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PubMed1988

Dexamethasone suppression test status does not predict differential response to nortriptyline versus amitriptyline.

Thirty-five (35) inpatients with nonpsychotic major depression were randomly assigned to either amitriptyline or nortriptyline on a double-blind basis, following a 4- to 10-day placebo run-in period. Thirty-two patients completed at least 3 weeks of active medication. The 1.0-mg dexamethasone suppression test (DST) was performed before treatment. Twelve of 32 patients were DST nonsuppressors. Both medications were equally effective. Pretreatment DST status failed to predict overall response to both medications combined. DST status also did not predict differential medication response. These data argue, along with several other studies, that pretreatment DST status may be of limited value in selecting a particular tricyclic antidepressant compound.

Adult↗
PubMed1988

Valpromide increases the plasma concentrations of amitriptyline and its metabolite nortriptyline in depressive patients.

The effects of valpromide on amitriptyline (AMT) and nortriptyline (NT) plasma levels were examined in 20 depressed inpatients. They all were treated with AMT, 125 mg once daily, and 10 patients also received 600 mg of valpromide daily after 10 days on AMT. In the 10 patients receiving valpromide in addition to AMT, the mean AMT level increased from 70.5 +/- 35 to 105.5 +/- 49 ng/ml (p less than 0.0003) and the mean NT level from 61.0 +/- 34 to 100.5 +/- 65 ng/ml (p less than 0.01). This increase was not related to valpromide metabolite plasma levels, nor to the age of the patients. The addition of valpromide to a stable AMT regimen may result in an increase of antidepressant plasma level with clinical implications.

Adult↗
PubMed1986

Quantitative homogeneous enzyme immunoassays for amitriptyline, nortriptyline, imipramine, and desipramine.

We describe specific EMIT homogeneous enzyme immunoassays for amitriptyline, nortriptyline, imipramine, and desipramine in patients' serum samples. Before analysis, an easily performed extraction step involving the use of 500 microL of sample and a 1-mL disposable column eliminates cross-reacting polar metabolites. The range of the standard curve for the first three drugs is 25 to 250 micrograms/L, and for desipramine is 50 to 500 micrograms/L. Within-run and between-run CVs are less than 10% throughout the range of the assays. Results for patients' samples obtained by this method and by "high-performance" liquid chromatography compare well, showing a slope range of 0.94-1.04 and correlation coefficients ranging from 0.93 to 0.96, depending on the assay.

Amitriptyline↗
PubMed1978

[A double-blind nomifensine-nortriptyline trial in ambulatory patients conducted by psychiatrists in private practice: results and comments].

Nomifensine and nortriptyline were compared in a collaborative trial by psychiatrists in private practice. The trial impiled:--selection of ambulatory depressed patients--randomization in parallel groups (respectively 31 and 34 subjects)--administration in double-blind condition of 4 capsuels daily of either compound during 4 weeks--quotation of depressvie syndrom with Hamilton depression scale before treatment after 2 and 4 weeks. The analysis of results shows clear improvment of depression scores, equivalent in both groups (non significant difference and posterior rejection of an alternative hypothesis). Practical problems encountered in controlled trials in psychiatrist's outpatients are discussed.

Adolescent↗
PubMed1987

Prediction of individual dosage of nortriptyline in depressed elderly outpatients.

Individual daily dosages of nortriptyline (NT) can be predicted from administration of a 50-mg or 100-mg single test dose, with a determination of the plasma level 24 hours later. Because the 50-mg or 100-mg test dose used in previous studies may cause unmanageable acute side effects in elderly patients, a 25-mg NT test dose was used to establish a 24-hour plasma level in 18 physically healthy, moderately depressed, geriatric outpatients. Correlations between the 24-hour test dose plasma level and steady state levels were done for maintenance dosages of 50, 75, and 100 mg/day. A nomogram was made from the regression equations to predict the dosage required to achieve a steady state concentration within a 50 to 150 ng/ml range. The importance of the ability to predict NT dosage requirements in geriatric patients is indicated by findings that at daily NT doses of 50 and 100 mg, nearly one-half of subjects had steady state levels below or above 50 or 150 ng/ml, respectively.

Aged↗
PubMed1985

Nortriptyline pharmacokinetics and plasma levels: implications for clinical practice.

The pharmacokinetics of TCAs are reviewed with particular emphasis on nortriptyline, the agent most extensively studied. The clinical uses of TCA plasma level-response studies are discussed in relationship to rational dosage adjustment to increase response rates and avoid iatrogenic toxicity. Other important topics discussed include the issue of active metabolites, single-dose prediction studies, and special considerations in treating the elderly and the medically ill.

Age Factors↗
PubMed1984

Targeting therapeutic plasma levels of nortriptyline from test dose plasma concentrations.

Computer programs, based on first order pharmacokinetic equations, were developed to predict steady state plasma levels and required daily maintenance doses of nortriptyline from plasma concentrations 24 hours after a test dose. These predictions are compared to clinical findings for geriatric and nongeriatric patients with a variety of accompanying medical disorders and concurrent medications.

Computers↗
PubMed1981

Excretion of nortriptyline into saliva.

The relationship between serum and unstimulated and stimulated mixed saliva concentrations of nortriptyline was studied in seven healthy volunteers given a single oral dose of 50 mg. The concentrations were shown to be statistically significantly but variably correlated. The stimulation of saliva flow with Parafilm caused a significant increase in the mean +/- s.e.m. saliva pH from 6.93 +/- 0.15 to 7.34 +/- 0.09 (p less than 0.01). Simultaneously the mean saliva/mean concentration ratio decreased from 0.28 +/- 0.04 to 0.14 +/- 0.03 (p less than 0.001). This decrease correlated significantly with increases in flow rate and pH. Serum concentration could not, however, be reliably calculated from saliva concentrations because of the great variability in the saliva/serum ratios at any given pH.

Adult↗
PubMed1994

Metabolic and physiologic consequences of nortriptyline treatment in the elderly.

The challenge in the pharmacotherapy of affective disorders is shifting to maintenance treatment. Hence, there is a need for systematic data on the somatic effects of long-term medication use. Twenty-six depressed patients (age > 60 yr) treated with therapeutic concentrations of nortriptyline were evaluated after an average of 7 months for changes in lipoproteins and cardiovascular parameters. Twelve patients were tested for debrisoquine (P450 2D6) metabolic status and creatinine clearance at these same intervals. There was no significant change in cholesterol levels, but triglycerides and very-low-density lipoproteins (VLDL) were significantly increased. Heart rate was also elevated by a mean of 15 beats per minute, and there were modest but significant increases in cardiac conduction parameters. Creatinine clearance declined significantly (by 34%), and blood pressure was unchanged. Small decrements in P450 2D6 could be quantitated. Older patients treated with maintenance psychotropic medications should be evaluated at the regular intervals, particularly with regard to the age-related complications of multiple illness and medications.

Aged↗
PubMed1993

Nortriptyline in the hospitalized elderly: tolerance and side effect reduction.

This article describes two separate but related studies regarding the use of nortriptyline (NT) in the treatment of depressed elderly inpatients. The first study assesses medication tolerance to NT during the acute treatment of late-life depression. The second describes a placebo-controlled study of the effect of bethanechol in reducing antimuscarinic side effects of NT. Antidepressant pharmacotherapy was considered for 72 patients with late-life depression; 17 (24%) did not receive NT; 5 (7%) because of absolute or relative medical contraindications. Of the 55 patients who started on NT, 9 percent had side effects that necessitated medication discontinuation. A separate sample of 26 elderly depressed patients being treated with NT participated in a double-blind, placebo-controlled trial of bethanechol. Patients receiving bethanechol had reduced subjective complaints of anticholinergic side effects and showed improvement on an objective measure of salivary flow.

Aged↗
PubMed1996

Nortriptyline-fluphenazine vs. carbamazepine in the symptomatic treatment of diabetic neuropathy.

We compared the efficacy and tolerance of the combination of nortriptyline-fluphenazine (NF) vs. carbamazepine (CMZ) in the symptomatic therapy of patients with severe, distal, symmetrical, predominantly sensitive diabetic polyneuropathy (DPN). We followed a double blind, crossover, randomized and double placebo design. Sixteen patients with severe DPN participated in the study. Patients received either NF (1 tablet three times a day (tid)), for 2 weeks and 2 tablets tid for the next 2 weeks or CMZ 1/2 tablet tid for 2 weeks and 1 tablet tid for the next 2 weeks. After this, patients received placebos of both drugs (wash-out period), until symptoms returned to baseline levels (100%), then they were crossed over to receive the other comparing drug schedule. A visual analogue scale was used to evaluate the percent changes in pain and paresthesia. HbA1, fasting serum glucose, and safety tests were performed at 2- and 4-week intervals, respectively. Both therapies produced significant improvement of both pain and paresthesia. No statistically significant differences were observed between both therapies for either pain or paresthesia. No significant biochemical changes were observed with any of the two therapies. Side effects were mild and more frequent in the NF period. In this study no superiority of either drug schedule was demonstrated; therefore, the decision to use any of them should be made according to the associated pathology and potential side effects of each drug.

Adult↗
PubMed1997

Effects of the postpartum period on nortriptyline pharmacokinetics.

The objective of this research was to investigate sequential serum levels and level/dose ratios of the tricyclic antidepressant nortriptyline (NTP) through the first 17 postpartum weeks. The initial NTP dose was given immediately postpartum to 16 mothers and increased gradually to 70 mg over the first week. A dose of 75 mg was prescribed until adjustment according to serum levels. Serum levels of NTP and its metabolites Z- and E-OH-NTP were determined. At postpartum Week 2, the women developed a mean level/dose (L/D) ratio for NTP of 1.11 (range 0.37 to 3.23), and subsequently experienced an increase in the L/D ratios which continued through Week 6. At Week 8, the NTP L/D ratios declined, and became relatively stable at Week 11 and beyond. For postpartum women treated with NTP, side effect profiles should be carefully followed during the first 6 weeks after delivery as a clinical marker for elevation of serum levels. Since our highest L/D ratios for NTP occurred at Week 6, a serum level is recommended at this time. If the dose needs to be lowered to maintain a nontoxic level, a repeat serum level should be obtained at Week 11, at which time an increase in dose may be required.

Adult↗
PubMed1998

Long-term ECG changes in depressed elderly patients treated with nortriptyline. A double-blind, randomized, placebo-controlled evaluation.

ECGs of 50 patients who completed a long-term nortriptyline (NT) study are presented at baseline, after 7 weeks on NT, and after 1 year. The ECGs of patients with preexisting cardiac disease were compared with non-cardiac patients. Significant ECG changes and increases in heart rate were observed by Week 7 and persisted at a mean of 55 weeks (range: 24-111) in patients who were continued on NT. No significant difference was found in long-term ECG effects in patients with preexisting cardiac disease; ECG changes reverted to baseline when placebo was substituted. Patients with known cardiac disease did not show significantly worse ECG changes on NT than non-cardiac patients.

Age Factors↗
PubMed1999

EEG sleep measures in later-life bereavement depression. A randomized, double-blind, placebo-controlled evaluation of nortriptyline.

The authors examined 1) effects of nortriptyline (NT) on electroencephalographic (EEG) sleep measures in elderly patients with bereavement-related depression in remission under randomized, double-blind, placebo-controlled conditions, and 2) the effects of clinical remission on sleep after discontinuation of medication. Subjects were classified as responders to placebo (n = 9) or NT (n = 18) and had EEG sleep studies at three time-points: before treatment (T1), remitted on medication or placebo (T2), and remitted off medication or placebo (T3). As compared with placebo, NT was differentially associated with decreases in REM sleep time and percent and increases in REM sleep density (T2). No changes in EEG sleep measures occurred in placebo responders. REM sleep measures in NT responders reverted to T1 levels after T3, with persistence of robust clinical remission and normal subjective sleep quality. These data suggest that NT alters REM sleep, but that EEG sleep characteristics in bereavement-related depression persist into remission.

Aged↗
PubMed2003

A comparative solid-phase extraction study for the simultaneous determination of fluoxetine, amitriptyline, nortriptyline, trimipramine, maprotiline, clomipramine, and trazodone in whole blood by capillary gas-liquid chromatography with nitrogen-phosphorus detection.

This paper reports the simultaneous detection of the seven antidepressants fluoxetine, amitriptyline, nortriptyline, trimipramine, maprotiline, clomipramine, and trazodone in whole blood at concentration levels of 100-2000 ng/mL by gas chromatography with a nitrogen-phosphorus detector (GC-NPD). A comparative and validation study using two solid-phase extraction (SPE) columns, Chem Elut and Bond Elut Certify, were developed regarding their recovery, precision, sensitivity, and matrix purification efficiency. The Chem Elut columns, a diatomaceous earth, are closely related to conventional liquid-liquid extraction. The Bond Elut Certify columns, more recently developed in the market, are a mixed SPE: reversed-phase and cation exchange sorbent. Recoveries of the compounds using Chem Elut columns at 500 ng/mL were in the range 30-50%, with intra- and interassay precisions of less than 9% and 17%, respectively. Limits of detection (LODs) and quantitation (LOQs) ranged from 13 to 146 ng/mL and from 44 to 485 ng/mL, respectively. Recoveries of the compounds using Bond Elut Certify columns at 500 ng/mL were in the range 59-84% with intra- and interassay precisions of less than 8% and 11%, respectively. LODs and LOQs ranged from 8 to 67 ng/mL and from 25 to 223 ng/mL, respectively. An excellent linearity was observed with both extraction procedures from the LOQs up to 2000 ng/mL. Higher recoveries, cleaner extracts, better sensitivity, better precision, and less solvent consumption and disposal were achieved for the screening of these antidepressants with the use of the mixed SPE Bond Elut Certify compared with Chem Elut columns.

Antidepressive Agents, Tricyclic↗
PubMed2002

Nortriptyline effective for smoking cessation.

Nortriptyline (Pamelor), in combination with weekly behavioral therapy, is effective in helping highly motivated smokers to quit. The medication may be an alternative for patients who cannot tolerate or do not benefit from bupropion. Given the high motivation of the group and the extensive behavioral therapy they also received, results are not likely to be as good in typical practice.

Comment↗