Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of studies on the pharmacokinetic and pharmacodynamic properties of some tricyclic antidepressants is reviewed. During treatment with the same oral dose of these drugs, patients develop widely differing plasma levels. The importance of this variability for the clinical effects has been studied in detail for the monomethylated compound, nortriptyline. There is an association between side-effects and high plasma levels of this drug. In endogenously depressed patients, the relationship between plasma level and effect appears to be curvilinear. The tricyclic antidepressants differ in their capacity to inhibit transmitter uptake into noradrenaline- and serotonin neurons respectively. Nortriptyline is a preferential noradrenaline uptake inhibitor, while the dimethylated compound, chlorimipramine also has a profound influence on serotonin neurons. These differential effects are also reflected in changes in the levels of the transmitter metabolites in cerebrospinal fluid (CSF). The CSF studies have also supported the hypothesis of a biochemical heterogeneity of the depressive syndrome. The levels of the serotonin metabolite, 5-HIAA were bimodally distributed in CSF. In patients with a low level of 5-HIAA there was a significant correlation between the CSF metabolite level and the severity of the depression, and these patients also appeared to be more suicide-prone than those with higher 5-HIAA levels. These patients seemed to be less amenable to treatment with nortriptyline. The effect of chlorimipramine treatment in this subgroup of depressives is presently being explored.
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PMID:Treatment of depression with tricyclic drugs--pharmacokinetic and pharmacodynamic aspects. 1 May 83

Therapeutic efficacy of Nomifensine and Nortriptyline was compared with a double blind study on 29 patients suffering from several kinds of depression. The patients were admitted to the Institute of Nervous and Mental Diseases of the University of Florence. Drugs were administered according to a flexible dosage varying from 50 mg to 125 mg/day, subdivided in 2-3 doses. The experiment is referred to the first 15 days of treatment. In order to estimate the effect of the drugs, the Hamilton's scale for depression was used. This scale was administered before treatment and on the 5th, 10th, 15th, day of therapy. Scores of Hamilton's scale and of some "Clusters" were computerized. It was found that Nomifensine has an antidepressant effect comparable to that of Nortriptyline. No relevant differences were noted in the range of action of these drugs. No side-effects were detected in the doses employed.
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PMID:[Controlled clinical trial of nomifensine in treatment of depression (author's transl)]. 40 45

Forty-one depressed outpatients were treated for six weeks after random assignment to amitriptyline hydrochloride (N = 22) or nortriptyline hydrochloride (N = 19). On a mean daily dose of 119 mg, amitriptyline-treated patients had a mean tricyclic level (amitriptyline plus nortriptyline) of 120 ng/ml. Nortriptyline-treated patients on a mean dose of 117 mg/day had a mean nortriptyline level of 141 ng/ml. The two drugs were equally effective in the treatment of depression. The correlation between the Hamilton Score and the mean tricyclic level was negative in the amitriptyline-treated patients (r = -0.54, P less than .025) and positive in the nortriptyline-treated patients (r = -0.49, P less than .05). Patients treated with amitriptyline or nortriptyline with plasma levels within the therapeutic range, defined in other laboratories, had a better response, as measured by the Hamilton Score (P less than .001), Zung Score (P less than .01), and percent recovered (P less than .001), than those above or below the therapeutic range.
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PMID:A comparison study of amitriptyline and nortriptyline with plasma levels. 86 Aug 94

Although recent epidemiologic studies have established that patients with chronic medical illness and depressed mood are more disabled than euthymic patients, detailed data on the benefits and risks of antidepressant treatment in medically high-risk patients have been slow to accumulate. The authors have examined multiple outcome indicators in patients with disabling chronic obstructive pulmonary disease and comorbid depression. Thirty patients completed a 12-week, randomized controlled trial of nortriptyline. Nortriptyline was clearly superior to placebo for treatment of depression. Nortriptyline treatment was accompanied by marked improvements in anxiety, certain respiratory symptoms, overall physical comfort, and day-to-day function; placebo effects were negligible. Physiological measures reflecting pulmonary insufficiency were generally unaffected by treatment. These data provide impetus for renewed efforts to improve recognition and treatment of mood disorders in even severely disabled medical patients.
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PMID:Improvement in mood, physical symptoms, and function with nortriptyline for depression in patients with chronic obstructive pulmonary disease. 155 84

Only a few of the eight tricyclic antidepressants available today have been studied systematically in the elderly. Tertiary amine tricyclics such as amitriptyline and imipramine have been reported to be effective in depressed geriatric patients, but because of their potential for side effects, it is not advisable to use them in the elderly. Desipramine has a less toxic side effect profile, especially with respect to anticholinergic effects, but its efficacy has not been well studied. This does not mean, however, that it is not an effective drug for the elderly depressed. Nortriptyline is the tricyclic that has been the most studied. The results of those studies show that it should be recommended as an antidepressant for older patients. It is effective in both the acute and continuation treatment of depression in the elderly. As far as its use in maintenance treatment, the results are mixed but at this moment there is nothing with which to compare it. It has a favorable side effect profile: low anticholinergic activity; relatively few cardiac side effects, even in patients with preexisting cardiac disease; and relatively less orthostatic hypotension. Nortriptyline also has the virtue of an established therapeutic range for its steady-state plasma level. The role of its 10-hydroxy metabolite needs to be further explored, but when its contribution to efficacy and toxicity is better understood, it may be possible to use nortriptyline in a more precise and safe way in elderly patients. The bulk of evidence suggests, partly by default, that nortriptyline should probably the tricyclic-of-first-choice in treating an elderly patient with major depression.
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PMID:Using tricyclic antidepressants in the elderly. 160 Apr 82

The effects of nortriptyline, phenelzine, and placebo on 13 symptoms of depression were compared in 75 patients, aged 55 or over, who were suffering from major depression. Nortriptyline and phenelzine were more effective than placebo in treating depression mood, guilt feelings, suicidal ideation, agitation, anxiety, loss of energy, and a.m. diurnal variation of mood. Nortriptyline was better than phenelzine or placebo in improving middle/late insomnia. Most of the symptoms did not show significant improvement until the fourth week of treatment.
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PMID:Response of depressive symptoms to nortriptyline, phenelzine and placebo. 367 6

Previous studies of the effect of tricyclic antidepressants on left ventricular function in depressed patients with moderate to severe ventricular impairment have focused primarily on imipramine hydrochloride. In a prior study, we found that although imipramine had no effect on ejection fraction as measured by first-pass radionuclide angiography, the treatment could not be tolerated by 50% of the patients because of intolerable drug-induced orthostatic hypotension. Nortriptyline hydrochloride is an effective antidepressant that, in depressed patients without heart disease, causes significantly less orthostatic hypotension than imipramine. To see if this advantage could be safely extended to patients with congestive failure, we measured the effect of nortriptyline on ejection fraction and blood pressure in 21 depressed patients with left ventricular impairment. Ejection fraction was unchanged by nortriptyline treatment, and orthostatic hypotension developed in only one (5%) of 21 patients. Nortriptyline emerges as a relatively safe treatment for depression in patients with left ventricular impairment.
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PMID:Nortriptyline in depressed patients with left ventricular impairment. 378 71

Twenty out-patients with depressive illness were studied with regard to thyroid hormone concentrations, basal and TRH-stimulated TSH, and prolactin levels before and during treatment with nortriptyline. Concentrations of plasma nortriptyline and 10-hydroxy-nortripyline were analysed while on 75 mg and 150 mg/day. No correlations between clinical outcome and side effects on the one hand and drug concentrations on the other were demonstrated. Provided the age factor was considered, basal and stimulated hormone levels did not differentiate between healthy controls and patients with "endogenous" and those with "exogenous" depression. Nortriptyline treatment did not influence serum hormone levels.
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PMID:Nortriptyline and pituitary-thyroid function in affective disorder. 678 69

The relationship between steady-state plasma concentration and clinical response was studied in 22 hospitalized unipolar depressed patients. In a double-blind format the patients were randomly assigned to receive amitriptyline or nortriptyline. Dosage was adjusted based on plasma level with the aim of achieving a concentration of 60-180 ng/ml. By week 4 of treatment, 83% of amitriptyline patients and all nortriptyline patients were within the targeted plasma range. Based on final ratings of clinical state, the drug level adjustment improved the outcome for nortriptyline-treated patients, but not amitriptyline-treated patients. Nortriptyline patients with plasma levels of 60-230 ng/ml had lower Hamilton Rating Scale depression scores than patients outside that range. By contrast, amitriptyline plasma levels were not associated with depression ratings. After 1 week, patients treated with nortriptyline had a significantly greater mean reduction in Hamilton depression score, i.e., 55% compared to 25% for amitriptyline patients.
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PMID:Amitriptyline and nortriptyline response profiles in unipolar depressed patients. 681 39

This study investigates the effects of assigned diagnostic labels, with their accompanying predictions of therapeutic response, and prescribed psychotropic drugs. It was thought that such 'labelling' effects might be important in ambiguous situations, such as neurotic anxiety-depressive states, where diagnoses of 'reactive depression' or 'anxiety state' might justifiably be made and treatment with either diazepam or nortriptyline legitimately given. The depression label and its concomitant two-weekly prediction of improvement with antidepressants produced a set towards slower response with higher self-report depression. Nortriptyline produced significantly more improvement in self-report depression than diazepam in the first 2 weeks of treatment. No significant interaction effects were detected between diagnosis or drug. One month after the initial diagnostic evaluation there were no significant effects from either diagnostic label or drug.
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PMID:Labelling and drug effects in the treatment of neurotic affective disorders: an experimental investigation. 687 27


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