Objective: We aimed to investigate the association between antidepressants and serum lipid levels in a population-based study in older adults. Methods: We included participants from the prospective Rotterdam Study with data on lipid levels (total, low-density lipoprotein (LDL) and high-density lipoprotein cholesterol, and triglycerides). We classified antidepressants based on binding affinity to the serotonin transporter (low/intermediate- and high-affinity antidepressants). We compared lipid levels in users of these groups of antidepressants with lipid levels in non-users. Furthermore, we studied effect modification by the 102C>T polymorphism (HTR2A gene), which is associated with antidepressant drug response and metabolic outcomes. Results: Compared with non-users (N = 6438), LDL cholesterol level was higher (2.9 versus 3.1 mmol/L, respectively; p = 0.05) in users of high-affinity antidepressants (N = 89). Similar levels of the other lipids were observed between the groups for the other lipids. The mean difference in serum LDL cholesterol level between non-users and users of high-affinity antidepressants was largest in participants with the CC genotype compared with the other genotypes (notably 0.47 mmol/L), indicative of effect modification (p-value for interaction = 0.03). Conclusion: Antidepressants with a high serotonin reuptake transporter affinity were associated with higher LDL cholesterol levels, which were modified by a common genetic variation in the HTR2A gene.

Additional Metadata
Keywords antidepressants, Cholesterol, Mendelian randomization analysis, serotonin receptor, single nucleotide polymorphism, triglycerides
Persistent URL dx.doi.org/10.1177/0269881115592340, hdl.handle.net/1765/88000
Journal Journal of Psychopharmacology
Citation
Noordam, R, Aarts, N, de Keyser, C.E, Hofman, A, Stricker, B.H.Ch, & Visser, L.E. (2015). Antidepressants with a high serotonin reuptake transporter affinity and serum lipid levels in a population-based study in older adults. Journal of Psychopharmacology, 29(10), 1112–1118. doi:10.1177/0269881115592340