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Dose–response relationship of duloxetine in placebo-controlled clinical trials in patients with major depressive disorder

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Abstract

Rationale

The optimal dose for achieving the maximum antidepressive effect of selective serotonin reuptake inhibitors (SSRIs) or serotonin-noradrenalin reuptake inhibitors (SNRIs) remains a controversial issue. The varying sensitivity of scales that measure the severity of depression is one of the many factors affecting the evaluation of the dose–response relationship with antidepressants.

Objectives

To determine if the 6-item Hamilton rating scale for depression (HAM-D6) demonstrates a clearer association between dose and antidepressive effect compared with the 17-item Hamilton rating scale for depression (HAM-D17) for fixed doses of duloxetine hydrochloride (40, 60, 80, and 120 mg daily) from six double-blind, randomized, placebo-controlled clinical trials assessing safety and efficacy in the acute treatment of patients with DSM-IV-defined major depressive disorder (MDD).

Methods

Mantel–Haenszel adjusted effect sizes were determined by dose for change from baseline to endpoint in HAM-D6 and HAM-D17 scores from the six studies. To confirm, assessments were repeated on the subset of the population corresponding to the 70% of patients with the longest duration of treatment regardless of study, treatment, dose, geography, or completion status.

Results

For the majority of assessments, HAM-D6 effect sizes were numerically larger than those estimated from the HAM-D17. Findings support that duloxetine 60 mg daily is the best effective dose.

Conclusions

In this assessment of patients with MDD, the HAM-D6 was shown to be more sensitive compared with the HAM-D17 at detecting treatment effects. These findings are consistent with published results of other effective antidepressants.

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Acknowledgements

The authors wish to thank Ling Ling Xie, MS; Barry M. Brolley, MS; Quan Zhao, MS; and Ying Yuan Chen, MS, for their assistance with statistical analyses and reporting. The clinical studies referred to in this work were conducted under the Declaration of Helsinki and confirmed to all applicable local and region regulations. All protocols and informed consent documents were approved by local or regional review boards before study initiation, and all patients were required to sign an informed consent before participation in any study-related activities.

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Authors and Affiliations

  1. Psychiatric Research Unit, Frederiksborg General Hospital, Dyrehavevej 48, DK-3400, Hilleroed, Denmark

    Per Bech

  2. Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, USA

    Daniel K. Kajdasz

  3. Eli Lilly A/S, Lyngby, Denmark

    Vibeke Porsdal

Authors
  1. Per Bech
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  2. Daniel K. Kajdasz
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  3. Vibeke Porsdal
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Corresponding author

Correspondence to Per Bech.

Additional information

Drs. Porsdal and Kajdasz are employees of Eli Lilly & Company.

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Bech, P., Kajdasz, D.K. & Porsdal, V. Dose–response relationship of duloxetine in placebo-controlled clinical trials in patients with major depressive disorder. Psychopharmacology 188, 273–280 (2006). https://doi.org/10.1007/s00213-006-0505-1

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  • DOI: https://doi.org/10.1007/s00213-006-0505-1

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