Effect of metabolic syndrome and thyroid hormone on efficacy of desvenlafaxine 50 and 100 mg/d in major depressive disorder

ABSTRACT

Objective This pooled, post hoc analysis evaluated the efficacy of desvenlafaxine vs placebo in adults with major depressive disorder (MDD) with and without metabolic syndrome, and above or at or below median baseline thyroid-stimulating hormone (TSH) levels.

Research design and methods Patients were randomly assigned to receive desvenlafaxine 50 or 100 mg/d or placebo in nine short-term, double-blind studies. Metabolic syndrome was defined as meeting at least three of five criteria based on body mass index, triglycerides, high-density lipoprotein, fasting glucose, blood pressure, current medication, and medical history.

Clinical trial registration NCT00072774; NCT00277823; NCT00300378; NCT00384033; NCT00798707; NCT00863798; NCT01121484; NCT00824291; NCT01432457

Main outcome measures Treatment effects on change from baseline in 17-item Hamilton Rating Scale for Depression (HAM-D₁₇) total score at week 8 (last observation carried forward [LOCF]) were analyzed in four subgroups—metabolic syndrome and no metabolic syndrome, baseline TSH levels above median or at or below median—using analysis of covariance with treatment, study, and baseline in the model. Metabolic syndrome and TSH were examined as predictors of change in HAM-D₁₇ total score using regression analysis.

Results The pooled analysis included 4279 patients; 971 (22.7%) patients had metabolic syndrome. In all subgroups, HAM-D₁₇ total scores improved significantly from baseline to week 8 (LOCF) with desvenlafaxine 50 or 100 mg/d compared with placebo (all p ≤ 0.006). There was no significant treatment by metabolic syndrome or by TSH interaction. Neither metabolic syndrome nor TSH above median predicted change in HAM-D₁₇ total scores, response (≥50% reduction in HAM-D₁₇ total score), or remission (HAM-D₁₇ total score ≤7; all p > 0.05).

Limitations Individual studies included in this analysis were not designed to examine the relationship between metabolic syndrome or TSH and response to desvenlafaxine treatment. Metabolic syndrome status was determined post hoc based on available baseline measures and not diagnosed at study entry. Exclusion criteria were selected to enroll medically healthy patients with a primary diagnosis of MDD (i.e., patients healthier than the general MDD population).

Conclusions Desvenlafaxine 50 and 100 mg/d significantly improved depression compared with placebo in patients with and without metabolic syndrome, and in patients with baseline TSH above median and at or below median levels.

Keywords:

• Blood pressure
• body mass index
• comorbidity
• depression
• HDL cholesterol
• metabolic syndrome X
• thyroid-stimulating hormone

Transparency

Declaration of funding

This study was sponsored by Pfizer Inc.

Declaration of financial/other relationships

R.S.M. has disclosed that he has participated in advisory boards with AstraZeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline, Janssen-Ortho, Eli Lilly, Lundbeck, Merck, Organon, Pfizer, and Shire; speakers bureaus with AstraZeneca, Eli Lilly, Janssen-Ortho, Lundbeck, Merck, and Pfizer; CME activities with AstraZeneca, Bristol-Myers Squibb, CME Outfitters, France Foundation, I3CME, Eli Lilly, Merck, Pfizer, Optum Health, and Physicians Postgraduate Press; and has received research grants from AstraZeneca, Janssen-Ortho, Eli Lilly, Lundbeck, Pfizer, and Shire. R.F., J.A.M., and M.B. have disclosed that they are full-time employees at Pfizer.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationship to disclose.

Acknowledgments

Medical writing support was provided by Kathleen M. Dorries, PhD, at Peloton Advantage, LLC, and was funded by Pfizer Inc.

Previous presentation

Medical writing support was provided by Kathleen M. Dorries PhD at Peloton Advantage LLC and was funded by Pfizer.

 Previous presentation: American Psychiatric Association 167th Annual Meeting, May 3–7, 2014, New York, NY, USA; and The 15th International Mental Health Conference, August 25–27, 2014, Gold Coast, Australia.