ISSN:0271-0749    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The clinical efficacy of lithium augmentation in refractory depression is hypothesized to depend on the ability of lithium to enhance presynaptic 5-hydroxytryptamine (5-HT) function. Since fenfluramine promotes release and inhibits reuptake of presynaptic 5-HT, we assessed its efficacy in augmenting ongoing tricyclic antidepressant treatment of refractory depression. Fifteen patients with DSM-III major depression failed to respond to treatment with desipramine 2.5 mg/kg/day or more (plasma levels of at least 125 ng/ml) given for at least 4 weeks. Fenfluramine 40–120 mg/day was then added to the ongoing desipramine in a placebo substitution design. There was no statistically significant evidence of either transient or sustained clinical improvement during the 2 weeks of fenfluramine augmentation. One patient appeared to respond to the treatment, but one appeared to worsen. Fenfluramine more than doubled steady-state plasma levels of desipramine. These findings suggest that lithium's efficacy as an augmenting agent depends on properties that are not shared by fenfluramine. Fenfluramine cannot be recommended in the routine management of refractory depression.

ISSN:0271-0749    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Twenty-four patients with refractory affective disorders who were taking carbamazepine were followed in an open-label fashion for an average of 4 years. Carbamazepine, usually in combination with lithium and other previously ineffective medications, reduced the number and severity of manic and depressive episodes. An overall illness index of morbidity (duration x severity) decreased 72% in the first year and 66% in the second year of carbamazepine treatment. One-half of the patients (N = 11) who were followed for more than 2 years showed a pattern of continued improvement (stable); the other half showed loss of prophylaxis (escape). Those showing the escape pattern had a more rapidly deteriorating course of illness in the 4 years before the study than those showing the stable improvement. Clinical and mechanistic implications of these findings are discussed, including the phenomenon of contingent tolerance as a possible explanation for the emergence of loss of efficacy in a subgroup of patients.

ISSN:0271-0749    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Bupropion hydrochloride is a new monocyclic antidepressant. In humans, its disposition results in the formation of three major metabolites: the morpholinol metabolite, the erythroamino alcohol, and the threoamino alcohol metabolite. Bupropion's disposition was monitored following a single oral 200 mg dose in eight healthy volunteers and eight age- (44.5 ± 8.4 years) and weight- (77.4 ± 6.7 kg) matched volunteers with alcoholic liver disease. This latter group is of interest because the incidence of depression is more frequent in alcoholics than in the general population, and the liver is the major route of elimination for cyclic antidepressants. The mean elimination half-life of the morpholinol metabolite was significantly prolonged in subjects with alcoholic liver disease (32.2 ± 13.5 vs. 21.1 ± 4.9 hours (p< 0.05), while the differences in bupropion (17.3 ± 8.6 hours vs. 16.5 ± 10.4 hours for healthy subjects and subjects with alcoholic liver disease, respectively), erythroamino alcohol (26.1 ± 13.3 hours vs. 29.8 ± 6.9 hours for healthy subjects and subjects with alcoholic liver disease, respectively), and threoamino alcohol (25.5 ± 8.6 hours vs. 23.4 ± 10.7 hours for healthy subjects and subjects with alcoholic liver disease, respectively) were minimal. Mean area under the plasma concentration time curves for bupropion and metabolites were increased in subjects with alcoholic liver disease; however, clear differences between means of these small groups did not emerge, probably due to the increased variability of bupropion pharmacokinetics in these subjects. As a therapeutic agent for the treatment of depression in chronic alcoholics who may consume alcohol in combination with their antidepressant therapy, the lack of sedation with bupropion could be advantageous. However, like other cyclic antidepressants, bupropion undergoes a first-pass effect, and liver dysfunction may alter the kinetics and dose-response relationship in this population. Patients with alcoholic liver disease should initially be dosed cautiously with bupropion.

ISSN:0271-0749    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Plasma concentration ofE-10-hydroxynortriptyline is increased in the elderly and may be related to both renal clearance of hydroxynortriptyline and rate of liver hydroxylation of nortriptyline. In 25 ambulatory, depressed elderly outpatients treated with therapeutic doses of nortriptyline, relationships among plasma levels of nortriptyline andE-10-hydroxynortriptyline, and an estimate of creatinine clearance were examined. Plasma levels ofE-10-hydroxynortriptyline (corrected for varying dosage) were significantly correlated with age and inversely correlated (r= −0.50) with creatinine clearance but not with nortriptyline orZ-10-hydroxynortriptyline concentration.E-10-hydroxynortriptyline concentration was about 5 1/2 times that ofZ-10-hydroxynortriptyline. By best subsets multiple regression analyses, the ratio ofE-10-hydroxynortriptyline to nortriptyline level was best predicted by plasma nortriptyline concentration, creatinine clearance, and age, all of which accounted for 63% of the variance. These results corroborate and extend previous findings in elderly inpatients in whom creatinine clearance was measured directly. In addition, age had an effect onE-10-hydroxynortriptyline independently of creatinine clearance. SinceE-10-hydroxynortriptyline concentration has been related to both therapeutic efficacy and toxicity during nortriptyline treatment, it may be important to assess nortriptyline hydroxymetabolites in elderly patients and in those with renal insufficiency.

ISSN:0271-0749    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The efficacy of continuation therapy with tricyclic antidepressants has been established in a number of controlled trials. This study investigated the efficacy of continuation therapy with a relatively new antidepressant, amoxapine, using a double-blind controlled comparison with amitriptyline. Subjects met DSM-III criteria for major depressive disorder and were randomized to treatment with either amoxapine 400 mg (N = 47) or amitriptyline 300 mg (N = 45). The acute phase lasted up to 8 weeks. Responders were continued on the same drug at the same dose for a 16-week continuation phase. Some measures found more rapid onset for amitriptyline, which is inconsistent with findings from some prior studies. Amitriptyline was more effective in inducing full recovery. There was a trend for higher relapse rates on amoxapine, perhaps related to the fact that there were more partial responders entering continuation therapy from this group. Side effect rates were equivalent in the two drugs. However, physicians rated amoxapine's side effects as more frequently interfering with its therapeutic effect. These data suggest that amoxapine does not offer any clear advantage over amitriptyline for continuation therapy in patients who have major depressive disorder. Of potential clinical relevance is the finding that achieving full recovery in the acute phase may reduce the likelihood of relapse in the continuation phase, regardless of the type of antidepressant medication prescribed.

ISSN:0271-0749    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Apathy, indifference, loss of initiative, or disinhibition (without concurrent sedation or hypomania) were observed among five patients receiving the serotonin reuptake blocking antidepressants fluvoxamine or fluoxetine. These effects appeared to be dose related. They disappeared rapidly when the dose of fluvoxamine, which has a short half-life, was reduced. Fluoxetine, which has a long half-life, was more difficult to titrate. A possible relationship between mild drug-induced indifference and the therapeutic effects of serotonin reuptake blocking medication in anxiety disorders is discussed.

ISSN:0271-0749    

出版商:OVID    

年代:1990

数据来源: OVID

ISSN:0271-0749    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

There is conclusive evidence that nonsteroidal anti-inflammatory drugs can increase serum lithium levels, diminish renal lithium clearance, and possibly induce lithium toxicity. Such an interaction has occurred in patients with normal renal function. The effect on serum lithium levels varies greatly among different nonsteroidal anti-inflammatory drugs, indomethacin seeming most potent. On the other hand, there is no convincing evidence that sulindac and asprin affect serum lithium levels to a clinically significant degree. Ibuprofen and naproxen can significantly increase serum lithium levels, but there is marked interindividual variation. Patients receiving nonsteroidal anti-inflammatory drugs must have their serum lithium levels checked every 4–5 days until the extent of drug interaction is assessed. A reduction in lithium dosage may be needed in some cases.

ISSN:0271-0749    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

A potential pharmacokinetic interaction between lithium and alprazolam was studied in 10 normal subjects. Pharmacokinetic parameters were determined from the following regimens: single-dose alprazolam, multiple-dose lithium, and multiple-dose alprazolam with lithium. Steady-state alprazolam clearance during multiple dosing with lithium was not different from that with the single dose of alprazolam. Lithium renal clearance decreased when it was coadministered with alprazolam (31.2 vs. 22.4 ml/minute.p< 0.05). There was a small but significant increase in the steady-state area under the curve for lithium in the presence of alprazolam (10.3 vs. 11.1 mEq/hour/liter). The small increase in the serum lithium concentrations and decrease in lithium renal clearance was probably the result of lower urine flow rates (1.46 vs. 0.98 ml/minute,p< 0.05) with the combination of the drugs. This is supported by a weak but significant linear relationship between urine flow rates and lithium renal clearance (N= 57,r= 0.353,p= 0.007). The percent of daily lithium dose recovered at steady-state from the 24-hour urine collection decreased significantly from 93.6% to 78.2% in the presence of alprazolam. This suggests that alprazolam may decrease lithium absorption. The results of this study do not support a definitive interaction of lithium and alprazolam and there is little clinical significance to the small rise in serum lithium concentrations.

ISSN:0271-0749    

出版商:OVID    

年代:1990

数据来源: OVID