Efficacy and tolerability of the novel triple reuptake inhibitor amitifadine in the treatment of patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial

Journal of Psychiatric Research

Volumn 46, Issue 1, 2012, Pages 64-71

  Tran, Pierre ^a   Skolnick, Phil ^b   Czobor, Pal ^b   Huang, N Y ^b   Bradshaw, Mark ^c   McKinney, Anthony ^a   Fava, Maurizio ^d  

^a Euthymics Bioscience Inc   (United States)

^b DOV Pharmaceutical   (United States)

^c Global Consulting Partners   (United States)

^d MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Amitifadine; Anhedonia; Major depressive disorder; Sexual function; Triple reuptake inhibitor; Weight

Indexed keywords

1 (3,4 DICHLOROPHENYL) 3 AZABICYCLO[3.1.0]HEXANE; AMITIFADINE; EB 1010; PLACEBO; TRIPLE REUPTAKE INHIBITOR; UNCLASSIFIED DRUG;

ABDOMINAL PAIN; ADULT; ANHEDONIA; ANXIETY; ARTICLE; CLINICAL GLOBAL IMPRESSION SCALE; CONTROLLED STUDY; DIARRHEA; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG TOLERABILITY; EMOTIONAL DISORDER; FEMALE; HAMILTON SCALE; HEADACHE; HUMAN; INTENTION TO TREAT ANALYSIS; IRRITABILITY; LASSITUDE; MAJOR CLINICAL STUDY; MAJOR DEPRESSION; MALE; MONTGOMERY ASBERG DEPRESSION RATING SCALE; MULTICENTER STUDY; NAUSEA; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RASH; SELF REPORT; SEXUALITY; SIDE EFFECT; UPPER RESPIRATORY TRACT INFECTION;

ADOLESCENT; ADULT; AGED; ANTIDEPRESSIVE AGENTS; AZA COMPOUNDS; BICYCLO COMPOUNDS, HETEROCYCLIC; DEPRESSIVE DISORDER, MAJOR; DOUBLE-BLIND METHOD; FEMALE; FOLLOW-UP STUDIES; HUMANS; INTERNATIONAL COOPERATION; MALE; MIDDLE AGED; PSYCHIATRIC STATUS RATING SCALES; TREATMENT OUTCOME; YOUNG ADULT;

EID: 81855211117     PISSN: 00223956     EISSN: 18791379     Source Type: Journal    
DOI: 10.1016/j.jpsychires.2011.09.003     Document Type: Article

References (65)

1. Diagnostic and statistical manual of mental disorders 2000, American Psychiatric Association, rev.: DSM-IV-R, American Psychiatric Association, Washington (DC). 4th ed.
2. Anderson I.M. Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability. Journal of Affective Disorders 2000, 58:19-36.
3. Axel A.M., Mikkelsen J.D., Hansen H.H. Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of alpha1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat. Neuropsychopharmacology 2010, 35:1464-1476.
4. Bech P., Cialdella P., Haugh M.C., Birkett M.A., Hours A., Boissel J.P., et al. Meta-analysis of randomised controlled trials of fluoxetine v. placebo and tricyclic antidepressants in the short-term treatment of major depression. British Journal of Psychiatry 2000, 176:421-428.
5. Blier P., Ward H.E., Tremblay P., Laberge L., Hébert C., Bergeron R. Combination of antidepressant medications from treatment initiation for major depressive disorder: a double-blind randomized study. American Journal of Psychiatry 2010, 167:281-288.
6. Blier P. Crosstalk between the norepinephrine and serotonin systems and its role in the antidepressant response. Journal of Psychiatry Neuroscience 2001, 26(Suppl.):S3-S10.
7. Bymaster F.P., McKinney A. Effects of the unbalanced triple transporter inhibitor EB-1010 on monoamine uptake transporters in vitro and in vivo. Neuropsychopharmacology 2010, 35:S174.
8. Cipriani A., Furukawa T.A., Salanti G., Geddes J.R., Higgins J.P., Churchill R., et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet 2009, 373:746-758.
9. Clayton A., Pradko J., Croft H., Montano C.B., Leadbetter R.A., Bolden-Watson C., et al. Prevalence of sexual dysfunction among newer antidepressants. Journal of Clinical Psychiatry 2002, 63:357-366.
10. Clayton A.H., Montejo A.L. Major depressive disorder, antidepressants, and sexual dysfunction. Journal of Clinical Psychiatry 2006, 67(Suppl. 6):33-37.
11. Derogatis L.R., Melisaratos N. The DSFI: a multidimensional measure of sexual functioning. Journal of Sex and Marital Therapy 1979, 5:244-281.
12. Dichter G.S. Anhedonia in unipolar major depressive disorder: a review. Psychiatric Journal 2010, 4:1-9.
13. Dunlop B.W., Nemeroff C.B. The role of dopamine in the pathophysiology of depression. Archives of General Psychiatry 2007, 64:327-337.
14. El Mansari M., Guiard B.P., Chernoloz O., Ghanbari R., Katz N., Blier P. Relevance of norepinephrine-dopamine interactions in the treatment of major depressive disorder. CNS Neuroscience and Therapeutics 2010, 16:e1-17.
15. Fava M., Graves L.M., Benazzi F., Scalia M.J., Iosifescu D.V., Alpert J.E., et al. A cross-sectional study of the prevalence of cognitive and physical symptoms during long-term antidepressant treatment. Journal of Clinical Psychiatry 2006, 67:1754-1759.
16. Fava M. Weight gain and antidepressants. Journal of Clinical Psychiatry 2000, 61(Suppl. 11):37-41.
17. Fournier J.C., DeRubeis R.J., Hollon S.D., Dimidjian S., Amsterdam J.D., Shelton R.C., et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA 2010, 303:47-53.
18. Gabryelewicz T., Styczynska M., Pfeffer A., Wasiak B., Barczak A., Luczywek E., et al. Prevalence of major and minor depression in elderly persons with mild cognitive impairment-MADRS factor analysis. International Journal of Geriatric Psychiatry 2004, 19:1168-1172.
19. Gamo N.J., Arnsten A.F. Molecular modulation of prefrontal cortex: rational development of treatments for psychiatric disorders. Behavioral Neuroscience 2011, 125:282-296.
20. Guiard B.P., El Mansari M., Blier P. Prospect of a dopamine contribution in the next generation of antidepressant drugs: the triple reuptake inhibitors. Current Drug Targets 2009, 10:1069-1084.
21. Guy W. The clinician global severity and impression scales. ECDEU assessment manual for psychopharmacology 1976, 218-222. Superintendent of Documents, US Government Printing Office, US Department of Health, Education, and Welfare Publication, Washington (DC), No. 76-338.
22. Hamilton M. A rating scale for depression. Journal of Neurology Neurosurgery and Psychiatry 1960, 23:56-62.
23. Hamilton M. The assessment of anxiety states by rating. British Journal of Medical Psychology 1959, 32:50-55.
24. Hammond M.F. Rating depression severity in the elderly physically ill patient: reliability and factor structure of the Hamilton and the Montgomery-Asberg depression rating scales. International Journal of Geriatric Psychiatry 1998, 1998(13):257-261.
25. Kennedy S.H., Andersen H.F., Lam R.W. Efficacy of escitalopram in the treatment of major depressive disorder compared with conventional selective serotonin reuptake inhibitors and venlafaxine XR: a meta-analysis. Journal of Psychiatry Neuroscience 2006, 31:122-131.
26. Kuzelova H., Ptacek R., Macek M. The serotonin transporter gene (5-HTT) variant and psychiatric disorders: review of current literature. Neurology and Endocrinology Letters 2010, 31:4-10.
27. Lengyel K., Pieschl R., Strong T., Molski T., Mattson G., Lodge N.J., et al. Ex vivo assessment of binding site occupancy of monoamine reuptake inhibitors: methodology and biological significance. Neuropharmacology 2008, 55:63-70.
28. Mallinckrodt C.H., Meyers A.L., Prakash A., Faries D.E., Detke M.J. Simple options for improving signal detection in antidepressant clinical trials. Psychopharmacology Bulletin 2007, 40:101-114.
29. Mallinckrodt C.H., Sanger T.M., Dubé S., DeBrota D.J., Molenberghs G., Carroll R.J., et al. Assessing and interpreting treatment effects in longitudinal clinical trials with missing data. Biological Psychiatry 2003, 53:754-760.
30. Marks D.M., Pae C.-U., Patkar A.A. Triple reuptake inhibitors: the next generation of antidepressants. Current Neuropharmacology 2008, 6:338-343.
31. McCabe C., Mishor Z., Cowen P.J., Harmer C.J. Diminished neural processing of aversive and rewarding stimuli during selective serotonin reuptake inhibitor treatment. Biological Psychiatry 2010, 2010(67):439-445.
32. Millan M.J. Dual- and triple-acting agents for treating core and co-morbid symptoms of major depression: novel concepts, new drugs. Neurotherapeutics 2009, 6:53-77.
33. Montejo A.L., Llorca G., Izquierdo J.A., Rico-Villademoros F. Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Journal of Clinical Psychiatry 2001, 62(Suppl. 3):10-21.
34. Montgomery S.A., åsberg M. A new depression scale designed to be sensitive to change. British Journal of Psychiatry 1979, 134:382-389.
35. Nemeroff C.B., Entsuah R., Benattia I., Demitrack M., Sloan D.M., Thase M.E. Comprehensive analysis of remission (COMPARE) with venlafaxine versus SSRIs. Biological Psychiatry 2008, 63:424-434.
36. Nutt D., Demyttenaere K., Janka Z., Aarre T., Bourin M., Canonico P.L., et al. The other face of depression, reduced positive affect: the role of catecholamines in causation and cure. Journal of Psychopharmacology 2007, 21:461-471.
37. Papakostas G.I., Thase M.E., Fava M., Nelson J.C., Shelton R.C. Are antidepressant drugs that combine serotonergic and noradrenergic mechanisms of action more effective than the selective serotonin reuptake inhibitors in treating major depressive disorder? A meta-analysis of studies of newer agents. Biological Psychiatry 2007, 62:1217-1227.
38. Parker R.D., Flint E.P., Bosworth H.B., Pieper C.F., Steffens D.C. A three-factor analytic model of the MADRS in geriatric depression. International Journal of Geriatric Psychiatry 2003, 18:73-77.
39. Perović B., Jovanović M., Miljković B., Vezmar S. Getting the balance right: established and emerging therapies for major depressive disorders. Neuropsychiatric Disease and Treatments 2010, 6:343-364.
40. Roose S.P., Miyazaki M. Pharmacologic treatment of depression in patients with heart disease. Psychosomatic Medicine 2005, 67(Suppl. 1):S54-S57.
41. Rosen R.C., Lane R.M., Menza M. Effects of SSRIs on sexual function. A critical review. Journal of Clinical Psychopharmacology 1999, 19:67-85.
42. Rotenberg V.S. Sexual disorders caused by antidepressants: considerations in the context of brain hemisphere functions. Activitas Nervosa Superior 2010, 52(2):47-61.
43. Rush A.J., Trivedi M.H., Wisniewski S.R., Nierenberg A.A., Stewart J.W., Warden D., et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. American Journal of Psychiatry 2006, 163:1905-1917.
44. Schildkraut J.J., Kety S.S. Biogenic amine and emotion. Science 1967, 156:21-30.
45. Schultz W. Multiple dopamine functions at different time course. Annual Review of Neuroscience 2007, 30:259-288.
46. Serretti A., Chiesa A. Sexual side effects of pharmacological treatment of psychiatric diseases. Clinical Pharmacology and Therapeutics 2011, 89:142-147.
47. Serretti A., Chiesa A. Treatment-emergency sexual dysfunction related to antidepressants. A meta-analysis. Journal of Clinical Psychiatry 2009, 29:259-266.
48. Serretti A., Mandelli L. Antidepressants and body weight: a comprehensive review and meta-analysis. Journal of Clinical Psychiatry 2010, 71:1259-1272.
49. Sheehan D.V., Lecrubier Y., Harnett-Sheehan K., Amorim P., Janavs J., Weiller E., et al. The mini international neuropsychiatric interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview. Journal of Clinical Psychiatry 1998, 59(Suppl. 20):22-33.
50. Shelton R.C., Tomarken A.J. Can recovery from depression be achieved?. Psychiatric Services 2001, 52:1469-1478.
51. Siddiqui O., Hung H.M., O'Neill R. MMRM vs. LOCF: a comprehensive comparison based on simulation study and 25 NDA datasets. Journal of Biopharmaceutical Statistics 2009, 19:227-246.
52. Skolnick P., Basile A.S. Triple reuptake inhibitors ("broad spectrum" antidepressants). CNS Neurological Disorders and Drug Targets 2007, 6:141-149.
53. Skolnick P., Popik P., Janowski A., Beer B., Lippa A.S. Antidepressant-like actions of DOV21,947: a "triple" reuptake inhibitor. European Journal of Pharmacology 2003, 461:99-104.
54. Skolnick P., Popik P., Janowsky A., Beer B., Lippa A.S. Broad spectrum"antidepressants: is more better for the treatment of depression?. Life Sciences 2003, 73:3175-3179.
55. Skolnick P. Dopamine and depression. Dopamine and glutamate in psychiatric disorders 2005, 199-214. Humana Press, Totowa, New Jersey. W.J. Schmidt, M.E.A. Reith (Eds.).
56. Taylor M.J., Freemantle N., Geddes J.R., Bhagwagar Z. Early onset of selective serotonin reuptake inhibitor antidepressant action: systematic review and meta-analysis. Archives of General Psychiatry 2006, 63:1217-1223.
57. Thase M.E., Tran P.V., Wiltse C., Pangallo B.A., Mallinckrodt C., Detke M.J. Cardiovascular profile of duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine. Journal of Clinical Psychopharmacology 2005, 25:132-140.
58. Thase M.E. Effectiveness of antidepressants: comparative remission rates. Journal of Clinical Psychiatry 2003, 64(Suppl. 2):3-7.
59. Tremblay P., Blier P. Catecholaminergic strategies for the treatment of major depression. Current Drug Targets 2006, 7:149-158.
60. Trivedi M.H., Fava M., Wisniewski S.R., Thase M.E., Quitkin F., Warden D., et al. for the STAR*D Study Team. Medication augmentation after the failure of SSRIs for depression. New England Journal of Medicine 2006, 354:1243-1252.
61. Turner E.H., Matthers A.M., Linardatos E., Tell R.A., Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. New England Journal of Medicine 2008, 358:252-260.
62. Turner E.H., Rosenthal R. Efficacy of antidepressants. British Medical Journal 2008, 336:516-517.
63. Walsh B.T., Seidman S.N., Sysko R., Gould M. Placebo response in studies of major depression: variable, substantial, and growing. JAMA 2002, 287:1840-1847.
64. Williams V.S., Baldwin D.S., Hogue S.L., Fehnel S.E., Hollis K.A., Edin H.M. Estimating the prevalence and impact of antidepressant-induced sexual dysfunction in 2 European countries: a cross-sectional patient survey. Journal of Clinical Psychiatry 2006, 67:204-210.
65. Wong D.T., Bymaster F.P., Engleman E.A. Prozac (fluoxetine, Lilly 110140), the first selective serotonin uptake inhibitor and an antidepressant drug: twenty years since its first publication. Life Sciences 1995, 57:411-441.