Safety and Tolerability of Edivoxetine for Long-Term Treatment of Major Depressive Disorder in Adult Patients


This 12-month open-label, but dose-blinded extension phase, evaluated the safety and tolerability of flexibly-dosed edivoxetine (6, 9, 12 or 18 mg once daily) in patients (N = 397) with major depressive disorder, who completed the 10-week randomized, double-blind, placebo-controlled acute phase of the study.All patients were treated with edivoxetine during the extension phase. The mean age of the patients was 45 years, and most were white females. Safety evaluations included assessment of treatment-emergent adverse events (TEAEs), laboratory and vital sign measures, and suicidality. Within-group t-tests based on a 2-sided significance level of 0.05 and 95% confidence levels were used to assess whether changes from baseline were statistically significant from zero. The overall completion rate was 54%. Adverse event was the most common (14.4%) reason for discontinuation, which included blood pressure increased (1.3%), heart rate increased (1.3%), anxiety (1.0%), and tachycardia (1.0%). At least 1 TEAE was reported by 72.3% of patients, of which headache (10.8%) and hyperhidrosis (10.1%) were the most common; 2.8% of patients had ≥1 serious adverse events, and there were no completed suicides. No clinically relevant changes were observed in most laboratory measures. Potentially clinically significant changes in ALT values occurred in 1.8% of patients, and either normalized or had decreased by the last assessment. Mean increases in blood pressure and pulse were consistent with those observed in the acute phase and appeared to reach a plateau within 3 to 5 months of treatment. In conclusion, safety and tolerability findings during this long-term extension phase evaluation of edivoxetine were consistent with its norepinephrine reuptake inhibition profile.

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Oakes, T. , Martinez, J. , Dellva, M. , Goldberger, C. , Pangallo, B. , Bangs, M. , Ahl, J. and White, W. (2014) Safety and Tolerability of Edivoxetine for Long-Term Treatment of Major Depressive Disorder in Adult Patients. Open Journal of Psychiatry, 4, 131-140. doi: 10.4236/ojpsych.2014.42017.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Hirschfeld, R.M. (2001) Clinical Importance of Long-Term Antidepressant Treatment. British Journal of Psychiatry, 42, S4-S8.
[2] Greden, J.F. (2001) The Burden of Recurrent Depression: Causes, Consequences, and Future Prospects. Journal of Clinical Psychiatry, 62(Suppl 22), 5-9.
[3] Keller, M.B. (2002) Rationale and Options for the Long-Term Treatment of Depression. Human Psychopharmacology, 17, S43-S46.
[4] Stahl, S.M., Zhang, L., Damatarca, C. and Grady, M. (2003) Brain Circuits Determine Destiny in Depression: A Novel Approach to the Psychopharmacology of Wakefulness, Fatigue, and Executive Dysfunction in Major Depressive Disorder. Journal of Clinical Psychiatry, 64(Suppl 14), 6-17.
[5] Pangallo, B., Dellva, M.A., D’Souza, D.N., Essink, B., Russell, J. and Goldberger, C. (2011) A Randomized, Double-Blind Study Comparing LY2216684 and Placebo in the Treatment of Major Depressive Disorder. Journal of Psychiatric Research, 45, 748-755.
[6] Sheehan, D.V., Lecrubier, Y., Sheehan, K.H., Amorim, P., Janavs, J., Weiller, E., Hergueta, T., Baker, R. and Dunbar, G.C. (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): The Development and Validation of a Structured Diagnostic Psychiatric Interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry, 59(Suppl 20), 22-33.
[7] Williams, J.B., Kobak, K.A., Bech, P., Engelhardt, H., Evans, K., Lipsitz, J., Olin, J., Pearson, J. and Kalali, A. (2008) The GRID-HAMD: Standardization of the Hamilton Depression Rating Scale. International Clinical Psychopharmacology, 23, 120-129. 2f948f5
[8] Guy, W. (1976) Clinical Global Impressions, ECDEU Assessment Manual for Psychopharmacology, revised (DHEW Publ. No. ADM 76-338). National Institute of Mental Health, Rockville, 218-222.
[9] Posner, K., Brown, G.K., Stanley, B., Brent, D.A., Yershova, K.V., Oquendo, M.A., Currier, G.W., Melvin, G.A., Greenhill, L., Shen, S. and Mann, J.J. (2011) The Columbia-Suicide Severity Rating Scale: Initial Validity and Internal Consistency Findings from Three Multisite Studies with Adolescents and Adults. American Journal of Psychiatry, 168, 1266-1277.
[10] Montgomery, S.A. and ?sberg, M. (1979) A New Depression Scale Designed to be Sensitive to Change. British Journal of Psychiatry, 134, 382-389.
[11] Matza, L.S., Phillips, G.A., Revicki, D.A., Murray, L. and Malley, K.G. (2011) Development and Validation of a Patient-Report Measure of Fatigue Associated with Depression. Journalof Affective Disorders, 134, 294-303.
[12] Sheehan, D.V. (1983) The Anxiety Disease. Scribner, New York.
[13] Dubé, S., Dellva, M.A., Jones, M., Kielbasa, W., Padich, R., Saha, A. and Rao, P. (2010) A Study of the Effects of LY2216684, a Selective Norepinephrine Reuptake Inhibitor, in the Treatment of Major Depression. Journal of Psychiatric Research, 44, 356-363. 2009.09.013
[14] Versiani, M., Mehilane, L., Gaszner, P. and Arnaud-Castiglioni, R. (1999) Reboxetine, a Unique Selective NRI, Prevents Relapse and Recurrence in Long-Term Treatment of Major Depressive Disorder. Journal of Clinical Psychiatry, 60, 400-406.
[15] Schweitzer, I., Burrows, G., Tuckwell, V., Polonowita, A., Flynn, P., George, T., Theodoros, M. and Mitchell, P. (2001) Sustained Response to Open-Label Venlafaxine in Drug-Resistant Major Depression. Journal of Clinical Psychopharmacology, 21, 185-189.
[16] Raskin, J., Goldstein, D.J., Mallinckrodt, C.H. and Ferguson, M.B. (2003) Duloxetine in the Long-Term Treatment of Major Depressive Disorder. Journal of Clinical Psychiatry, 64, 1237-1244.
[17] Wohlreich, M.M., Mallinckrodt, C.H., Watkin, J.G. and Hay, D.P. (2004) Duloxetine for the Long-Term Treatment of Major Depressive Disorder in Patients Aged 65 and Older: An Open-Label Study. BMC Geriatrics, 7, 4-11.
[18] Wade, A., Despiegel, N. and Heldbo Reines, E. (2006) Escitalopram in the Long-Term Treatment of Major Depressive Disorder. Annals of Clinical Psychiatry, 18, 83-89.
[19] Chokka, P. and Legault, M. (2008) Escitalopram in the Treatment of Major Depressive Disorder in Primary-Care Settings: An Open-Label Trial. Depression and Anxiety, 25, E173-E181.
[20] Dunner, D.L., Wilson, M., Fava, M., Kornstein, S., Munoz, R., O’Reardon, J., Trivedi, M. and Wohlreich, M. (2008) Long-Term Tolerability and Effectiveness of Duloxetine in the Treatment of Major Depressive Disorder. Depression and Anxiety, 25, E1-E8.
[21] Tourian, K.A., Pitrosky, B., Padmanabhan, S.K. and Rosas, G.R. (2011) A 10-Month, Open-Label Evaluation of Desvenlafaxine in Outpatients with Major Depressive Disorder. Primary Care Companionto CNS Disorders, 13, ii: PCC.10m00977.
[22] Mago, R., Forero, G., Greenberg, W.M., Gommoll, C. and Chen, C. (2013) Safety and Tolerability of Levomilnacipran ER in Major Depressive Disorder: Results from an Open-Label, 48-Week Extension Study. Clinical Drug Investigations, 33, 761-771.
[23] Kelly, K., Posternak, M. and Alpert, J.E. (2008) Toward Achieving Optimal Response: Understanding and Managing Antidepressant Side Effects. Dialogues in Clinical Neuroscience, 10, 409-418.
[24] Citrome, L. (2013) Levomilnacipran for Major Depressive Disorder: A Systematic Review of the Efficacy and Safety Profile for This Newly Approved Antidepressant—What Is the Number Needed to Treat, Number Needed to Harm and Likelihood to be Helped or Harmed? International Journal of Clinical Practice, 67, 1089-10104.
[25] Serretti, A. and Chiesa, A. (2009) Treatment-Emergent Sexual Dysfunction Related to Antidepressants: A MetaAnalysis. Journal of Clinical Psychopharmacology, 29, 259-266.

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