Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “NORTRIPTYLINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 847 records · Page 47Linked to original sources
PubMed1986

Analgesic and antidepressive effects of low-dose amitriptyline in relation to its metabolism in patients with chronic pain.

The analgesic and antidepressive effects of amitriptyline (AT) in relation to its kinetics and metabolism were studied in 19 outpatients with chronic pain who received a daily dose of 75 mg AT for at least 6 weeks. Riboflavin was added to the medication to check compliance. On days 0, 4, and 8 and weeks 3, 6, 9, and 12 after the start of dosing, blood samples were drawn from the patients 10 +/- 1 hours after the first morning dose and a sample of the first morning urine was taken to check riboflavin. Serum levels of AT and its metabolites, especially nortriptyline (NT) and E-10-hydroxy-nortriptyline (E-10-OH-NT), were measured by HPLC. On day 0 and at 3, 6, and 12 weeks the severity of depression was scored by means of a self-rating depression scale and pain intensity scores were measured. In addition, after 6 weeks of dosing patients estimated their percentage of pain in comparison with baseline. Mean (+/- SD) steady-state concentrations of AT, NT, and E-10-OH-NT were 36 +/- 23.5, 28 +/- 14.9, and 52 +/- 23.7 micrograms/L, respectively, in male patients (n = 8; age 45 +/- 7.4 years) and 34 +/- 14.6, 45 +/- 25.1, and 40 +/- 15.6 micrograms/L, respectively, in female patients (n = 11; age 46 +/- 6.8 years). There was a significant sex-related difference in the NT/AT ratio, which was higher in women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

Does antidepressant therapy improve cognition in elderly depressed patients?

OBJECTIVES: To analyze the effects of antidepressants on cognitive functioning in elderly depression. METHODS: Data were pooled for elderly participants with major depression from two double-blind 12-week studies (n = 444) comparing sertraline to fluoxetine and to nortriptyline. A cognitive battery was performed pre-treatment and post-treatment that included the Shopping List Task (SLT), which quantifies short-term and long-term memory storage and retrieval, and the Digit Symbol Substitution Test (DSST), which measures visual tracking, motor performance, and coding. RESULTS: Older age, male gender, higher systolic blood pressure, and higher illness severity were associated with lower performance on specific cognitive measures at baseline. For the entire group, improved depression and a lower anticholinergic side effect (dry mouth and constipation) severity were associated with statistically significant improvement in the SLT and DSST. The correlations between improvements in depression and improvement in tested cognitive function were highest for sertraline followed by nortriptyline and then fluoxetine. CONCLUSIONS: Acute improvement in depression is associated with cognitive improvement as measured by the SLT and DSST. Prospective studies are warranted to study the effects of potential differences among antidepressant therapies on long-term cognitive outcomes in geriatric depression.

Aged↗
PubMed1989

Validation of a therapeutic plasma level range in amitriptyline treatment of depression.

In the course of a double-blind study, 29 depressed patients received amitriptyline 150 mg/day for 4 weeks. Scores on the Hamilton Depression Rating Scale were assessed before treatment and after 2 and 4 weeks, and plasma levels of amitriptyline, nortriptyline, and (E)-10-hydroxynortriptyline were monitored weekly. Response reflected by percent reduction of Hamilton Depression Rating Scale score and by final score was better at steady-state amitriptyline + nortriptyline concentrations of 125-210 ng/ml than at lower and higher plasma levels. This applied to the total group and to the subgroup of 22 female patients. The data confirm the results of a previous study performed in the same hospital. An influence of the (E)-10-hydroxynortriptyline concentration in plasma on therapeutic outcome was not discernible. The results suggest that plasma level monitoring may be helpful when patients do not respond to conventional amitriptyline doses.

Adolescent↗
PubMed1995

Amitriptyline metabolism in elderly depressed patients and normal controls in relation to hypothalamic-pituitary-adrenal system function.

The pharmacokinetics of amitriptyline (AMI) have been extensively studied, and a large interindividual variability between oral dose and concentration of the drug in plasma has been documented. The aim of this study was twofold: first, to compare AMI kinetics in depressed patients with those of healthy controls and, second, to describe the relationship between AMI levels in plasma and hypothalamic-pituitary-adrenal (HPA) system changes during depression. Thirty-eight patients with a DSM-III-R diagnosis of major depression and 13 healthy control persons received 75 mg of AMI daily for 6 weeks. Levels of AMI and nortriptyline in plasma were determined, and neuroendocrine testing with the combined dexamethasone-suppression/CRH-stimulation test (DST) was done before AMI administration and after weeks 1, 3, and 6 of medication. AMI levels in plasma were significantly higher in the patient group compared with controls during the entire treatment period, whereas nortriptyline levels did not differ between the two groups. Drug levels correlated significantly with age, but gender had no effect on the concentration of the drug in plasma. Twenty-two patients remitted after treatment. There was no difference in drug levels between responders and nonresponders. Fifteen patients were DST nonsuppressors before treatment; 23 patients and all controls suppressed cortisol after dexamethasone. DST suppressors had significantly higher AMI levels in plasma at weeks 3, 5, and 6 compared with DST nonsuppressors. In comparison to patients with high AMI levels in plasma, those with low drug concentration had higher postdexamethasone cortisol and adrenocorticotropic hormone levels and an increased hormone release after additional CRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2002

Decreased plasma levels of amitriptyline and its metabolites on comedication with an extract from St. John's wort ( Hypericum perforatum ).

Extracts of St. John's wort ( Hypericum perforatum ) became increasingly popular as easily available remedies for mild to moderate depression. Comedication with hypericum extract was recently shown to drastically reduce plasma concentration of ciclosporin, digoxin, and indinavir. We investigated the possible interaction of hypericum extract LI160 with amitriptyline. Both antidepressants have a high probability of concomitant use. Twelve patients requiring amitriptyline treatment received a single dose of hypericum extract (900 mg) at day 1, continued by a 12-to 14-day treatment with retarded amitriptyline (75 mg twice daily). Then hypericum (900 mg/day) was added for another 14 to 16 days. Steady-state pharmacokinetics of amitriptyline were compared before and after multiple-dose treatment with hypericum extract. Furthermore, comparisons were made for single-dose kinetics of hypericum-extract ingredients hypericin, pseudohypericin, and hyperforin between the first day of concomitant treatment and LI160 alone. Multiple-dose comedication with LI160 led to a statistically significant decrease in the area under the plasma concentration-time curve within one dosing interval of amitriptyline by 22% ( p = 0.03) and nortriptyline by 41% ( p = 0.002), as well as of all hydroxylated metabolites, except for 10-E-hydroxynortriptyline. Plasma levels of amitriptyline and hydroxylated metabolites gradually decreased, whereas nortriptyline concentrations were already markedly decreased after 3 days of cotreatment with hypericum. Cumulative urinary amounts of amitriptyline and metabolites decreased to the same extent as plasma concentrations upon hypericum comedication. Induction of cytochrome P-450 enzymes or drug transporters (P-glycoprotein) by St. John's wort extract may explain this pharmacokinetic interaction. Physicians should be aware of this interaction when treating patients with amitriptyline.

Adult↗
PubMed1990

Myoclonus caused by a tricyclic antidepressant.

I have reported a case of myoclonus induced by nortriptyline. Serum nortriptyline levels were measured in an attempt to find whether there was any correlation between serum level and onset of myoclonus. There is clearly a need for scientific research in the neuropharmacologic features of myoclonus caused by tricyclic antidepressants, as well as possible methods of treatment.

Adult↗
PubMed1998

Quantitative determination of tricyclic antidepressants and their metabolites in plasma by solid-phase extraction (Bond-Elut TCA) and separation by capillary gas chromatography with nitrogen-phosphorous detection.

An analytical method for the simultaneous determination of amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, and desmethylclomipramine in human plasma using promazine as internal standard is described. The method is based on a solid-phase extraction procedure using the Bond-Elut TCA columns followed by separation and detection using capillary gas chromatography with a specific nitrogen phosphorous detector (GC/NPD). Using the new extraction procedure, the problem of adsorption losses was overcome, and good recoveries were achieved for all compounds tested (>87%). Furthermore, clean extracts free of chromatographic interferences were obtained. Complete separation of underivatized, tricyclic antidepressant compounds was achieved in <11 minutes with reliable chromatographic performance. The limits of detection ranged from 1.2 to 5.8 microg/l. Calibration curves, showing good linearity, were prepared covering the therapeutic concentrations range expected (20 to 500 microg/l). The interassay precision values (RSD) ranged from 4.5% to 9.8%. It is concluded that extraction of amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, and desmethylclomipramine, with Bond Elut TCA solid-phase columns followed by their detection using GC/NPD provides a sensitive and reproducible method that can be easily automated for immediate and routine analysis of clinical samples.

Amitriptyline↗
PubMed2006

Sequence-based CYP2D6 genotyping in the Korean population.

For clinical application of pharmacogenetic tests, quantitative prediction of enzyme activity based on accurate determination of genotype is essential. There has been limited information available on the genetic polymorphism of CYP2D6 in the Korean population. In this study, CYP2D6 genotypes were assessed in 400 Korean subjects. Twenty-eight different CYP2D6 alleles and 35 genotypes were detected. On the basis of the genotype determined, the frequency of poor metabolizers and ultrarapid metabolizers were 0.22% and 1.25%, respectively. The CYP2D6 activity expected in regard to different allele combinations varies widely within the extensive and intermediate metabolizer groups. The frequencies of CYP2D6*10 and CYP2D6*5 were 45.00% and 6.13%, respectively. CYP2D6*10xN was found in 4 out of 9 cases with a CYP2D6 duplication. Fifteen heterozygotes for *41 were noted. In addition, the authors measured plasma concentrations of 16 healthy volunteers after administration of nortriptyline and identified the impact of the CYP2D6 genotype on nortriptyline metabolism. This is the first large-scale study to examine the genetic polymorphism of CYP2D6 using sequence-based genotyping in an Asian population. Our results further the understanding of CYP2D6 pharmacogenetics and could be helpful for future clinical studies in the Asian population.

Adult↗
PubMed1987

Clinical pharmacology of a new antidepressant, Y-8894 in healthy young and elderly volunteers.

In the first experiment the influences of a single oral administration of a new antidepressant, Y-8894 50 mg, nortriptyline 50 mg, and placebo on physiological and psychological parameters were evaluated by a double-blind, crossover method in 10 healthy male volunteers. As the second experiment eight elderly healthy men were also recruited to examine the clinical pharmacology of Y-8894. Y-8894 50 mg showed no significant anticholinergic, sedative, or cardiovascular effect on any of the measures used in young subjects. In the elderly Y-8894 50 mg increased pulse rate (P less than 0.05-0.01), lowered systolic blood pressure (P less than 0.05-0.005), and decreased salivary flow (P less than 0.05) compared with those of pre-drug baseline. C.f.f. was improved after Y-8894 50 mg, but not significantly. Neither psychomotor performance nor immediate memory was influenced after either treatment in young subjects. Furthermore, in the elderly Y-8894 50 mg did not affect these parameters. In the elderly both k21 and ke were smaller, t1/2,z was longer, and AUC was larger compared with young subjects (P less than 0.01). In conclusion, Y-8894 50 mg seemed to lack the anticholinergic, sedative and cardiovascular effects which were observed after nortriptyline 50 mg in young subjects. In the elderly some affects were recognized, in part, due to pharmacokinetic alteration.

Adult↗
PubMed1981

The use of the rat right ventricle strip in studies on noradrenergic transmission.

1. The possibility of using contractility studies with the rat right ventricle strip to assess the effects of drugs on all aspects of noradrenergic transmission has been examined. 2. The force of the contractile responses to field stimulation at 0.5 and 2, but not 5 Hz, markedly decreased with time. About 55% of the tissues responded directly to (-)-isoprenaline, 1 X 10(-6)M (123 tissues from 220 tested) in the absence of other stimuli. In these tissues the force of the contractile responses remained constant and the rate increased with time. Thus it is essential to provide time controls in studies with rat right ventricle. 3. Under conditions in which the responses to (-)-isoprenaline, 1 X 10(-6)M, alone were unaffected the responses to field stimulation at 5 Hz were inhibited by 66 and 86% by 9 X 10(-6)M tetrodotoxin and 1 X 10(-5)M guanethidine, respectively. (+/-)-Propranolol and timolol (both at 1 X 10(-6)M), but not phentolamine, 1 X 10(-6)M, inhibited responses to (-)-isoprenaline, 1 X 10(-6)M alone and responses to field stimulation at 5 Hz. This demonstrates that the responses to field stimulation are largely due to activation of noradrenergic nerves, the released noradrenaline acting at postsynaptic beta-adrenoreceptors. 4. Although nortriptyline is a potent inhibitor of the neuronal uptake of noradrenaline, at 1 X 10(-6)M it had no effect on the contractile responses to field stimulation at 5 Hz and inhibited responses to (-)-isoprenaline, 1 X 10(-6)M, alone and at a higher concentration (1 X 10(-5)M) nortriptyline abolished both responses. It is suggested that the rat ventricle preparation may be useful in examining the effects of drugs on noradrenergic transmission in the heart.

Adrenergic beta-Antagonists↗
PubMed1984

Potentiation of the action of adenosine on cerebral cortical neurones by the tricyclic antidepressants.

The effects of four tricyclic antidepressants, nortriptyline, iprindole, chlorimipramine and desipramine on adenosine-evoked depressions of the firings of rat cerebral cortical neurones has been studied. When applied iontophoretically, all four substances enhanced the depressant actions of iontophoretically applied adenosine but did not affect the depressant actions of the uptake-resistant analogue, adenosine 5'-N-ethylcarboxamide (NECA). Nortriptyline and iprindole administered intravenously (1 mg kg-1) enhanced the depressant actions of iontophoretically applied adenosine. When applied by larger iontophoretic currents, all four antidepressants inhibited the firing of cerebral cortical neurones. Chlorimipramine- and desimipramine-elicited depressions were antagonized by intravenously administered caffeine, an adenosine antagonist. Earlier studies showed the tricyclic antidepressants inhibit the uptake of adenosine by rat brain cerebral cortical synaptosomes. The present results demonstrate that four antidepressants are able to potentiate the action of adenosine and that this occurs when these compounds are given in behaviourally meaningful doses. The specificity of the potentiation is demonstrated by the failure of these compounds to potentiate the depressant actions of an uptake-resistant analogue of adenosine, NECA. Antagonism of the inhibitory effects of the antidepressants on neuronal firings by caffeine, indicates that these compounds can enhance the extracellular levels of endogenously released adenosine sufficiently to depress cell firing.

Action Potentials↗
PubMed1978

Plasma and erythrocyte levels of tricyclic antidepressants in depressed patients.

Plasma and red blood cells (RBCs), amitriptyline, nortriptyline, imipramine, desipramine, doxepin, and desmethyl doxepin levels were measured in depressed inpatients during steady-state kinetics. A strong positive correlation between the drug levels in plasma and RBCs was found for amitriptyline, nortriptyline, desipramine, and desmethyl doxepin. However, at a given plasma level, up to a 6-fold interindividual variation in the RBC drug levels was found. The correlations between plasma and RBC imipramine and doxepin levels were low. The interindividual variation in the RBC-plasma tricyclic level ratios was large enough to warrant further clinical studies on the relationship between efficacy and pharmacokinetics of tricyclic antidepressants.

Adult↗
PubMed1998

Effects of age at onset of first lifetime episode of recurrent major depression on treatment response and illness course in elderly patients.

OBJECTIVE: The goal of this study was to examine treatment outcome differences in relation to age at onset of first lifetime episode of recurrent major depression in elderly patients. METHOD: Patients were grouped as having early-onset (N = 129) or late-onset (N = 58) depression. Early onset was defined as having a first lifetime episode of major depression at age 59 or earlier; late onset was defined as age 60 or later. The two groups of patients were compared with respect to demographic and clinical characteristics, types of treatment given (nortriptyline and interpersonal psychotherapy), and treatment outcomes. RESULTS: The groups did not differ in the percentage of patients who remitted, recovered, or relapsed during continuation treatment or in the percentage who experienced a recurrence of major depression during the first year of maintenance treatment. However, early-onset patients took 5-6 weeks longer to achieve remission than did late-onset patients, and a higher proportion had a history of suicide attempts. CONCLUSIONS: These data suggest that age at lifetime onset of recurrent major depression does not influence short- or long-term treatment response in elderly patients treated with combined interpersonal psychotherapy and nortriptyline, with the exception of slowing the speed of remission in early-onset cases. Difference in remission speed may reflect the greater number of previous episodes in the early-onset patients. Nevertheless, the likelihood of a longer time to remission, together with a higher rate of past suicide attempts, suggests that elderly depressed patients with a history of early-onset illness need particularly careful management.

Age Factors↗
PubMed2003

Mortality and poststroke depression: a placebo-controlled trial of antidepressants.

OBJECTIVE: Poststroke depression has been shown to increase mortality for more than 5 years after the stroke. The authors assessed whether antidepressant treatment would reduce poststroke mortality over 9 years of follow-up. METHOD: A total of 104 patients were randomly assigned to receive a 12-week double-blind course of nortriptyline, fluoxetine, or placebo early in the recovery period after a stroke. Mortality data were obtained for all 104 patients 9 years after initiation of the study. Demographic and clinical measurements were collected at 3, 6, 9, 12, 18, and 24 months after the stroke. Survival data were analyzed by using the Kaplan-Meier method. RESULTS: Of the 104 patients, 50 (48.1%) had died by the time of the 9-year follow-up. Of 53 patients who were given full-dose antidepressants, 36 (67.9%) were alive at follow-up, compared with only 10 (35.7%) of 28 placebo-treated patients, a significant difference. Logistic regression analysis showed that the beneficial effect of antidepressants remained significant both in patients who were depressed and in those who were nondepressed at enrollment, after the effects of other factors associated with mortality (i.e., age, coexisting diabetes mellitus, and chronic relapsing depression) were controlled. There were no intergroup differences in severity of stroke, impairment in cognitive functioning and activities of daily living impairment, and other medications received. CONCLUSIONS: Treatment with fluoxetine or nortriptyline for 12 weeks during the first 6 months poststroke significantly increased the survival of both depressed and nondepressed patients. This finding suggests that the pathophysiological processes determining the increased mortality risk associated with poststroke depression last longer than the depression itself and can be modified by antidepressants.

Adrenergic Uptake Inhibitors↗
PubMed1989

10-Hydroxynortriptyline and treatment effects in elderly depressed patients.

Sixty-four elderly depressed outpatients were treated with nortriptyline for seven weeks. Plasma nortriptyline and its main metabolite, 10-hydroxynortriptyline, were measured weekly. No relationship was found between levels of 10-hydroxynortriptyline and clinical response. Plasma levels of the trans isomer, E-10-hydroxynortriptyline, were significantly lower when dizziness and symptoms of orthostatic hypotension were reported, although there was no significant correlation with actual orthostatic drop in systolic pressure. Plasma level of 10-hydroxynortriptyline was not significantly correlated with the other reported side effects.

Aged↗
PubMed1980

A double-blind comparison of dothiepin and amitriptyline in patients with primary affective disorder: serum levels and clinical response.

In a double-blind parallel group study, thirty-two patients suffering from a primary affective disorder received either dothiepin or amitriptyline. Serum concentrations of total dothiepin plus northiaden or amitriptyline and nortriptyline were estimated. A similar therapeutic response was seen with both drugs but there was no correlation with serum concentrations of amitriptyline or nortriptyline, whereas serum dothiepin correlated positively with clinical response.

Adult↗
PubMed2005

Biphasic effects of losartan potassium on immobility in mice.

The effects of losartan potassium, an angiotensin AT(1) receptor blocker on immobility in forced swim test have been studied. Effect of losartan potassium, nortriptyline HCl, fluoxetine HCl and reserpine per se and in combination on forced swimming-induced immobility in mice have also been studied. In mice, losartan potassium elicits biphasic responses i.e. positive responses at lower doses (0.1, 1.0 and 5 mg/kg, i.p.) in the forced swim test, a test of potential antidepressant activity and vice versa at higher dose (20 and 100 mg/kg, i.p.). In chronic studies, enhancement in immobility was observed for losartan potassium (3 and 30 mg/kg, p.o., 21 days). In acute combination studies, losartan potassium (1 and 5 mg/kg) significantly reversed the reserpine-induced immobility, but vice versa at 100 mg/kg. Losartan potassium (0.1 and 5 mg/kg) potentiate antidepressant activity of nortriptyline (30 mg/kg, i.p.) in mice, but vice versa at 100 mg/kg. Likewise, Losartan potassium (100 mg/kg), significantly reversed antidepressant activity of fluoxetine HCl, but at 0.1 and 5 mg/kg, failed to modify fluoxetine HCl induced immobility. The obtained biphasic effect of losartan potassium on immobility in mice might be due to inhibitory effect on AT(1) receptor at lower dose and pronounced effect on AT(2) receptor at higher dose (large concentrations of losartan potassium can displace Angiotensin II (Ang II) from its AT(1) receptor to AT(2) receptor.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2001

Comparison of noradrenergic and serotonergic antidepressants in reducing immobility time in the tail suspension test.

We examined the effects of two noradrenergic tricyclic antidepressants and two selective serotonin re-uptake inhibitors in the tail suspension test, with a suspension period of 30 min instead of the usual 10 min. Within the first 10 min, desipramine, nortriptyline and fluvoxamine significantly reduced the duration of immobility. Whereas desipramine and nortriptyline were also efficacious in the rest of the test period, fluvoxamine was not. Fluoxetine showed no significant effect throughout the study period. These results suggest that a prolonged tail suspension test results in functional changes in the noradrenergic and serotonergic systems and alters the sensitivity to antidepressants.

Adrenergic Uptake Inhibitors↗