Download PDF
Pharmacopsychiatry 2007; 40(1): 14-19
DOI: 10.1055/s-2007-958523
Original Paper

© Georg Thieme Verlag KG Stuttgart · New York

Reboxetine Combination in Treatment-resistant Depression to Selective Serotonin Reuptake Inhibitors

F. López-Muñoz 1 , C. Álamo 1 , G. Rubio 2 , P. García-García 1 , A. Pardo 3
  • 1Pharmacology Department, Faculty of Medicine, University of Alcalá, Madrid, Spain
  • 2Retiro Mental Health Services, Department of Psychiatry, Complutense University, Madrid, Spain
  • 3Department of Social Psychology and Methodology, Faculty of Psychology, Autónoma University, Madrid, Spain
Further Information

Publication History

received 15. 5. 2006 revised 29. 9. 2006

accepted 10. 10. 2006

Publication Date:
27 February 2007 (online)

Also available at
    Permissions and Reprints

Abstract

Introduction: Treatment-resistant depression is a relatively common clinical occurrence: between 60-70% of depressive patients fail to achieve total remission to the initial treatment with selective serotonin reuptake inhibitors (SSRI).

Methods: In this prospective 12-week open-label study, we evaluated the effectiveness of the addition of reboxetine to 141 outpatients diagnosed with major depressive disorder, according to DSM-IV-TR criteria, who were partial responders or non-responders over a period of 6 weeks, to previous treatment in monotherapy with SSRI. Evaluation of antidepressant efficacy was carried out through the application of the Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impressions-Global Improvement Scale (CGI-I). Data were analyzed on an intent-to-treat basis, using the last-observation-carried-forward method.

Results: Mean score on the HDRS at baseline was 26.24±7.21, falling to 13.96±8.00 in week 12 (mean decrease of 46.79%; p<0.0001) The percentages of responders (HDRS total score ≥50%) and patients considered as benefiting from complete remission (HDRS score ≤10) at 12 weeks were 50.4% and 34.5%, respectively. By the end of the treatment, a mean decrease in CGI-I score of 1.88 points was obtained (41.14% of reduction; p<0.0001), and 77% of the patients were evaluated as improved (CGI-I score <4). Nervousness was the adverse effect most frequently reported (5.21%), followed by dryness of mouth (4.38%), and insomnia (3.56%).

Conclusion: The results of this study suggest that the combination strategy with reboxetine appears to be a potentially useful tool in cases of SSRI-resistant depression.

References

  • 1 Agüera LF, Rojo JE, Ros S, De la Gándara J, De Pedro JM. Antidepressant combinations: epidemiological considerations.  Acta Psychiatr Scand. 2005;  112 7-10
    CrossrefPubMedGoogle Scholar
  • 2 Amsterdam JD, García-España F, Rosenzweig M. Clomipramine augmentation in treatment-resistant depression.  Depress Anxiety. 1997;  5 84-90
    CrossrefPubMedGoogle Scholar
  • 3 Avenoso A, Facciolà G, Scordo MG, Spina E. No effect of the new antidepressant reboxetine on CYP2D6 activity in healthy volunteers.  Ther Drug Monit. 1999;  21 577-579
    CrossrefPubMedGoogle Scholar
  • 4 Berman RM, Narasimhan M, Charney DS. Treatment-Refractory Depression: Definitions and Characteristics.  Depress Anxiety. 1997;  5 154-164
    CrossrefPubMedGoogle Scholar
  • 5 Blazer DG, Kessler RC, McGonagle KA, Swartz MS. The prevalence and distribution of major depression in a National Community Sample: The National Comorbidity Survey.  Am J Psychiatry. 1994;  151 979-986
    PubMedGoogle Scholar
  • 6 Bodkin JA, Lasser RA, Wines JD, Gardner DM, Baldessarini RJ. Combining serotonin reuptake inhibitors and bupropion in partial responders to antidepressant monotherapy.  J Clin Psychiatry. 1997;  58 137-145
    PubMedGoogle Scholar
  • 7 Carpenter LL, Jocic Z, Hall JM, Rasmussen SA, Price LH. Mirtazapine augmentation in the treatment of refractory depression.  J Clin Psychiatry. 1999;  60 45-49
    PubMedGoogle Scholar
  • 8 Carpenter LL, Yasmin S, Price LH. A double-blind, placebo-controlled study of antidepressant augmentation with mirtazapine.  Biol Psychiatry. 2002;  51 183-188
    CrossrefPubMedGoogle Scholar
  • 9 Cuenca E, Alamo C, López-Muñoz F, Coullaut-Jáuregui J. Perfil farmacodinámico y farmacocinético de un nuevo antidepresivo.  Psiquiatr Biol. 1999;  6 86-90
    PubMedGoogle Scholar
  • 10 De la Gándara J, Ágüera L, Ros S, De Pedro JM. Use of antidepressant combinations: which, when and why? Results of a Spanish survey.  Acta Psychiatry Scand. 2005;  112 32-35
    PubMedGoogle Scholar
  • 11 De la Gándara J, Rojo JE, Agüera L, De Pedro JM. Neuropharmacological basis of combining antidepressants.  Acta Psychiatry Scand. 2005;  112 11-13
    PubMedGoogle Scholar
  • 12 Devarajan S, Dursun SM. Citalopram plus reboxetine in treatment-resistant depression.  Can J Psychiatr. 2000;  45 489-490
    PubMedGoogle Scholar
  • 13 Dodd S, Horgan D, Malhi GS, Berk M. To combine or not to combine? A literature review of antidepressant combination therapy.  J Affect Disord. 2005;  89 1-11
    CrossrefPubMedGoogle Scholar
  • 14 Fava M. Diagnosis and definition of treatment-resistant depression.  Biol Psychiatr. 2003;  53 649-659
    CrossrefPubMedGoogle Scholar
  • 15 Fava M, Davidson KG. Definition and epidemiology of treatment-resistant depression.  Psychiatry Clin North Am. 1996;  19 179-200
    CrossrefPubMedGoogle Scholar
  • 16 Fava M, Rosenbaum JF, McGrath PJ, Stewart JW, Amsterdam JD, Quitkin FM. Lithium and tricyclic augmentation of fluoxetina treatment for resistant major depression: a double-blind, controlled study.  Am J Psychiatry. 1994;  151 1372-1374
    PubMedGoogle Scholar
  • 17 Fredman SJ, Fava M, Kienke AS, White CN, Nierenberg AA, Rosenbaum JF. Partial response, nonresponse, and relapse with selective serotonin reuptake inhibitors in major depression: a survey of current “next-step” practices.  J Clin Psychiatr. 2000;  61 403-408
    PubMedGoogle Scholar
  • 18 Harkin A, Kelly JP, McNamara M, Connor TJ, Dredge K, Redmond A. et al . Activity and onset of action of reboxetine and effect of combination with sertraline in an animal model of depression.  Eur J Pharmacol. 1999;  364 123-132
    CrossrefPubMedGoogle Scholar
  • 19 Hawley CJ, Sivakumaran T, Ochocki M, Bevan J. Coadministration therapy with reboxetine and serotonin specific reuptake inhibitors in twenty-four patients with major depression. 13th Congress of European College of Neuropsychopharmacology. Munich, Germany, September.  2000;  9-13
    PubMedGoogle Scholar
  • 20 Hirschfeld RM, Montgomery SA, Aguglia E, Amore M, Delgado PL, Gastpar M. et al . Partial response and nonresponse to antidepressant therapy: current approaches and treatment options.  J Clin Psychiatry. 2002;  63 826-837
    PubMedGoogle Scholar
  • 21 Joffe RT. Substitution Therapy in Patients with Major Depression.  CNS Drugs. 1999;  11 175-180
    CrossrefPubMedGoogle Scholar
  • 22 Kennedy SH, McCann SM, Masellis M, McIntyre RS, Raskin J, McKay G, Baker GB. Combining bupropion SR with venlafaxine, paroxetine, or fluoxetine: a preliminary report on pharmacokinetic, therapeutic, and sexual dysfunction effects.  J Clin Psychiatry. 2002;  63 181-186
    PubMedGoogle Scholar
  • 23 Kent JM. SNaRIs, NaSSAs, and NaRIs: new agents for the treatment of depression.  Lancet. 2000;  355 911-918
    CrossrefPubMedGoogle Scholar
  • 24 Lam RW, Hossie H, Solomons K, Yatham LN. Citalopram and bupropion-SR: combining versus switching in patients with treatment-resistant depression.  J Clin Psychiatry. 2004;  65 337-340
    PubMedGoogle Scholar
  • 25 Lam RW, Wan DDC, Cohen NL, Kennedy SH. Combining antidepressants for treatment-resistant depression: a review.  J Clin Psychiatry. 2002;  63 685-693
    CrossrefPubMedGoogle Scholar
  • 26 Lepine JP, Gastpar M, Mendlewicz J, Tylee A. Depression in the community: The first pan-European study DEPRES (Depression Research in European Society).  Int Clin Psychopharmacol. 1997;  12 19-29
    PubMedGoogle Scholar
  • 27 López-Ibor JJ, Alamo C, López-Muñoz F, Cuenca E, Rubio G, Otero FJ. Evolution of the management of depression in Spain from the psychiatrist's perspective. A comparative analysis: 1997 vs. 1982.  Eur Psychiatry. 2000;  15 362-369
    CrossrefPubMedGoogle Scholar
  • 28 Lucca A, Serretti A, Smeraldi E. Effect of reboxetine augmentation in SRRI resistant patients.  Hum Psychopharmacol Clin Exp. 2000;  15 143-145
    CrossrefPubMedGoogle Scholar
  • 29 Martín-Águeda B, López-Muñoz F, Rubio G, Guerra JA, Silva A, Álamo C. Management of depression in primary care: a survey of general practitioners in Spain.  Pharmacopsychiatry. 2005;  27 305-312
    PubMedGoogle Scholar
  • 30 Moret C. Combination/augmentation strategies for improving the treatment of depression.  Neuropsychiatr Dis Treat. 2005;  1 301-309
    PubMedGoogle Scholar
  • 31 Nelson JC. Synergistic benefits of serotonin and noradrenaline reuptake inhibition.  Depress Anxiety. 1998;  7 ((Suppl 1)) 5-6
    CrossrefPubMedGoogle Scholar
  • 32 Nelson JC, Mazure CM, Bowers MB, Jatlow PI. A preliminary open study if the combination of fluoxetine and desipramine for rapid treatment of major depression.  Arch Gen Psychiatry. 1991;  48 303-307
    PubMedGoogle Scholar
  • 33 Nelson JC, Mazure CM, Jatlow PI, Bowers MB, Price LH. Combining norepinephrine and serotonin reuptake inhibition mechanisms for treatment of depression: a double-blind, randomized study.  Biol Psychiatry. 2004;  55 296-300
    CrossrefPubMedGoogle Scholar
  • 34 Nemeroff CB. Augmentation strategies in patients with refractory depression.  Depression. 1997;  4 169-181
    PubMedGoogle Scholar
  • 35 Nierenberg AA, Amsterdam JD. Resistant depression: Definition and treatment approaches.  J Clin Psychiatry. 1990;  51 S39-S47
    PubMedGoogle Scholar
  • 36 O'Reardon JP, Brunswick DJ, Amsterdam JD. Treatment-resistant depression in the age of serotonin: evolving strategies.  Curr Opin Psychiatry. 2000;  13 93-98
    CrossrefPubMedGoogle Scholar
  • 37 Pilhatsch MK, Burhgardt R, Wandinger KP, Bauer M, Adli M. Augmentation with atomoxetine in treatment-resistant depression with psychotic features.  Pharmacopsychiatry. 2006;  39 79-80
    Article in Thieme ConnectPubMedGoogle Scholar
  • 38 Rojo JE, Ros S, Agüera L, De la Gándara J, De Pedro JM. Combined antidepressant: clinical experience.  Acta Psychiatry Scand. 2005;  112 25-31
    PubMedGoogle Scholar
  • 39 Ros S, Agüera L, De la Gándara J, Rojo JE, De Pedro JM. Potentiation strategies for treatment-resistant depression.  Acta Psychiatr Scand. 2005;  112 14-24
    CrossrefPubMedGoogle Scholar
  • 40 Rubio G, San L, López-Muñoz F, Alamo C. Reboxetine adjunct for partial or nonresponders to antidepressant treatment.  J Affect Disord. 2004;  81 67-72
    CrossrefPubMedGoogle Scholar
  • 41 Rubio G, San L, López-Muñoz F, García-García P, Álamo C. Tratamiento de combinación con reboxetina en pacientes con depresión mayor no respondedores o con respuesta parcial a inhibidores selectivos de la recaptación de serotonina.  Actas Esp Psiquiatr. 2003;  31 315-324
    PubMedGoogle Scholar
  • 42 Serretti A, Lucca A, Cusin C, Smeraldi E. Associazione di reboxetine nella depressione resistente a SSRI. .  Giorn Ital Psicopatol. 2001;  7 9-14
    PubMedGoogle Scholar
  • 43 Spier SA. Use of bupropion with SRIs and venlafaxine.  Depress Anxiety. 1998;  7 73-75
    CrossrefPubMedGoogle Scholar
  • 44 Stanley B. An integration of ethical and clinical considerations in the use of placebos.  Psychopharmacol Bull. 1988;  24 180-220
    PubMedGoogle Scholar
  • 45 Tanum L. Reboxetine: tolerability and safety profile in patients with major depression.  Acta Psychiatr Scand. 2000;  101 ((Suppl 402)) 37-40
    CrossrefPubMedGoogle Scholar
  • 46 Tse WS, Bond AJ. Noradrenaline might enhance assertive human social behaviours: an investigation in a flatmate relationship.  Pharmacopsychiatry. 2006;  39 175-179
    Article in Thieme ConnectPubMedGoogle Scholar
  • 47 Zajecka JM, Jeffriess H, Fawcett J. The Efficacy of Fluoxetine Combined with a Heterocyclic Antidepressant in Treatment-Resistant Depression: A Retrospective Analysis.  J Clin Psychiatry. 1995;  56 338-343
    PubMedGoogle Scholar

Correspondence

F. López-Muñoz

Pharmacology Department · University of Alcalá

C/Juan Ignacio Luca de Tena 8

28027 Madrid

Spain

Phone: +34/91/724 82 10

Fax: +34/91/724 82 05

Email: frlopez@juste.net