin increased heart rate (69 +/- 12 to 81 +/- 13 beats per minute; p = 0.0003) and prolonged QTc(from 417 +/- 36 to 439 +/- 28 msec; p <0.03); overall QRS duration was not prolonged but was correlated with serum doxepin concentrations (r = 0.78, p < 0.0001). Fluoxetine had no effect on QTc(428 +/- 24 msec at baseline vs. 430 +/- 24 msec at 6 weeks) or QRS duration (97 +/- 12 msec at baseline vs. 94 +/- 12 msec at 6 weeks). The standard 12-lead electrocardiogram showed no significant change in QRS or QTcfor either drug.Using a sensitive measure of electrocardiographic effects, doxepin prolongs repolarization and may slow cardiac conduction.Fluoxetine has no measurable electrocardiographic effects, which suggests an increased safety margin for cardiac adverse effects. The ability of the signal-averaged electrocardiogram to resolve small changes in the electrocardiogram is useful in the assessment of drugs with subtle electrophysiologic effects. (J Clin Psychopharmacol 1997;17:15-21).

ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Recently, the therapeutic benefit of lithium augmentation in old age has come into question.These data, in light of the documented high incidence of side effects after lithium use in elderly patients, resulted in the design of a prospective, placebo-controlled lithium augmentation withdrawal study in elderly patients with unipolar depression. Twelve eligible geriatric patients (10 women and 2 men; mean [+/- SD] age, 76.2 +/- 5.7 years) with DSM-III-R unipolar depression receiving adjunct lithium therapy were randomized to receive continued lithium augmentation or matching placebo (withdrawal rate 150 mg/day/wk). At each clinic visit, patients were assessed for depression (Montgomery-Asberg Depression Rating Scale and Geriatric Depression Rating Scale) and lithium-induced toxicities (a 21-item side-effect checklist, renal and thyroid biochemistry). Over the 2-year observation period, the placebo group reported a decrease in composite 21-item side-effect score and specific lithium toxicities (e.g., urinary urgency, hand tremor, and renal/thyroid abnormalities). Two patients in the lithium maintenance group had a recurrence of depression at 61 and 96 weeks, respectively, immediately after a stressful life event (cerebrovascular accident [CVA] or death of spouse), and two patients had a recurrence in the placebo group at 7 and 92 weeks, respectively, without any apparent changes in life stresses. No other prognostic risk factors for recurrence were identified. Depression that recurred in patients who were receiving placebo was relatively resistant to reinstitution of lithium augmentation therapy. In otherwise stable geriatric patients with unipolar depression, the documented benefits of reduced side effects should be weighed against the risk of recurrence and subsequent lithium resistance before withdrawal of lithium augmentation. (J Clin Psychopharmacol 1997;17:22-26).

ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The effect of nefazodone on the pharmacokinetics of a single dose of phenytoin was evaluated in 18 healthy male subjects.The subjects received a single oral dose of phenytoin, 300 mg, on day 1 of the study and the pharmacokinetic profile of the drug was determined. After a washout period followed by oral administration of nefazodone, 200 mg twice daily for 7 days, subjects received a single dose of phenytoin, 300 mg concomitantly with the morning dose of nefazodone on day 12, and the pharmacokinetic profile of phenytoin was determined again. Minimum plasma concentrations of nefazodone and its main metabolites indicated that steady state had been achieved for nefazodone when phenytoin and nefazodone were administered concomitantly. No significant differences were demonstrated between mean single-dose pharmacokinetic parameters of phenytoin when administered alone on day 1 and concomitantly with nefazodone on day 12. Assessment of adverse events, clinical laboratory parameters, electrocardiograms, vital signs, and physical examinations indicated that concomitant administration of nefazodone and phenytoin was safe and well tolerated. These data demonstrate that nefazodone does not affect the single-dose pharmacokinetics of phenytoin, but do not preclude the possibility of such an interaction when phenytoin is administered on a long-term basis. A clinically significant interaction between nefazodone and phenytoin through a pharmacokinetic mechanism is unlikely. (J Clin Psychopharmacol 1997;17:27-33).

ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We studied the process that triggers spontaneous recurrences of methamphetamine (MAP) psychosis, a phenomenon known as flashbacks, in 28 female patients who experienced flashbacks, by comparing them with 92 female nonflashbackers with a history of previous MAP psychosis.The study evaluated plasma monoamine neurotransmitter function in 12 of the 28 flashbackers and in 8 of the 92 nonflashbackers. Control data were obtained from 28 normal, healthy females composed of 13 MAP users and 15 nonusers, none of whom became psychotic. The 28 flashbackers had experienced significantly greater frequencies of threatening events and frightening paranoid-hallucinatory states during previous MAP abuse than the 92 nonflashbackers. The dominant triggering factor was a mild fear of other persons. Plasma norepinephrine (NE) levels were significantly higher in the 12 flashbackers during flashbacks than during periods of normalcy and were significantly higher than those in the 13 user and 15 nonuser control subjects. Plasma NE levels in the 12 flashbackers during periods of normalcy were significantly higher than those in the 13 user control subjects. The eight nonflashbackers had significantly higher NE levels than the 13 user control subjects. This suggests that an increase in peripheral noradrenergic activity may be related to the occurrence of flashbacks. The present study suggests that repeated MAP use with frightening experiences may induce sensitivity to psychosocial stressors. A mild fear of other persons may have actualized the encoded frightening memories associated with the frightening experiences via increased sensitivity to psychosocial stressors. Thus, flashbacks may have been caused through an increase in peripheral noradrenergic activity. (J Clin Psychopharmacol 1997;17:34-43).

ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The objective of this study was to compare the onset, rate of antidepressant (AD) response, and treatment outcome of depressed patients treated for 5 weeks with either the concomitant administration of the tricyclic AD desipramine (DMI) and lithium carbonate (Lithium) or with DMI alone.In this double-blind, placebo-controlled study, 31 nonpsychotic, mild to moderately depressed outpatients (DSM-III-R unipolar or bipolar major depression) were randomly assigned to 5 weeks of treatment with DMI plus Lithium (N = 16) or DMI plus placebo (N = 15). Drug dosages were adjusted to achieve therapeutic plasma levels. Clinical state was rated weekly by the Hamilton Rating Scale for Depression, the Clinical Global Impression Scale, a Visual Analogue Self-Report Scale, and an adverse-effect form. Twenty-seven patients completed the study, 12 in the DMI-Lithium group and 15 in the DMI-placebo group. Four patients dropped out due to adverse events, all from the DMI-Lithium group. Both groups responded well to treatment, without a significant difference between them in the rate of response or final outcome. Sixty-seven percent (10/15) of the patients taking DMI only and 75% (9/12) of the patients taking DMI plus Lithium met our response criteria. The combination of DMI and Lithium was associated with significantly more adverse effects than DMI alone. Concurrent treatment with Lithium did not demonstrate an enhancement of either DMI's efficacy or its onset of action in these patients, suggesting that this strategy may not confer any additional benefit compared with DMI alone in mild to moderately depressed patients who are not preselected for nonresponse to an AD during their current depressive episode. (J Clin Psychopharmacol 1997;17:44-48).

ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Preliminary results of a double-blind clozapine study in a population of chronic psychotic patients at a state psychiatric facility are reported. Thirty "treatment-refractory" schizophrenic patients given a diagnosis according to DSM-III-R criteria (mean age of 44 +/- 9.1 years and a duration of illness of 24.9 +/- 8.8 years) who received 300 mg or 600 mg of clozapine and randomized in a double-blind fashion were analyzed. Subjects were evaluated using the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression (CGI) Scale on a weekly basis for 16 weeks. Based on the changes in their CGI scores at week 16 of clozapine treatment, subjects were retrospectively categorized as "improvers" (N = 12) and "nonimprovers" (N = 18). The two groups were compared for changes in total BPRS and BPRS factor scores. In terms of total BPRS scores, we expected a difference between the two groups because they were categorized based on changes in their CGI scores. However, the total BPRS scores in improvers showed a significant decrease by week 6 of clozapine treatment. On analyzing the four BPRS factors, the improvers showed improvement in the thinking disturbance factor by week 1 that remained steady from week 7. On the hostility-suspiciousness factor, the improvers showed an improvement across time when compared with nonimprovers. The withdrawal-retardation factor showed improvement in both groups across time, whereas the anxiety-depression factor was least influenced by clozapine. These observations suggested that all BPRS symptom factors did not uniformly contribute to improvement in overall psychopathology, which was observed as a decrease in total BPRS scores. (J Clin Psychopharmacol 1997;17:49-53).

ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID