ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Because depression with atypical features is poorly responsive to imipramine, treatment trials including a tricyclic antidepressant arm should assess depressive subtype.Sotsky and Simmens had previously reanalyzed data from the National Institute of Mental Health Treatment of Depression Collaborative Research Program (TDCRP) providing independent confirmation that imipramine is ineffective for patients with atypical features. The TDCRP was a 16-week study in which 239 outpatients with major depression were randomly assigned to cognitive behavior therapy (CBT), interpersonal psychotherapy (IPT), imipraminecase management (IMI-CM), or pill placebo-case management (Pbo-CM). We used Sotsky and Simmens' algorithm to investigate the effect of diagnostic subtype on all four treatments. Hierarchical multiple regression analyses demonstrated IMI-CM benefit relative to Pbo-CM in patients without but not in those with atypical features. These analyses did not demonstrate differential psychotherapy efficacy between depressive subtypes. In conclusion, subsequent analyses of the TDCRP study demonstrated the need to identify the subgroup of depressed patients who have atypical features. Failure to identify this subtype underestimates imipramine's benefit in the appropriately treated subgroup. Comparisons of other treatments with imipramine may be misleading if they do not account for diagnostic subtype. (J Clin Psychopharmacol 1998;18:429-434)

ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

As many as 45% of patients with major depressive episode also meet DSM-IV criteria for bipolar II (BP II) disorder. Although some clinicians advocate using a mood stabilizer in treating BP II depression, antidepressant monotherapy has been less well studied in this disorder. As part of a prospective, placebo-controlled, relapse-prevention study in 839 patients, the efficacy and safety of short- and long-term fluoxetine treatment in patients with BP II major depression compared with patients with unipolar (UP) major depression was retrospectively examined. Eighty-nine BP II patients (mean age, 41 +/- 11 years) were compared with 89 age- and gender-matched UP patients and with 661 unmatched UP patients (mean age, 39 +/- 11 years). All received short-term fluoxetine therapy at 20 mg daily for up to 12 weeks. Complete remission was defined as a final Hamilton Rating Scale for Depression score <or=to 7 by week 9 that was then maintained for 3 additional weeks. Remitted patients were then randomly assigned to receive double-blind treatment with one of the following: (1) fluoxetine 20 mg daily for 52 weeks; (2) fluoxetine for 38 weeks, then placebo for 14 weeks; (3) fluoxetine for 14 weeks, then placebo for 38 weeks; or (4) placebo for 52 weeks. Anti-depressant efficacy was similar in BP and UP patients during short-term therapy. Discontinuation for lack of efficacy was lower in BP II (5%) than in UP (12%) patients (p = not significant [NS]), whereas dropouts for adverse events were similar in BP II (11%) and UP (9%) patients. During long-term relapse-prevention therapy, relapse rates were similar in BP II and UP patients (p = NS). During short-term fluoxetine therapy, three BP II (3.8%) versus no matched UP (p = NS) and 0.3% unmatched UP (p = 0.01) patients had a "manic switch." During long-term fluoxetine therapy, one (2%) BP II and three (1%) unmatched UP patients (one taking placebo) had a manic switch (p = NS). In conclusion, fluoxetine may be a safe and effective antidepressant monotherapy for the short-term treatment of BP II depression with a relatively low manic switch rate. Fluoxetine may also be effective in relapse-prevention therapy in patients with BP II disorder. (J Clin Psychopharmacol 1998;18:435-440)

ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

This double-blind, controlled study was undertaken to investigate whether the addition of pindolol could improve the therapeutic response to fluvoxamine of depressed patients with psychotic features. After a 1-week placebo run-in period, 72 patients received fluvoxamine 300 mg/day in combination with placebo or pindolol 7.5 mg/day. At study completion, 28 (80%) of 35 patients treated with fluvoxamine plus placebo and 29 (80.5%) of 36 patients treated with fluvoxamine plus pindolol were categorized as responders (reduction of their score on the 21-item Hamilton Rating Scale for Depression to 8 or less and on the Dimension for the Delusional Experience Rating Scale to 0). In the third and fourth weeks, the response rates were significantly superior in the fluvoxamine plus pindolol group (p = 0.0001, p = 0.023, respectively). Treatment response seemed to be unrelated to the demographic and the clinical characteristics recorded.No significant difference was found comparing plasma levels of fluvoxamine between groups, thus excluding a pharmacokinetic interaction.Other than mild nausea and sedation in a few patients, treatments were well tolerated. No medically significant adverse events occurred. Depressed patients with psychotic features who were administered pindolol experienced a more rapid improvement during fluvoxamine treatment. Thus, the combination of fluvoxamine with pindolol may be a useful pharmacologic strategy in the treatment of this disorder. A rapid clinical response in such patients is of relevance in clinical practice as well as in economic fields, given the direct and indirect costs of depression. (J Clin Psychopharmacol 1998;18:441-446)

ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Several hypotheses regarding the physiopathology of major depression exist.Attention has been focused on cerebral monoaminergic systems, the dysfunction of which is thought to underlie various aspects of depressive symptomatology. There is extensive literature describing the involvement of serotonergic and dopaminergic systems in the mechanism of action of antidepressant drugs. However, a unitary analysis of the data in terms of interaction between different monoaminergic systems is still lacking. In this article, studies reporting the biochemical, behavioral, and clinical effects of tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), selective blockers of presynaptic dopamine (DA) receptors, and antagonists of serotonin-2 (5-hydroxytryptamine-2 [5-HT (2)]) receptors were reviewed. Analysis of the current literature indicates that long-term treatment with antidepressants causes adaptive changes of the serotonergic and dopaminergic systems. In particular, long-term administration of TCAs enhances the responsiveness of postsynaptic serotonin receptors to iontophoretically applied serotonin and potentiates the behavioral responses to both direct and indirect dopaminergic agonists. Repeated administration of SSRIs and MAOIs increases serotonergic transmission by desensitizing the inhibitory 5-HT1Asomatodendritic and terminal 5-HT1B/1Dautoreceptors. Selective blockers of DA autoreceptors exert their antidepressant effect by enhancing DA release. A similar mechanism of action could be hypothesized for 5-HT2receptor antagonists. There is general agreement that the clinical effect of antidepressant drugs, which becomes evident only after long-term treatment, is caused by their ability to induce adaptive changes of the monoaminergic systems. Increases in both serotonergic and dopaminergic function have been consistently found after long-term treatment with various classes of antidepressant drugs. Recent studies have focused on the functional interaction between the serotonergic and dopaminergic systems to explain the mechanism of the antidepressant action of SSRIs and 5-HT2antagonists. (J Clin Psychopharmacol 1998;18:447-454)

ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

In a randomized, prospective, multicenter study with an observation period of 2.5 years, the differential prophylactic efficacy of lithium versus carbamazepine was compared in 171 patients fulfilling DSM-IV criteria for bipolar disorder. Serum drug levels were 0.6 +/- 0.1 mmol/L for lithium and 6.1 +/- 1.3 [micro sign]g/mL for carbamazepine. Patients were subdivided into a classical subgroup (bipolar I patients without mood-incongruent delusions and without comorbidity, N = 67) and a nonclassical subgroup including all other patients (N = 104). Classical bipolar patients had a lower rehospitalization rate with lithium than with carbamazepine prophylaxis (p = 0.005). For the nonclassical group, a trend in favor of carbamazepine was found. In the lithium group, there was a positive association between hospitalization rate and number of nonclassical features (bipolar II/not otherwise specified, mood-incongruent delusions, comorbidity; p = 0.035). For carbamazepine, this association was negative (p = 0.033). Analyses including mixed states as an additional nonclassical feature confirmed the results. In conclusion, lithium seems to be superior to carbamazepine in treating classical bipolar cases. Patients with nonclassical features might profit more from prophylaxis with carbamazepine, which seems to have a broader spectrum of activity. (J Clin Psychopharmacol 1998;18:455-460)

ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Lithium (Li) and gabapentin are both exclusively eliminated by renal excretion.When used in combination, a competitive drug-drug interaction could possibly alter Li renal excretion with important clinical implications considering the rather narrow therapeutic index of Li. This study examined the single-dose pharmacokinetic profiles of Li in 13 patients receiving placebo and then steady-state gabapentin (mean daily dose: 3,646.15 mg). During both phases, a single 600-mg dose of Li was orally administered with serial Li levels obtained at time zero and at 0.25, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, and 72 hours. The pharmacokinetic parameters assessed were the following: area under the concentration time curve (AUC) for Li, maximal concentration of Li (Li Cmax), and time to reach peak Li concentration (Li Tmax). For patients receiving gabapentin, the mean Li AUC at 72 hours was 9.91 +/- 3.54 mmol x hr/mL and did not differ significantly from the mean Li AUC of 10.19 +/- 2.89 mmol x hr/mL for patients receiving placebo. The mean Li Cmaxwas 0.69 +/- 0.13 mmol/L for gabapentin patients and did not differ from the mean Li Cmaxof 0.72 +/- 0.15 mmol/L for placebo patients. The mean serum Li Tmaxwas 1.38 +/- 0.62 hours for gabapentin patients and did not differ significantly from the mean serum Li T (max) of 1.5 +/- 0.91 hours for placebo patients. These data indicate that gabapentin treatment at this high therapeutic dose does not cause clinically significant alterations in short-term Li pharmacokinetics in patients with normal renal function. These preliminary data warrant further controlled study in a larger, more heterogenous patient sample and a longer duration of assessment, but they do suggest that these two medications may be administered in combination for the management of bipolar disorder. (J Clin Psychopharmacol 1998;18:461-464)

ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

6 weeks at recommended dosage) received buspirone (20-30 mg/day) for 4 or 5 weeks in addition to their existing antidepressant. Of the 22 patients who had buspirone added to their selective serotonin reuptake inhibitor antidepressant regimen (fluoxetine, paroxetine, or citalopram), 59% (13/22) showed complete or partial remission of their depressive symptomatology. Similarly, 63% (5/8) of patients treated with buspirone in addition to clomipramine showed complete or partial remission. The mean score on the Clinical Global Impressions Scale fell by 64% (from 4.7 to 1.7; p < 0.0001) in treatment responders (complete and partial). No serious side effects were observed during combination therapy. Seventy-nine percent (11/14) of initial responders (both complete and partial) who remained on augmentation therapy for at least 4 months were symptom-free at follow-up. Buspirone augmentation may produce marked clinical improvement in depressed patients who are initially unresponsive to standard antidepressant therapy. (J Clin Psychopharmacol 1998;18:465-469)

ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The pharmacokinetic parameters of clozapine and its two main metabolites, N-desmethylclozapine (norclozapine, active metabolite) and clozapine N-oxide, were evaluated, after oral administration, in 19 patients with chronic schizophrenia. Plasma and red blood cell (RBC) drug concentrations were determined by high-performance liquid chromatography. Large interpatient variations in pharmacokinetic parameters of clozapine and its two metabolites were observed. Plasma clozapine concentration peaked, on average, at 2.3 hours. The mean volume of distribution and the total plasma clearance, uncorrected for bioavailability, were 6 L/kg and 38 L/hr, respectively. The terminal elimination half-lives averaged 7.6 hours for clozapine, 13 hours for norclozapine, and 7 hours for the N-oxide metabolite. The mean RBC/plasma concentration ratios were 23, 61, and 81% for clozapine, N-desmethylclozapine, and clozapine N-oxide, respectively. From RBC concentration data, the mean elimination half-lives were 7.6 hours for clozapine, 16 hours for N-desmethylclozapine, and 8 hours for the N-oxide metabolite. The average value for blood clearance of clozapine was 54.7 L/hr. Significant correlations were observed between dose and maximum plasma concentrations and between dose and area under the curve concentrations; these results suggested linear steady-state pharmacokinetics over the range of concentrations studied. (J Clin Psychopharmacol 1998;18:470-476)

ISSN:0271-0749    

出版商:OVID    

年代:1998

数据来源: OVID