Impact of fatigue on outcome of selective serotonin reuptake inhibitor treatment: secondary analysis of STAR*D

Abstract

Objective:

To explore relationships between baseline and changes in fatigue during treatment with outcomes in patients with major depressive disorder (MDD) receiving citalopram monotherapy.

Research design and methods:

Secondary analyses of data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Level 1 treatment phase (≤14 weeks citalopram monotherapy). Fatigue was assessed with item 14 on energy level from the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR₁₆; scored 0–3: 0 = no fatigue, 3 = maximal fatigue); prospective fatigue: assessment of fatigue at Level 1 entry and exit (no fatigue, treatment-emergent fatigue, remitted fatigue, or residual fatigue).

Clinical trial registration:

Http://clinicaltrials.gov, NCT00021528.

Main outcome measures:

Remission of depressive symptoms (17-item Hamilton Rating Scale for Depression ≤7 or QIDS-SR₁₆ ≤5); Quality of Life Enjoyment and Satisfaction Questionnaire–Short Form; Short-Form Health Survey Mental and Physical subscales; and Work and Social Adjustment Scale (WSAS).

Results:

At baseline, of 2868 patients included in the analyses, 5.5% had a QIDS-SR₁₆ item 14 score of 0; 22.9%, a score of 1; 53.6%, a score of 2; and 18.0%, a score of 3. During Level 1 treatment, 3.5% of patients had no prospective fatigue, 2.1% had treatment-emergent fatigue, 33.6% had fatigue remitting during treatment, and 60.8% had residual fatigue. Female gender, unemployment, fewer years of education, and lower monthly income were significantly associated with higher rates of baseline fatigue (all P < 0.0001). Higher levels of baseline or prospective fatigue were associated with reduced likelihood of remission, decreased overall satisfaction (P < 0.0001), and reduced mental and physical function at outcome (P ≤ 0.05). Patients with higher baseline or prospective fatigue reported higher WSAS total scores (P < 0.0001), indicative of more severe functional impairment.

Conclusions:

Lower baseline fatigue and remission of fatigue during antidepressant treatment in patients with MDD are associated with higher rates of remission of depressive symptoms and better function and quality of life. Study limitations include use of the STAR*D Level 1 sample (citalopram as only antidepressant), use of a proxy measure of energy/fatigue (item 14 from the QIDS-SR₁₆), and the secondary post-hoc analysis design.

Keywords::

• Antidepressant
• Fatigue
• Major depressive disorder
• Quality of life

Transparency

Declaration of funding

This study was sponsored by Eli Lilly and Company.

Declaration of financial/other relationships

M.F., E.B.D., L.B.M., and J.M. have disclosed that they are full-time employees and shareholders of Eli Lilly and Company. S.R.W. has disclosed that he received research grants from Eli Lilly and Company, is a board member for Cyberonics, and served as a consultant for ImaRx Therapeutics Inc. (2006), Bristol-Myers Squibb Company (2007–2008), Organon (2007), Case-Western University (2007), Singapore Clinical Research Institute (2009), Dey Pharmaceuticals (2010), Venebio (2010), and Dey (2010).

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank Dr. Alexandra Heinloth and Ms. Maria Rovere MTSC, both with inVentiv Health Clinical LLC, for writing and editorial assistance. Eli Lilly and Company contracted inVentiv Health Clinical LLC for writing and editorial services.

Previous presentation: American Psychiatric Association 166th Annual Meeting, San Francisco, CA, USA, 18–22 May 2013; and Neuroscience Education Institute Psychopharmacology Congress, Colorado Springs, CO, USA, 14–17 November 2013.