Ricardo E. Jorge

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.

Apathy following stroke

Objective: We will review the available evidence on the frequency, clinical correlates, mechanism, and treatment of apathy following stroke. Methods: We have explored relevant databases (that is, PubMed, MEDLINE, and PsycINFO) using the following keywords and their combinations: apathy, motivation, abulia, stroke, cerebrovascular disease, basal ganglia, prefrontal cortex, anterior cerebral infarction, and thalamus. Results: The frequency of apathy following stroke has been consistently estimated between 20% and 25%. It appears to be associated with the presence of cognitive impairment, a chronic course characterized by progressive functional decline, and with disruption of neural networks connecting the anterior cingulate gyrus, the dorsomedial frontal cortex, and the frontal pole with the ventral aspects of the caudate nucleus, the anterior and ventral globus pallidus, and the dorsomedian and intralaminar thalamic nuclei. Published treatment studies have been mostly limited to anecdotal case reports, generally using dopamine agonists or stimulant medications. Cholinesterase inhibitors and nefiracetam may significantly reduce apathetic symptoms. However, their efficacy was examined in relatively small clinical trials that require replication. Conclusion: Apathy is a frequent neuropsychiatric complication of stroke that, although often associated with depression and cognitive impairment, may occur independently of both. Its presence has been consistently associated with greater functional decline. However, there is no conclusive evidence about which is the best treatment for this condition.

Increased risk of alcohol and drug use among children from deployed military families

AIMS To examine the association between military deployment of a parent and use of alcohol and drugs among children of deployed military personnel. DESIGN Observational and cross-sectional study. SETTING Data from the USA 2010 Iowa Youth Survey, a statewide survey of 6th, 8th and 11th graders, were analyzed during 2011. PARTICIPANTS Of all 6th-, 8th- and 11th-grade students enrolled in Iowa in 2010, 69% (n = 78 240) completed the survey. MEASUREMENTS Ever drink more than a few sips of alcohol and past 30-day: binge drinking, marijuana consumption, other illegal drug use and prescription drug misuse. FINDINGS The rates of alcohol use [risk difference (RD) = 7.85, 99.91% confidence interval (CI) = 4.44-11.26], binge drinking (RD = 8.02, 99.91% CI = 4.91-11.13), marijuana use (RD = 5.30, 99.91% CI = 2.83-7.77), other illegal drug use (RD = 7.10, 99.91% CI = 4.63-9.56) and prescription drug misuse (RD = 8.58, 99.91% CI = 5.64-11.51) are greater for children of currently or recently deployed parents than for children of parents who are not in the military. The magnitude of the effects is consistent across 6th, 8th and 11th grades. Disrupted living arrangements further accentuate increased substance use, with the largest effect seen in children with a deployed parent who was not living with a parent or relative. CONCLUSIONS Children of deployed military personnel should be considered at higher risk for substance use than children of non-military citizens.

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.

Decreased heart rate variability is associated with poststroke depression.

OBJECTIVE Although decreased heart rate variability (HRV) has been well-documented in association with depression after myocardial infarction, this phenomenon has not been studied in patients with stroke. The present study was designed to prospectively assess heart rate in relationship to depression among patients with acute stroke. DESIGN Using 24-hour Holter monitoring, HRV was assessed. SETTING A large university rehabilitation hospital. PARTICIPANTS Patients with first ever stroke and no other severe physical illness, cigarette smoking, or drug therapy that could affect HRV were evaluated over 24 hours for HRV. MEASUREMENTS Patients were evaluated using the Structured Clinical Interview for depression diagnosis. Severity was assessed by the Hamilton Depression Rating Scale. Stroke severity was assessed by the National Institutes of Health Stroke Scale, the Barthel Index, and the Mini- Mental State Exam. The standard deviation (SD) of time in milliseconds of normal to normal beats (SDNN) was the primary measure of HRV. RESULTS Among patients with poststroke major or minor depression (N = 33), the SDNN was 109 +/- 32.6 SD compared with nondepressed patients (N = 16) whose SDNN was 133.9 +/- 40.1 SD (Wilcoxon rank test S = 492, p = 0.048). The SDNN was significantly and independently related to the existence of depression, but no other intergroup differences. CONCLUSIONS These findings, for the first time, have provided some evidence that both major and minor poststroke depression may lead to decreased HRV. Future research in larger groups of patients should determine whether other measures of HRV more specific to sympathetic-parasympathetic tone are decreased in patients with poststroke depression.

Low-activity allele of Catechol-O-Methyltransferase (COMTL) is associated with increased lateral ventricles in patients with first episode non-affective psychosis

BACKGROUND Structural brain anomalies are present at early phases of psychosis. The objective was to examine the impact of Catechol-O-Methyltransferase (COMT) gene variations on brain morphology in first-episode non-affective psychosis. We hypothesized that the low activity-COMT (COMT(L)) allele would be associated with the presence of structural brain changes as assessed by quantitative magnetic resonance imaging (MRI). METHODS Fifty-two males and 23 females underwent COMT genotyping and MRI. Patients were categorized into three genetic subgroups: COMT(H/H), COMT(L/H) and COMT(L/L). MRI data were analyzed using BRAINS2. Global and lobar volumes of grey matter (GM) and cerebrospinal fluid (CSF) were compared among the three groups after controlling for total intracranial volume and age of illness onset. RESULTS COMT(L) carriers showed a significant enlargement of the lateral ventricles (F = 7.13, p = 0.009), right lateral ventricle (F = 5.99, p = 0.017) and left lateral ventricle (F = 6.22, p = 0.015). No other significant differences in any of the brain structures were found among subgroups. CONCLUSIONS Our findings suggest that genetic variations of COMT can contribute to the enlargement of the lateral ventricles described in early phases of non-affective psychosis.

Is Family History of Depression a Risk Factor for Poststroke Depression? Meta-Analysis

OBJECTIVE To determine whether family history of psychiatric disorder constitutes a risk factor for the development of poststroke depression. DESIGN A meta-analysis setting: patients examined for depression following stroke seen in acute care, rehabilitation hospital, or outpatient care settings. PARTICIPANTS All patients who were reported in the worlds literature in English language publications in which information was provided about the existence or not of poststroke depression and the presence or absence of a family history of psychiatric disorder. MEASUREMENTS The frequency of family history of psychiatric disorder was determined for each study as well as the relationship of family history to the presence of poststroke depression. RESULTS Based on data obtained from 903 patients with stroke, the fixed model analysis found a risk ratio of 1.51 and the random model a risk ratio of 1.46 for the existence of poststroke depression if there is a positive family history of psychiatric disorder compared with a negative family history. CONCLUSIONS The existence of a positive family history of psychiatric disorder constitutes a risk factor for development of poststroke depression. The role of family history in poststroke depression, however, appears to be substantially lower than among elderly depressed patients without evidence of vascular disease.

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.

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.

Citalopram for Continuation Therapy After Repetitive Transcranial Magnetic Stimulation in Vascular Depression

OBJECTIVES The authors previously reported that repetitive transcranial magnetic stimulation (rTMS) produced a response rate of 39.4% among 62 patients with treatment resistant vascular depression. This study was undertaken to assess the outcome of continuation therapy to prevent relapse among these patients during 9 weeks after completion of rTMS. DESIGN Patients were randomly assigned to 18,000 pulses of rTMS given over 3 weeks or sham treatment using double blind methods. After rTMS, all patients were given 20 mg/day of citalopram for 9 weeks and reevaluated at 3, 6, and 9 weeks. SETTING Outpatient continuation treatment trial. PARTICIPANTS Patients with vascular depression (N = 62), as determined by magnetic resonance imaging hyperintensities and three or more clinical risk factors for vascular disease without other major medical illness, were recruited. They had onset of major depression after age 50 and failed at least one trial of antidepressants. INTERVENTION After rTMS or sham treatment, all treatment responders were given citalopram for 9 weeks. RESULTS Among the 33 patients who were given rTMS, 13 responded (i.e., >50% decline in Hamilton Depression Scale score). Of these 13, all completed the 9 weeks of continuation treatment. There were nine patients who continued to be responders and four who had a relapse of depression. CONCLUSION More effective methods are needed to treat elderly patients with treatment resistant vascular depression and to prevent relapse among treatment responders.