DUAGs historie

History, goals, and activities

The Danish University Antidepressant Group (DUAG) was formally founded in 1983 in the course of a Danish multicenter trial involving the three university psychiatry clinics as well as other psychiatry departments and a department of clinical pharmacology in Denmark. The founders, Per Bech, Lars F. Gram, Per Kragh-Sørensen, Ole J. Rafaelsen, Niels Reisby and Per Vestergaard, represented these departments. The aim of DUAG was to establish an organization that could carry out high quality, investigator-driven trials in a setting of a permanent multicenter group. This, in turn, would create a better basis for understanding the basic elements of antidepressant therapy and trial conduct and thereby contribute to the long-term strategies and development in the field.

The DUAG studies have been initiated and planned by the DUAG-steering committees. Financial support has been obtained from interested drug companies. The DUAG steering committees have had the principal responsibility for data analyses and publications. The supporting drug companies have, to a varying extent, contributed to monitoring, data handling and data analyses. In the last four studies (DUAG-4,-5,-6,-7), these functions have entirely been undertaken by the DUAG Coordination Center and the steering groups. The individual members of DUAG have been encouraged to carry out more specific studies based on the DUAG material and this has resulted in publications on pharmacokinetics, clinical symptom profiles, adverse drug reactions and long-term prognosis (suicide); see publication list.

 

The DUAG-studies

DUAG has carried out four short-term trials, and two prophylaxis studies have recently been completed. In 2009 a post-ECT treatment study was started, this study was finalized in 2013.

The first two DUAG-studies (DUAG-1, DUAG-2) published 1986 and 1990 respectively, have received considerable international attention, each of them being cited 25 -30 times per year during the first 15 – 20 years following there publication. They showed a clearly weaker antidepressant effect of the two SSRIs citalopram and paroxetine in comparison with the tricyclic antidepressant clomipramine.

In a subsequent study, moclobemide was also found to be less effective than clomipramine (DUAG-3, 1993).

The dose-effect study on clomipramine (DUAG-4, 1999) showed flat and overlapping dose-effect curves for therapeutic effect and tolerability. High doses (125–200 mg/d) in comparison with the lower doses (25–50 mg/d), yielded better and/or faster antidepressant response, but with a higher rate of tolerability problems.

A prophylaxis study aimed at comparing the effect of citalopram versus clomipramine versus placebo in unipolar depression (DUAG-5). Final reports have dealed with the 6-month outcome in the pre-phase (published) and the prophylaxis part and the unsurmontable methodological issues in the severely ill patients enrolled for this study (published).

A prophylaxis study in bipolar depression, comparing litium and lamotrigine (DUAG-6) indicating that lithium might perform better after episodes of mania and that lamotrigine might perform better after episodes of depression or mixed mania, was published in 2010.

A randomised controlled 6-month double-blind study on relapse prevention with escitalopram or nortriptyline following Electro-Convulsive Treatment (DUAG-7) was started in 2009 and finalized in 2013.

Derived studies, based on material from several of the DUAG-studies have dealt with pharmacokinetics, adverse events, baseline variables (age, gender, symptomatology) and long-term morbidity, suicidality etc.

A common database for the first four DUAG-studies with about 10.000 patient-years is presently being prepared for future register-based studies on psychiatric and somatic morbidity and mortality.

Earlier heads of Centers (DUAG-study no.)
Ole J. Rafaelsen (1,2), Søren Bøjholm (1,2), Niels Reisby (1,2,3,4), Per Kragh-Sørensen (1,2,3,4,5), Per Vestergaard (1,2,3,4,5,6), Lars F. Gram (principal coordinator: 1,2,3,4,5), Per Bech (1,2,3,4,5,6,7), Jens-Knud Larsen (2,3,4,5,6,7), Tom G. Bolwig (3,4), Jens Schmidt (3,4), John Andersen (4,5), Ib Scheel-Thomsen (4,5,6), Ellen Margrethe Christensen (4,5,6,7), John-Erik Andersson (5), Annette Gjerris (5), Niels-Anton Rasmussen (5), Kurt B. Stage (5), Rasmus W. Licht (5, principal coordinator:6), Birgitte Bjerg Bendsen (5,6,7), Klaus Martiny (5,6, principal coordinator:7), Connie Thurøe Nielsen (7), Dariusz Juchnowics (7), Erik Roj Larsen (7), Henrik Kirsmeier (7), Henrik Lublin (7), Inger Brødsgaard (7), Jens Kristoffersen (7)

Reference List

DUAG 1-3

Vestergaard, P., et al. "Therapeutic potentials of recently introduced antidepressants. Danish University Antidepressant Group." Psychopharmacol.Ser. 10 (1993): 190-98.

DUAG 4

Clomipramine dose-effect study in patients with depression: clinical end points and pharmacokinetics. Danish University Antidepressant Group (DUAG). Clin.Pharmacol.Ther. 66.2 (1999): 152-65.

DUAG 5

Gram, L. F. "Acute and continuation therapy in unipolar depression: observations from the run-in phase of a maintenance trial." Acta Psychiatr.Scand. 118.2 (2008): 123-29.

Licht, R. W. "Is it possible to evaluate true prophylactic efficacy of antidepressants in severely ill patients with recurrent depression? Lessons from a placebo-controlled trial. The fifth trial of the Danish University Antidepressant Group (DUAG-5)." J.Affect.Disord. 148.2-3 (2013): 286-90.

DUAG 6

Licht, R. W., et al. "Lamotrigine versus lithium as maintenance treatment in bipolar I disorder: an open, randomized effectiveness study mimicking clinical practice. The 6th trial of the Danish University Antidepressant Group (DUAG-6)." Bipolar.Disord. 12.5 (2010): 483-93.

DUAG 7

Martiny, K., et al. "Relapse Prevention in Major Depressive Disorder After Successful Acute Electroconvulsive Treatment: a 6-month Double-blind Comparison of Three Fixed Dosages of DUAG Escitalopram and a Fixed Dose of Nortriptyline - Lessons from a Failed Randomised Trial of the Danish University Antidepressant Group (DUAG-7)." Pharmacopsychiatry 48.7 (2015): 274-78.

DUAG 8

 

Erik Roj Larsen, Rasmus W Licht, René Ernst Nielsen, Annette Lolk, Bille Borck, Claus Sørensen, Ellen Margrethe Christensen, Gustav Bizik, Janus Ravn, Klaus Martiny, Maj Vinberg, Odeta Jankuviené, Pernille Blenker Jørgensen, Poul Videbech, Per Bech. "Transcranial pulsed electromagnetic fields for treatment-resistant depression: A multicenter 8-week single-arm cohort study: The eighth trial of the Danish University Antidepressant Group"