Author response to Dr. Aziz: Confounding-by-indication
Jordan L.Schultz, Clinical Pharmacy Speciality, University of Iowa
Submitted July 23, 2018
We appreciate Dr. Aziz's thoughtful comment and agree that "confounding-by-indication" is an important issue to consider in this analysis. [1] Weighting cases based on this method would be more useful if the frequency and severity of depression and suicidal ideation were known when tetrabenazine was prescribed. However, in this cross-sectional analysis, tetrabenazine users were on therapy for 2.58 years at the baseline visit, making it difficult to determine if depression or suicidality factored into the decision to initiate therapy. [2] Nevertheless, we performed the same analyses described in the manuscript after applying inverse probability of treatment weighting, using propensity scores that were calculated based on whether a participant had a personal history of depression. [1] Tetrabenazine use was associated with a decreased risk of depression (OR = 0.81, p = 0.001) and suicidality (OR = 0.70, p = 0.002) among all participants, as well as those with only a personal history of depression (OR = 0.75, p < 0.0001, and OR = 0.64, p < 0.0001, respectively). There were no significant differences among participants without a personal history of depression. These findings only support the conclusion that tetrabenazine may be safely used to suppress chorea in patients with HD who have a history of depression or suicidality, but should not be interpreted as being beneficial for depressive symptoms.
Schultz JL, Killoran A, Nopoulos PC, et al. Evaluating depression and suicidality in tetrabenazine users with Huntington disease. Neurology 2018;91:e202-e207.
Paulsen JS, Nehl C, Hoth KF, et al. Depression and stages of Huntington's disease. J Neuropsychiatry Clin Neurosci 2005;17:496-502.
We appreciate Dr. Aziz's thoughtful comment and agree that "confounding-by-indication" is an important issue to consider in this analysis. [1] Weighting cases based on this method would be more useful if the frequency and severity of depression and suicidal ideation were known when tetrabenazine was prescribed. However, in this cross-sectional analysis, tetrabenazine users were on therapy for 2.58 years at the baseline visit, making it difficult to determine if depression or suicidality factored into the decision to initiate therapy. [2] Nevertheless, we performed the same analyses described in the manuscript after applying inverse probability of treatment weighting, using propensity scores that were calculated based on whether a participant had a personal history of depression. [1] Tetrabenazine use was associated with a decreased risk of depression (OR = 0.81, p = 0.001) and suicidality (OR = 0.70, p = 0.002) among all participants, as well as those with only a personal history of depression (OR = 0.75, p < 0.0001, and OR = 0.64, p < 0.0001, respectively). There were no significant differences among participants without a personal history of depression. These findings only support the conclusion that tetrabenazine may be safely used to suppress chorea in patients with HD who have a history of depression or suicidality, but should not be interpreted as being beneficial for depressive symptoms.
For disclosures, please contact the editorial office at journal@neurology.org.