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D Brunswick

Publications and source records attributed to D Brunswick.

16 recordsLinked to original sources

Imipramine and amitriptyline plasma concentrations and clinical response in major depression.

Plasma drug concentrations and clinical response were measured in two groups of hospitalised depressed patients, who received amitriptyline or imipramine double-blind, in a dosage of 250 mg for four weeks. Virtually no significant linear or curvilinear relationships were found between any plasma measure and any measure of clinical response. Modest but significant direct relationships were found between age and concentration of parent drugs but not demethylated metabolites. Blood drug level measurement therefore appears to be of little value in monitoring drug treatment of depressed in-patients.

Age Factors

Cerebrospinal fluid levels of amitriptyline, nortriptyline, imipramine and desmethylimipramine. Relationship to plasma levels and treatment outcome.

Fifty-five (55) depressed patients were treated with amitriptyline (AMI) or imipramine (IMI). Concentrations of AMI, IMI, and their metabolites, nortriptyline (NT) and desmethylimipramine (DMI), were measured in cerebrospinal fluid (CSF) and plasma at steady state by gas chromatography mass spectrometry (GC/MS). Highly significant correlations between CSF and plasma levels of AMI, NT, IMI, and DMI were found (r greater than 0.75; P less than 0.0001 in all cases). There were no significant sex, diagnostic subgroup, or geographic difference in any of the drug parameters measured. An evaluation of the relationship between CSF levels of drug variables and clinical response showed essentially no significant correlations between these various parameters. The results obtained do not support the concept of a 'therapeutic window' for levels of plasma NT in AMI-treated patients. Furthermore, the highly significant correlations between CSF and plasma compartments in terms of drug and metabolite levels would argue against the need to measure CSF levels of these parameters in clinical practice. Plasma level measurements should be equally informative, and simpler to obtain.

Amitriptyline

Plasma and erythrocyte electrolytes in affective disorders.

Plasma and erythrocyte sodium (Na+), total and free (ultrafiltrable) plasma magnesium (Mg2+) as well as erythrocyte magnesium were measured in patients with affective disorders and in healthy control subjects. Depressed and manic patients had higher total plasma Mg2+ than did hospitalized healthy control subjects, but concentrations of ultrafiltrable Mg2+ did not differ. Although erythrocyte Mg2+ was significantly elevated in the depressed subjects in comparison with that found in the non-hospitalized healthy controls, this difference was not seen between the depressives and the hospitalized healthy controls. Depressed, manic or healthy control subjects did not differ with respect to either plasma or erythrocyte.

Adult

Double-blind comparison of doxepin and desipramine in patients with primary affective disorder.

A double-blind comparison of doxepin versus desipramine was performed in carefully defined patients with research diagnosis of Primary Affective Disorder. While both drugs showed equal efficacy after 4 weeks, doxepin demonstrated a more rapid onset of action and surprisingly few side effects. Desipramine did not prove to be "activating" and did not worsen agitated depression. Although doxepin showed few autonomic side effects, it was nevertheless sedating, indicating that tricyclics with more anticholinergic effects are not necessarily more sedating drugs.

Adult

Variability of hormonal responses to a series of neuroendocrine challenges in depressed patients.

Abnormalities of hormonal responses to a number of neuroendocrine challenges have been reported in depressed patients. The authors used a series of four neuroendocrine challenges-thyrotropin-releasing hormone (TRH) and gonadotropin-releasing hormone (GnRH) stimulation, insulin tolerance test (ITT), and overnight dexamethasone suppression test (DST)-and examined eight hormonal responses in 24 healthy subjects and 26 patients with primary unipolar affective disorder. Seven control subjects (29.2%) and 25 depressed patients (96.2%) had at least one abnormal response, and 15 depressed patients (57.7%) had two or mor abnormal responses. These findings suggest that depressed patients show variability in hormonal response across a number of neuroendocrine axes. No consistent patterns of abnormality of hormonal response were observed.

Adult

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

Erythrocyte concentrations of the lithium ion: clinical correlates and mechanisms of action.

When lithium carbonate is administered to individuals, there is considerable intersubject variation in the extent of accumulation of Li+ by erythrocytes. The primary reason for this is differences in the activity of a Li+-Na+ counterflow system, which, under clinical conditions, removes Li+ from the cell. It appears that some bipolar patients accumulate more Li+ in their red cells than either unipolar depressives or normal controls. The precise clinical characteristics of the bipolar patients who accumulate relatively large amounts of erythrocyte Li+ need to be clarified in future research. Finally, the measurement of red cell concentrations of Li+, in addition to the usual plasma measurement, can be used as an indicator of patient compliance.

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