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Predictors of change in suicidal ideation across treatment phases of major depressive disorder: analysis of the STAR*D data.

ABSTRACT: The effects of common antidepressants on suicidal ideation (SI) is unclear. In the landmark STAR*D trial antidepressants were effective for Major Depressive Disorder (MDD) in early treatment phases, but less effective in later phases. The effects of antidepressants on SI across the entire sample of the STAR*D trial has never been investigated. We performed a secondary analysis of the STAR*D data with the primary outcome of change in score on the suicide item (item three) of the Hamilton Rating Scale for Depression (HRSD₁₇) across all four study levels. We used descriptive statistics and logistic regression analyses. Pearson correlation was used for change in SI versus change in depression (HRSD₁₆). Reduction in mean (SD) SI was greater in levels one: 0.29 (±0.78) (p < 0.001) and two: 0.26 (±0.88) (p < 0.001) than in levels three: 0.16 (±0.92) (p = 0.005) and four: 0.18 (±0.93) (p = 0.094). A history of past suicide attempts (OR 1.72, p = 0.007), comorbid medical illness (OR 2.23, p = 0.005), and a family history of drug abuse (OR 1.69, p = 0.008) were correlated with worsening of SI across level one. Treatment with bupropion (OR 0.24, p < 0.001) or buspirone (OR 0.24, p = 0.001) were correlated with lowering of SI across level two. Improvement in SI was correlated with improvement in overall depression (HRSD₁₆) at level one: r(3756) = 0.48; level two: r(1027) = 0.38; level three: r(249) = 0.31; and level four: r(75) = 0.42 (p < 0.001 for all levels). Improvement in SI is limited with pharmacotherapy in patients with treatment-resistant depression. Treatments with known anti-suicidal effects in MDD, such as ECT, should be considered in these patients.

SUBMITTER: Weissman CR

PROVIDER: S-EPMC7819691 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Major depressive disorder (MDD) and suicidal behavior have been associated with structural and functional changes in the brain. However, little is known regarding alterations of brain networks in MDD patients with suicidal ideation. We investigated whether or not MDD patients with suicidal ideation have different topological organizations of white matter networks compared with MDD patients without suicidal ideation. Participants consisted of 24 patients with MDD and suicidal ideation, 25 age- and gender-matched MDD patients without suicidal ideation and 31 healthy subjects. A network-based statistics (NBS) and a graph theoretical analysis were performed to assess differences in the inter-regional connectivity. Diffusion tensor imaging (DTI) was performed to assess topological changes according to suicidal ideation in MDD patients. The Scale for Suicide Ideation (SSI) and the Korean version of the Barrett Impulsiveness Scale (BIS) were used to assess the severity of suicidal ideation and impulsivity, respectively. Reduced structural connectivity in a characterized subnetwork was found in patients with MDD and suicidal ideation by utilizing NBS analysis. The subnetwork included the regions of the frontosubcortical circuits and the regions involved in executive function in the left hemisphere (rostral middle frontal, pallidum, superior parietal, frontal pole, caudate, putamen and thalamus). The graph theoretical analysis demonstrated that network measures of the left rostral middle frontal had a significant positive correlation with severity of SSI (r=0.59, P=0.02) and BIS (r=0.59, P=0.01). The total edge strength that was significantly associated with suicidal ideation did not differ between MDD patients without suicidal ideation and healthy subjects. Our findings suggest that the reduced frontosubcortical circuit of structural connectivity, which includes regions associated with executive function and impulsivity, appears to have a role in the emergence of suicidal ideation in MDD patients.

Project description:Irritability in pediatric samples is associated with higher rates of subsequent suicide-related outcomes. No study, to date, has evaluated the longitudinal association between irritability and suicidal ideation (SI) in adults with major depressive disorder (MDD). This report evaluated whether irritability is associated with SI at the same visit (i.e., concurrently) and whether early changes in irritability with antidepressant treatment predict subsequent levels of SI. Participants of Combining Medications to Enhance Depression Outcomes (CO-MED, n = 665), Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC, n = 296), and Suicide Assessment Methodology Study (SAMS, n = 266) were included. Repeated-measures mixed model analyses evaluated concurrent association throughout the trial between irritability (five-item irritability domain of Concise Associated Symptom Tracking scale) and SI (three-item suicidal thoughts factor of Concise Health Risk Tracking scale) after controlling for overall depression (excluding suicidality-related item), and predicted subsequent levels of SI (repeated observations from week-2-to-week-8) based on early (baseline-to-week-2) changes in irritability after controlling for early changes in overall depression. Higher irritability was associated with higher SI concurrently; estimates (standard error) were 0.18 (0.02, p < 0.0001), 0.64 (0.02, p < 0.0001), and 0.26 (0.04, p < 0.0001) in CO-MED, EMBARC, and SAMS respectively. Greater baseline-to-week-2 reductions in irritability predicted lower levels of subsequent SI; estimates (standard errors) were -0.08 (0.03, p = 0.023), -0.50 (0.05, p < 0.0001), and -0.12 (0.05, p = 0.024) in CO-MED, EMBARC, and SAMS, respectively. Controlling for anxiety or insomnia produced similar results. In conclusion, irritability and SI were consistently linked in adults with MDD. These findings support careful assessment of irritability in suicide risk assessment.

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Predictors of change in suicidal ideation across treatment phases of major depressive disorder: analysis of the STAR*D data.

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