Ariel Gildengers

Identification of Suicidal Ideation and Prevention of Suicidal Behaviour in the Elderly

In almost all industrialised countries, men aged 75 years and older have the highest suicide rate among all age groups. Although in younger age groups suicide attempts are often impulsive and communicative acts, suicide attempts in older people (defined as aged 65 years and older) are often long planned and involve high-lethality methods. These characteristics, in addition to the fact that elderly are more fragile and frequently live alone, more often lead to fatal outcome.In later life, in both sexes, the most common diagnosis in those who attempt or complete suicide is major depression. In contrast to other age groups, comorbidity with substance abuse and personality disorders is less frequent. Physical illness plays an important role in the suicidal behaviour of the elderly: most frequently, depression and illness co-occur; less often, the physical illness or the treating medications are causally related to the depressive symptoms. However, only 2 to 4% of terminally ill elderly commit suicide. In addition to physical illness, complicated or traumatic grief, anxiety, unremitting hopelessness after recovery from a depressive episode and history of previous suicide attempts are risk factors for suicide attempts and completed suicide. During a depressive episode, elderly patients with suicidal ideation have higher levels of anxiety and, during treatment, anxiety decreases the probability of remission and recovery. As well as overt suicide attempts, indirect self-destructive behaviours, which often lead to premature death, are common, especially in residents of nursing homes, where more immediate means to commit suicide are restricted.Although we do not have randomised trials of treatment, studies suggest that antidepressant treatment may decrease suicide risk. Prevention and treatment trials are underway to detect the effectiveness of improved treatment of depression by primary care physicians as a means of reducing the prevalence of depressive symptoms, hopelessness and suicidal ideation.

Maintenance Treatment of Depression in Old Age: A Randomized, Double-blind, Placebo-Controlled Evaluation of the Efficacy and Safety of Donepezil Combined With Antidepressant Pharmacotherapy

CONTEXT Cognitive impairment in late-life depression is a core feature of the illness. OBJECTIVE To test whether donepezil hydrochloride and antidepressant therapy is superior to placebo and antidepressant therapy in improving cognitive performance and instrumental activities of daily living and in reducing recurrences of depression over 2 years of maintenance treatment. DESIGN Randomized, double-blind, placebo-controlled maintenance trial. SETTING University clinic. PARTICIPANTS One hundred thirty older adults aged 65 years and older with recently remitted major depression. INTERVENTIONS Random assignment to maintenance antidepressant pharmacotherapy and donepezil or to maintenance antidepressant pharmacotherapy and placebo. MAIN OUTCOME MEASURES Global neuropsychological performance, cognitive instrumental activities of daily living, and recurrent depression. RESULTS Donepezil and antidepressant therapy temporarily improved global cognition (treatment × time interaction, F₂,₂₁₆ = 3.78; P = .03), but effect sizes were small (Cohen d = 0.27, group difference at 1 year). A marginal benefit to cognitive instrumental activities of daily living was also observed (treatment × time interaction, F₂,₁₃₇ = 2.94; P = .06). The donepezil group was more likely than the placebo group to experience recurrent major depression (35% [95% confidence interval {CI}, 24%-46%] vs 19% [95% CI, 9%-29%], respectively; log-rank χ² = 3.97; P = .05; hazard ratio = 2.09 [95% CI, 1.00-4.41]). Post hoc subgroup analyses showed that of 57 participants with mild cognitive impairment, 3 of 30 participants (10% [95% CI, 0%-21%]) receiving donepezil and 9 of 27 participants (33% [95% CI, 16%-51%]) receiving placebo had a conversion to dementia over 2 years (Fisher exact test, P = .05). The mild cognitive impairment subgroup had recurrence rates of major depression of 44% with donepezil vs 12% with placebo (likelihood ratio = 4.91; P = .03). The subgroup with normal cognition (n = 73) showed no benefit with donepezil and no increase in recurrence of major depression. CONCLUSIONS Whether a cholinesterase inhibitor should be used as augmentation in the maintenance treatment of late-life depression depends on a careful weighing of risks and benefits in those with mild cognitive impairment. In cognitively intact patients, donepezil appears to have no clear benefit for preventing progression to mild cognitive impairment or dementia or for preventing recurrence of depression. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00177671.

Medical burden in late-life bipolar and major depressive disorders.

BACKGROUND Elderly patients with bipolar disorder have been found to have higher mortality than those with major depressive disorder. The authors compare medical burden in elderly patients with bipolar disorder with that in those with major depressive disorder. METHODS Fifty-four patients with bipolar I or II disorder who were 60 years of age and older were equated 1-to-2 to 108 patients with nonpsychotic, major depressive disorder according to age, sex, race, and lifetime duration of mood disorder illness. Variables examined included the following: Cumulative Illness Rating Scale for Geriatrics (CIRS-G) total scores, body mass index (BMI), and CIRS-G subscale scores. RESULTS Compared with patients with major depressive disorder, patients with bipolar disorder had similar levels of general medical comorbidity on the CIRS-G total score and number of systems affected but higher BMI. After controlling for multiple comparisons, the endocrine/metabolic and respiratory subscale scores on the CIRS-G were higher for patients with bipolar disorder. CONCLUSION Although overall medical burden appears comparable in elderly patients with bipolar and those with major depressive disorder, patients with bipolar disorder have higher BMI and greater burden of endocrine/metabolic and respiratory disease.

Time course of response to antidepressants in late-life major depression: Therapeutic implications

In the treatment of depression, there is considerable interest in the time course of response and, in particular, the speed with which individuals recover from depressive episodes. Examination of the time course and speed of response is critical for assessing the usefulness of specific treatments. However, while this issue has received attention in mid-life adult populations, it has received little consideration in the context of late-life major depression. The synthesis of empirical reports indicates that, while older adults with depression seem to respond with the same speed as mid-life adults, several factors have consistently been associated with reduced speed of response to antidepressant treatment, including greater severity of depressive symptoms and co-occurring anxiety symptoms. Limited evidence suggests that sleep impairment and genetic factors (e.g. presence of the s allele of the serotonin transporter gene promoter region) may also be associated with reduced speed of response. Some factors have consistently been found to be unrelated to speed of response (demographic characteristics, nonpsychiatric physical illnesses) whereas other factors have only mixed evidence supporting any effect (psychosocial and other clinical factors). While there is little work available to date, some evidence suggests that time course and speed of response affect longer-term outcomes of depression pharmacotherapy; thus, older adults with more rapid versus slower patterns of response may differ in the types of maintenance treatment needed to avert additional depressive episodes.None of potential strategies for accelerating speed of response have been clearly shown to be effective in late-life depression. Future treatment studies for late-life depression should routinely consider not only overall efficacy of a given pharmacotherapy (i.e. total rate of response), but time course and speed of response. To this end, new investigations must be designed to overcome the methodological limitations of prior studies that have examined time course and they should include a range of potential covariates and outcomes of between-patient differences in speed of response. Better understanding of factors related to such differences may suggest new intervention strategies to accelerate response.

A report on older‐age bipolar disorder from the International Society for Bipolar Disorders Task Force

In the coming generation, older adults with bipolar disorder (BD) will increase in absolute numbers as well as proportion of the general population. This is the first report of the International Society for Bipolar Disorder (ISBD) Task Force on Older‐Age Bipolar Disorder (OABD).

What is the optimal duration of a short-term antidepressant trial when treating geriatric depression?

Background: To determine the optimal duration of an antidepressant trial in elderly patients, the authors examined the probability of eventually responding to treatment based on early improvement. Methods: Four hundred seventy-two elderly patients with major depression (nonpsychotic, nonbipolar) were treated under protocolized conditions for up to 12 weeks and assessed weekly with the Hamilton Rating Scale for Depression. The probability of full response after 12 weeks of treatment was calculated in patients who had not fully responded after periods of treatment that lasted for 4 to 10 weeks. Results: Most of the patients who had shown a partial improvement after 4 weeks of treatment became full responders after 4 or more additional weeks of treatment. By contrast, only a few of those who were nonresponders became full responders even after up to 8 additional weeks of treatment. Conclusions: After 4 weeks of treatment, it is possible to reliably identify a subgroup of elderly patients with depression who are more likely to benefit from a change in their treatment than from a few additional weeks of treatment with the same agent.

Cognition in older adults with bipolar disorder versus major depressive disorder.

Gildengers AG, Butters MA, Chisholm D, Anderson SJ, Begley A, Holm M, Rogers JC, Reynolds CF III, Mulsant BH. Cognition in older adults with bipolar disorder versus major depressive disorder. Bipolar Disord 2012: 14: 198–205.

The relationship between interleukin-1 receptor antagonist and cognitive function in older adults with bipolar disorder

Cognitive impairments are a feature of bipolar disorder (BD) and could be worsened by inflammatory cytokines. We determined whether (i) serum interleukin‐1 receptor antagonist (IL‐1RA) was increased in elderly BD subjects; (ii) whether IL‐1RA was associated with worse neurocognitive function; and (iii) whether IL‐1RA was associated with white matter integrity.

Treating Depression to Remission in Older Adults: A Controlled Evaluation of Combined Escitalopram with Interpersonal Psychotherapy versus Escitalopram with Depression Care Management

More than half of the older adults respond only partially to first‐line antidepressant pharmacotherapy. Our objective was to test the hypothesis that a depression‐specific psychotherapy, Interpersonal Psychotherapy (IPT), when used adjunctively with escitalopram, would lead to a higher rate of remission and faster resolution of symptoms in partial responders than escitalopram with depression care management (DCM).

Early Intervention to Preempt Major Depression Among Older Black and White Adults

OBJECTIVE The study objective was to assess the efficacy of problem-solving therapy for primary care (PST-PC) for preventing episodes of major depression and mitigating depressive symptoms of older black and white adults. The comparison group received dietary coaching. METHODS A total of 247 participants (90 blacks, 154 whites, and three Asians) with subsyndromal depressive symptoms were recruited into a randomized depression prevention trial that compared effects of individually delivered PST-PC and dietary coaching on time to major depressive episode and level of depressive symptoms (Beck Depression Inventory) over two years. Cumulative intervention time averaged 5.5-6.0 hours in each study arm. RESULTS The two groups did not differ significantly in time to major depressive episodes, and incidence of such episodes was low (blacks, N=8, 9%; whites, N=13, 8%), compared with published rates of 20%-25% over one year among persons with subsyndromal symptoms and receiving care as usual. Participants also showed a mean decrease of 4 points in depressive symptoms, sustained over two years. Despite greater burden of depression risk factors among blacks, no significant differences from whites were found in the primary outcome. CONCLUSIONS Both PST-PC and dietary coaching are potentially effective in protecting older black and white adults with subsyndromal depressive symptoms from developing episodes of major depression over two years. Absent a control for concurrent usual care, this conclusion is preliminary. If confirmed, both interventions hold promise as scalable, safe, nonstigmatizing interventions for delaying or preventing episodes of major depression in the nations increasingly diverse older population.