Jordan L.Schultz, Assistant Professor of Psychiatry, Clinical Pharmacy Specialist, Carver College of Medicine at the University of Iowa
AnnieKilloran, Clinical Assistant Professor of Neurology, Carver College of Medicine at the University of Iowa
Peg C.Nopoulos, Professor of Psychiatry, Carver College of Medicine at the University of Iowa
David J.Moser, Professor of Psychiatry, Carver College of Medicine at the University of Iowa
John A.Kamholz, Professor of Neurology, Carver College of Medicine at the University of Iowa
Submitted September 12, 2018
We thank Sampaio et al. for the comment on our article. [1] The Enroll-HD dataset does not contain information regarding why participants abandoned a particular therapy. [2] Therefore, making the assumption that abandonment of tetrabenazine (TBZ) therapy occurs secondary to depression/suicidality could falsely induce a spurious positive association between TBZ and depression/suicidality that is equally dangerous. Furthermore, participants who abandoned TBZ prior to their baseline visit were included in the TBZ nonuser group. [1] If the assumptions being made by Sampaio et al. are accurate, then it is reasonable to assume that an increased percentage of participants in the TBZ nonuser group have a history of depression. However, the percentage of participants with a history of depression is nearly identical between the two groups, [1] indicating that few participants discontinued TBZ due to depression/suicidality.
We disagree that antidepressant use is a collider variable; it is more of a confounding variable that should be controlled. Regardless, if antidepressant use is excluded from the analysis, there is no significant association between TBZ use and depression (OR = 0.783, 95% CI [0.602-1.019], p = 0.069), but the significant negative association between TBZ use and suicidality remains [OR = 0.613, 95% CI (0.381-0.984), p = 0.043] [1]. Therefore, controlling for antidepressant use makes no difference in the overall interpretation of the results.
Schultz JL, Killoran A, Nopoulos PC, et al. Evaluating depression and suicidality in tetrabenazine users with Huntington disease. Neurology 2018;91:e202-e207.
Landwehrmeyer GB, Fitzer-Attas CJ, Giuliano JD, et al. Data analytics from Enroll-HD, a global clinical research platform for Huntington's disease. Mov Disord Clin Pract 2017;4:212–224.
We thank Sampaio et al. for the comment on our article. [1] The Enroll-HD dataset does not contain information regarding why participants abandoned a particular therapy. [2] Therefore, making the assumption that abandonment of tetrabenazine (TBZ) therapy occurs secondary to depression/suicidality could falsely induce a spurious positive association between TBZ and depression/suicidality that is equally dangerous. Furthermore, participants who abandoned TBZ prior to their baseline visit were included in the TBZ nonuser group. [1] If the assumptions being made by Sampaio et al. are accurate, then it is reasonable to assume that an increased percentage of participants in the TBZ nonuser group have a history of depression. However, the percentage of participants with a history of depression is nearly identical between the two groups, [1] indicating that few participants discontinued TBZ due to depression/suicidality.
We disagree that antidepressant use is a collider variable; it is more of a confounding variable that should be controlled. Regardless, if antidepressant use is excluded from the analysis, there is no significant association between TBZ use and depression (OR = 0.783, 95% CI [0.602-1.019], p = 0.069), but the significant negative association between TBZ use and suicidality remains [OR = 0.613, 95% CI (0.381-0.984), p = 0.043] [1]. Therefore, controlling for antidepressant use makes no difference in the overall interpretation of the results.
Supplemental Data: Full-length version.
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