Poststroke Depression: An Update.

The presence of neuropsychiatric disorders after stroke has been recognized for more than 100 years, but controlled systematic studies did not begin until the 1970s. The most clinically important advances, however, have been in the treatment and prevention of poststroke depression (PSD). Recent meta-analyses of randomized controlled trials (RCTs) for the treatment of PSD have demonstrated the efficacy of antidepressants. Similarly, RCTs for the prevention of PSD have shown that antidepressants significantly decrease the incidence of PSD compared with placebo. Early treatment of PSD with antidepressants also appears to enhance both physical and cognitive recovery from stroke and may increase survival up to 10 years. Genetic and epigenetic variations, white matter disease, cerebrovascular deregulation, altered neuroplasticity, and changes in glutamate neurotransmission may be relevant etiological factors.

Effective Tools to Predict Depression in Acute and Subacute Phase of Ischemic Stroke.

OBJECTIVE: Despite the high frequency of depression in the first year following stroke, few studies have predicted risk of depression after the acute and subacute stroke periods. The aim of this study was to identify, in the acute and subacute periods, measures that would predict major depression during the first year after stroke. METHODS: Study subjects were inpatients with ischemic stroke aged 20-85 years within 6 weeks of onset. Patients were evaluated at baseline and at 3, 6, 9, and 12 months. Patients were diagnosed with major depression using the Structured Clinical Interview for DSM-IV. The severity of depressive symptoms was measured with the Patient Health Questionnaire-9 (PHQ-9) and the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Of the 152 potential patients who met inclusion criteria, 49 had follow-up evaluations; one patient with major depression in the acute and subacute periods was excluded from the analysis. Among the remaining 48 patients, the number of those with major depression during the first year of stroke onset was five (10.4%). Patients who developed major depression had significantly more depressive symptoms in the acute and subacute stroke phase as assessed by both the PHQ-9 and MADRS. Patients with PHQ-9 scores ≥9 in the acute and subacute stroke phases were significantly more likely to develop major depression in a chronic phase of stroke. CONCLUSIONS: The self-administered PHQ-9 can identify patients in the acute and subacute stroke periods who are at increased risk for developing major depression during the first year after stroke.

Prevention of Poststroke Mortality Using Problem-Solving Therapy or Escitalopram.

OBJECTIVE: This study re-examined patients from a 1-year randomized controlled double-blind trial of escitalopram, problem-solving therapy (PST), or placebo to prevent depression among patients less than 3 months after a stroke. The objective of the current study was to determine if preventive treatment would predict time to death over 8-10 years of follow-up. Based on the importance of depression in poststoke mortality and a previous study of this population at 18 months' follow-up showing that stopping escitalopram but not PST led to a significant increase in depression, the authors hypothesized that PST would be associated with the longest time to death. METHODS: Of 129 eligible patients, 122 were contacted and 7 were lost to follow-up. Families and surviving patients were interviewed to determine current health status or the date and cause of death. RESULTS: Using the Weibull model of log time (years) to death, controlled for age, severity of physical illness, gender, severity of stroke, and history of depression after study entry, there was a significant independent effect of treatment. PST significantly and independently increased the time to mortality, whereas older age and major depression significantly and independently decreased the time to death. CONCLUSION: To the authors' knowledge, this is the first time a psychological antidepressant treatment administered for 1 year has been associated with increased survival among patients who have suffered a stroke.

A Randomized, Placebo-Controlled, Double-Blind Efficacy Study of Nefiracetam to Treat Poststroke Apathy.

BACKGROUND: To evaluate the efficacy of treatment with nefiracetam compared to placebo in poststroke apathy. METHODS: A parallel group, randomized, placebo-controlled, double-blind two-center trial in patients with recent stroke and apathy was conducted in 2 tertiary teaching hospitals in Perth, Western Australia, between March 2010 and October 2014. Consenting patients hospitalized with stroke were screened for participation at the time of hospitalization and, if diagnosed with apathy 8-36 weeks later, they were randomized to 12 weeks of 900 mg/day nefiracetam or placebo. The primary efficacy parameter was change in apathy at 12 weeks defined by the 14-item Apathy Scale (AS). RESULTS: Of 2514 patients screened, only 377 (15%) were eligible for the study after the first screening, 233 declined further participation, and 144 were assessed for apathy at 8-36 weeks post stroke to confirm eligibility. Twenty patients out of 106 with a complete psychiatric assessment had apathy (19%). Of this sample, 13 patients were randomized. Overall, the AS score decreased by a mean of 7.0 points (95% CI = -14.6 to .6), but there was no significant between-group difference at week 12 (mean paired t-tests, P > .14). CONCLUSIONS: Treatment with nefiracetam did not prove to be more efficacious than placebo in ameliorating apathy in stroke. The main limitation was the very small sample randomized, highlighting the limitations of conducting drug trials for behavioral problems among stroke patients. Pharmacological studies of apathy in stroke will require a large multicenter study and a massive sample of patients.

Results of the citalopram to enhance cognition in Huntington disease trial.

BACKGROUND: The objective of this study was to evaluate citalopram for executive functioning in Huntington's disease (HD). METHODS: The study was randomized, double-blind, and placebo-controlled. Thirty-three adults with HD, cognitive complaints, and no depression (Hamilton Depression [HAM-D] rating scale ≤ 12) were administered citalopram 20 mg or placebo (7 visits, 20 weeks), with practice and placebo run-ins. The primary outcome was change in executive functioning. RESULTS: The intent to treat analysis was controlled for practice effects, comparing visits 1 and 2 to visits 5 and 6 for citalopram versus placebo. There were no significant benefits on the executive function composite (treatment-placebo mean difference -0.167; 95% confidence interval [CI], -0.361 to 0.028; P = .092). Citalopram participants showed improved clinician-rated depression symptoms on the HAM-D (t = -2.02; P = 0.05). There were no group differences on motor ratings, self-reported executive functions, psychiatric symptoms, or functional status. CONCLUSIONS: There was no evidence that short-term treatment with citalopram improved executive functions in HD. Despite excluding patients with active depression, participants on citalopram showed improved mood, raising the possibility of efficacy for subsyndromal depression in HD.

Prevention of post-stroke generalized anxiety disorder, using escitalopram or problem-solving therapy.

This study examined the efficacy of antidepressant treatment for preventing the onset of generalized anxiety disorder (GAD) among patients with recent stroke. Of 799 patients assessed, 176 were randomized, and 149 patients without evidence of GAD at the initial visit were included in this double-blind treatment with escitalopram (N=47) or placebo (N=49) or non-blinded problem-solving therapy (PST; 12 total sessions; N=53). Participants given placebo over 12 months were 4.95 times more likely to develop GAD than patients given escitalopram and 4.00 times more likely to develop GAD than patients given PST. Although these results should be considered preliminary, the authors found that both escitalopram and PST were effective in preventing new onset of post-stroke GAD.

Efficacy of a DVD-based smoking cessation intervention for African Americans.

INTRODUCTION: Previous research suggests that African American smokers may have improved outcomes if interventions are culturally specific. However, few interventions sufficiently address the unique needs of this population in a format with large reach potential. The purpose of this study was to test the efficacy of a newly developed digital video disc (DVD)-based cessation intervention targeting African Americans. METHODS: In a 2-arm randomized trial, smokers (N = 140) were randomly assigned to view either the new Pathways to Freedom (PTF) DVD or a standard control DVD. Participants were assessed at baseline, immediately postviewing the DVD, and at a 1-month follow-up. The primary outcomes were feasibility and process variables, including intervention evaluations, readiness to quit, and risk perceptions, and smoking-related behavior changes were examined as secondary outcomes. RESULTS: Findings demonstrated the hypothesized positive effects of the PTF DVD compared with the control DVD on content evaluations, risk perceptions, and readiness to quit at follow-up. CONCLUSIONS: We found initial evidence for the efficacy of the PTF DVD as a stand-alone intervention. Future research will test the efficacy of the DVD for smoking cessation in a larger randomized trial. The ultimate goal of this research is to validate a new intervention for an underserved community of smokers that can be used in multiple settings, such as community health clinics, primary care, quitlines, cessation clinics, and seminars/workshops.

Incident apathy during the first year after stroke and its effect on physical and cognitive recovery.

OBJECTIVE: This prospective study examined the course of cognitive, physical, and social impairment among patients who developed apathy during the first year after stroke. METHODS: Patients diagnosed with apathy (N = 23) were compared with patients who had no apathy (N = 33) at initial, 3, 6, 9, and 12 months after stroke for severity of global cognitive impairment as measured by Mini-Mental State Examination, severity of impairment in activities of daily living (ADLs) as measured by Functional Independence Measure, and severity of impairment in social functioning as measured by Social Functioning Exam. RESULTS: A total of 41.1% of patients met diagnostic criteria for apathy during the first year after stroke. The mean time from stroke to onset of apathy was 3.8 (3.3 SD) months and the mean duration was 5.6 (2.3 SD) months. Using a linear mixed model, after controlling for age, initial severity of impairment, and major depression, patients in the apathy group had significantly less recovery in cognition (t(149) = -2.06; p = 0.0411) and ADLs (t(104) = -3.37; p = 0.0011) during the first year after stroke compared with nonapathic patients. CONCLUSION: Apathy is common after stroke and leads to less recovery in cognition and ADLs over the first year after stroke compared with similar nonapathic patients.

Prevention of poststroke apathy using escitalopram or problem-solving therapy.

OBJECTIVE: Apathy occurs frequently following stroke and prior studies have demonstrated the negative effect of apathy on recovery from stroke. This study was a secondary analysis examining the efficacy of escitalopram, problem-solving therapy (PST), or placebo administered for 1 year to prevent the onset of apathy among patients with recent stroke. METHODS: Patients within 3 months of an index stroke who did not meet DSM-IV diagnostic criteria for major or minor depression and who did not have a serious comorbid physical illness were enrolled. Patients were recruited from three sites: University of Iowa, University of Chicago, and Burke Rehabilitation Hospital. One hundred fifty-four patients without evidence of apathy at initial evaluation were included in the randomized controlled trial using escitalopram (10 mg patients ≤65 years; 5 mg patients >65 years) (N = 51) or placebo (N = 47) or non-blinded PST (12 total sessions) (N = 56) over 1 year. At 3, 6, 9, and 12 months, patients were assessed for diagnosis and severity of apathy using the Apathy Scale. RESULTS: Using a Cox proportional hazards model of time to onset of apathy, participants given placebo were 3.47 times more likely to develop apathy than patients given escitalopram and 1.84 times more likely to develop apathy than patients given PST after controlling for age, sex, cognitive impairment, and diabetes mellitus status (adjusted hazard ratio: 3.47, 95% CI: 1.79-6.73 [escitalopram group]; adjusted hazard ratio: 1.84, 95% CI: 1.21-2.80 [PST group]). CONCLUSION: Escitalopram or PST was significantly more effective in preventing new onset of apathy following stroke compared with placebo.

Neuropsychiatric symptoms and interleukin-6 serum levels in acute stroke.

The role of interleukin-6 (IL-6) as a risk factor for developing depressive symptoms, neuropsychological impairment, and related functional and neurological symptom severity during the acute phase of ischemic stroke is still underexplored. Here, the authors assessed this issue, in 48 patients without significant clinical history for major medical illnesses or other factors that promote inflammation, 72 hours after a first-ever acute ischemic stroke. In the acute phase of ischemic stroke, increased IL-6 plays a key role in the onset of depressive disorders, apathy/amotivation, somatic symptoms of depression, and neurological/functional symptoms, resulting in higher disability and poor outcome of stroke patients.

Increased frequency of first-episode poststroke depression after discontinuation of escitalopram.

BACKGROUND AND PURPOSE: The purpose of this study was to compare escitalopram, problem-solving therapy, and placebo to prevent poststroke depression during 6 months after discontinuation of treatment. METHODS: We examined for depression 33 patients assigned to placebo, 34 to escitalopram, and 41 to problem-solving therapy. RESULTS: After controlling for age, gender, prior mood disorder, and severity of stroke, new-onset major depression and Hamilton Depression scores were significantly higher 6 months after escitalopram was discontinued compared with the problem-solving therapy or placebo groups. CONCLUSIONS: Discontinuation of escitalopram may increase poststroke depressive symptoms.

Diagnostic criteria for depression in Parkinson's disease: a study of symptom patterns using latent class analysis.

Although major depression is one of the most frequent psychiatric disorders among patients with Parkinson's disease, diagnostic criteria have yet to be validated. The main aim of our study was to validate depressive symptoms using latent class analysis for use as diagnostic criteria for major depression in Parkinson's disease. We examined a consecutive series of 259 patients with Parkinson's disease admitted to 2 movement disorders clinics for regular follow-ups. All patients were assessed with a comprehensive psychiatric interview that included structured assessments for depression, anxiety, and apathy. The main finding was that all 9 Diagnostic and Statistical Manual (4th edition) diagnostic criteria for major depression (ie, depressed mood, diminished interest or pleasure, weight or appetite changes, sleep changes, psychomotor changes, loss of energy, feelings of worthlessness or inappropriate guilt, poor concentration, and suicidal ideation) identified a patient class (severe depression group) with high statistical significance. Latent class analysis also demonstrated a patient class with minimal depressive symptoms (no-depression group), and a third patient class with intermediate depressive symptoms (moderate depression). Anxiety and apathy were both significant comorbid conditions of moderate and severe depression. Taken together, our findings support the use of the full Diagnostic and Statistical Manual (4th edition) criteria for major depression for use in clinical practice and research in Parkinson's disease and suggest that anxiety may be included as an additional diagnostic criterion.

Diagnostic criteria for depression in Alzheimer disease: a study of symptom patterns using latent class analysis.

CONTEXT: Although depression in Alzheimer disease (AD) has a negative emotional and functional impact on patients and caregivers, specific criteria to diagnose depression in AD are still to be validated. OBJECTIVE: To validate a set of diagnostic criteria for major depression in AD. DESIGN: Cross-sectional design using latent cluster analysis (LCA). SETTING: Participants were recruited from consecutive referrals to a Memory Clinic of a tertiary hospital. PARTICIPANTS: A consecutive series of 971 outpatients with probable AD. MAIN OUTCOME MEASURE: Clusters of patients with or without major depression as determined with LCA. RESULTS: A LCA demonstrated three clusters that were considered to represent major depression, minor depression, and no depression. All nine Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for major depression were significantly associated with the major depression cluster. Although a diagnosis of generalized anxiety disorder (GAD) and apathy were also associated with the major depression cluster, irritability was not. CONCLUSIONS: The DSM-IV criteria for major depression should be used unmodified to diagnose depression in AD. Future studies should determine whether GAD should be included as an additional diagnostic criterion.

Effect of antidepressants on the course of disability following stroke.

OBJECTIVE: Stroke often produces marked physical and cognitive impairments leading to functional dependence, caregiver burden, and poor quality of life. We examined the course of disability during a 1-year follow-up period after stroke among patients who were administered antidepressants for 3 months compared to patients given placebo for 3 months. METHODS: A total of 83 patients entered a double-blind randomized study of the efficacy of antidepressants to treat depressive disorders and reduce disability after stroke. Patients were assigned to either fluoxetine (N = 32), nortriptyline (N = 22) or placebo (N = 29). Psychiatric assessment included administration of the Present State Examination modified to identify DSM-IV symptoms of depression. The severity of depression was measured using the 17-item Hamilton Depression Rating Scale. The modified Rankin Scale was used to evaluate the disability of patients at initial evaluation and at quarterly follow-up visits for 1 year. Impairment in activities of daily living was assessed by Functional Independence Measure at the same time. RESULTS: During the 1-year follow-up period, and after adjusting for critical confounders including age, intensity of rehabilitation therapy, baseline stroke severity, and baseline Hamilton Depression Rating Scale, patients who received fluoxetine or nortriptyline had significantly greater improvement in modified Rankin Scale scores compared to patients who received placebo (t [156] = -3.17, p = 0.002). CONCLUSIONS: Patients treated with antidepressants had better recovery from disability by 1-year post stroke (i.e., 9 months after antidepressants were stopped) than patients who did not receive antidepressant therapy. This effect was independent of depression suggesting that antidepressants may facilitate the neural mechanisms of recovery in patients with stroke.

Treatment of late-life depression: a role of non-invasive brain stimulation techniques.

Late-life depression (LLD) is a frequent complication of the ageing process, occurring in up to 5% of community-dwelling elderly and in a higher proportion of subjects with coexistent medical illnesses. Its presence has been consistently associated with cognitive impairment, greater disability and increased mortality. Approximately half of patients with LLD have evidence of subcortical ischaemic damage in prefrontal circuits revealed by MRI. This might constitute the biological substrate of the cardinal symptoms of depression and of executive dysfunction. An important proportion of patients with LLD do not achieve remission of their depressive symptoms in spite of adequate pharmacological and psychotherapeutic treatment. In addition, a group of LLD patients progress to further impairment and disability in the form of a dementing disorder. There is an imperative need to develop new treatment strategies for LLD. Non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are safe and efficacious interventions that might be used in combination with other therapeutic options to improve treatment outcomes. However, there are still questions regarding the optimal way in which rTMS and dTCS should be delivered as well as to the way in which we may identify the subjects who will benefit the most from these interventions.

Altered neural activity and emotions following right middle cerebral artery stroke.

Stroke of the right MCA is common. Such strokes often have consequences for emotional experience, but these can be subtle. In such cases diagnosis is difficult because emotional awareness (limiting reporting of emotional changes) may be affected. The present study sought to clarify the mechanisms of altered emotion experience after right MCA stroke. It was predicted that after right MCA stroke the anterior cingulate cortex (ACC), a brain region concerned with emotional awareness, would show reduced neural activity. Brain activity during presentation of emotional stimuli was measured in 6 patients with stable stroke, and in 12 age- and sex-matched nonlesion comparisons using positron emission tomography and the [(15)O]H(2)O autoradiographic method. MCA stroke was associated with weaker pleasant experience and decreased activity ipsilaterally in the ACC. Other regions involved in emotional processing including thalamus, dorsal and medial prefrontal cortex showed reduced activity ipsilaterally. Dorsal and medial prefrontal cortex, association visual cortex and cerebellum showed reduced activity contralaterally. Experience from unpleasant stimuli was unaltered and was associated with decreased activity only in the left midbrain. Right MCA stroke may reduce experience of pleasant emotions by altering brain activity in limbic and paralimbic regions distant from the area of direct damage, in addition to changes due to direct tissue damage to insula and basal ganglia. The knowledge acquired in this study begins to explain the mechanisms underlying emotional changes following right MCA stroke. Recognizing these changes may improve diagnoses, management and rehabilitation of right MCA stroke victims.

Limbic metabolic abnormalities in remote traumatic brain injury and correlation with psychiatric morbidity and social functioning.

The aim of this study was to investigate limbic metabolic abnormalities in remote traumatic brain injury (TBI) and their psychiatric correlates. Twenty patients and 13 age-matched comparison subjects received complete psychiatric evaluation and brain MRI and MR spectroscopy at 3 Tesla. Patients had reduced NAA to creatine ratio in the left hippocampus relative to comparison subjects (mean=1.3 [SD=0.21] compared with mean=1.55 [SD=0.21]; F=10.73, df=1, 30, p=0.003), which correlated with the Social Functioning Examination scores (r(s)=-0.502, p=0.034). Furthermore, patients with mood disorders had reduced NAA to creatine ratio in the left cingulate relative to patients without mood disorders (1.47 compared with 1.68; F=3.393, df=3, 19, p=0.044). Remote TBI displays limbic metabolic abnormalities, which correlate to social outcome and psychiatric status.

Subgenual cingulate theta activity predicts treatment response of repetitive transcranial magnetic stimulation in participants with vascular depression.

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression. Increased metabolism in the anterior cingulate cortex (ACC) is a known predictor for antidepressant response. The authors assessed whether increased theta power within the ACC predicts rTMS response in participants with vascular depression. Sixty-five participants were randomized to active or sham rTMS. Outcome was assessed using the Hamilton Depression Rating Scale. Electroencephalography was obtained, and comparisons were made among each group with a normative database using low-resolution electromagnetic tomography. Results suggest that vascular depression participants respond well to rTMS and that increased low-theta power in the subgenual ACC predicts response to rTMS.

Poststroke depression: a review.

OBJECTIVE: To review the world's (English-language) publications related to depression following stroke. METHOD: The databases from MEDLINE and PubMed were reviewed for articles related to poststroke depression (PSD), depression and cerebral vascular accident, depression and cerebral vascular disease, and depression and cerebral infarction. RESULTS: Most studies examined prevalence rates of depression and the clinical correlates of depression. Based on pooled data, the overall prevalence of major depression was 21.7% and minor depression was 19.5%. The strongest single correlate of depression was severity of impairment in activities of daily living. However, the existence of depression at baseline was found to be associated with greater impairment at follow-up, ranging from 6 weeks to 2 years in 83% of studies. Further, depression following acute stroke was also associated with greater cognitive impairment and increased mortality. PSD has been shown in 6 double-blind controlled studies to be effectively treated with antidepressants, and 1 study has recently shown that PSD can be effectively prevented. CONCLUSIONS: During the past 20 years, significant progress has been made in the identification and treatment of depression following stroke. In the future, antidepressant treatment will likely play an increasing role in the management of patients with acute stroke. Further research is needed to identify the mechanisms of depression and why antidepressants lead to improved physical and cognitive recovery and decreased mortality.