Long-Term, Open-Label, Safety Study of Edivoxetine as Adjunctive Treatment for Adult Patients with Major Depressive  Disorder Who Were Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment in Japan

Emel Serap Monkul; Mark Bangs; Keita Asato; Masashi Takahashi; Yasushi Takita; Mary Anne Dellva; Jonna Ahl; Celine Goldberger

doi:10.4236/ojpsych.2015.52022

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Open Journal of Psychiatry > Vol.5 No.2, April 2015

Long-Term, Open-Label, Safety Study of Edivoxetine as Adjunctive Treatment for Adult Patients with Major Depressive Disorder Who Were Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment in Japan ()

Emel Serap Monkul¹, Mark Bangs¹, Keita Asato², Masashi Takahashi², Yasushi Takita², Mary Anne Dellva¹, Jonna Ahl¹, Celine Goldberger¹

¹Eli Lilly and Company, Indianapolis, IN, USA.
²Eli Lilly Japan K.K. Office, Kobe, Japan.

DOI: 10.4236/ojpsych.2015.52022 PDF HTML XML 2,434 Downloads 2,996 Views

Abstract

Edivoxetine is a highly selective norepinephrine reuptake inhibitor (NRI) that has been investigated in short-term studies as adjunctive therapy to selective serotonin reuptake inhibitor antidepressants (SSRIs) in patients with major depressive disorder (MDD) who were partial responders to their SSRIs. This 52-week open-label study investigated the safety and tolerability of longer-term treatment with adjunctive edivoxetine in patients with MDD in Japan, who had completed one of two placebo-controlled acute studies of edivoxetine as adjunctive therapy to SSRIs. All patients continued on their stable dose of SSRI. Two hundred eighty-eight patients were enrolled and assessed for up to 1 year using standard safety and tolerability measures. Of these, 195 patients previously received only placebo in the parent study and, therefore, were first exposed to edivoxetine in this study. Approximately 46% of patients completed the study. The most frequently cited (>5%) reasons for discontinuation were sponsor decision (19.4%, which included patients discontinued due to early study termination), adverse event (17.4%) and subject decision (8.7%). Adverse events leading to discontinuation in more than 2 patients (>1%) were palpitations, vomiting, hepatic function abnormal, hypertension, nausea, and tachycardia. Treatment-emergent elevations in diastolic blood pressure and pulse were at least twice that reported in the literature for non-Asian patients. Twenty percent of patients had sustained elevations in pulse. Treatment-emergent changes in laboratory measures were small and not clinically meaningful. Assessment across all safety measures in this study indicated that the safety profile of edivoxetine was consistent with that expected for a selective NRI.

Keywords

Edivoxetine, Depression, SSRI, NRI, Japan, Adjunctive Therapy

Share and Cite:

Monkul, E. , Bangs, M. , Asato, K. , Takahashi, M. , Takita, Y. , Dellva, M. , Ahl, J. and Goldberger, C. (2015) Long-Term, Open-Label, Safety Study of Edivoxetine as Adjunctive Treatment for Adult Patients with Major Depressive Disorder Who Were Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment in Japan. Open Journal of Psychiatry, 5, 186-194. doi: 10.4236/ojpsych.2015.52022.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Kawakami, N., Takeshima, T., Ono, Y., Uda, H., Hata, Y., Nakane, Y., et al. (2005) Twelve-Month Prevalence, Severity, and Treatment of Common Mental Disorders in Communities in Japan: Preliminary Finding from the World Mental Health Japan Survey 2002-2003. Psychiatry and Clinical Neuroscience, 59, 441-452. http://dx.doi.org/10.1111/j.1440-1819.2005.01397.x
[2]	Varnik, P. (2012) Suicide in the World. International Journal of Environmental Research and Public Health, 9, 760-771. http://dx.doi.org/10.3390/ijerph9030760
[3]	Sado, M., Yamauchi, K., Kawakami, N., Ono, Y., Furukawa, T.A., Tsuchiya, M., et al. (2011) Cost of Depression among Adults in Japan in 2005. Psychiatry and Clinical Neuroscience, 65, 442-450. http://dx.doi.org/10.1111/j.1440-1819.2011.02237.x
[4]	Bakish, D. (2001) New Standard of Depression Treatment: Remission and Full Recovery. The Journal of Clinical Psychiatry, 62, S5-S9.
[5]	McGirr, A., Séguin, M., Renaud, J., Benkelfat, C., Alda, M. and Turecki, C. (2006) Gender and Risk Factors for Suicide: Evidence for Heterogeneity in Predisposing Mechanisms in a Psychological Autopsy Study. Journal of Clinical Psychiatry, 67, 1612-1617. http://dx.doi.org/10.4088/JCP.v67n1018
[6]	Trivedi, M.H., Rush, A.J., Wisniewski, S.R., Nierenberg, A.A., Warden, D., Ritz, L., et al. (2006) Evaluation of Outcomes with Citalopram for Depression Using Measurement-Based Care in STAR*D: Implications for Clinical Practice. The American Journal of Psychiatry, 163, 28-40. http://dx.doi.org/10.1176/appi.ajp.163.1.28
[7]	Lucca, A., Serretti, A. and Smeraldi, E. (2000) Effect of Reboxetine Augmentation in SSRI Resistant Patients. Human Psychopharmacology: Clinical and Experimental, 15, 143-145. http://dx.doi.org/10.1002/(SICI)1099-1077(200003)15:2<143::AID-HUP152>3.0.CO;2-N
[8]	Ball, S., Dellva, M.A., D’Souza, D.N., Marangell, L.B., Russell, J.M. and Goldberger, C. (2014) A Double-Blind, Placebo-Controlled Study of Edivoxetine as an Adjunctive Treatment for Patients with Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment. Journal of Affective Disorders, 167, 215-223. http://dx.doi.org/10.1016/j.jad.2014.06.006
[9]	Ball, S.G., Ferguson, M.B., Martinez, J.M., Pangallo, B.A., Nery, E.S., Dellva, M.A., Sparks, J., Liu, P., Zhang, Q. and Bangs, M. (in Press) Efficacy Outcomes from 3 Clinical Trials of Edivoxetine as Adjunctive Treatment for Patients with Major Depressive Disorder who are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment. Unpublished. Journal of Clinical Psychiatry.
[10]	Martinez, J.M., Ferguson, M.B., Pangallo, B.A., Oakes, T.M., Sparks, J., Dellva, M.A., Zhang, Q., Liu, P., Bangs, M.E., Ahl, J. and Goldberger, C. (in Press) Safety and Tolerability of Edivoxetine as Adjunctive Treatment to Selective Serotonin Reuptake Inhibitor Antidepressants for Patients with Major Depressive Disorder. Drugs in Context.
[11]	Ball, S., Atkinson, S., Sparks, J., Bangs, M., Goldberger, C. and Dubé, S. (2015) Long-term, Open-label, Safety Study of Edivoxetine 12 to 18 mg Once Daily as Adjunctive Treatment for Patients with Major Depressive Disorder Who Are Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment. Journal of Clinical Psychopharmacology (in Press).
[12]	Malhotra, A.K., Myrphym Jr., G.M. and Kennedy, J.L. (2004) Pharmacogenetics of Psychotropic Drug Response. American Journal ofPsychiatry, 161, 780-796. http://dx.doi.org/10.1176/appi.ajp.161.5.780
[13]	Geller, S.E., Koch, A., Pellettier, B. and Carnes, M. (2011) Inclusion, Analysis, and Reporting of Sex and Race/Ethnicity in Clinical Trials: Have We Made Progress? Journal of Women’s Health, 20, 315-320. http://dx.doi.org/10.1089/jwh.2010.2469
[14]	Montgomery, S.A. and ?sberg, M. (1979) A New Depression Scale Designed to be Sensitive to Change. The British Journal of Psychiatry, 134, 382-389. http://dx.doi.org/10.1192/bjp.134.4.382
[15]	Williams, J.B., Kobak, K.A., Bech, P., Engelhardt, N., Evans, K., Lipsitz, J., et al. (2008) The GRID-HAMD: Standardization of the Hamilton Depression Rating Scale. International Clinical Psychopharmacology, 23, 120-129. http://dx.doi.org/10.1097/YIC.0b013e3282f948f5
[16]	Chandler, G.M., Iosifescu, D.V., Pollack, M.H., Targum, S.D. and Fava, M. (2010) Research: Validation of the Massachusetts General Hospital Antidepressant Treatment History Questionnaire (ATRQ). CNS Neuroscience and Therapeutics, 16, 322-325. http://dx.doi.org/10.1111/j.1755-5949.2009.00102.x
[17]	Posner, K., Brown, G.K., Stanley, B., Brent, D.A., Yershova, K.V., Oquendo, M.A., et al. (2011) The Columbia-Suicide Severity Rating Scale: Initial Validity and Internal Consistency Findings from Three Multisite Studies with Adolescents and Adults. The American Journal of Psychiatry, 168, 1266-1277. http://dx.doi.org/10.1176/appi.ajp.2011.10111704
[18]	McGahuey, C.A., Gelenberg, A.J., Laukes, C.A., Moreno, F.A., Delgado, P.L., McKnight, K.M., et al. (2000) The Arizona Sexual Experience Scale (ASEX): Reliability and Validity. Journal of Sex and Marital Therapy, 26, 25-40. http://dx.doi.org/10.1080/009262300278623
[19]	Fava, M., Iosifescu, D.V., Pedrelli, P. and Baer, L. (2009) Reliability and Validity of the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire. Psychotherapy and Psychosomatics, 78, 91-97. http://dx.doi.org/10.1159/000201934
[20]	Hirata, Y., Goto, T., Takita, Y., Trzepacz, P.T., Allen, A.J., Ichikawa, H. and Takahashi, M. (2014) Long-Term Safety and Tolerability of Atomoxetine in Japanese Adults with Attention Deficit Hyperactivity Disorder. Asia-Pacific Psychiatry, 6, 292-301. http://dx.doi.org/10.1111/appy.12119
[21]	Adler, L.A., Spencer, T.J., Williams, D.W., Moore, R.J. and Michelson, D. (2008) Long-Term, Open-Label Safety and Efficacy of Atomoxetine in Adults with ADHD: Final Report of a 4-Year Study. Journal of Attention Disorders, 12, 248-253. http://dx.doi.org/10.1177/1087054708316250
[22]	Adler, L.A., Spencer, T., Brown, T.E., Holdnack, J., Saylor, K., Schuh, K., et al. (2009) Once-Daily Atomoxetine for Adult Attention-Deficit/Hyperactivity Disorder: A 6-Month, Double-Blind Trial. Journal of Clinical Psychopharmacology, 29, 44-50.
[23]	Young, J.L., Sarkis, E., Qiao, M. and Wietecha, L. (2011) Once-Daily Treatment with Atomoxetine in Adults with Attention-Deficit/Hyperactivity Disorder in Adults: A 24-Week, Randomized, Double-Blind, Placebo-Controlled Trial. Clinical Neuropharmacology, 34, 51-60.