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PubMed1973

Benzodiazepines and tricyclic antidepressant plasma levels.

Twelve patients acted successfully as subjects to study what effect if any the benzodiazepines nitrazepam, diazepam, oxazepam, and chlordiazepoxide might have on steady-state plasma levels of nortriptyline and amitriptyline. No significant detectable effect was discovered. In view of the known interaction effects of other alternative tranquillizing drugs and hypnotics it seems reasonable to choose benzodiazepines wherever possible when anxiolytics or hypnotics need to be added during treatment of depression with tricyclic antidepressants.

Amitriptyline↗
PubMed1985

Tricyclic antidepressants and acid secretory response of rabbit gastric cells.

Tricyclic antidepressants have been tested for their effect on the H2-receptor-mediated changes in cAMP, O2 consumption, and acid secretion in mucosal cells isolated from rabbit stomach. Amitriptyline (AMT) inhibited the action of histamine on both cAMP generation and O2 consumption in an apparent competitive fashion without altering these parameters in unstimulated cells. The onset of this inhibition was rapid and the time at which the increases in these functions had reached steady state was not changed. The Schild regression line for AMT was close to unity, and its Ki values for cAMP production or O2 consumption were 0.75 microM AMT. Imipramine and nortriptyline also caused a rightward shift in the dose-response curve of histamine-induced cAMP generation. The inhibitory action of AMT was specific to histamine in that AMT neither altered the effect of isobutylmethylxanthine on cAMP and respiration nor inhibited the increase in respiration caused by carbachol. However, at relatively high concentrations (250-500 microM), AMT inhibited the increase in cAMP caused by 5 and 100 microM prostaglandin E1 and inhibited the increase in respiration caused by both dibutyryl cAMP (DBcAMP) and by the combination of DBcAMP plus carbachol. Antidepressant drugs were also very potent inhibitors of acid formation as measured by [14C]aminopyrine accumulation (Ki, 1 microM). They inhibited acid formation in control cells, in cells stimulated by histamine, carbachol, and DBcAMP, and also the potentiated response to carbachol plus histamine or DBcAMP. The onset of this inhibition was also rapid, and adding 5 microM AMT to the cell suspension either together with histamine or after stimulation by histamine caused a rapid decline in aminopyrine accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed2000

Electrophysiologic analysis of antidepressant drug effects on the GABA(A) receptor complex based upon antagonist-induced encephalographic power spectrum changes.

To better understand antidepressant drug effects on the GABA(A) receptor complex (the GABA(A) receptor, chloride ionophore and benzodiazepine receptor), we investigated how antidepressants influenced power spectrum changes induced by pentylenetetrazol (PTZ), a chloride ionophore antagonist, in the rat hippocampal electroencephalogram (EEG). In control recording, PTZ (27.5 mg/kg i. p.) increased EEG power at frequencies under 12 Hz up to five times. After rats were pretreated with imipramine, fluoxetine or trazodone for 7 days (10 mg/kg i.p., twice a day), PTZ could not increase EEG power to more than three times the power before injection; this effect was not observed after pretreatment for 3 days. These three antidepressants inhibit serotonin uptake, while two other antidepressants, desipramine and nortriptyline, that inhibit norepinephrine uptake failed to counter the PTZ effect. We concluded that antidepressants with serotonergic effects enhanced the function of the GABA(A) receptor complex.

Animals↗
PubMed2003

Serum cholesterol in treatment-resistant depression.

OBJECTIVE: Patients with major depressive disorder (MDD) may have significant differences in cholesterol levels compared with healthy controls. A previous study by our group reported that depressed patients with elevated cholesterol levels (>or=200 mg/dl) were significantly more likely to be nonresponders to fluoxetine treatment than depressed patients with nonelevated cholesterol levels. However, very little is known regarding cholesterol in patients with treatment-resistant depression (TRD). The purpose of this study was to compare cholesterol levels at baseline between depressed patients with and without TRD and to test whether cholesterol levels at baseline can predict clinical response in patients with TRD treated with open-label nortriptyline (NT). METHODS: Ninety-two patients with TRD entered a 6-week open trial of NT. Baseline cholesterol levels were randomly collected for 59 of these patients. Controlling for age and gender, we compared baseline cholesterol and triglyceride levels for 35 patients with TRD who did not respond to NT with 205 non-TRD patients who responded to an 8-week open trial of fluoxetine. Furthermore, with the use of logistic regression, we tested whether baseline cholesterol levels predicted clinical response to NT in the patients with TRD. RESULTS: Patients with TRD had higher triglyceride levels at baseline compared with depressed patients without TRD. Cholesterol defined as a dichotomous variable being elevated if equal to or greater than 200 mg/dl, predicted poor response to a 6-week open trial of NT in patients with TRD. CONCLUSIONS: The results of this study confirm the relationship between hypercholesterolemia and poor outcome in the treatment of MDD for patients with TRD.

Adolescent↗
PubMed1982

Tricyclic antidepressant plasma levels: the state of the art and clinical prospects.

The authors review the main pharmacological factors playing a role in the kinetics of tricyclic antidepressant plasma levels. The current data concerning the relationship between tricyclic plasma levels and their clinical responses indicate that there is a therapeutic window at 50-150 ng/ml for the secondary derivatives (nortriptyline and desipramine). The lower limit of efficiency for the primary derivatives (imipramine and amitriptyline) is estimated at 200 ng/ml. The boundaries and prospects of the clinical use of antidepressant plasma levels are discussed in their various methodological aspects.

Amitriptyline↗
PubMed1984

Serum levels and response to amitriptyline in depressed out-patients.

Serum levels of amitriptyline plus nortriptyline were measured by radioimmunoassay at 1 and 6 weeks in depressed out-patients treated with amitriptyline for 6 weeks. Serum concentrations at 6 weeks were higher in older patients. Serum levels showed no relationship to clinical response at 6 weeks, and a week inverse relationship with response at 2 weeks. Routine monitoring of serum levels appears to be of little value in depressed out-patients treated with amitriptyline.

Adult↗
PubMed1995

Combined cognitive-behavioral, psychopharmacological and nutritional therapy in eating disorders. 1. Anorexia nervosa--restricted type.

Twenty-two female patients with anorexia nervosa, restricted type, 14-35 years old, were treated with a 4-month course of combined cognitive-behavioral therapy, nutritional counselling and antidepressant drugs (nortriptyline for 7, fluoxetine for 15). Patients were monitored for body mass index (BMI), for eating disorder symptoms by the Eating Disorder Inventory (EDI) and the Bulimic Investigation Test (BITE) and for depression and anxiety by the Hamilton Rating Scales for Depression and for Anxiety (HRS-D and -A). The scores were determined before and after 1, 2 and 4 months of therapy. BMI, depression, anxiety and EDI scores improved significantly and equally in both groups during the 4 months of therapy, while BITE scores did not change.

Adolescent↗
PubMed1996

Antidepressant and anxiolytic profiles of E-10-hydroxynortriptyline on electrocorticograms of rats.

Electrocorticograms of rats were recorded after administration of increasing doses of the major metabolite of nortriptyline (NT), E-10-hydroxynortriptyline (E-10-OH-NT). The results were compared with those of NT administration. In visual as well as computerized evaluations, E-10-OH-NT demonstrated clear antidepressant properties, thus confirming previous experiments in depressed patients. There is some evidence that E-10-OH-NT also has an anxiolytic profile. The results with the parent drug NT were not so pronounced. Since E-10-OH-NT has been shown to be devoid of side effects when previously administered to humans, this substance is clearly to be considered of interest for potential development into a new antidepressant. Whether or not the anxiolytic profile is of clinical interest needs to be investigated further.

Animals↗
PubMed1979

Relationship between surface activity and toxicity to Chang liver cultures of tricyclic antidepressants.

Chang liver cell cultures were exposed to the tricyclic antidepressants, chlorimipramine (CIM), nortriptyline (NT), amitriptyline (AT), imipramine (IM), and dosepin (DOX). Loss of enzymes into surrounding media and cytopathic changes were used to quantitate cytotoxicity. Time- and concentration-related cytotoxic effects were evident for all drugs. The order of cytotoxic potency was CIM greater than NT greater than AT greater than IM greater than DOX. All tricyclic antidepressants tested lowered the surface tension of the salt solution contained in the tissue culture media and the order of their surface activity was identical to that of their cytotoxicity. It is postulated that the cellular toxicity induced by tricyclic antidepressants in vitro is related to a function of their surface activity.

Amitriptyline↗
PubMed1986

New aspects in research on blood levels and bioavailability of antidepressants.

Recent research has been oriented towards the study of the clinical relevance of measuring free and total plasma levels of antidepressants and their hydroxylated metabolites, as animal experiments suggest that the latter may be clinically active. In central Europe, about 5-10% of the population has a genetic defect in metabolizing debrisoquine. This is of importance for pharmacopsychiatry, as some antidepressants like desipramine, nortriptyline, amitriptyline, imipramine (and possibly maprotiline) are metabolized by the same enzyme as debrisoquine. This observation helps to understand not only the large interindividual differences in the steady-state levels of these drugs but also drug interferences.

Amitriptyline↗
PubMed1975

Hostility, somatic symptoms and recovery with antidepressants.

Patients were treated with protriptyline or nortriptyline (double-blind). They were assessed on the Zung Depression Scale and on the Hostility and Direction of Hostility Questionnaire (HDHQ). A good response was heralded by low ratings on criticism of self and others,and on projected (paranoid) hostility. The outcome was better with initial low scores on depressive symptoms, particularly unworthiness, restlessness and constipation. As to reported side effects, initial loss of interest augured badly for drowsiness, lack of clear mind for blurred vision, loss of libido for constipation and ideas of suicide for dry mouth.

Depression↗
PubMed1978

Tricyclic antidepressants: plasma levels and clinical findings in overdose.

Following amitriptyline or imipramine overdose by 30 patients, total plasma concentrations ranged from 29 to 1732 ng/ml but did not correlate well with physical findings or most electrocardiographic changes. Only those patients with a QRS interval greater than 0.1 second had significantly elevated plasma levels. However, a plasma level ratio of the parent drug (amitriptyline, imipramine) to its respective N-desmethyl metabolite (nortriptyline, desmethylimipramine) greater than or equal to 2.0 was associated with an acute overdose. This ratio was more useful than total plasma levels in differentiating an overdose from a therapeutic dose with associated toxicity and an elevated steady-state plasma level.

Adolescent↗
PubMed1980

Urinary MHPG and clinical response to amitriptyline in depressed patients.

The authors treated 18 rigorously diagnosed depressed patients with amitriptyline after baseline urine samples were collected for the measurement of 3-methoxy-4-hydroxphenylglycol (MHPG). Neither age nor severity of depression before treatment correlated with MHPG excretion. There was also no significant correlation between baseline MHPG excretion and clinical response at the end of at least 25 days' treatment with amitriptyline. The authors discuss the relevance of amitriptyline and nortriptyline plasma levels to MHPG and the noradrenergic/serotonergic theories of depression.

Adolescent↗
PubMed1980

The clinical application of tricyclic antidepressant pharmacokinetics and plasma levels.

The authors present a clinical approach for predicting and using plasma concentrations of tricyclic antidepressants in the treatment of depressed patients. They review the pharmacokinetics of this group of drugs and their side effects and toxicity. There is a suggested therapeutic range for plasma concentrations of imipramine, amitriptyline, and nortriptyline; more definitive studies are needed to determine the necessary plasma levels for achieving clinical response with the other tricyclic antidepressants (desmethylimipramine, protriptyline, doxepin, clomipramine, impiramine N-oxide, and butriptyline). A more thorough knowledge of the clinical pharmacokinetics of tricyclic antidepressants should lead to more rational use of these drugs, with a higher response rate and fewer adverse reactions.

Amitriptyline↗
PubMed1982

Interaction between antidepressants and perphenazine in psychiatric inpatients.

In a study of 99 patients receiving amitriptyline or nortriptyline alone and 60 patients receiving one of these antidepressants in combination with perphenazine, the patients receiving the combination medication had up to 70% higher antidepressant plasma levels than patients receiving the antidepressant alone. The groups did not differ significantly in sex, age, smoking behavior, or antidepressant dose level. Due to the possibility of side effects from such combination medication, the authors recommend that depressed patients not responding to the tertiary amine tricyclic antidepressants receive a trial of high doses of the drugs before antidepressant-neuroleptic combinations are administered.

Adult↗
PubMed1985

Tricyclic antidepressants--blood level measurements and clinical outcome: an APA Task Force report. Task Force on the Use of Laboratory Tests in Psychiatry.

The Task Force examines the present status of studies investigating the relationship between blood plasma concentrations of tricyclic antidepressants and clinical outcome. It discusses some of the discrepancies that have developed among various antidepressant drugs and evaluates the clinical implications of the current status of blood level monitoring. The Task Force concludes that plasma level measurements of imipramine, desmethylimipramine, and nortriptyline are unequivocally clinically useful in certain situations, that these measurements are helpful in many situations, and that plasma level measurements are likely to grow in usefulness.

Antidepressive Agents, Tricyclic↗
PubMed1988

Depression associated with nifedipine-induced calcium channel blockade.

Four cases are reported in which substantial depression was associated with the use of the calcium channel blocker nifedipine. In one instance, a patient became unresponsive to treatment with nortriptyline when nifedipine was introduced. In each case, the depression resolved following discontinuation of nifedipine. Possible mechanisms by which nifedipine may influence affective states are discussed.

Aged↗
PubMed1994

Hopelessness in suicide attempters after acute treatment of major depression in late life.

The relation between hopelessness and suicide attempts in the elderly was examined by studying the course of hopelessness in depressed patients. Sixty-three elderly patients with recurrent major depression were treated with nortriptyline and interpersonal psychotherapy and underwent serial ratings of hopelessness and depression during the acute and continuation phases of treatment. Patients who had made a suicide attempt in the past had significantly higher hopelessness scores than nonattempters during both phases of treatment. They were also more likely to drop out of treatment. A high degree of hopelessness persisting after remission of depression in elderly patients appears to be associated with a history of suicidal behavior. It may also increase the likelihood of premature discontinuation of treatment and lead to future suicide attempts or suicide.

Age Factors↗