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BACKGROUND: Treatment-Emergent Suicidal Ideation (TESI) in older adults is poorly understood. We characterized TESI in older depressed adults during treatment with venlafaxine and explored whether TESI is related to antidepressant exposure versus dimensions of the psychiatric illness. We examined the relationship among medication exposure, onset of TESI, and clinical characteristics. METHODS: We analyzed data on 233 clinical trial participants with major depression and no baseline suicidal ideation who were treated for up to 12 weeks with venlafaxine XR (target dose: 150-300 mg/day). Suicidal ideation was assessed weekly with the Scale for Suicide Ideation. A Kaplan-Meier curve displayed the time course of TESI. Differences in baseline demographic and clinical variables between the TESI and Non-TESI groups were assessed with analyses of covariance or logistic regression. A final multivariate logistic regression model indicated baseline predictors of TESI. Depression treatment outcomes in subjects developing TESI versus those who did not were examined with a mixed effects model. RESULTS: TESI occurred in 10% of participants, typically with onset within 4 weeks of the start of treatment. Anxiety, and depression severity at baseline were predictors of TESI. Most TESI was mild and transient, with 6/233 participants having TESI considered clinically meaningful. TESI was not associated with venlafaxine blood levels or side effects. CONCLUSIONS: In older depressed adults, TESI is relatively uncommon and it is likely related to the underlying illness rather than to a medication adverse effect. This suggests that TESI requires continuing rather than discontinuing antidepressant treatment.Copyright © 2016 John Wiley & Sons, Ltd. Language: en

Objectives In older adults with anxiety disorders, chronically elevated cortisol may contribute to cognitive impairment and elevated anxiety. We conducted a pilot study with mifepristone, a glucocorticoid receptor antagonist, as a potential treatment for late-life anxiety disorders and co-occurring cognitive dysfunction. Methods Fifteen individuals 60 years and older with an anxiety disorder plus cognitive dysfunction participated in the 12-week study. In the first week, participants were randomly assigned to mifepristone 300 mg daily or placebo. In the subsequent 3 weeks, all participants received mifepristone 300 mg. Mifepristone was then discontinued, and the participants were reassessed 8 weeks later. We examined the following: (1) cognitive changes; (2) worry symptom severity; (3) safety and tolerability; and (4) salivary cortisol before, during, and after mifepristone exposure. Results Overall safety, tolerability, and high retention supported the feasibility of this research. Participants with higher baseline cortisol levels (peak cortisol >6.0 ng/ml, n = 5) showed improvements in memory, executive function, and worry severity after 3-4 weeks of mifepristone with persistent memory and worry improvements 8 weeks after mifepristone discontinuation. Individuals with low-to-normal baseline cortisol (n = 8) showed little to no improvement. As expected, cortisol levels rose during mifepristone exposure and returned to pretreatment levels 8 weeks after mifepristone discontinuation. In the first week of treatment, there were no differences between placebo-treated and mifepristone-treated participants. Conclusion The results of this pilot study warrant further testing of antiglucocorticoid agents in late-life anxiety disorders with co-occurring cognitive dysfunction. Mifepristone is hypothesized to have benefits in patients with evidence of glucocorticoid excess. Directions for further study are discussed.

Background Mindfulness-based stress reduction (MBSR) has the potential to reduce worry and improve cognitive functioning. Objectives In this treatment development project, we examined MBSR in older adults with worry symptoms and co-occurring cognitive dysfunction. We examined (i) acceptability of MBSR, (ii) whether MBSR needs to be lengthened providing more repetition, (iii) MBSR's benefits for worry reduction and cognitive improvements, and (iv) continued use of MBSR techniques during follow-up. Methods Two sites (St. Louis and San Diego) enrolled individuals aged 65 years or older with significant anxiety-related distress plus subjective cognitive dysfunction, into traditional 8-session MBSR groups and 12-session groups that had the same content but more repetition of topics and techniques. We examined measures of mindfulness, worry, and a neuropsychological battery focused on memory and executive function before and after the MBSR program, and we followed up participants for 6 months after the completion of MBSR regarding their continued use of its techniques. Results Participants (N = 34) showed improvements in worry severity, increases in mindfulness, and improvements in memory as measured by paragraph learning and recall after a delay, all with a large effect size. Most participants continued to use MBSR techniques for 6 months post-instruction and found them helpful in stressful situations. There was no evidence that the extended 12-week MBSR produced superior cognitive or clinical outcomes, greater satisfaction, or greater continuation of MBSR techniques than 8-week MBSR. Conclusions These preliminary findings are promising for the further testing and use of MBSR in older adults suffering from clinical worry symptoms and co-occurring cognitive dysfunction. These are common problems in a broad range of older adults, many of whom have anxiety and mood disorders; therefore, stress reduction intervention for them may have great public health value. Copyright © 2014 John Wiley & Sons, Ltd.

Objective Older adults with anxiety disorders are burdened by impairment in neurocognition, which may be mediated by elevated circulating cortisol levels. In a randomized controlled trial of acute serotonin-reuptake inhibitor treatment for late-life anxiety disorder, we examined whether change in salivary cortisol concentrations during treatment predicted improvements in measures of memory and executive function. Methods We examined 60 adults aged 60 years and older, who took part in a 12-week trial of escitalopram versus placebo for generalized anxiety disorder. All subjects had pre-treatment and post-treatment assessments that included monitoring of peak and total daily cortisol and a comprehensive neuropsychological evaluation. Results Salivary cortisol changes during treatment showed significant associations with changes in immediate and delayed memory but no association with executive tasks (measures of working memory and set shifting). Analyses suggested that a decrease in cortisol due to serotonin-reuptake inhibitor treatment was responsible for the memory changes: memory improvement was seen with cortisol reduction among patients receiving escitalopram but not among patients receiving placebo. Conclusion Serotonin-reuptake inhibitor-induced alteration in circulating cortisol during treatment of generalized anxiety disorder predicted changes in immediate and delayed memory. This finding suggests a novel treatment strategy in late-life anxiety disorders: targeting hypothalamic–pituitary– adrenal axis dysfunction to improve memory. Copyright © 2011 John Wiley & Sons, Ltd.

Treatment-Emergent Suicidal Ideation (TESI) in older adults is poorly understood. We characterized TESI in older depressed adults during treatment with venlafaxine and explored whether TESI is related to antidepressant exposure versus dimensions of the psychiatric illness. We examined the relationship among medication exposure, onset of TESI, and clinical characteristics.We analyzed data on 233 clinical trial participants with major depression and no baseline suicidal ideation who were treated for up to 12 weeks with venlafaxine XR (target dose: 150-300 mg/day). Suicidal ideation was assessed weekly with the Scale for Suicide Ideation. A Kaplan-Meier curve displayed the time course of TESI. Differences in baseline demographic and clinical variables between the TESI and Non-TESI groups were assessed with analyses of covariance or logistic regression. A final multivariate logistic regression model indicated baseline predictors of TESI. Depression treatment outcomes in subjects developing TESI versus those who did not were examined with a mixed effects model.TESI occurred in 10% of participants, typically with onset within 4 weeks of the start of treatment. Anxiety, and depression severity at baseline were predictors of TESI. Most TESI was mild and transient, with 6/233 participants having TESI considered clinically meaningful. TESI was not associated with venlafaxine blood levels or side effects.In older depressed adults, TESI is relatively uncommon and it is likely related to the underlying illness rather than to a medication adverse effect. This suggests that TESI requires continuing rather than discontinuing antidepressant treatment. Copyright © 2016 John WileySons, Ltd.

Mindfulness-based stress reduction (MBSR) has the potential to reduce worry and improve cognitive functioning.In this treatment development project, we examined MBSR in older adults with worry symptoms and co-occurring cognitive dysfunction. We examined (i) acceptability of MBSR, (ii) whether MBSR needs to be lengthened providing more repetition, (iii) MBSR's benefits for worry reduction and cognitive improvements, and (iv) continued use of MBSR techniques during follow-up.Two sites (St. Louis and San Diego) enrolled individuals aged 65 years or older with significant anxiety-related distress plus subjective cognitive dysfunction, into traditional 8-session MBSR groups and 12-session groups that had the same content but more repetition of topics and techniques. We examined measures of mindfulness, worry, and a neuropsychological battery focused on memory and executive function before and after the MBSR program, and we followed up participants for 6 months after the completion of MBSR regarding their continued use of its techniques.Participants (N = 34) showed improvements in worry severity, increases in mindfulness, and improvements in memory as measured by paragraph learning and recall after a delay, all with a large effect size. Most participants continued to use MBSR techniques for 6 months post-instruction and found them helpful in stressful situations. There was no evidence that the extended 12-week MBSR produced superior cognitive or clinical outcomes, greater satisfaction, or greater continuation of MBSR techniques than 8-week MBSR.These preliminary findings are promising for the further testing and use of MBSR in older adults suffering from clinical worry symptoms and co-occurring cognitive dysfunction. These are common problems in a broad range of older adults, many of whom have anxiety and mood disorders; therefore, stress reduction intervention for them may have great public health value.

Older adults with anxiety disorders are burdened by impairment in neurocognition, which may be mediated by elevated circulating cortisol levels. In a randomized controlled trial of acute serotonin-reuptake inhibitor treatment for late-life anxiety disorder, we examined whether change in salivary cortisol concentrations during treatment predicted improvements in measures of memory and executive function.We examined 60 adults aged 60 years and older, who took part in a 12-week trial of escitalopram versus placebo for generalized anxiety disorder. All subjects had pre-treatment and post-treatment assessments that included monitoring of peak and total daily cortisol and a comprehensive neuropsychological evaluation.Salivary cortisol changes during treatment showed significant associations with changes in immediate and delayed memory but no association with executive tasks (measures of working memory and set shifting). Analyses suggested that a decrease in cortisol due to serotonin-reuptake inhibitor treatment was responsible for the memory changes: memory improvement was seen with cortisol reduction among patients receiving escitalopram but not among patients receiving placebo.Serotonin-reuptake inhibitor-induced alteration in circulating cortisol during treatment of generalized anxiety disorder predicted changes in immediate and delayed memory. This finding suggests a novel treatment strategy in late-life anxiety disorders: targeting hypothalamic-pituitary- adrenal axis dysfunction to improve memory.