Innovations In Clinical Neuroscience

SEP-OCT 2014

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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Innovations in CLINICAL NEUROSCIENCE [ V O L U M E 1 1 , N U M B E R 9 – 1 0 , S E P T E M B E R – O C T O B E R 2 0 1 4 ] 98 SUICIDE SIGNAL DETECTION TESTING There is a growing recognition of the need for signal detection in pharmacovigilance. 20 While the S-STS is used to detect suicidal signals as adverse events, it has also been used to identify an anti-suicidal efficacy signal in randomized, double-blind, controlled efficacy studies, including the study that compared BMS 562086, escitalopram, and placebo for treatment of GAD (as previously discussed); 13 a study that compared c italopram augmented by lithium to citalopram with placebo in a four- week study of suicidality in major depressive disorder (MDD), dysthymia, and depressive disorder not otherwise specificed (NOS); 21 and a study that examined a new investigational compound in pre- dementia Alzheimer's disease. 2 2 In the Coric et al study 13 comparing BMS 562086, escitalopram, and placebo (n=82, 61 with a post- baseline S-STS assessment) for treatment of GAD, there was a positive signal on the S-STS over eight weeks of treatment. A power analysis in this study showed that a sample size of 123 per treatment arm would be needed to detect this anti- suicidality efficacy signal for escitalopram on the S-STS at p<0.05 level in an adult GAD study. This sample size is less than the usual sample size per treatment arm in a typical multicenter clinical trial in central nervous system (CNS) research. It offers hope that the S- STS could be used as an efficacy signal detector in many CNS clinical trials searching for anti-suicidal effects from future investigation drugs. Khan et al 21 used the S-STS to study the anti-suicidal effects of citalopram augmented by lithium versus citalopram with placebo (n=80). The subgroup of patients on lithium with a blood level of 0.5mEq/L or higher showed significantly higher S-STS remission rates (45% compared to 19%, p<0.05). In this same study, the Beck Suicide Scale did not have adequate sensitivity to detect this signal at a p<0.05 level. Figure 5 shows the percent symptom reduction in suicidal thoughts and behaviors and depressive symptoms as measured by the S-STS and the Montgomery Asberg Depression Rating Scale (MADRS) in the Khan et al 21 study. It shows that the anti-suicidal effects of lithium (as measured by the S-STS) FIGURE 3. Percentage disagreement between the clinician-rated version of the S-STS and the ISST-Plus using FDA 2012 CASA categories Category 1: Passive suicidal ideation: wish to be dead; Category 2: Active suicidal ideation: nonspecific (no method, intent, or plan); Category 3: Active suicidal ideation: method, but no intent or plan; Category 4: Active suicidal ideation: method and intent, but no plan; Category 5: Active suicidal ideation: method, intent, and plan; Category 6: Completed suicide; Category 7: Suicide attempt; Category 8: Interrupted suicide attempt; Category 9: Aborted suicide at- tempt; Category 10: Preparatory acts toward imminent suicidal behavior; Category 11: Self- Injurious Behavior Without Suicidal Intent S-STS: Sheehan-Suicidality Tracking Scale; ISST-Plus: InterSePT Scale for Suicidal Thinking- Plus; FDA-CASA 2012: United States Food and Drug Administration-Classification Algorithm for Suicide Assessment FIGURE 4. Comparison of the self-rated, clinician-rated, and reconciliation versions of the S-STS by FDA-CASA 2012 category using AUC by FDA-CASA 2012 categories S-STS: Sheehan-Suicidality Tracking Scale; ISST-Plus: InterSePT Scale for Suicidal Thinking- Plus; FDA-CASA 2012: United States Food and Drug Administration-Classification Algorithm for Suicide Assessment; AUC: area under the curve

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