Risk factors for suicidality in Huntington disease: An analysis of the 2CARE clinical trial

Neurology. 2019 Apr 2;92(14):e1643-e1651. doi: 10.1212/WNL.0000000000007244. Epub 2019 Mar 8.


Objective: Most suicidality literature in Huntington disease (HD) is based on natural history studies or retrospective reviews, but reports on risk factors from clinical trials are limited.

Methods: We analyzed 609 participants from 2CARE, a randomized, double-blind, placebo-controlled clinical trial with up to 5 years of follow-up, for risk factors related to suicidality. The primary outcome variable was the time from randomization until the first occurrence of either suicidal ideation or attempt. We also considered time from randomization until the first suicide attempt as a secondary outcome variable.

Results: Depression, anxiety, bipolar disorder, antidepressant or anxiolytic use, and prior suicide attempt at baseline were associated with time to ideation or attempt. Baseline employment status, marital status, CAG repeat length, tetrabenazine use, and treatment assignment (coenzyme Q10 or placebo) were not associated with suicidality. Time-dependent variables from the Unified Huntington's Disease Rating Scale Behavioral Assessment were associated with time to suicidal ideation or attempt, driven mainly by items related to depressed mood, low self-esteem/guilt, anxiety, suicidal thoughts, irritability, and compulsions. Variables associated with time to suicide attempt alone were generally similar.

Conclusion: These data suggest psychiatric comorbidities in HD are predictive of suicidal behavior while participating in clinical trials, reinforcing the importance of clinical surveillance and treatment towards lessening risk during participation and perhaps beyond. Designing a composite algorithm for early prediction of suicide attempts in HD may be of value, particularly given anticipated trials aimed at disease modification are likely to be long-term.

Clinicaltrialsgov identifier: NCT00608881.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenergic Uptake Inhibitors / therapeutic use
  • Adult
  • Anti-Anxiety Agents / therapeutic use
  • Antidepressive Agents / therapeutic use
  • Anxiety Disorders / drug therapy
  • Anxiety Disorders / epidemiology
  • Bipolar Disorder / epidemiology
  • Depressive Disorder / drug therapy
  • Depressive Disorder / epidemiology
  • Employment
  • Female
  • Humans
  • Huntingtin Protein / genetics
  • Huntington Disease / drug therapy
  • Huntington Disease / epidemiology*
  • Huntington Disease / psychology
  • Male
  • Marital Status
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Suicidal Ideation*
  • Suicide, Attempted / statistics & numerical data*
  • Tetrabenazine / therapeutic use
  • Trinucleotide Repeat Expansion
  • Ubiquinone / analogs & derivatives
  • Ubiquinone / therapeutic use
  • Vitamins / therapeutic use


  • Adrenergic Uptake Inhibitors
  • Anti-Anxiety Agents
  • Antidepressive Agents
  • HTT protein, human
  • Huntingtin Protein
  • Vitamins
  • Ubiquinone
  • coenzyme Q10
  • Tetrabenazine

Associated data

  • ClinicalTrials.gov/NCT00608881