摘要:

The worldwide scope of depressive illness and lack of fully effective pharmacotherapy mandates significant improvements in treatment paradigms. Current antidepressant medications remain limited by poor efficacy, slow onset of action, and untoward side effects. While the introduction of serotoninspecific reuptake inhibitors (SSRIs) offered significant improvements in tolerability, no improvements in efficacy or speed of onset have been made relative to the traditional and poorly tolerated tricyclic antidepressants (TCA). The dominant efforts toward improving antidepressant medications are guided by cumulative evidence from neurochemical and clinical studies supporting the therapeutic potential of enhancing monoamine function in depression. A number of novel antidepressant drugs, including mirtazapine, milnacipran, venlafaxine, and duloxetine have been developed based on their interaction with both 5-HT and NE. Current clinical evidence suggests that these new agents may offer improved efficacy and/or faster onset of action compared with SSRIs and an improved side effect profile compared with TCAs. Potential neurobiological substrates mediating the enhanced antidepressant activity of dual reuptake inhibitors are discussed.

ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Clozapine (CLZ) dose-related adverse effects may be more common in children than adults, perhaps reflecting developmental pharmacokinetic (PK) differences. However, no pediatric CLZ PK data are available. Accordingly, we studied CLZ and its metabolites, norclozapine (NOR), and clozapine-N-oxide (NOX) in six youth, ages 9–16 years, with childhood onset schizophrenia (COS). At the time of the PK study, mean CLZ dose was 200 mg (3.4 mg/kg). Serum was collected during week 6 on CLZ before and 0.5–8 h after a morning dose. Serum concentrations were assayed by liquid chromatography/UV-detection. Mean concentration, area-under-the-curve (AUC), and clearance were calculated. CLZ clearance averaged 1.7 L/kg-h. NOR concentrations (410) exceeded CLZ (289) and NOX (63 ng/ml) and AUC0–8hof NOR (3,356) > CLZ (2,359) > NOX (559 ng/ml-h) [53, 38, and 9% of total analytes, respectively]. In adults, NOR serum concentrations on average are 10–25% < CLZ, differing significantly from our sample. Dose normalized concentrations of CLZ (mg/kg-d) did not vary with age and were similar to reported adult values. Clinical improvement seen in 5/6 patients correlated with serum CLZ concentrations. In addition, clinical response and total number of side effects correlated with NOR concentrations. NOR (a neuropharmacologically active metabolite) and free CLZ may contribute to the effectiveness and adverse effects in youth.

ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Lithium augmentation, the most studied augmentation strategy for depression, has not been evaluated in patients with a history of non-response to multiple antidepressants. The objective of this study was to assess the efficacy of lithium augmentation for patients with a history of treatment resistant depression who also failed a prospective trial of nortriptyline. We enrolled 92 subjects with treatment resistant depression. Treatment resistance was defined by at least one, but no more than five, adequate trials of antidepressants during the current episode. Subjects were treated with nortriptyline (NT) for 6 weeks. Those subjects who tolerated NT for 6 weeks and whose depression did not respond (n=35) were randomized to receive either lithium (n=18) or placebo (N=17) augmentation of nortriptyline for an additional 6 weeks. Response was defined as an equal to or greater than 50% decrease in HAM-D-17 scores. After 6 weeks of double-blind augmentation, 12.5 % of subjects responded to lithium and 20.0% to placebo. Our results revealed no significant difference between lithium and placebo augmentation. While lithium augmentation seems to be useful in depression refractory to a single medication in some studies, our data suggest limited usefulness of this option for patients refractory to multiple treatments. More definitive data await the outcome of the NIMH Sequential Treatment Alternatives to Relieve Depression (STAR*D) study.

ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

DHEA is marketed and readily available as a daily nutritional supplement to counteract the effects of aging. The effect of DHEA administration on 24-hour plasma cortisol profiles has not been investigated. In this single-blind placebo-controlled crossover study, the effect of DHEA administration on cortisol concentrations was evaluated in healthy older women and men. Once each morning, subjects took either placebo (Days 1 to 7, and 23 to 29) or oral DHEA 200 mg (Days 8 to 22: doses 1 to 15). Twenty-four hour DHEA and cortisol concentrations were measured on Day 1 (placebo), Day 8 (DHEA dose 1), Day 15 (DHEA dose 8), Day 22 (DHEA dose 15), and Day 29 (placebo washout dose 7). DHEA administration resulted in a decrease in plasma cortisol concentrations (mean, peak, and/or AUC) in healthy older women and men. The cortisol-lowering effect of DHEA was more pronounced in women than in men in our study; pairwise differences in concentrations between days showed that relative to Day 1, cortisol was lower on Days 15, 22, and 29 in women (p = 0.0001) and on Day 15 in men (p = 0.002). The mechanism by which DHEA lowers plasma cortisol concentrations merits further investigation.

ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID