Laura Acion

Escitalopram and Problem-Solving Therapy for Prevention of Poststroke Depression: A Randomized Controlled Trial

CONTEXT Depression occurs in more than half of patients who have experienced a stroke. Poststroke depression has been shown in numerous studies to be associated with both impaired recovery in activities of daily living and increased mortality. Prevention of depression thus represents a potentially important goal. OBJECTIVE To determine whether treatment with escitalopram or problem-solving therapy over the first year following acute stroke will decrease the number of depression cases that develop compared with placebo medication. DESIGN, SETTING, AND PARTICIPANTS A multisite randomized controlled trial for prevention of depression among 176 nondepressed patients was conducted within 3 months following acute stroke from July 9, 2003, to October 1, 2007. The 12-month trial included 3 groups: a double-blind placebo-controlled comparison of escitalopram (n = 59) with placebo (n = 58), and a nonblinded problem-solving therapy group (n = 59). MAIN OUTCOME MEASURES The main outcome measure was the development of major or minor poststroke depression based on symptoms elicited by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) and the diagnostic criteria from DSM-IV for depression due to stroke with major depressive-like episode or minor depression (ie, research criteria). RESULTS Patients who received placebo were significantly more likely to develop depression than individuals who received escitalopram (11 major and 2 minor cases of depression [22.4%] vs 3 major and 2 minor cases of depression [8.5%], adjusted hazard ratio [HR], 4.5; 95% confidence interval [CI], 2.4-8.2; P < .001) and also more likely than individuals who received problem-solving therapy (5 major and 2 minor cases of depression [11.9%], adjusted HR, 2.2; 95% CI, 1.4-3.5; P < .001). These results were adjusted for history of mood disorders and remained significant after considering possible confounders such as age, sex, treatment site, and severity of impairment in the model. Using an intention-to-treat conservative method of analyzing the data, which assumed that all 27 patients who did not start randomized treatment would have developed depression, and controlling for prior history of mood disorders, escitalopram was superior to placebo (23.1% vs 34.5%; adjusted HR, 2.2; 95% CI, 1.2-3.9; P = .007), while problem-solving therapy was not significantly better than placebo (30.5% vs 34.5%; adjusted HR, 1.1; 95% CI, 0.8-1.5; P = .51). Adverse events, including all-cause hospitalizations, nausea, and adverse effects associated with escitalopram were not significantly different between the 3 groups. CONCLUSIONS In this study of nondepressed patients with recent stroke, the use of escitalopram or problem-solving therapy resulted in a significantly lower incidence of depression over 12 months of treatment compared with placebo, but problem-solving therapy did not achieve significant results over placebo using the intention-to-treat conservative method of analysis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00071643.

Repetitive Transcranial Magnetic Stimulation as treatment of poststroke depression: A preliminary study

BACKGROUND Depression has a significant impact on poststroke recovery and mortality. There are a proportion of patients with poststroke depression (PSD) who do not respond to antidepressants. Repetitive Transcranial Magnetic Stimulation (rTMS) might be a safe and effective alternative in these refractory cases. METHODS We conducted a randomized, parallel, double-blind study of active versus sham left prefrontal rTMS in patients with refractory PSD. After discontinuing antidepressants, patients were randomly assigned to receive 10 sessions of active (10 Hz, 110% of the motor threshold, 20 trains of 5 seconds duration) or sham left prefrontal rTMS. Efficacy measures included HAM-D scores, response and remission rates. Patients completed a neuropsychological battery at baseline and after completing the protocol. RESULTS When compared with sham stimulation, 10 sessions of active rTMS of the left dorsolateral prefrontal cortex were associated with a significant reduction of depressive symptoms. This reduction was not influenced by patients age, type or location of stroke, volume of left frontal leukoaraiosis or by the distance of the stimulating coil to the prefrontal cortex. However, there was a significant positive correlation between the percentage of reduction of Ham-D scores and frontal gray and white matter volumes. There were no significant changes in cognitive functioning between the active and the sham stimulation groups. In addition, there were few and mild adverse effects that were equally distributed among groups. CONCLUSIONS Taken together, these preliminary findings suggest that rTMS may be an effective and safe treatment alternative for patients with refractory depression and stroke.

Treatment of Vascular Depression Using Repetitive Transcranial Magnetic Stimulation

CONTEXT The term vascular depression (VD) has been used to describe late-life depressive disorders in patients with clinical evidence of cerebrovascular disease. Preliminary data on poststroke depression suggest that repetitive transcranial magnetic stimulation (rTMS) might also be effective among patients with VD. OBJECTIVE To examine the efficacy and safety of rTMS to treat VD. DESIGN Prospective, randomized, sham-controlled study. SETTING University hospital. METHODS After discontinuation of antidepressant therapy, 92 patients with clinically defined VD were randomly assigned to receive active or sham rTMS of the left dorsolateral prefrontal cortex. Approximately half of the patients met criteria for magnetic resonance imaging-defined VD. In experiment 1, we administered a total cumulative dose (TCD) of 12 000 pulses (TCD-12K); in experiment 2, 18,000 pulses (TCD-18K). Sham stimulation was performed using a sham coil. RESULTS In experiment 1, the sham group showed a 13.6% decrease in the 17-item Hamilton Depression Rating Scale (HAMD-17) scores compared with a 33.1% decrease in the TCD-12K group (P = .04). Response rates were 6.7% in the sham group and 33.3% in the active-stimulation group (P = .08); remission rates were 6.7% and 13.3%, respectively (P = .50). In experiment 2, the sham group showed a 17.5% decrease in the 17-item Hamilton Depression Rating Scale scores compared with a 42.4% decrease observed in the TCD-18K group (P < .001). Response rates were 6.9% in the sham group and 39.4% in the active-stimulation group (P = .003); remission rates were 3.5% and 27.3%, respectively (P = .01). Response rates to rTMS were negatively correlated with age and positively correlated with higher frontal gray matter volumes. CONCLUSIONS To our knowledge, this is the first controlled trial that demonstrates the efficacy of rTMS among geriatric patients with VD. Older age and smaller frontal gray matter volumes were associated with a poorer response to rTMS.

Escitalopram and Enhancement of Cognitive Recovery Following Stroke

CONTEXT Adjunctive restorative therapies administered during the first few months after stroke, the period with the greatest degree of spontaneous recovery, reduce the number of stroke patients with significant disability. OBJECTIVE To examine the effect of escitalopram on cognitive outcome. We hypothesized that patients who received escitalopram would show improved performance in neuropsychological tests assessing memory and executive functions than patients who received placebo or underwent Problem Solving Therapy. DESIGN Randomized trial. SETTING Stroke center. PARTICIPANTS One hundred twenty-nine patients were treated within 3 months following stroke. The 12-month trial included 3 arms: a double-blind placebo-controlled comparison of escitalopram (n = 43) with placebo (n = 45), and a nonblinded arm of Problem Solving Therapy (n = 41). OUTCOME MEASURES Change in scores from baseline to the end of treatment for the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Trail-Making, Controlled Oral Word Association, Wechsler Adult Intelligence Scale-III Similarities, and Stroop tests. RESULTS We found a difference among the 3 treatment groups in change in RBANS total score (P < .01) and RBANS delayed memory score (P < .01). After adjusting for possible confounders, there was a significant effect of escitalopram treatment on the change in RBANS total score (P < .01, adjusted mean change in score: escitalopram group, 10.0; nonescitalopram group, 3.1) and the change in RBANS delayed memory score (P < .01, adjusted mean change in score: escitalopram group, 11.3; nonescitalopram group, 2.5). We did not observe treatment effects in other neuropsychological measures. CONCLUSIONS When compared with patients who received placebo or underwent Problem Solving Therapy, stroke patients who received escitalopram showed improvement in global cognitive functioning, specifically in verbal and visual memory functions. This beneficial effect of escitalopram was independent of its effect on depression. The utility of antidepressants in the process of poststroke recovery should be further investigated. Trial Registration clinicaltrials.gov Identifier: NCT00071643.

White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer's disease.

Background and objective: Methodological variability in the assessment of white matter hyperintensities (WMH) in dementia may explain inconsistent reports of its prevalence and impact on cognition. We used a method of brain MRI segmentation for quantifying both tissue and WMH volumes in Alzheimer’s disease (AD) and examined the association between WMH and structural and cognitive variables. Methods: A consecutive series of 81 patients meeting NINCDS-ADRDA criteria for probable AD was studied. Nineteen healthy volunteers of comparable age served as the control group. Patients had a complete neurological and neuropsychological evaluation, and a three dimensional MRI was obtained. Images were segmented into grey matter, white matter, and cerebrospinal fluid. WMH were edited on segmented images, and lobar assignments were based on Talairach coordinates. Results: Mild and moderate to severe AD patients had significantly more WMH than controls (p<0.05). WMH preferentially involved the frontal lobes (70%), were inversely correlated with grey matter cortical volume (R2 = 0.23, p<0.001), and were significantly associated with vascular risk factors and with a worse performance on memory tasks. Conclusion: Objective measurements of tissue volumes in AD demonstrated that WMH are significantly related to cortical atrophy and neuropsychological impairment.

Weight Gain and Metabolic Abnormalities During Extended Risperidone Treatment in Children and Adolescents

OBJECTIVE The aim of this study was to investigate the prevalence of clinical and laboratory metabolic abnormalities during long-term risperidone treatment in children and adolescents. METHODS Medically healthy 7- to 17-year-old children chronically treated, in a naturalistic setting, with risperidone were recruited through child psychiatry clinics. Anthropometric measurements and laboratory testing were conducted. Developmental and medication histories were obtained from medical records. RESULTS In 99 patients treated with risperidone for an average of 2.9 years, a significant increase in age- and gender-adjusted weight and body mass index (BMI) (i.e., z-scores) was observed. Concomitant treatment with psychostimulants did not attenuate this weight gain. Risperidone-associated weight gain was negatively correlated with the BMI z-score obtained at the onset of risperidone treatment. Compared to lean children, overweight and obese children had higher odds of metabolic abnormalities, including increased waist circumference, hypertriglyceridemia, and low high-density lipoprotein cholesterol (HDL-C). They also tended to have a higher insulin level and homeostasis model assessment insulin resistance (HOMA-IR) index. As a result, upon recruitment in the study, children with excessive weight were 12 times more likely to have at least one laboratory metabolic abnormality and seven times more likely to have at least one criterion of the metabolic syndrome compared to lean subjects. In contrast to excessive weight status, gaining > or =0.5 BMI z-score point during risperidone treatment was not associated with a significantly higher occurrence of metabolic disturbances. CONCLUSIONS The long-term use of risperidone, especially when weight is above normal, is associated with a number of metabolic abnormalities but a low prevalence of the metabolic syndrome phenotype. Future studies should evaluate the stability of these abnormalities over time.

Variants of the dopamine D2 receptor gene and risperidone-induced hyperprolactinemia in children and adolescents.

Objective To investigate the association between hyperprolactinemia and variants of the dopamine D2 receptor (DRD2) gene in children and adolescents in long-term treatment with risperidone. Methods Medically healthy 7 to 17-year-old patients chronically treated with risperidone but receiving no other antipsychotics were recruited in a cross-sectional study. Four DRD2 variants were genotyped and prolactin concentration was measured. Medication history was obtained from the medical records. The effect of the TaqIA variants of the DRD2 on the risk of risperidone-induced hyperprolactinemia was the primary outcome measure. Results Hyperprolactinemia was present in 50% of 107 patients (87% males) treated with risperidone for an average of 2.9 years. Age, stage of sexual development, and the dose of risperidone independently predicted a higher prolactin concentration, whereas the dose of psychostimulants was negatively correlated with it. However, these four predictors became nonsignificant when risperidone serum concentration was entered into the model. Adverse events potentially related to hyperprolactinemia were more common in participants with elevated prolactin concentration and in girls (45%) compared with boys (10%). After controlling for risperidone concentration and the dose of psychostimulants, the TaqIA A1 and the A-241G alleles were associated with higher prolactin concentration, whereas the –141C Ins/Del and C957T variants had no significant effect. In addition, adverse events potentially related to hyperprolactinemia were four times more common in TaqIA A1 allele carriers. Conclusion Prolactin concentration is closely related to central DRD2 blockade, as reflected by risperidone serum concentration. Furthermore, the TaqIA and A-241G variants of the DRD2 gene could be useful in predicting the emergence of hyperprolactinemia and its potential adverse events.

Leptin gene -2548G/A variants predict risperidone-associated weight gain in children and adolescents.

Objective As the use of atypical antipsychotics in children and adolescents has increased, concerns have been raised about their long-term safety. We aimed to investigate the association between risperidone-induced weight gain, leptin concentration, and the leptin gene (LEP) –2548G/A variants in youths. Methods Medically healthy 7- to 17-year-old children and adolescents, in extended naturalistic treatment with risperidone, were recruited through pediatric psychiatry clinics. Anthropometric measures and laboratory testing were conducted. Growth and medication history was obtained from the medical record. The effect of the LEP genotypes on leptin concentration and on the slopes of the weight and body mass index (BMI) Z-score curves before and after the onset of risperidone treatment was investigated. Results In 74 individuals, chronically treated with risperidone, the A allele was associated with higher leptin concentration at low weight and BMI Z-scores. There was no effect of the LEP genotypes on weight or BMI Z-scores before risperidone was started. Afterwards, however, the A-allele carriers showed a steeper rate of increase in weight and BMI Z-scores. As a result, the GG-genotype carriers were 2.5 times less likely to be overweight/obese (i.e. having a BMI above the 85th percentile). This genetic effect on risperidone-associated weight gain did not extend to weight loss related to psychostimulants. Conclusion The LEP −2548G/A variants seem to moderate the weight-altering effect of risperidone but not psychostimulants. This may be related to genetic differences in tissue sensitivity to leptin, resulting in differential body composition.

How the states stack up: Disparities in substance abuse outpatient treatment completion rates for minorities

BACKGROUND This study was an exploratory investigation of state-level minority disparities in successfully completing outpatient treatment, a major objective for attending substance abuse treatment and a known process outcome measure. METHOD This was a retrospective analysis of state discharge and admission data from the 2006 to 2008 Treatment Episode Datasets-Discharge (TEDS-D). Data were included representing all discharges from outpatient substance abuse treatment centers across the United States. All first treatment episode clients with admission/discharge records meeting inclusion criteria who could be classified as White, Latino, or Black/African American were used (n=940,058). RESULTS States demonstrated racial and ethnic disparities in their crude and adjusted completion rates, which also varied considerably among the states. Minorities typically showed a disadvantage. A few states showed significantly higher completion rates for Blacks or Latinos. CONCLUSIONS Realistically, a variety of factors likely cause the state race/ethnic differences in successful completion rates. States should investigate their delivery systems to reduce completion disparities.

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.