Dr. Bob's Psychopharmacology Tips

Reboxetine

Date: Mon, 29 Sep 1997 10:32:21 -0400
From: Cyrus Wolfman <cwolfman@ix.netcom.com>
Subject: Reboxetine

The following material may be helpful re reboxetine:

PRNewswire:Pharmaceutical (via farcast.com) reported on 4/17/97 that Pharmacia & Upjohn announced that it received marketing authorization from the United Kingdom Medicines Control Agency to market Edronax (reboxetine) for the treatment of depressive illness. They described it as a selective noradrenaline reuptake inhibitor.

The following is from Reuters-9/16/97 (via quote.com).

New Antidepressant Superior to Prozac

By Elizabeth Fullerton

VIENNA, Sept 16 (Reuter) - A new drug has outperformed Eli Lilly's best-selling Prozac in treating depression and getting patients back into everyday life faster, experts said on Tuesday.

Professor of psychiatry Stuart Montgomery of Imperial College, London, said that studies on Edronax (reboxetine), produced by Swedish-U.S. drugs group Pharmacia & Upjohn Inc, had shown remarkable results.

"In a direct head-to-head comparison Edronax is significantly better in treating severe depression than Prozac," he told Reuters, summarising a report presented at a European College of Neuropsychopharmacology forum in Vienna.

Montgomery said that the trials also included a scale measuring patients' ability to be rehabilitated in society.

"Edronax showed a similar efficacy but it seemed to be significantly faster than Prozac in making people start participating socially again," he said...

Edronax is unique because it acts purely on the noradrenalin reuptake inhibitor... Experts believe drive and motivation are related to noradrenaline, whereas mood states are associated with serotonin. Edronax has been found to have a direct and fast-working impact on patient motivation and drive...

"Edronax is different as social phobias seem to respond very well early on," said Brian Leonard, psychiatry professor at University College, Gallway.

Leonard also said Edronax had no sedative qualities and did not produce the major adverse side effects shown with tricyclics such as sexual dysfunction, which often cause patients to discontinue treatment...

"There is good evidence from placebo-controlled trials of acute efficacy and in long term treatment the drug certainly works in depression, and particularly in the severe depression group, which is difficult to treat," he added...

"This (drug) is a very important step because it helps to delineate both how depression is working and aspects of social function. It's a very exciting development," Montgomery said.

Date: Tue, 23 Dec 1997 11:41:12 -0500
From: Stephen Bazire <SBazire@compuserve.com>
Subject: Reboxetine

Reboxetine (Edronax) is a new antidepressant licensed in the UK and a few other EC countries for depression. It is a selective noradrenaline (norepinephrine) reuptake inhibitor and has no dopamine, histamine, adrenergic or serotonin effects but a weak anticholinergic action.

4 mg bid is the adult dose, and use in the elderly has recently been removed from the indications due to the lack of a double-blind trial against placebo.

At present there is little published data but in short-term studies it appears as effective as imipramine (Berzewski et al, Eur Neuropsychopharmacol 1997, (Suppl 1), S37-S47), desipramine and fluoxetine in major depression. A higher level of social functioning has been shown with reboxetine, using a validated scale (SASS) but equivalent assessment against other antidepressants is awaited. Relapse prevention has been shown in a one year study against placebo. There is no effect on reaction time (Hindmarsh, Eur Neuropsychopharmacol 1997, (Suppl 1), S17-S21). Dostert et al, Eur Neuropsychopharmacol 1997, (Suppl 1), S23-S35).

It has been marketed in the UK as an "activator", and the company managed to get several articles in newspapers about the drug, which created quite a bit of interest. There has been some obvious thought about use as an adjunct to SSRIs, but there is a lack of safety data on this combination.

Date: Tue, 28 Apr 1998 23:44:17 -0500
From: Larry Ereshefsky <ereshefsky@uthscsa.edu>
Subject: Reboxetine

At 22:25 -0500 4/27/98, Jonathan Nye wrote:

Does anyone know if there are plans to market reboxetine in the US?

Date: Thu, 30 Apr 1998 22:59:03 -0700
From: Frank Feiner <nfrank@pol.net>
Subject: Reboxetine

Reboxetine is a "structurally novel" antidepressant that actually looks more than a little like fluoxetine (Prozac) (both are 3-aryloxy-3-phenyl-n-propylamines), that is billed as a norepinephrine specific reuptake inhibitor ("NARI").

Is there a role for a pure noradrenergic drug in the treatment of depression? Montgomery-SA Eur-Neuropsychopharmacol. 1997 Apr; 7 Suppl 1: S3-9; discussion S71-3:

Depression is thought to result from a dysfunction in the noradrenergic or serotonergic systems. The noradrenergic system appears to be associated with increased drive, whereas the serotonergic system relates more to changes in mood and it is possible that the different symptoms of depression may benefit from drugs acting mainly on one or other of the neurotransmitter systems. A series of studies has shown that interruption of serotonin synthesis compromises the efficacy of serotonin but not noradrenaline reuptake inhibitors, and interruption of noradrenaline synthesis compromises the efficacy of noradrenaline but not serotonin reuptake inhibitors (SSRIs). This suggests that the two classes of drugs owe their activity to functional changes in different neurotransmitter systems. Reboxetine represents a new class of drugs-the selective noradrenaline reuptake inhibitors (NARIs). It acts specifically at noradrenergic sites unlike the non-selective tricyclic antidepressants (TCAs). NARIs have a role in the treatment of depression, either alone or as adjunctive therapy.

Review of the pharmacokinetics and metabolism of reboxetine, a selective noradrenaline reuptake inhibitor. Dostert-P; Benedetti-MS; Poggesi-I Eur-Neuropsychopharmacol. 1997 Apr; 7 Suppl 1: S23-35; discussion S71-3:

The pharmacokinetics and metabolism of reboxetine, a selective noradrenaline reuptake inhibitor, in humans and animal models are reviewed here. Reboxetine has potent antidepressant activity, low affinity for alpha-adrenergic and muscarinic receptors and low toxicity in animals... Humans rapidly absorb reboxetine (tmax about 2 h) with a terminal half-life of elimination (t1/2) of 13 h, allowing twice-daily administration... Food does not affect bioavailability. There were no major inter-species differences in the metabolic profile of reboxetine. Elimination is principally renal in humans and monkeys. Reboxetine has linear pharmacokinetics in young, healthy males for single doses of 1-5 mg and in elderly, female depressed patients (up to 4 mg b.i.d.). Multiple dosing, gender or liver insufficiency had no significant effects on the pharmacokinetics. Elderly (particularly frail elderly) patients and patients with severe renal impairment may need dose reduction. Reboxetine shows no clinically relevant interaction with lorazepam and has no inhibitory effects on the major enzymes involved in drug metabolism. It may be possible to use reboxetine in combination with monoamine oxidase inhibitors as it has no inhibitory effect on this enzyme; in addition, it may protect patients against tyramine-induced reactions. In conclusion, reboxetine seems to be an antidepressant with negligible interference with the pharmacokinetics of other drugs thus fewer drug-drug interactions are expected.

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