Plasma levels and effects of nortriptyline in geriatric depressed patients

Kumar, Vinod; Smith, R. C.; Reed, Kenneth L.; Leelavathi, D.E.

doi:10.1111/j.1600-0447.1987.tb02746.x

Cited by 20 publications

(9 citation statements)

References 25 publications

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“…However, the resulting kinetic interactions are generally not compensated for by lowering of the antidepressant dose. The higher mean plasma concentration of NT achieved in the combination groups (Table 1) Clearance (I h-1) 25 50 Clearance (I h-1) [41,45] but others did not [46][47][48][49][50]. Most of them included few old patients or used historical controls of young subjects.…”

Section: Discussionmentioning

confidence: 99%

“…The height of the surface corresponds to the probability. (24,50) 35 (27,46) > 60 years (10-94) CL0 (1 h-') 39 (23,54) 44 (25,66) women < 65 kg (17-124) men < 75 kg CL0 (1 h-') 31 (25,50) 46 (31,66) women > 65 kg Clearance (I h-1) Figure 3 Cumulative distribution of oral NT-clearance in the absence of interacting drugs in women (A) and men (B), and during concomitant therapy with CYP2D6-inhibiting drugs in women (C) and men (D).…”

Section: Smoothed Distributions Including Covariatesmentioning

confidence: 99%

“…On dividing the whole discrete distribution into two subgroups according to age and weight, it is apparent, that the capacity to eliminate NT was slightly decreased above 60 years of age and that body weight was not correlated with clearance (Table 3). (27,46) > 60 years (10-94) CL0 (1 h-') 39 (23,54) 44 (25,66) women < 65 kg (17-124) men < 75 kg CL0 (1 h-') 31 (25,50) 46 (31,66) women > 65 kg…”

Section: Smoothed Distributions Including Covariatesmentioning

confidence: 99%

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Population pharmacokinetics of nortriptyline during monotherapy and during concomitant treatment with drugs that inhibit CYP2D6‐an evaluation with the nonparametric maximum likelihood method.

Jerling

Merlé

Mentré

et al. 1994

Brit J Clinical Pharma

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Section: Discussionmentioning

confidence: 99%

Section: Smoothed Distributions Including Covariatesmentioning

confidence: 99%

Section: Smoothed Distributions Including Covariatesmentioning

confidence: 99%

See 1 more Smart Citation

Population pharmacokinetics of nortriptyline during monotherapy and during concomitant treatment with drugs that inhibit CYP2D6‐an evaluation with the nonparametric maximum likelihood method.

Jerling

Merlé

Mentré

et al. 1994

Brit J Clinical Pharma

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“…Thayssen et al (1981) examined the cardiovascular effects of 6 weeks of nortriptyline treatment Clin. Kumar et al (1987) studied 13 geriatric depressed patients (60 to 78 years) with no physical ailments and compared them with 4 younger patients, all receiving oral nortriptyline 150 mg! 24 (2) 1993 in 10 elderly hospitalised patients (60 to 84 years, mean 70 years).…”

Section: Nortriptylinementioning

confidence: 99%

Clinical Pharmacokinetics of Antidepressants in the Elderly

Moltke

Greenblatt

Shader

1993

Clinical Pharmacokinetics

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The prevalence of depression in the elderly suggests that a substantial number of older patients will be treated with an antidepressant medication such as one of the tricyclics, trazodone, fluoxetine or lithium. The physiological changes that accompany aging raise the possibilities of altered pharmacokinetics, patterns of efficacy and adverse effect profiles. The literature addressing the subject of antidepressant use in the elderly has not provided a clear, consistent picture of how these drugs behave in this population in comparison with younger patients. Particularly in the case of the tricyclic antidepressants (TCAs), a large degree of interindividual variation in drug clearance (CL) confounds attempts to find differences attributable to age per se. Study design, however, is also a problem in that very few investigators include a young control group, choosing instead to compare their data with previously reported outcomes. Designations of statistical significance and positive correlation also differ among investigators, and the clinical significance of any finding is not always addressed. The available data suggest that imipramine CL is reduced in the elderly and that amitriptyline CL may be reduced. Desipramine CL does not appear to be affected by age, although decreased renal function in the elderly may lead to accumulation of the hydroxylated metabolite, the clinical importance of which is not known. Nortriptyline is the most thoroughly studied TCA in the elderly. CL seems decisively lower only in elderly patients with concurrent medical illness. The hydroxylated metabolite probably accumulates with diminishing renal function. Not enough data are available on doxepin to make a conclusion. Trazodone CL is diminished somewhat in elderly men. Lithium CL appears to diminish with the declining renal function associated with aging. Fluoxetine data are sparse. Available data do not show any decrease in CL of the parent drug; more information is needed on the metabolite norfluoxetine. Although knowledge of CL changes with aging can help the clinician more accurately achieve the desired steady-state concentration of a drug during long term therapy, much work is still needed to evaluate the relationships among drug concentrations at steady-state, efficacy and adverse effects in the elderly.

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“…If they become elevated, decreasing the dose or withdrawal of the drug should result in return to normallevels. [154] Despite these potential shortcomings in the use of tacrine, research efforts are continuing because of the observations that cognitive, memory and functional improvements have correlated with plasma concentrations oftacrine [141 ,142,155] and with an increase in CSF acetylcholinesterase.l l561 Also, none of the other compounds tested have been successful in improving cognitive function; these include precursors of acetylcholine such as lecithin and phosphatidylcholine, [157] muscarinic agonists (e.g. pilocarpine, arecoline), [158,159] ergoloid mesylates, alaproclate, zimeldine and levodopa.l160-165] Rational pharmacotherapy is dependent on more research on the possible aetiologies of AD.…”

Section: Tacrinementioning

confidence: 99%

Recent Advances in Geriatric Psychopharmacology

et al. 1995

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Psychopharmacotherapy of the elderly must take into account the effects of age-related changes in the structure and function of the brain and various organs. In general, older people are more sensitive than young people to both the therapeutic and toxic effects of psychotropic medications, necessitating lower doses and longer dosage intervals. This holds true for the treatment of 5 major types of psychiatric illness (depression, bipolar disorder, anxiety, psychotic disorders and dementia). The tricyclic antidepressants, although efficacious, inexpensive, and backed by 30 years of experience, are less well tolerated by the elderly than are newer antidepressants such as the selective serotonin uptake inhibitors. Problems with monoamine oxidase (MAO) inhibitors, including orthostatic hypotension and restrictions in diet and other medication use, have been overcome by the advent of reversible selective inhibitors of MAO-A, but the efficacy of these in the elderly has yet to be proven in clinical trials. Lithium remains the mainstay for the treatment of bipolar disorder. However, careful dosing and monitoring of plasma lithium concentrations are required in the elderly due to changes in pharmacokinetics and pharmacodynamics which make older patients very sensitive to the toxic effects of this medication. Similarly, age-related changes in the pharmacokinetics and pharmacodynamics of the benzodiazepines, the most frequently prescribed medications for anxiety in the elderly, result in recommendations for lower doses and preferential use of those agents metabolised by conjugation (e.g. oxazepam). Buspirone, a partial serotonin 5-HT1A-agonist which is better tolerated than benzodiazepines in the elderly, may be used as an alternative. The elderly are extremely sensitive to extrapyramidal adverse effects which the typical antipsychotics (neuroleptics) exhibit to varying extents. The selection of a suitable agent for the treatment of a psychotic disorder should be based upon the adverse effect profile of the drug and the specific symptoms and situation of the patient. The newer atypical antipsychotics, clozapine and risperidone, have yet to be well-studied in the elderly. Dementia, exemplified by Alzheimer's disease, is almost exclusively an illness of the elderly. Only one medication, tacrine, has been approved for its treatment, based on extensive basic research and positive results of several clinical trials. Its long-term benefits have yet to be determined and it has several adverse effects, including a tendency to increase liver enzymes to the extent that the medication has to be discontinued.(ABSTRACT TRUNCATED AT 400 WORDS)

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Plasma levels and effects of nortriptyline in geriatric depressed patients

Cited by 20 publications

References 25 publications

Population pharmacokinetics of nortriptyline during monotherapy and during concomitant treatment with drugs that inhibit CYP2D6‐an evaluation with the nonparametric maximum likelihood method.

Population pharmacokinetics of nortriptyline during monotherapy and during concomitant treatment with drugs that inhibit CYP2D6‐an evaluation with the nonparametric maximum likelihood method.

Clinical Pharmacokinetics of Antidepressants in the Elderly

Recent Advances in Geriatric Psychopharmacology

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