Elsevier

Journal of Affective Disorders

Volume 238, 1 October 2018, Pages 542-546
Journal of Affective Disorders

Research paper
Comparative risk of lipophilic and hydrophilic statins on incident depression: A retrospective cohort study

https://doi.org/10.1016/j.jad.2018.06.021Get rights and content

Highlights

  • Lipophilic statins cross the blood-brain barrier and associated with mood disorders.

  • 1:1 propensity score matched cohort of 299,298 patients initiating a lipophilic v hydrophilic statin was created.

  • The study did not find an increase in the risk of incident depression in patients initiating a lipophilic statin.

Abstract

Objectives

To evaluate the risk of new-onset depression in a cohort of US adult patients initiating lipophilic statin therapy compared to hydrophilic statin therapy.

Design

Retrospective cohort study.

Setting

Large US commercial claims database

Participants

1:1 propensity score matched cohort of lipophilic (atorvastatin, lovastatin and simvastatin) and hydrophilic (pravastatin and rosuvastatin) statin initiators between January 2009 to June 2015.

Outcome

New onset of depression.

Results

In a propensity-score matched cohort of 299,298 statin initiators, the crude incidence of depression in the hydrophilic and lipophilic group was 136.6 and 142.8 per 10,000 person-years respectively. Compared to hydrophilic statin use, lipophilic statin use was not associated with a statistically significant increase in the risk of depression, adjusted HR 1.05 (95% CI, 1.00–1.10, p = 0.078) and excess incidence of 6.3 (95% CI, -0.7–13.7) per 10,000 person-years. Findings were consistent across the subgroups of patients with history of psychiatric conditions HR 1.05 (95% CI, 0.94–1.16, p = 0.41), and those initiating statins for primary or secondary prevention, HR 1.03 (95% CI, 0.97–1.10, p = 0.33) and 1.07 (95% CI, 0.99–1.16, p = 0.10) respectively. Within individual lipophilic statins, only simvastatin was associated with a moderate increase in the risk of depression HR 1.09 (95% CI, 1.02–1.16, p = 0.003), followed by lovastatin HR 1.07 (95% CI, 0.93–1.24, p = 0.34) and atorvastatin HR 1.05 (95% CI, 0.97–1.13, p = 0.27).

Limitations

Findings are generalizable to patients with commercial insurance.

Conclusions

Lipophilic statin use was not associated with a significant increase in the risk of incident depression.

Section snippets

Methods

The University of Florida Institutional Review Board exempted this study from review.

Patient characteristics

There were 155,885 hydrophilic and 339,297 lipophilic statin initiators that met the cohort membership criteria (Appendix Table 1), out of which a 1:1 propensity score matched cohort of 299,298 statin initiators was created. Table 1 presents the baseline characteristics for select variables for lipophilic versus hydrophilic statins prior to, and after propensity score matching (Appendix Table 3 presents the data for all variables). Prior to propensity score matching, the baseline

Discussion

It has been previously postulated that based on their pharmacodynamic profile, lipophilic statins may increase the risk of depression compared to their hydrophilic counterparts; however, this association has not been studied. This study found that patients initiating lipophilic statins did not have a statistically significant increase in the risk for developing depression – and suicidal ideations – compared to hydrophilic statin initiators. This finding was consistent across subgroups of

Conflict of interest

The authors have no conflicts of interest to disclose.

Author contributions

Dr Dave had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: All authors. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Dave. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Dave. Administrative, technical, or material support: Hartzema. Study supervision: Hartzema.

Funding

None

Funding source

None

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