Intravenous Versus Oral Administration of Amitriptyline in Patients With Major Depression

Abstract

Antidepressants can be administered by different routes. Advantages for either the oral or the intravenous administration have been suggested from pharmacokinetic as well as from clinical points of view. Controlled comparison studies of the two routes do not provide unequivocal recommendations. In this investigation, amitriptyline was studied over a 4-week period consisting of a 2-week, double-blind/double-dummy phase with either oral (150 mg/day), high-dose intravenous (150 mg/day), or medium-dose intravenous (100 mg/day) treatment and a 2-week phase of open oral treatment in 80 patients with major depression. A psychopathologic assessment was made using the Hamilton Rating Scale for Depression, the Clinical Global Impressions Scale, the von Zerssen's "Befindlichkeitsskala," an adjective checklist, and a Visual Analog Scale. No significant differences were found concerning the mean scores of the rating scales or time of onset of action in the physicians' ratings. In the patients' self-ratings, there was an earlier therapeutic effect in the high-dose intravenous group. The number of improvers after 7 days was significantly higher in the high-dose intravenous group compared with both other groups. After 14 days, no significant differences in the numbers of improvers and responders between groups were detected. The results of this study do not clearly favor one of the tested options. The main differences found in this study seem to be dose-related rather than differentiating between oral and intravenous routes of administration.

M1and M2Muscarinic Receptor Subtypes Regulate Antidepressant-Like Effects of the Rapidly Acting Antidepressant Scopolamine

“…Clinical findings have been replicated and extended to other antimuscarinics and treatment populations (Howland, 2009;Dagyt_ e et al, 2011;Janowsky, 2011;Drevets et al, 2013;Jaffe et al, 2013). It is noteworthy that amitriptyline, a tricyclic antidepressant with greater efficacy than SSRIs (Anderson, 1998;Deisenhammer et al, 2000), has one of the richest of antimuscarinic profiles (Rathbun and Slater, 1963). Given the reenergizing of both the cholinergic hypothesis of MDD and the pressing need for improved antidepressant agents, we undertook the present series of studies.…”

Antidepressant Efficacy of the Antimuscarinic Drug Scopolamine

“…The difference in muscarinic receptor affinity across TCAs may explain why amitriptyline was the only antidepressant drug that proved more effective than more selective agents (eg, selective serotonin reuptake inhibitors) in inpatients with MDD. 46,54,57 Nevertheless, in clinical practice, the amitriptyline dose is gradually titrated upward, so potentially rapid responses to full therapeutic amitriptyline doses would not have been detected.…”

“…One shortcoming of conventional antidepressant treatments is that the several-week delay needed to achieve clinically meaningful improvement prolongs patients' vulnerability to suicide and disability. Treatments that produce antidepressant responses within 1 week-electroconvulsive therapy, high-dose TCA drug administration, total sleep deprivation, and ketamine use [44][45][46][47][48] -have not proved amenable to widespread clinical application because of their adverse effects or the transient nature of their therapeutic benefits. In contrast, the absence of serious adverse effects encountered in this study suggests that scopolamine may provide a relatively safe and well-tolerated intervention for achieving rapid antidepressant responses.…”

Intravenous antidepressants: A review

“…In the case of maprotiline [Kissling et al, 1985], oral administration was found to be more advantageous. For amitryptiline [Deisenhammer et al, 2000], no significant differences were reported between oral, i.v., and high-dose i.v. administration despite a trend in favor of high-dose i.v.…”