The efficacy and tolerability of Lu AA21004 in the prevention of relapse of major depressive disorder (MDD) in patients in remission after acute treatment was evaluated. Patients (n=639) aged 18–75 years with a primary diagnosis of MDD with a current major depressive episode (MDE) ≥4 weeks’ duration, at least one prior MDE and a MADRS total score ≥26 received 12-week, open-label Lu AA21004 at 5 or 10mg/day. Patients in remission (MADRS ≤10) at both weeks 10 and 12 were assigned to double-blind treatment with either placebo or Lu AA21004 (fixed dose from Week 8).Patients (n=396) were treated, after random assignment to placebo (n=192) or Lu AA21004 (n=204). The primary analysis of time to relapse (full-analysis set, Cox proportional hazard model) showed a statistically significant difference in favour of Lu AA21004 versus placebo with a hazard ratio of 2.01 (95% confidence interval: 1.26–3.21; p=0.0035). The proportion of patients who relapsed was 13% in the Lu AA21004 group (n=27) and 26% in the placebo group (n=50). The withdrawal rates due to adverse events were 8% (open-label), and 3% (placebo) and 8% (Lu AA21004) (double-blind). Thus, Lu AA21004 was effective in preventing relapse of MDD and was well tolerated as maintenance treatment.
AdellA (2010) Lu AA21004, a multimodal serotonergic agent for the potential treatment of depression and anxiety. Drugs13: 900–910.
2.
AllgulanderCFloreaIHuusomAKT (2006) Prevention of relapse in generalised anxiety disorder by escitalopram treatment. Int J Neuropsychopharmacol9: 495–505.
3.
AlvarezEPerezVDragheimM. (2012). A double-blind, randomized, placebo-controlled, active-reference study of Lu AA21004 in patients with major depressive disorder (MDD). Int J Neuropsychopharmacol15: 589–600.
4.
American Psychiatric Association (2000) Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision (DSM-IV-TR). Washington DC: American Psychiatric Association.
5.
BaldwinDS (2004) Sexual dysfunction associated with antidepressant drugs. Expert Opin Drug Saf3: 457–470.
6.
BaldwinDSLoftHDragheimM. (2012) A randomised, double-blind, placebo controlled, duloxetine-referenced, fixed-dose study of three dosages of Lu AA21004 in acute treatment of major depressive disorder (MDD). Eur Neuropsychopharmacol22: 482–491.
7.
BandelowBBaldwinDSDolbergOT (2006) What is the threshold for symptomatic response and remission for major depressive disorder, panic disorder, social anxiety disorder, and generalized anxiety disorder?J Clin Psychiatry67: 1428–1434.
8.
Bang-AndersenBRuhlandTJørgensenM. (2011) Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): A novel multimodal compound for the treatment of major depressive disorder. J Med Chem54: 3206–3221.
9.
DoesschateMCTBocktingCLHKoeterMWJ. (2010) Prediction of recurrence in recurrent depression: A 5.5 year prospective study. J Clin Psychiatry71: 984–991.
GeddesJRCarneySMDaviesC. (2003) Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet361: 653–661.
12.
GuyW (1976) (ed.) ECDEU Assessment Manual for Psychopharmacology. Revised ed.Rockville, MD: National Institute of Mental Health.
13.
HamiltonM (1959) The assessment of anxiety states by rating. Br J Med Psychol32: 50–55.
14.
HamiltonM (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry23: 56–62.
15.
HenigsbergNMahableshwarkarAJacobsenP. (2011) Efficacy and tolerability of multiple doses of Lu AA21004 in an 8-week trial of adults with major depressive disorder. Eur Neuropsychopharmacol21(Suppl. 3): S393.
16.
HollonSDSheltonRCWisniewskiS. (2006) Presenting characteristics of depressed outpatients as a function of recurrence: Preliminary findings from the STAR*D clinical trial. J Psychiatr Res40: 59–69.
JainRMahableshwarkarARJacobsenP. (2011) Efficacy and tolerability of Lu AA21004 5 mg in a 6-week treatment of adults with Major Depressive Disorder. Poster NR4-29 presented at the 164th annual meeting of the American Psychiatric Association (APA), Honolulu, Hawaii, USA, 14–18 May 2011. Abstract available at: http://www.psych.org/lib_archives/archives/am_newresearch_2011.pdf (accessed on 3 October 2011).
LecrubierYSheehanDVWeillerE. (1997) The Mini International Neuropsychiatric Interview (MINI). A short diagnostic structured interview: Reliability and validity according to the CIDI. Eur Psychiatry12: 224–231.
21.
McGrathPJStewartJWPetkovaE. (2000) Predictors of relapse during fluoxetine continuation or maintenance treatment of major depression. J Clin Psychiatry61: 518–524.
22.
MontgomerySÅsbergM (1979) A new depression scale designed to be sensitive to change. Br J Psychiatry134: 382–389.
23.
MørkAFallonSMBrennumLT. (2011) Lu AA21004, a novel antidepressant with multimodal activity exerted through serotonergic targets. Biol Psychiatry69(9 Suppl. 1): 186S.
SeemüllerFMöllerHJObermeierM. (2010) Do efficacy and effectiveness samples differ in antidepressant treatment outcome? An analysis of eligibility criteria in randomized controlled trials. J Clin Psychiatry71: 1425–1433.
26.
World Medical Association (1964, and its amendments in force at the initiation of the study) Declaration of Helsinki: Ethical principles for medical research involving human subjects. Available at: http://www.wma.net/en/30publications/10policies/b3/ (accessed on 3 October 2011).
27.
ZetinMHoepnerCT (2007) Relevance of exclusion criteria in antidepressant clinical trials: A replication study. J Clin Psychopharmacol27: 295–301.
28.
ZimmermanMMattiaJLPosternakMA (2002) Are subjects in pharmacological trials of depression representative of patients in routine clinical practice?Am J Psychiatry159: 469–473.
