Skip to main content
PMC home page
Current Therapeutic Research, Clinical and Experimental logoLink to Current Therapeutic Research, Clinical and Experimental
. 2005 Nov;66(6):522–540. doi: 10.1016/j.curtheres.2005.12.003

Clinical consequences of initial duloxetine dosing strategies: Comparison of 30 and 60 mg QD starting doses

David L Dunner 1, Madelaine M Wohlreich 2,*, Craig H Mallinckrodt 2, John G Watkin 2, Maurizio Fava 3
PMCID: PMC3966005  PMID: 24678074

Abstract

Background:

To reduce the risk for treatment-emergent adverse events and increase patient compliance, clinicians frequently prescribe a suboptimal starting dose of antidepressants, with the goal of increasing the dose once the patient has demonstrated tolerability.

Objective:

The aim of this study was to examine the tolerability and effectiveness associated with an initial week of duloxetine hydrochloride treatment at 30 mg QD and subsequent dose increase to 60 mg QD, compared with a starting dose of 60 mg QD.

Methods:

In this open-label study, all patients met the criteria for major depressive disorder (MDD) described in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Patients were required to wash out from previous antidepressant medications for 21 days, and were then randomized to receive duloxetine 30 or 60 mg QD for 1 week. After 1 week, patients receiving duloxetine 30 mg QD had their dose increased to 60 mg QD. Patients returned for assessments at weeks 2, 4, 6, 8, and 12. During the remainder of the 12-week study period, the duloxetine dose could be titrated based on the degree of response from 60 mg QD (minimum) to 120 mg QD (maximum), with 90 mg QD as an intermediate dose. Tolerability was assessed by means of discontinuation rates, spontaneously reported adverse events, changes in vital signs, and laboratory tests. Effectiveness measures included the 17-item Hamilton Rating Scale for Depression (HAMD17) total score, HAMD17 core and Maier subscales, individual HAMD17 items, the Hamilton Rating Scale for Anxiety total score, and the Clinical Global Impression of Severity.

Results:

One hundred thirty-seven patients were enrolled (82 women, 55 men; mean age, 42 years; duloxetine 30 mg QD, 67 patients; duloxetine 60 mg QD, 70 patients). The rate of discontinuation due to adverse events did not differ significantly between patients starting duloxetine at 30 mg QD and 60 mg QD (13.4% vs 18.6%). The most frequently reported adverse events across both treatment groups were nausea, headache, dry mouth, insomnia, and diarrhea. In the first week of treatment, patients receiving duloxetine 30 mg QD had a significantly lower rate of nausea compared with patients receiving 60 mg QD (16.4% vs 32.9%; P = 0.03). Over the 12-week acute-treatment phase, patients starting duloxetine treatment at 30 mg QD had a significantly lower rate of nausea compared with patients initiating treatment at 60 mg QD (P = 0.047). Although between-group differences in the HAMD17 total score were not statistically significant at any visit, patients starting at 30 mg QD experienced significantly less improvement in HAMD17 core and Maier subscales at week 1 compared with patients starting at 60 mg QD (core, P= 0.044; Maier, P = 0.047). After 2 weeks of treatment, the magnitude of improvement among patients starting at 30 mg QD did not differ significantly from that observed in patients who started treatment at 60 mg QD, and there were no significant between-group differences in effectiveness at any subsequent visit.

Conclusions:

Results from this open-label study in patients with MDD suggest that starting duloxetine treatment at 30 mg QD for 1 week, followed by escalation to 60 mg QD, might reduce the risk for treatment-emergent nausea in these patients while producing only a transitory impact on effectiveness compared with a starting dose of 60 mg QD.

Key words: duloxetine, tolerability, safety, efficacy

Full Text

The Full Text of this article is available as a PDF (1,016.0 KB).

Footnotes

Presented in part at the 17th US Psychiatric and Mental Health Congress, November 18–21, 2004, San Diego, California.

References

  • 1.Kessler R.C., Berglund P., Demler O., National Comorbidity Survey Replication The epidemiology of major depressive disorder: Results from the National Comorbidity Survey Replication (NCS-R) JAMA. 2003;289:3095–3105. doi: 10.1001/jama.289.23.3095. [DOI] [PubMed] [Google Scholar]
  • 2.Harris E.C., Barraclough B. Suicide as an outcome for mental disorders. A meta-analysis. Br J Psychiatry. 1997;170:205–228. doi: 10.1192/bjp.170.3.205. [DOI] [PubMed] [Google Scholar]
  • 3.Hirschfeld R.M., Keller M.B., Panico S. The National Depressive and ManicDepressive Association consensus statement on the undertreatment of depression. JAMA. 1997;277:333–340. [PubMed] [Google Scholar]
  • 4.American Psychiatric Association Practice guideline for the treatment of patients with major depressive disorder (revision) Am J Psychiatry. 2000;157(Suppl 4):1–45. [PubMed] [Google Scholar]
  • 5.Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56–61. doi: 10.1136/jnnp.23.1.56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Hamilton M. Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol. 1967;6:278–296. doi: 10.1111/j.2044-8260.1967.tb00530.x. [DOI] [PubMed] [Google Scholar]
  • 7.Judd L.L., Paulus M.J., Schettler P.J. Does incomplete recovery from first lifetime major depressive episode herald a chronic course of illness? Am J Psychiatry. 2000;157:1501–1504. doi: 10.1176/appi.ajp.157.9.1501. [DOI] [PubMed] [Google Scholar]
  • 8.2004 Physicians' Desk Reference. 58th ed. Thomson PDR; Montvale, NJ: 2004. [Google Scholar]
  • 9.Donoghue J.M., Tylee A. The treatment of depression: Prescribing patterns of antidepressants in primary care in the UK. Br J Psychiatry. 1996;168:164–168. doi: 10.1192/bjp.168.2.164. [DOI] [PubMed] [Google Scholar]
  • 10.Detke M.J., Lu Y., Goldstein D.J. Duloxetine, 60 mg once daily, for major depressive disorder: A randomized double-blind placebo-controlled trial. J Clin Psychiatry. 2002;63:308–315. doi: 10.4088/jcp.v63n0407. [DOI] [PubMed] [Google Scholar]
  • 11.Detke M.J., Lu Y., Goldstein D.J. Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression. J Psychiatr Res. 2002;36:383–390. doi: 10.1016/s0022-3956(02)00060-2. [DOI] [PubMed] [Google Scholar]
  • 12.Detke M.J., Wiltse C.G., Mallinckrodt C.H. Duloxetine in the acute and long-term treatment of major depressive disorder: A placebo- and paroxetine-controlled trial. Eur Neuropsychopharmacol. 2004;14:457–470. doi: 10.1016/j.euroneuro.2004.01.002. [DOI] [PubMed] [Google Scholar]
  • 13.Goldstein D.J., Mallinckrodt C., Lu Y., Demitrack M.A. Duloxetine in the treatment of major depressive disorder: A double-blind clinical trial. J Clin Psychiatry. 2002;63:225–231. doi: 10.4088/jcp.v63n0309. [DOI] [PubMed] [Google Scholar]
  • 14.Goldstein D.J., Lu Y., Detke M.J. Duloxetine in the treatment of depression: A double-blind placebo-controlled comparison with paroxetine. J Clin Psychopharmacol. 2004;24:389–399. doi: 10.1097/01.jcp.0000132448.65972.d9. [DOI] [PubMed] [Google Scholar]
  • 15.Cymbalta (duloxetine hydrochloride) [product information] Eli Lilly and Company; Indianapolis, Ind: 2005. [Google Scholar]
  • 16.Nemeroff C.B., Schatzberg A.F., Goldstein D.J. Duloxetine for the treatment of major depressive disorder. Psychopharmacol Bull. 2002;36:106–132. [PubMed] [Google Scholar]
  • 17.Greist J., McNamara R.K., Mallinckrodt C.H. Incidence and duration of anti-depressantinduced nausea: Duloxetine compared with paroxetine and fluoxetine. Clin Ther. 2004;26:1446–1455. doi: 10.1016/j.clinthera.2004.09.010. [DOI] [PubMed] [Google Scholar]
  • 18.Wohlreich M.M., Martinez J.M., Mallinckrodt C.H. An open-label study of duloxetine for the treatment of major depressive disorder: Comparison of switching versus initiating treatment approaches. J Clin Psychopharmacol. 2005;25:552–560. doi: 10.1097/01.jcp.0000185429.10053.c8. [DOI] [PubMed] [Google Scholar]
  • 19.World Medical Association (WMA) Declaration of Helsinki . Recommendations Guiding Medical Doctors in Biomedical Research Involving Human Subjects [WMA Web site] WMA; Ferney-Voltaire, France: 1989. http://www.wma.net Available at: Accessed November 21, 2005. [Google Scholar]
  • 20.American Psychiatric Association . Task Force on DSM-IV. American Psychiatric Association; Washington, DC: 2000. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) [Google Scholar]
  • 21.Guy W. National Institute of Mental Health, Psychopharmacology Research Branch; Rockville, Md: 1976. pp. 217–222. (ECDEU Assessment Manual for Psychopharmacology). [Google Scholar]; Guy W. National Institute of Mental Health, Psychopharmacology Research Branch; Rockville, Md: 1976. pp. 313–331. (ECDEU Assessment Manual for Psychopharmacology). [Google Scholar]
  • 22.Hamilton M. The assessment of anxiety states by rating. Br J Psychiatry. 1959;32:50–55. doi: 10.1111/j.2044-8341.1959.tb00467.x. [DOI] [PubMed] [Google Scholar]
  • 23.Sheehan D.V., Lecrubier Y., Sheehan K.H. The mini-international interview (MINI): The development and validation of a structured diagnostic interview for DSM-IV and ICD-10. 1998. [PubMed] [Google Scholar]
  • 24.Detke M., Gilaberte I., Perahia D.G. Duloxetine vs. placebo in the prevention of relapse of major depressive disorder. Presented at the 42nd Annual ACNP Meeting; December 7–11; 2003. San Juan, Puerto Rico. [Google Scholar]
  • 25.Fava M., Evins A.E., Dorer D.J., Schoenfeld D.A. The problem of the placebo response in clinical trials for psychiatric disorders: Culprits, possible remedies, and a novel study design approach. Psychother Psychosom. 2003;72:115–127. doi: 10.1159/000069738. [published correction appears in Psychother Psychosom. 2004;73:123] [DOI] [PubMed] [Google Scholar]

Articles from Current Therapeutic Research, Clinical and Experimental are provided here courtesy of Elsevier

RESOURCES