L. Potter

Adinazolam, a new triazolobenzodiazepine, and imipramine in the treatment of major depressive disorder

This study evaluated the clinical efficacy and safety of a new triazolobenzodiazepine, adinazolam, and imipramine in 40 patients with carefully diagnosed major depressive disorder. Overall, adinazolam was found to be as effective as imipramine. In addition, when patients with more severe, melancholic, subtype of depression were examined, adinazolam was also as effective as imipramine. With the exception of sedation, adinazolam patients demonstrated fewer overall adverse events than imipramine subjects. These results suggest that adinazolam may represent an interesting antidepressant compound.

Cimetidine-induced alterations in desipramine plasma concentrations

Concurrent administration of cimetidine for 4 days to eight patients taking maintenance doses of desipramine led to significant elevations of desipramine (P<0.001) and its hydroxylated metabolite 2-hydroxydesipramine (P<0.001). The mean increase in desipramine plasma levels was 51% and that for 2-hydroxydesipramine was 46%. The present results suggest that tricyclic antidepressant plasma level monitoring might be indicated for certain patients taking concurrent cimetidine and desipramine.

Relationship between tricyclic antidepressant plasma levels and clinical response in patients treated with desipramine or doxepin

ABSTRACT– A study examining the relationship between plasma levels of tricyclic antidepressants (TCA), clinical response, and side effects was performed in patients with major affective disorder. Patients received either desmethylimipramine (DMI) (150–200 mg/day) or doxepin (200 mg/day) for 4 weeks. No significant correlations were found between plasma levels and either clinical response or side effects when males and females were analyzed together. A significant correlation between plasma levels and response was found in females taking desmethylimipramine. Support for the finding that females may show a stronger relationship than males between clinical response and plasma TCA levels is provided from analysis of previous studies in the literature.

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 diagnoses 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.

Possible Nonlinear Pharmacokinetics of Desipramine after Once Daily Dosing

Desipramine (DMI) plasma concentrations were measured in depressed outpatients treated with desipramine hydrochloride. Plasma level determinations were measured 24 hours after a single dose of DMI 50 mg, and then at weekly intervals thereafter while receiving once daily bedtime dosing with DMI 150 mg or 200 mg. The 24 hour DMI concentration was significantly, and rather closely correlated with steady state DMI levels (r = 0.74, p less than .001) (prediction coefficient [r2] = 55%). However, steady state plasma levels of DMI were higher than would be predicted based upon prior studies which also examined the relationship between steady state and 24 hour desipramine plasma concentrations. We speculate that the single bedtime administration of DMI in the present study may have led to saturation of metabolic hepatic enzymes during the first pass of the drug through the liver. The possibility of nonlinear DMI pharmacokinetics may be of clinical importance to some patients receiving a single, daily, high dose of medication.