Persistent Impairment of Clomipramine Demethylation in Recently Detoxified Alcoholic Patients

Balant-Gorgia, A. E.; Gay, Martha D.; Gex‐Fabry, Marianne; Balant, L

doi:10.1097/00007691-199204000-00007

Cited by 9 publications

(2 citation statements)

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“…Seizures in these cases are typically generalized tonicclonic and may occur in flurries [56]. Individuals metabolize TCAs at different rates; the elderly and genetically slower metabolizers who typically have higher serum levels of these drugs are consequently at higher risk [57][58][59]. As with the parent compound, the metabolites of many TCAs can lower seizure threshold.…”

Section: Drug-induced Seizuresmentioning

confidence: 99%

Changing Presentation of Seizures with Aging: Clinical and Etiological Factors

DeToledo

1999

Gerontology

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Background: The historically higher incidence of seizures in children has changed, the elderly now have a higher incidence than any age-group, 2–3 times of that found in children. Classical teachings on etiologies, clinical presentation and progression of seizures are based on observations of a younger population and need to be revised in view of features unique to this age-group. The findings of two large VA cooperative studies show that even in sophisticated medical environments, up to 30% of patients 60 years and older with recurrent partial seizures go undiagnosed for more than 1 year of seizure onset. Objective: (a) To characterize the manifestations of auras, seizures and postictal states in the elderly and the relevance of various etiologies to these presentations. (b) To identify and discuss factors that contribute to the difficulties in the diagnosis of seizures in this population. Methods: A review of our experience in treating a large population of elderly patients in a university epilepsy center and a review of the literature relating to the problem. Conclusions: Seizures in the elderly are both overdiagnosed and underdiagnosed: either situation can have serious adverse consequences. Diversity of etiologies and atypical presentations make recognition of seizures difficult. Histories are frequently inadequate: complaints of multiple physical symptoms confuse the picture, unwillingness of elderly patients to admit to problems they believe are physiological in nature by the fear others may think they are ‘losing their mind’ and high staff turnover result in erratic identification of problems. The significant morbidity and mortality associated with poorly controlled seizures in this population are in large part preventable since excellent response to treatment can be achieved in more than 80% of individuals. The correct diagnosis of seizures is more likely if both physician and patients are familiar with the nuances of epilepsy in the elderly.

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Section: Drug-induced Seizuresmentioning

confidence: 99%

Changing Presentation of Seizures with Aging: Clinical and Etiological Factors

DeToledo

1999

Gerontology

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“…[52] Smoking decreases steady-state concentrations of clomipramine, but has less effect on the concentration of the metabolite because tobacco affects demethylation without affecting hydroxylation.l 53 ,51] Long term alcohol ingestion leads to decreased demethylation, but has little effect on hydroxylation. This effect occurs for up to 2 weeks post-cessation of alcohol intake, and occasionally has been reported to persist for months.l 50 , 54) There have not been any specific studies on the effects of hepatic and renal dysfunction on the clearance of clomipramine. There is recent evidence that Japanese individuals have larger interindividual variation in demethylation and hydroxylation of clomipramine.…”

Section: Clomipraminementioning

confidence: 99%

Pharmacokinetic Optimisation of Therapy with Newer Antidepressants

Goodnick

1994

Clinical Pharmacokinetics

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Since the early 1950s, when imipramine was first introduced, a whole series of antidepressants with differences in structures, neurochemical effects and pharmacokinetics have been developed. Structurally or functionally, they have been classified as tricyclic antidepressants (TCAs), tetracyclic antidepressants, monoamine oxidase inhibitors (MAOIs), or selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). In addition, there is a series of antidepressants with unique structures. Many of the newer TCAs appear to have shorter half-lives than the standard TCAs (e.g. imipramine), allowing for the possibility of a more rapid response, but requiring the drugs to be given in multiple daily doses, which may reduce patient compliance. The short time to peak plasma concentration (tmax) can also lead to rapid onset of adverse effects. The tetracyclic antidepressants have longer elimination half-lives (t1/2) than the TCAs, but there is only very minimal evidence for a relationship between drug concentrations in the blood and clinical response. The triazolopyridines, like the newer TCAs, show pharmacokinetic evidence for rapid onset of adverse effects and the need for multiple daily doses due to short tmax and t1/2. The newer MAOIs are a significant addition to therapy, as the rapid binding action of these medications increases their safety margin with regard to tyramine interactions. Further information in this area is required. In addition, moclobemide has pharmacokinetic features that are clinically beneficial (e.g. aging and renal dysfunction have little effect on the elimination of the drug), but also features that are not beneficial (e.g. nonlinear pharmacokinetics). Among the SSRIs, there are a range of t1/2 values for the parent drugs, from relatively short t1/2 values of less than 24 hours (paroxetine, fluvoxamine) to among the longest found (e.g. 2 days for fluoxetine). Only 2 of the agents (sertraline and citalopram) have linear pharmacokinetics, and 1 drug has nonlinear pharmacokinetics within the usual therapeutic range (fluvoxamine). Once a therapeutic blood concentration is established, linearity is helpful in avoiding the small dose changes and repeated rechecking of concentrations of medications that would be required for those agents with nonlinear pharmacokinetics. Sertraline stands out as having the best effects on behaviour among all antidepressants. However, fluoxetine and fluvoxamine are least likely to penetrate into breast milk. All 3 of the structurally unique newer antidepressants [amfebutamone (bupropion), viloxazine venlafaxine] have relatively short tmax values (1 to 2 hours), which may relate to the early onset of adverse effects. Amfebutamone has the benefits of linear pharmacokinetics with potential for defined therapeutic blood concentrations, lack of effect of liver enzymes on metabolism of the drug, and lack of significant effects of either aging or hepatic dysfunction on elimination of the drug. Thus, the antidepressants best suited for pharmacokinetic optimisation of ...

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