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Suicide is a public health concern in older adults. Recent cross sectional studies suggest that impairments in executive functioning, memory and attention are associated with suicidal ideation in older adults. It is unknown whether these neuropsychological features predict persistent suicidal ideation. We analyzed data from 468 individuals ≥ age 60 with major depression who received venlafaxine XR monotherapy for up to 16 weeks. We used latent class growth modeling to classify groups of individuals based on trajectories of suicidal ideation. We also examined whether cognitive dysfunction predicted suicidal ideation while controlling for time-dependent variables including depression severity, and age and education. The optimal model using a zero inflated Poisson link classified individuals into four groups, each with a distinct temporal trajectory of suicidal ideation: those with 'minimal suicidal ideation' across time points; those with 'low suicidal ideation'; those with 'rapidly decreasing suicidal ideation'; and those with 'high and persistent suicidal ideation'. Participants in the 'high and persistent suicidal ideation' group had worse scores relative to those in the "rapidly decreasing suicidal ideation" group on the Color-Word 'inhibition/switching' subtest from the Delis-Kaplan Executive Function Scale, worse attention index scores on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and worse total RBANS index scores. These findings suggest that individuals with poorer ability to switch between inhibitory and non-inhibitory responses as well as worse attention and worse overall cognitive status are more likely to have persistently higher levels of suicidal ideation. CLINICALTRIAL., Gov Number: NCT00892047., (Published by Elsevier Ltd.)

Background: Treatment-resistant major depression is common and potentially life-threatening in elderly people, in whom little is known about the benefits and risks of augmentation pharmacotherapy. We aimed to assess whether aripiprazole is associated with a higher probability of remission than is placebo., Methods: We did a randomised, double-blind, placebo-controlled trial at three centres in the USA and Canada to test the efficacy and safety of aripiprazole augmentation for adults aged older than 60 years with treatment-resistant depression (Montgomery Asberg Depression Rating Scale [MADRS] score of ≥15). Patients who did not achieve remission during a pre-trial with venlafaxine extended-release (150-300 mg/day) were randomly assigned (1:1) to the addition of aripiprazole (target dose 10 mg [maximum 15 mg] daily) daily or placebo for 12 weeks. The computer-generated randomisation was done in blocks and stratified by site. Only the database administrator and research pharmacists had knowledge of treatment assignment. The primary endpoint was remission, defined as an MADRS score of 10 or less (and at least 2 points below the score at the start of the randomised phase) at both of the final two consecutive visits, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00892047., Findings: From July 20, 2009, to Dec 30, 2013, we recruited 468 eligible participants, 181 (39%) of whom did not remit and were randomly assigned to aripiprazole (n=91) or placebo (n=90). A greater proportion of participants in the aripiprazole group achieved remission than did those in the placebo group (40 [44%] vs 26 [29%] participants; odds ratio [OR] 2·0 [95% CI 1·1-3·7], p=0·03; number needed to treat [NNT] 6·6 [95% CI 3·5-81·8]). Akathisia was the most common adverse effect of aripiprazole (reported in 24 [26%] of 91 participants on aripiprazole vs 11 [12%] of 90 on placebo). Compared with placebo, aripiprazole was also associated with more Parkinsonism (15 [17%] of 86 vs two [2%] of 81 participants), but not with treatment-emergent suicidal ideation (13 [21%] of 61 vs 19 [29%] of 65 participants) or other measured safety variables., Interpretation: In adults aged 60 years or older who do not achieve remission from depression with a first-line antidepressant, the addition of aripiprazole is effective in achieving and sustaining remission. Tolerability concerns include the potential for akathisia and Parkinsonism., Funding: National Institute of Mental Health, UPMC Endowment in Geriatric Psychiatry, Taylor Family Institute for Innovative Psychiatric Research, National Center for Advancing Translational Sciences, and the Campbell Family Mental Health Research Institute., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Fibromyalgia (FM) is common in older adults suffering from mood disorders. However, clinical diagnosis of FM is challenging, particularly in psychiatric settings. We examined the prevalence of FM and the sensitivity of three simple screeners for FM., Methods: Using cross-sectional data, we evaluated three tests against the American College of Rheumatology (ACR) 1990 Criteria for the Classification of FM: a "Do you often feel like you hurt all over?" question, a pain map score, and the Pope and Hudson (PH) interview for FM. Participants were 185 community-dwelling adults ≥ 60 years old with comorbid depression and chronic low back pain evaluated at a late-life mental health clinic., Results: Fifty three of 185 participants (29%) met the ACR 1990 FM criteria. Compared to those without FM, the FM group had more "yes" answers to the "hurt all over?" question and higher pain map scores. To reach a sensitivity of at least 0.90, the cut-off score for the pain map was 8. The sensitivity of the pain map, "hurt all over?" question, and PH criteria were 0.92 [95%CI 0.82-0.98], 0.91 [95%CI 0.79-0.97], and 0.94 [95%CI 0.843-0.99] respectively., Conclusions: Nearly one in three older adults suffering from depression and chronic low back pain met ACR 1990 FM criteria. Three short screening tests showed high sensitivity when compared to the ACR 1990 FM criteria. Implementation of one of the simple screeners for FM in geriatric psychiatry settings may guide the need for further diagnostic evaluation.

Late-life depression (LLD, major depression occurring in an adult 60 years or older) is a common condition that frequently presents with cognitive impairment. Up to half of individuals with LLD are estimated to have cognitive impairment greater than that of age- and education-matched comparators, with impairments of episodic memory, speed of information processing, executive functioning, and visuospatial ability being most common. To inform our understanding of the state- versus trait-effects of depression on neuropsychological functioning, and to overcome limitations of previous studies, we utilized baseline data from the longitudinal Pathways study to compare differences in single time point performance on a broad-based neuropsychological battery across three diagnostic groups of older adults, each comprised of unique participants (n = 438): currently depressed (n = 120), previously depressed but currently euthymic (n = 190), and never-depressed (n = 128). Consistent with our hypotheses, we found that participants with a history of depression (currently or previously depressed) performed significantly worse than never-depressed participants on most tests of global cognition, as well as on tests of episodic memory, attention and processing speed, verbal ability, and visuospatial ability; in general, differences were most pronounced within the domain of attention and processing speed. Contrary to our hypothesis, we did not observe differences in executive performance between the two depression groups, suggesting that certain aspects of executive functioning are "trait deficits" associated with LLD. These findings are in general agreement with the existing literature, and represent an enhancement in methodological rigor over previous studies given the cross-sectional approach that avoids practice effects on test performance.

Objective: To describe the clinical effect and safety of low-dose buprenorphine, a κ-opioid receptor antagonist, for treatment-resistant depression (TRD) in midlife and older adults., Method: In an 8-week open-label study, buprenorphine was prescribed for 15 adults aged 50 years or older with TRD, diagnosed with the Structured Clinical Interview for DSM-IV, between June 2010 and June 2011. The titrated dose of buprenorphine ranged from 0.2-1.6 mg/d. We assessed clinical change in depression, anxiety, sleep, positive and negative affect, and quality of life. The Montgomery-Asberg Depression Rating scale (MADRS) served as the main outcome measure. Tolerability was assessed by documenting side effects and change in vital signs, weight, and cognitive function. Clinical response durability was assessed 8 weeks after discontinuation of buprenorphine., Results: The mean dose of buprenorphine was 0.4 mg/d (mean maximum dose = 0.7 mg/d). The mean depression score (MADRS) at baseline was 27.0 (SD = 7.3) and at week 8 was 9.5 (SD = 9.5). A sharp decline in depression severity occurred during the first 3 weeks of exposure (mean change = -15.0 [SD = 7.9]). Depression-specific items measuring pessimism and sadness indicated improvement during exposure, supporting a true antidepressant effect. Treatment-emergent side effects (in particular, nausea and constipation) were not sustained, vital signs and weight remained stable, and executive function and learning improved from pretreatment to posttreatment., Conclusion: Low-dose buprenorphine may be a novel-mechanism medication that provides a rapid and sustained improvement for older adults with TRD. Placebo-controlled trials of longer duration are required to assess efficacy, safety, and physiologic and psychological effects of extended exposure to this medication., Trial Registration: ClinicalTrials.gov identifier: NCT01071538., (© Copyright 2014 Physicians Postgraduate Press, Inc.)

Objective: To identify actionable predictors of remission to antidepressant pharmacotherapy in depressed older adults and to use signal detection theory to develop decision trees to guide clinical decision making., Method: We treated 277 participants with current major depression using open-label venlafaxine XR (up to 300 mg/day) for 12 weeks, in an NIMH-sponsored randomized, placebo-controlled augmentation trial of adjunctive aripiprazole. Multiple logistic regression and signal detection approaches identified predictors of remission in both completer and intent-to-treat samples., Results: Higher baseline depressive symptom severity (odds ratio [OR]: 0.86, 95% confidence interval [CI]: 0.80-0.93; p <0.001), smaller symptom improvement during the first two weeks of treatment (OR: 0.96, 95% CI: 0.94-0.97; p <0.001), male sex (OR: 0.41 95% CI: 0.18-0.93; p = 0.03), duration of current episode ≥2 years (OR: 0.26, 95% CI: 0.12-0.57; p <0.001) and adequate past depression treatment (ATHF ≥3) (OR: 0.34, 95% CI: 0.16-0.74; p = 0.006) predicted lower probability of remission in the completer sample. Subjects with Montgomery Asberg (MADRS) decreasing by greater than 27% in the first 2 weeks and with baseline MADRS scores of less than 27 (percentile rank = 51) had the best chance of remission (89%). Subjects with small symptom decrease in the first 2 weeks with adequate prior treatment and younger than 75 years old had the lowest chance of remission (16%)., Conclusion: Our results suggest the clinical utility of measuring pre-treatment illness severity and change during the first 2 weeks of treatment in predicting remission of late-life major depression., (Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to explore how the level of shiftwork exposure during an individual's working life might be related to subjectively reported sleep quality and timing during retirement. Telephone interviews regarding past employment and sleep timing and quality (among other variables) were conducted using a pseudo-random age-targeted sampling process. Subjective sleep quality was assessed using a telephone version of the Pittsburgh Sleep Quality Index. Timing of reported habitual bedtimes and rise-times were assessed using the Sleep Timing Questionnaire. Questions measuring morningness and subjective health were also given. Retired seniors (aged >65 years, n = 1113) were studied. Analysis was by analysis of variance, with shiftwork exposure in three bins [0 (n = 387), 1-15 (n = 371) and >15 years (n = 355)], gender (n = 634 male, 479 female) and former occupation [in two broad categories, 'managerial' (n = 437) versus 'other' (n = 676)] as factors. In retired shiftworkers, relative to retired day workers, past exposure to shiftwork was associated with higher (worse) PSQI scores by 1.0 units (1-15 years) and 0.6 units (>15 years) (main effect P = 0.005). There were also main effects of gender and former occupation (males and managerials reporting better sleep), but neither variable interacted with shiftwork exposure. The timing of current mean habitual bedtimes and rise-times (and also the variance around them) were very similar for the three shiftwork exposure groups. The shiftwork exposure effect did not appear to be mediated by either morningness or current health. Prior exposure to shiftwork would appear to be related to currently reported sleep problems during retirement., (© 2012 European Sleep Research Society.)

Objective: Preclinical data suggests that memantine, a noncompetitive glutamate N-methyl- D-aspartate-receptor blocker used for the treatment of moderate to severe Alzheimer's disease, could reduce depressive and amotivated behavior occurring in the context of psychosocial stress. Therefore, we examined whether memantine could reduce depressive symptoms and amotivation manifesting in older adults after a disabling medical event, thereby improving their functional recovery., Method: We recruited subjects aged 60 years and older who had recently suffered a disabling medical event and were admitted to a skilled nursing facility for rehabilitation. Participants with significant depressive symptoms, defined as a Hamilton Rating Scale for Depression score of 10 or greater, and/or significant apathy symptoms, defined as an Apathy Evaluation Scale score of 40 or greater, were randomized to memantine (10 mg/d for 1 week, then 10 mg twice daily) or placebo, for 12 weeks. We also recruited participants without depressive or apathy symptoms for naturalistic follow-up as a non-depressed comparison group. Depressive and apathy symptoms were main outcomes; functional recovery, and self-report rating of helplessness, and onset of new depressive disorders were secondary outcomes., Results: Thirty-five older adults with significant depressive and/or apathy symptoms were randomized, of whom 27 (77.1%) completed the 12 week randomized controlled trial. Both groups showed reduction in depressive symptoms (but no significant reduction in apathy symptoms) and improved function. However, there were no group differences between the memantine-randomized and placebo randomized participants on any outcome., Conclusion: Memantine was not associated with superior affective or functional outcome compared with placebo in medically rehabilitating older adults with depressive and apathy symptoms., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background: Socioeconomically disadvantaged adults experience greater healthcare disparities and increased risk of depression compared to higher-income groups., Aim: To create a depression care model for disadvantaged adults utilizing service agencies, through a community-academic partnership., Methods: Using participatory research methods, an organizational needs assessment was performed to ascertain depression care needs, identify barriers to clients receiving treatment, and marshal resources. Interviews and surveys were conducted with community organizational leaders. Focus groups were conducted with clients who used the service agencies., Results: Interviews and surveys identified barriers including discontinuity of care and unmet basic needs for food, housing, health insurance and transportation. Focus groups enriched the understanding of barriers including lack of motivation to seek depression care, lack of social support and needed resources for the uninsured, underinsured and homeless. The findings were used to develop a depression care model combining depression management with motivational interviewing to evaluate and meet needs, and peer education to motivate and provide support., Conclusions: This partnership facilitated the development of a community-driven intervention that academic researchers acting alone could not realize. To provide depression care to socioeconomically disadvantaged individuals, the intervention must include mitigating solutions to barriers.

Background: Generalised anxiety disorder (GAD) in older adults is associated with neuropsychological impairment. Aims We examined neuropsychological functioning in older adults with GAD in comparison with psychiatrically healthy older adults at baseline, and we examined changes following a 12-week placebo-controlled trial of escitalopram., Method: A total of 160 participants without dementia aged ≥60 with current GAD and 37 individuals in a comparison group without psychiatric history underwent neuropsychological assessment. Of these, 129 participants with GAD were reassessed post-treatment (trial registration: NCT00105586)., Results: The participants with GAD performed worse than the comparison group in information processing speed, working memory, inhibition, problem-solving (including concept formation and mental flexibility) and immediate and delayed memory. Neuropsychological functioning was correlated with everyday functioning. After treatment, those with low cognitive scores experienced working memory, delayed memory and visuospatial ability improvement and those who reported clinical improvement in anxiety exhibited improvement in the ability to engage inhibition and episodic recall. These improvements were modest and of similar magnitude in both treatment conditions., Conclusions: Generalised anxiety disorder in older adults is associated with neuropsychological impairments, which are associated with functional impairment. Those with GAD who either have a low cognitive performance or report clinical improvement in anxiety post-treatment, show improvement in multiple cognitive domains. These findings underscore the importance of treatments that aid cognition as well as anxiety symptoms.

Some of the sleep disruption seen in seniors (>65 yrs) may be due to alteration of the circadian pacemaker phase and/or its phase angle with bedtime. The purpose of this study was to determine the effects of 2 h changes in the timing of bedtime (both earlier and later) on the sleep of seniors. Ten healthy seniors (9 F, 1 M, age 70-82 yrs) were each studied individually during three 120 h sessions (each separated by >2 weeks) in a time-isolation laboratory. On nights 1 and 2, bedtime and rise-time occurred at the subjects' habitual times; on nights 3-5, bedtime was specified by the experiment, but rise-time was at the subjects' discretion (without knowledge of clock time). Under the control condition, subjects went to bed at their habitual bedtime (HBT), under the earlier bedtime condition at (HBT-2 h), and under the later bedtime condition at (HBT+2 h). Sleep was polysomnnographically recorded and rectal temperature continuously monitored. Although total sleep time increased in the earlier compared to the later condition (p<0.01), sleep efficiency decreased and wake after sleep onset increased (p<0.01). Subjective ratings of sleep were also worse under the earlier (HBT-2 h) than under later (HBT+ 2 h) condition (p<0.05). Performance did not differ between the earlier and later conditions. The larger the phase angle between actual bedtime and circadian temperature minimum (Tmin), the longer the time spent in bed and total sleep time, and the worse the sleep efficiency and subjective sleep ratings. There were no effects related to the phase angle between Tmin and rise-time. The relative benefits of longer vs. more efficient sleep in the elderly require further investigation.

Background: Co-morbid anxiety symptoms are common in late-life depression (LLD) and predict poorer treatment outcomes. No research has delineated the impact of different dimensions of anxiety (such as worry/anxious apprehension and panic/anxious arousal) on treatment response in LLD. We explored the impact of the dimensions of worry and panic on acute and maintenance treatment outcomes in LLD., Methods: We measured anxiety symptoms in 170 LLD subjects receiving protocolized treatment. Exploratory principal component analysis was used to delineate dimensions of anxiety symptoms. We defined sub-groups based on factor scores. We used survival analysis to test the association of pretreatment anxiety dimensions with time to response and time to recurrence of LLD., Results: The principal component analysis found two factors: "worry" and "panic." Three sub-groups were defined: low panic-low worry, low panic-high worry, and high panic-high worry. The low panic-high worry and high panic-high worry sub-groups had longer time to response than the low panic-low worry sub-group. Time to recurrence was longer in low panic-low worry subjects randomized to drug. Among subjects with high worry, there was no difference between those with low versus high panic regarding both time to response and time to recurrence of LLD., Conclusion: High levels of worry were associated with longer time to response and earlier recurrence with pharmacotherapy for LLD. There was no additional effect of panic symptoms on treatment outcomes when accounting for the effects of excessive worry. These results suggest that worry symptoms should be a focus of strategies to improve acute and maintenance treatment response in LLD., ((c) 2009 Wiley-Liss, Inc.)

Age-associated alterations in hypothalamic-pituitary-adrenal (HPA) axis functioning may make individuals more susceptible to HPA dysregulation in the context of mood and anxiety disorders. Little to no research has been done to examine HPA axis function in generalized anxiety disorder (GAD), particularly in late-life GAD, the most prevalent anxiety disorder in the elderly. The study sample consisted of 71 GAD subjects and 40 nonanxious comparison subjects over 60 years of age. We examined the hypotheses that elderly individuals with GAD will have elevated salivary cortisol levels compared to nonanxious subjects, and that elevated cortisol levels in GAD will be associated with measures of symptom severity. We report that late-life GAD is characterized by elevated basal salivary cortisol levels, with higher peak cortisol levels and larger areas under the curve, compared to nonanxious subjects. Additionally, severity of GAD as measured by the GAD Severity Scale and the Penn State Worry Questionnaire are positively correlated with cortisol levels. These data demonstrate HPA axis dysfunction in late-life GAD and suggest the need for additional research on the influence of aging on HPA axis function in mood and anxiety disorders.

A laboratory study of sleep and circadian rhythms was undertaken in 28 spousally bereaved seniors (> or =60 yrs) at least four months after the loss event. Measures taken included two nights of polysomnography (second night used), approximately 36 h of continuous core body temperature monitoring, and four assessments of mood and alertness throughout a day. Preceding the laboratory study, two-week diaries were completed, allowing the assessment of lifestyle regularity using the 17-item Social Rhythm Metric (SRM) and the timing of sleep using the Pittsburgh Sleep Diary (PghSD). Also completed were questionnaires assessing level of grief (Texas Revised Inventory of Grief [TRIG] and Index of Complicated Grief [ICG]), subjective sleep quality (Pittsburgh Sleep Quality Index [PSQI]), morningness-eveningness (Composite Scale of Morningness [CSM]), and clinical interview yielding a Hamilton Depression Rating Scale (HDRS) score. Grief was still present, as indicated by an average TRIG score of about 60. On average, the bereaved seniors habitually slept between approximately 23:00 and approximately 06:40 h, achieving approximately 6 h of sleep with a sleep efficiency of approximately 80%. They took about 30 min to fall asleep, and had their first REM episode after 75 min. About 20% of their sleep was in Stage REM, and about 3% in Stages 3 or 4 (slow wave sleep). Their mean PSQI score was 6.4. Their circadian temperature rhythms showed the usual classic shape with a trough at approximately 01:00 h, a fairly steep rise through the morning hours, and a more gradual rise to mid-evening, with an amplitude of approximately 0.8 degrees C. In terms of lifestyle regularity, the mean regularity (SRM) score was 3.65 (slightly lower than that usually seen in seniors). Mood and alertness showed time-of-day variation with peak alertness in the late morning and peak mood in the afternoon. Correlations between outcome sleep/circadian variables and level of grief (TRIG score) were calculated; there was a slight trend for higher grief to be associated with less time spent asleep (p=0.07) and reduced alertness at 20:00 h (p=0.05). Depression score was not correlated with TRIG score (p>0.20). When subjects were divided into groups by the nature of their late spouse's death (expected/after a long-term chronic illness [n=18] versus unexpected [n=10]), no differences emerged in any of the variables. In conclusion, when studied at least four months after the loss event, there appears to be some sleep disruption in spousally bereaved seniors. However, this disruption does not appear to be due to bereavement-related disruptions in the circadian system.

Longitudinal studies are used in psychiatric research to address outcome changes over time within and between individuals. However, because participants may drop out of a study prematurely, ignoring the nature of dropout often leads to biased inference, and in turn, wrongful conclusions. The purpose of the present paper is: (1) to review several dropout processes, corresponding inferential issues and recent methodological advances; (2) to evaluate the impact of assumptions regarding the dropout processes on inference by simulation studies and an illustrative example using psychiatric data; and (3) to provide a general strategy for practitioners to perform analyses of longitudinal data with dropouts, using software available commercially or in the public domain. The statistical methods used in this paper are maximum likelihood, multiple imputation and semi-parametric regression methods for inference, as well as Little's test and index of sensitivity to nonignorability (ISNI) for assessing statistical dropout mechanisms. We show that accounting for the nature of the dropout process influences results and that sensitivity analysis is useful in assessing the robustness of parameter estimates and related uncertainties. We conclude that recording the causes of dropouts should be an integral part of any statistical analysis with longitudinal psychiatric data, and we recommend performing a sensitivity analysis when the exact nature of the dropout process cannot be discerned.

Objective: This study sought to characterize cognitive functioning in elderly patients with generalized anxiety disorder (GAD), as compared with normal comparison subjects and patients with major depression., Methods: The cognitive functioning in GAD (N=19) was assessed with the Mattis Dementia Rating Scale and across specific domains of naming, executive ability, and memory, in comparison with late-life major depressive disorder (MDD; N=68) and versus no psychiatric illness (N=40)., Results: In comparison to healthy normal comparison subjects, anxious subjects were impaired on measures of short-term and delayed memory. Depressed subjects also performed worse than normal comparison subjects on delayed memory, as well as in naming. Anxious subjects did not differ significantly from depressed subjects in any measure of cognitive function., Conclusion: In this preliminary study, anxious subjects displayed cognitive impairments in short-term memory; while depressed patients compared to normal comparison subjects showed executive dysfunction and more general cognitive impairments not evident in anxious subjects. Studies of neuropsychological function in elderly anxious subjects may be informative in developing treatment interventions that mitigate cognitive dysfunction and illuminate the course of illness and underlying neural pathways.

Background: Comorbid anxiety is common in depressive disorders in both middle and late life, and it affects response to antidepressant treatment., Aims: To examine whether anxiety symptoms predict acute and maintenance (2 years) treatment response in late-life depression., Method: Data were drawn from a randomised double-blind study of pharmacotherapy and interpersonal psychotherapy for patients age 70 years and over with major depression. Anxiety symptoms were measured using the Brief Symptom Inventory. Survival analysis tested the effect of pre-treatment anxiety on response and recurrence., Results: Patients with greater pretreatment anxiety took longer to respond to treatment and had higher rates of recurrence. Actuarial recurrence rates were 29% (pharmacotherapy, lower anxiety), 58% (pharmacotherapy, higher anxiety), 54% (placebo, lower anxiety) and 81% (placebo, higher anxiety)., Conclusions: Improved identification and management of anxiety in late-life depression are needed to achieve response and stabilise recovery.

OSWALD (Object-oriented Software for the Analysis of Longitudinal Data) is flexible and powerful software written for S-PLUS for the analysis of longitudinal data with dropout for which there is little other software available in the public domain. The implementation of OSWALD is described through analysis of a psychiatric clinical trial that compares antidepressant effects in an elderly depressed sample and a simulation study. In the simulation study, three different dropout mechanisms: completely random dropout (CRD), random dropout (RD) and informative dropout (ID), are considered and the results from using OSWALD are compared across mechanisms. The parameter estimates for ID-simulated data show less bias with OSWALD under the ID missing data assumption than under the CRD or RD assumptions. Under an ID mechanism, OSWALD does not provide standard error estimates. We supplement OSWALD with a bootstrap procedure to derive the standard errors. This report illustrates the usage of OSWALD for analyzing longitudinal data with dropouts and how to draw appropriate conclusions based on the analytic results under different assumptions regarding the dropout mechanism.

Background: ECT, an effective treatment for major depression, is associated with a high relapse rate. Roughly half of all responders during the acute treatment phase relapse during continuation treatment. Recent literature has pointed out an "efficacy-effectiveness gap" in outcomes of patients enrolled in study protocols when compared to "care as usual." This study compares the effectiveness of usual care versus protocolized pharmacotherapy in preventing relapse following ECT., Methods: One hundred twenty-six depressed patients responded to acute ECT. Seventy-three were randomized to continuation pharmacotherapy consisting of nortriptyline, nortriptyline-plus-lithium, or placebo. The 53 patients that refused to participate in the randomized trial were followed naturalistically for 6 months or until depression relapse in usual care settings., Results: All but one "usual care" patient received pharmacotherapy following ECT; 27 (51%) relapsed within 6 months. Only one usual care patient received continuation ECT as a first-line treatment. The "usual care" relapse rate was intermediate to the relapse rates of the patients receiving protocolized nortriptyline (60%) and nortriptyline-plus-lithium (39%), but superior to placebo (84%)., Conclusions: The relapse rate associated with usual care following ECT was comparable to that of protocolized pharmacotherapy. This suggests that high relapse rates following ECT are not due solely to an "efficacy-effectiveness gap."

Objective: Persistent pain and cognitive impairment are each common in older adults. Mental flexibility, memory, and information-processing speed may be particularly vulnerable in the aging brain. We investigated the effects of persistent pain on these cognitive domains among community-dwelling, nondemented older adults., Setting: Older Adult Pain Management Program., Design: A total of 56 new patients (mean age 76.1 years) were recruited to describe 1) rates of persistent pain conditions and pain intensity; 2) cognition (mental flexibility, short-term memory, and psychomotor speed); 3) severity of depression; and 4) sleep quality. All patients had nonmalignant pain for at least 3 months. Pain intensity was measured with the McGill Pain Questionnaire and depression severity with the 17-item Hamilton Rating Scale for Depression. Cognition was assessed with 1) Mini-Mental State Exam; 2) Number-Letter-Switching and Motor Speed subtests of the Delis-Kaplan Executive Function System Trail Making Test; 3) Digit Symbol Subtest (DSST) of the Wechsler Adult Intelligence Scales-III; and 4) free and paired recall of the DSST digit-symbol pairs. Multiple linear regression modeled whether these variables predicted poorer cognitive outcomes, after adjusting for the effects of opioids, sleep impairment, depression, medical comorbidity, and years of education., Results: In univariate analysis, pain severity was associated with a greater impairment on number-letter switching (r = -0.42, P = 0.002). This association remained after adjusting for the effects of depression, sleep, medical comorbidity, opioid use, and years of education (t = -1.97, P = 0.056)., Conclusions: In community dwelling older adults, neither pain nor mood was associated with measures of short-term memory or information-processing speed. However, pain severity was associated with decreased performance on a test of number-letter switching, indicating a relationship between pain and mental flexibility.

Background: Potential cardiovascular side effects from venlafaxine-XR must be considered when prescribing this medication, especially in geriatric patients, who often present with comorbid medical conditions., Methods: Participants age 60 and older with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of a major depressive episode without psychotic features were treated openly with venlafaxine-XR for 12 weeks during which venlafaxine-XR was titrated based on tolerability and response according to predefined guidelines. Sitting and standing blood pressures and heart rates were measured. A 12-lead electrocardiogram was obtained at baseline and at week 12., Results: Sixty-two participants started treatment; 59 completed at least two weeks of the 12-week study. The mean final dose of venlafaxine-XR was 195.5 mg/day (standard deviation: 72.2). Twenty-four percent (95% confidence interval [CI]: 7.3%-40.7%) of initially normotensive participants and 54% (95% CI: 34.3%-74%) of those with preexisting hypertension experienced an increase in blood pressure. Twenty-nine percent (95% CI: 14.6%-43.4%) of participants developed orthostatic hypotension. Two participants experienced a clinically significant increase in QTc interval. One participant reported new-onset mild dizziness, whereas four participants reported new-onset tachycardia or palpitation. Overall, 17 unique participants (28.8%; 95% CI: 17.3%-40.4%) experienced a new-onset cardiovascular problem, potentially related to the study medication., Conclusion: Overall, venlafaxine-XR was well tolerated. However, similar to previous reports, venlafaxine-XR was associated with some undesirable cardiovascular effects in some of the participants. Systematic monitoring of cardiovascular parameters during treatment with venlafaxine-XR should be strongly recommended, especially in the elderly.

Introduction: The elderly are at increased risk for medication-related adverse events. Recent reports indicate that venlafaxine may put the elderly at increased risk of cardio- and cerebrovascular adverse events. We investigated the relationship between the CYP2D6 polymorphism and steady-state plasma concentration of venlafaxine (VEN) and its primary metabolite o-desmethylvenlafaxine (ODV) in elderly participants receiving venlafaxine-XR for major depression in order to explore the contribution of pharmacogenetics to medication tolerability., Methods: Forty-six elderly participants received venlafaxine-XR for the treatment of major depression. CYP2D6 genotype and steady-state plasma levels of VEN and ODV were determined., Results: Sixty-five percent of participants were homozygous of the wild type (WT) allele, whereas 35% carried one or more variant alleles associated with intermediate and poor 2D6 metabolizer status. VEN concentration per unit dose was significantly higher and ODV concentration per unit dose was significantly lower in participants who carried one or more variant alleles compared to participants who were homozygous for the WT allele. The VEN and ODV concentrations per unit dose were also correlated with creatinine clearance. CYP2D6 genotype was not associated with medication associated side-effects., Conclusions: Plasma dose-corrected concentrations of VEN and ODV correlated with genetically determined CYP2D6 enzymatic activity in depressed elders treated with venlafaxine-XR. This relationship was not masked by the effects of age-related illness or polypharmacy. Future clinical application of pharmacogenetics to examine 2D6-dependent medications may help reduce the incidence of medication adverse events particularly in those elders at higher risk for medication adverse events due to impaired renal or cardiac function.

Objective: Cognitive impairment in late-life depression (LLD) is prevalent, disabling, and persists despite the remission of depressive symptoms. This article characterizes neuropsychologic functioning during remission in LLD., Methods: The authors examined longitudinal performance on a comprehensive neuropsychologic battery in 56 nondemented subjects age 60 or older who initially presented with an episode of nonpsychotic unipolar major depression and 40 nondemented, age- and education-equated comparison subjects with no history of depression. Subjects were assessed at baseline (in a depressed state) and one year later (when remitted)., Results: After one year, 45% of the LLD subjects were cognitively impaired despite remission of depression. Visuospatial ability, information-processing speed, and delayed memory were most frequently impaired; 94% of the patients who were impaired at baseline remained impaired one year later. Twenty-three percent of the patients who were cognitively normal while depressed developed impairment one year later., Conclusions: Most older individuals who are cognitively impaired during a depressive episode remain impaired when their depression remits. In addition, a substantial proportion of older depressed individuals who are cognitively intact when depressed are likely to be impaired one year later, although their depression has remitted.

Context: Electroconvulsive therapy (ECT) is the most effective biological treatment for major depression. However, there is little agreement about clinically useful predictors of acute ECT outcomes., Objective: To assess whether age, sex, burden of comorbid physical illness, age at onset, history of recurrence, episode duration, chronic depression or comorbid dysthymia, melancholic features, episode severity, and medication resistance are predictors of remission after an acute course of ECT., Design: We performed an analysis using data gathered prospectively in 328 patients with unipolar major depression (according to Research Diagnostic Criteria) treated with ECT. The study was conducted from 1993 through 1999. Patients had a pretreatment score of 21 or higher on the 24-item Hamilton Rating Scale for Depression (HAM-D). Treatment history was assessed using the Antidepressant Treatment History Form. Remission was defined as a 24-item HAM-D score of 10 or less and a 60% or more relative reduction of the HAM-D score., Results: On univariate logistic regression, statistically significant predictors of nonremission were chronic depression/dysthymia, medication resistance, longer episode duration, and younger age. On backward elimination logistic regression, only medication resistance (OR = 1.67, 95% CI = 1.05 to 2.67) and chronic depression/ dysthymia (OR = 1.84, 95% CI = 1.06 to 3.21) were statistically significant predictors of nonremission., Conclusions: In patients with major depression, lower rates of remission after acute ECT are associated with medication resistance and chronicity, but not with age or burden of physical illness.

Objective: The authors sought to determine the feasibility of treating elderly adults with bipolar disorder under standardized-treatment conditions., Methods: Thirty-one patients age 60 and older with bipolar disorder were treated in standardized pathways. Mood state was checked at each study visit with the Hamilton Rating Scale for Depression-17 item (Ham-D-17) and the Young Mania Rating Scale (YMRS)., Results: Defining "well days" as both Ham-D and YMRS scores of

Objectives: To determine the frequency of poor patient participation during inpatient physical (PT) and occupational therapy (OT) sessions and to examine the influence of poor participation on functional outcome and length of stay (LOS)., Design: Prospective observational study., Setting: University-based, freestanding acute rehabilitation hospital., Participants: Two hundred forty-two inpatients, primarily elderly (age range, 20-96y), with a variety of impairment diagnoses (eg, stroke), who were admitted for inpatient rehabilitation., Interventions: Not applicable., Main Outcome Measures: The Pittsburgh Rehabilitation Participation Scale, the 13 motor items from the FIM instrument (FIM motor), LOS, and discharge disposition., Results: We categorized the sample into 3 groups: "good" participators were those for whom all inpatient PT and OT sessions were rated 4 or greater (n=139), "occasional poor" participators were those with less than 25% of scores rated below 4 (n=53), and "frequent poor" participators were those with 25% or more of scores rated below 4 (n=50). Change in FIM motor scores during the inpatient rehabilitation stay was significantly better for good and occasional poor participators, compared with frequent poor participators (mean FIM improvement: 23.2, 22.8, and 17.6, respectively; repeated-measures analysis of variance group by time interaction, P <.002). LOS was significantly longer for occasional poor participators, compared with good and frequent poor participators controlling for admission FIM differences (adjusted means: 13.9d, 11.0d, and 10.9d, respectively; analysis of covariance, P <.001)., Conclusions: Poor participation in therapy is common during inpatient rehabilitation and has important clinical implications, in terms of lower improvement in FIM scores and longer LOS. These results suggest that poor inpatient rehabilitation participation and its antecedents deserve further attention.

Objective: The authors tested the hypothesis that impaired executive functioning leads to high rates of relapse and recurrence in late-life depression., Methods: They analyzed data from subjects participating in two independent intervention trials. Study I included 53 elderly depressed patients who participated in an open trial comparing the efficacy of paroxetine and nortriptyline and recurrence prevention over 18 months. Study II focused on 146 elderly depressed patients who received open treatment with paroxetine in a relapse-prevention study over 4 months of continuation treatment. They examined the effect of cognitive functioning, in general, and executive functioning, in particular, on time-to-relapse/recurrence, using baseline and post-treatment measures of neuropsychological functioning., Results: The associations between cognitive measures and both probability of, and time-to-relapse/recurrence were small and statistically nonsignificant., Conclusion: Data failed to support the hypothesis that cognitive impairment, in general, or executive dysfunction, in particular, predicts relapse or recurrence of major depression in late life. Authors recommend future testing of the hypothesis with detailed, comprehensive measures over longer periods of observation during maintenance trials.

Context: Cognitive impairment in late-life depression (LLD) is highly prevalent, disabling, poorly understood, and likely related to long-term outcome., Objectives: To determine the characteristics and determinants of neuropsychological functioning LLD., Design: Cross-sectional study of groups of LLD patients and control subjects., Setting: Outpatient, university-based depression research clinic., Participants: One hundred patients without dementia 60 years and older who met DSM-IV criteria for current episode of unipolar major depression (nonpsychotic) and 40 nondepressed, age- and education-equated control subjects., Main Outcome Measures: A comprehensive neuropsychological battery., Results: Relative to control subjects, LLD patients performed poorer in all cognitive domains. More than half exhibited significant impairment (performance below the 10th percentile of the control group). Information processing speed and visuospatial and executive abilities were the most broadly and frequently impaired. The neuropsychological impairments were mediated almost entirely by slowed information processing (beta =.45-.80). Education (beta =.32) and ventricular atrophy (beta =.28) made additional modest contributions to variance in measures of language ability. Medical and vascular disease burden, apolipoprotein E genotype, and serum anticholinergicity did not contribute to variance in any cognitive domain., Conclusions: Late-life depression is characterized by slowed information processing, which affects all realms of cognition. This supports the concept that frontostriatal dysfunction plays a key role in LLD. The putative role of some risk factors was validated (eg, advanced age, low education, depression severity), whereas others were not (eg, medical burden, age at onset of first depressive episode). Further studies of neuropsychological functioning in remitted LLD patients are needed to parse episode-related and persistent factors and to relate them to underlying neural dysfunction.

Objective: To demonstrate interrater reliability and predictive validity of the Pittsburgh Rehabilitation Participation Scale (PRPS), a clinician-rated 6-point Likert-type item measuring patient participation in inpatient rehabilitation sessions., Design: Prospective measurement of patient participation in physical and occupational therapy sessions during inpatient rehabilitation., Setting: University-based, freestanding acute rehabilitation hospital., Participants: Two hundred forty-two inpatients, primarily elderly, with a variety of impairment diagnoses (eg, stroke), who were admitted for inpatient rehabilitation., Interventions: Not applicable., Main Outcome Measures: Change in the 13 motor items from the FIM trade mark instrument, from admission to discharge., Results: The PRPS had high interrater reliability (intraclass correlation coefficient [ICC]=.91 for occupational therapists; ICC=.96 for physical therapists). The subjects had mean PRPS scores +/- standard deviation of 4.73+/-0.76. Mean PRPS scores predicted rehabilitation outcome (N=242, r=.32, P<.0001), as measured by change in motor FIM. The strength of this association did not change in a multivariate model that controlled for age, gender, race, impairment group, medical comorbidity count, length of stay, and admission FIM., Conclusions: Patient participation during acute inpatient rehabilitation can be easily and reliably measured, and PRPS scores predict functional outcome. The PRPS may have applicability in clinical and research outcome measurement.

Background: Older depressed patients are at high risk for development of hyponatremia after initiation of the selective serotonin reuptake inhibitor paroxetine, despite clinical monitoring and preventive management. The purposes of this study were to determine the incidence and etiology of paroxetine-induced hyponatremia in older patients and to identify patient characteristics that may account for variability in susceptibility to this adverse event., Methods: This prospective, longitudinal study was conducted in a university-based ambulatory psychiatric research clinic from August 1999 through September 2001. Patients included 75 men and women aged 63 through 90 years (mean +/- SD age, 75.3 +/- 6.0 years) who received a diagnosis of a current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, major depressive episode and were prescribed paroxetine. We monitored plasma sodium levels before initiating paroxetine therapy and after 1, 2, 4, 6, and 12 weeks of treatment. In a subset of individuals, we measured levels of antidiuretic hormone, glucose, serum urea nitrogen, and creatinine. Hyponatremia was defined as a plasma sodium level of less than 135 mEq/L after initiation of paroxetine therapy., Results: Hyponatremia developed in 9 (12%) of the 75 patients after initiation of paroxetine treatment. Mean +/- SD time to development of hyponatremia was 9.3 +/- 4.7 days (median, 9 days; range, 1-14 days; n = 8). In the multivariate regression, lower body mass index and lower baseline plasma sodium level (<138 mEq/L) were significant risk factors for the development of hyponatremia in these patients., Conclusions: Hyponatremia is an under recognized and potentially serious complication of paroxetine treatment in older patients. Our results provide a foundation for understanding the etiology and risk factors associated with paroxetine-induced hyponatremia.

Objective: There is a recognized but poorly understood relationship between late-life depression (LLD) and progressive dementia. Both cognitive impairment co-occurring with LLD and a late age-of-onset of first lifetime depressive episode appear to be associated with subsequent progressive dementia. A history of major depression, especially when the first onset occurs in late-life, has been identified as a risk factor for Alzheimer's disease (AD). The major genetic risk factor for sporadic AD is carrying one or more apolipoprotein E4 (APOE4) alleles. We hypothesized that the association between LLD and dementia risk would be mediated by APOE4, specifically that APOE4 allele frequency would be associated with cognitive impairment and later age-of-depression-onset. We also predicted that APOE4 allele frequency would be increased among subjects with LLD., Methods: We compared the distribution of APOE2, APOE3, and APOE4 alleles in groups of LLD (n=160), AD (n=568) and elderly control (EC; n=156) subjects., Results: The allele distribution of the cognitively impaired LLD subgroup was not different from either the cognitively normal subgroup or the EC group but was different from the AD group. However, mean age-of-onset of depression in APOE4 carriers (51.4+/-20.7) was significantly lower than non-carriers (58.8+/-16.8). The allele distribution in LLD overall was significantly different from the AD but not the EC group., Conclusions: The finding that neither LLD, accompanying cognitive impairment, nor late age-of-onset was associated with an increased APOE4 allele frequency suggests that LLD acts as a risk factor for developing AD as well as non-AD dementia through mechanisms independent of APOE4. The unexpected finding that age-of-onset of LLD was significantly reduced in APOE4 carriers is similar to the association between APOE4 and age-of-onset in AD. Replication of the association of APOE4 with earlier age-of-depression-onset is indicated., (Copyright 2003 John Wiley & Sons, Ltd.)

Serum alphal-acid glycoprotein (AAG) concentrations were examined in relationship to age, medical burden, depression, and mental status in elderly control (n = 19, mean age = 72.1 +/- 6.8 years) and depressed (n = 58, mean age = 71.9 +/- 7.1 years) subjects. DNA was analyzed for allelic variants of the AGP1 (ORM1) gene in both groups. Depressed subjects' AAG serum levels were measured at baseline and after 6 weeks of antidepressant treatment. Before treatment, depressed subjects had significantly higher serum AAG concentrations than nondepressed controls (t49.2 = -3.48, P = .0011). Pretreatment AAG levels also correlated with degree of medical burden, measured by the Cumulative Illness Rating Scale-Geriatrics (r = 0.28, P = .0303), but not with age, depression severity, or cognitive scores. There was no significant difference between responders and nonresponders on changes in AAG levels from baseline to week 6. Frequency differences in ORM1 allelic variants apparently did not influence increased AAG concentrations in depressed patients.

Background: Prior studies have found that antidepressant medications are associated with an increased risk of falling in elderly persons. However, little is known about the prevention of falls during treatment for depression in elderly persons. This study evaluated the time course and potential risk factors for falls in a treatment protocol for late-life depression to identify specific at-risk periods and risk factors for falls in this population., Method: One hundred four subjects aged 69 years and over were treated in a protocolized manner using paroxetine and interpersonal psychotherapy. Those who did not respond received augmentation therapy with bupropion, nortriptyline, or lithium. Subjects were assessed at baseline and weekly during treatment; demographic and clinical characteristics of those who experienced a fall during treatment were compared with those who did not fall. Cox proportional hazards models were used to define risk factors for falls in univariate and multivariate models., Results: During a mean of 21 weeks of treatment, 40 subjects (38%) fell. About half (53%) of the subjects fell during the first 6 weeks of treatment. In the multivariate model, memory impairment and orthostatic changes in blood pressure during treatment were risk factors for falling. Additionally, augmentation with bupropion appeared to be a risk factor for falls in univariate analysis, but this result is preliminary due to the small number of subjects who took bupropion., Conclusion: Increased monitoring for falls is warranted during the acute treatment of late-life depression. When treating such patients, clinicians should be especially watchful of those with memory impairments or those who develop orthostatic blood pressure changes; orthostatic blood pressure should be measured throughout acute treatment. Additionally, augmenting paroxetine with bupropion may also increase the risk of falls, and this medication combination should be used with caution in elderly patients.

Objective: The vascular depression hypothesis posits that depression can arise in late life from cerebrovascular damage and that depression arising this way has a different clinical presentation and is more chronic and treatment-resistant than early-onset depression. This study tested the relationship of cerebrovascular risk factors (CVRF) to clinical presentation and treatment outcome in 156 subjects enrolled in a long-term maintenance treatment study of late-life recurrent major depression., Methods: CVRF scores were generated with the Probability of Stroke Risk Profile. Subjects with the highest one-third of scores were designated High CVRF, and their baseline clinical presentation and treatment outcomes were compared with the remaining subjects., Results: In the High-CVRF group, a greater proportion of subjects had first-onset depression after age 60. However, high CVRF score, late onset of depression, and their interaction had no effect on time-to-remission, need for adjunctive medication, or increased risk for recurrence during 3-year follow-up. Furthermore, high CVRF score and late onset of depression did not predict the associated clinical features of vascular depression, such as psychomotor retardation and lack of insight, previously described in the literature., Conclusion: Optimism about the outcome of late-life depression treatment should not be diminished by the presence of high cerebrovascular risk.

Objective: This study examined the effects of maintenance treatment for late-life depression on social adjustment. The authors hypothesized that elderly patients recovering from depression would have better social adjustment with medication and interpersonal psychotherapy than with medication or psychotherapy alone., Method: Patients aged 60 and older recovering from recurrent major depression were randomly assigned to one of four treatments: nortriptyline and interpersonal psychotherapy, nortriptyline and clinic visits, placebo and psychotherapy, or placebo and clinic visits. The Social Adjustment Scale was administered every 3 months until illness recurrence. Combined treatment was compared to monotherapy on scores over 1 year among patients who remained in recovery (N=49)., Results: Patients receiving nortriptyline and interpersonal psychotherapy maintained social adjustment, which declined in those receiving monotherapy., Conclusions: Treatment of late-life depression with nortriptyline and psychotherapy is more likely to maintain social adjustment than treatment with either alone. Combination therapy improves not only duration but quality of wellness.

Background: Prior research suggests that elderly patients are less likely to respond to antidepressant treatment if they have low self-rated health. However, successful treatment for depression has been associated with improvement in self-rated health and other health measures., Objectives: To examine measures of self-rated health, physical disability, and social function as predictors of treatment response in late-life depression, and to assess these same health measures as treatment outcomes. We hypothesized that greater impairment in these measures would predict poorer treatment response, and that these measures would show significant improvements with recovery from depression., Method: Subjects were enrolled in a depression intervention study for people aged 60 and older with recurrent unipolar major depression; they were assessed with measures of self-rated health, physical disability, and social functioning at baseline and at the end of treatment. Baseline measures were compared between the 88 remitters, 11 non-remitters, and seven dropouts. Additionally, changes in the measures were examined in subjects who recovered from the index depressive episode., Results: Subjects with poorer self-rated health at baseline were more likely both to drop out of treatment and to not respond to adequate treatment. This relationship was independent of demographic measures, severity of depression, physical and social functioning, medical illness, personality, hopelessness, overall medication use, and side effects or non-compliance with treatment., Conclusion: Although this finding is preliminary because of the small number of dropouts and non-remitters, it suggests that lower self-rated health may independently predict premature discontinuation of treatment for depression. Additionally, subjects who recovered from depression showed significant improvements in self-rated health, physical disability, and social functioning., (Copyright 2001 John Wiley & Sons, Ltd.)

Objective: To conduct the first randomized study comparing the efficacy of an antidepressant alone versus an antidepressant plus a neuroleptic in the treatment of late-life psychotic depression., Method: The efficacy of nortriptyline plus placebo versus nortriptyline plus perphenazine was compared in 36 patients aged 50 years or older presenting with a major depressive episode with psychotic features (DSM-III-R criteria). Patients were started openly on nortriptyline treatment titrated to therapeutic levels. They were then randomly assigned under double-blind conditions to addition of perphenazine or placebo. Outcomes were compared in the 2 treatment groups using measures including the Hamilton Rating Scale for Depression (HAM-D) and the Brief Psychiatric Rating Scale (BPRS); side effects were assessed with the Geriatric Movement Disorder Assessment., Results: Both treatments were well tolerated. Of the 36 randomly assigned patients, 2 (1 in each group) dropped out due to treatment-related adverse effects. Four additional patients dropped out for administrative reasons. Thirty patients received nortriptyline for at least 4 weeks combined with either perphenazine (N = 14) or placebo (N = 16) for at least 2 weeks (median = 9 weeks). There was no significant difference between the completers in the 2 treatment groups when comparing their scores on the HAM-D, the BPRS, its psychoticism subscale, or any side effects measure. Rates of response (defined as resolution of both depression and psychosis) did not differ significantly in the 2 groups (nortriptyline-plus-perphenazine group, 50% vs. nortriptyline-plus-placebo group, 44%)., Conclusion: When treating older patients with psychotic depression, the addition of a moderate dose of a traditional neuroleptic to a tricyclic antidepressant was well tolerated but did not improve efficacy. This finding supports existing data suggesting that the pathophysiology (and thus the required treatment) of psychotic depression may be different early and late in life.

We tested two interventions for improving sleep consolidation and depth in normal elderly participants: a modification of sleep-restriction therapy and sleep-hygiene education. Twenty-one elderly participants without sleep disorders were randomized to sleep hygiene plus bed restriction (i.e., restricting time in bed by 30 minutes nightly for one year) or to sleep hygiene alone. Participants in the bed-restriction group showed a median increase in sleep efficiency of 6.1% versus 1.8% in participants receiving sleep hygiene instruction, and an increase in allnight delta EEG power. Self-reported mood on awakening in the morning showed greater improvement over the first eight weeks in the sleep-hygiene condition. The use of sleep hygiene was associated with initial improvement in daytime well-being, whereas bed restriction led to sustained improvements in sleep continuity and sleep depth.

Elderly depressed patients are vulnerable to recurrence of depression and benefit from long-term antidepressant therapy. Physicians increasingly use selective serotonin re-uptake inhibitors (SSRIs) as maintenance therapy, although in the absence of data showing that SSRIs are as efficacious as tricyclic antidepressants (TCAs) in the prevention of depression relapse and recurrence. Our objective was to evaluate, in an open trial, the efficacy of paroxetine versus nortriptyline for preventing recurrence of depression in the elderly. Elderly patients with major depression were randomly assigned in a double-blinded fashion to receive either paroxetine or nortriptyline for the acute treatment of depression. Patients who did not respond or tolerate their assigned medications were crossed over openly to the comparator agent. Patients whose depression remitted continued antidepressant medication (paroxetine n = 38; nortriptyline n = 21) during an open 18-month follow-up study. We examined the rates of and times to relapse and to termination of treatment for any reason. Paroxetine (PX) and nortriptyline (NT) patients had similar rates of relapse (16% vs. 10%, respectively) and time to relapse (60.3 weeks vs. 58.8 weeks, respectively) over 18 months. A lower burden of residual depressive symptoms and side effects during continuation and maintenance treatment was evident in nortriptyline-treated patients. Paroxetine and nortriptyline demonstrated similar efficacy in relapse and recurrence prevention in elderly depressed patients over an 18-month period.

Selective serotonin-reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) have been reported to induce extrapyramidal signs and symptoms (EPS). The authors examined the change from baseline EPS, measured by an objective rating scale, in a group of elderly depressed patients participating in an ongoing randomized, double-blind comparison of nortriptyline and paroxetine. Mild baseline EPS were present in both groups. After 6 weeks of antidepressant treatment, patients in the nortriptyline group showed a significant decrease in total EPS scores. Patients in the paroxetine group showed a similar decrease in EPS from baseline, which did not reach statistical significance. There was no significant difference between nortriptyline and paroxetine in the change in EPS.

Objective: Anxiety disorders are common in adults with depressive disorders, but several studies have suggested a relatively low prevalence of anxiety disorders in older individuals with depression. This cross-sectional study measured current and lifetime rates and associated clinical features of anxiety disorders in depressed elderly patients., Method: History of anxiety disorders was assessed by using a structured diagnostic instrument in 182 depressed subjects aged 60 and older seen in primary care and psychiatric settings. Associations between comorbid anxiety disorders and baseline characteristics were measured. The modified structured instrument allowed detection of symptoms that met inclusion criteria for generalized anxiety disorder in a depressive episode., Results: Thirty-five percent of older subjects with depressive disorders had at least one lifetime anxiety disorder diagnosis, and 23% had a current diagnosis. The most common current comorbid anxiety disorders were panic disorder (9.3%), specific phobias (8.8%), and social phobia (6.6%). Symptoms that met inclusion criteria for generalized anxiety disorder, measured separately, were present in 27.5% of depressed subjects. Presence of a comorbid anxiety disorder was associated with poorer social function and a higher level of somatic symptoms. Symptoms of generalized anxiety disorder were associated with a higher level of suicidality., Conclusions: Contrary to previous reports, the present study found a relatively high rate of current and lifetime anxiety disorders in elderly depressed individuals. Comorbid anxiety disorders and symptoms of generalized anxiety disorder were associated with a more severe presentation of depressive illness in elderly subjects.

Objective: There are few data addressing the outcome of ECT for persons over 75 years of age. In a prospective, multisite study, the authors compared characteristics and treatment outcomes of adult (59 and younger), young-old (60 to 74 years), and old-old (75 and older) patients treated with ECT for major depression., Method: At four hospitals, 268 patients with primary unipolar major depression and scores of at least 20 on the 24-item Hamilton Depression Rating Scale were treated with suprathreshold right unilateral or bilateral ECT in a standardized manner. Demographic variables, clinical characteristics, and short-term outcomes of the three groups were compared., Results: The demographic and clinical characteristics of the old-old patients were similar to those of the young-old patients, whereas both groups differed from the adult patients on these variables. Both older groups had significantly greater burdens from physical illness and global cognitive impairment at baseline than the adult subjects. Both older groups had shorter index depressive episodes and were less likely to have had inadequate responses to adequate medication trials before ECT. The older groups had higher seizure thresholds, but the three groups received similar courses of treatment. The adult patients experienced a significantly lower rate of ECT response (54%) than the young-old patients (73%), while the old-old patients had an intermediate rate of response (67%)., Conclusions: Despite a higher level of physical illness and cognitive impairment, even the oldest patients with severe major depression tolerate ECT in a manner similar to that for younger patients and demonstrate similar or better acute response.

The authors report on 62 inpatients over age 60 who met DSM-III-R criteria for bipolar disorder, divided into early- and late-onset groups by their median age at lifetime onset, 49 years, in order to examine differences in demographic and clinical characteristics, treatment parameters, and outcome in the two groups during a short-term hospitalization. The late-onset group was more likely to have psychotic features and to demonstrate cerebrovascular risk/burden. However, both groups had similar and highly significant improvements in the Brief Psychiatric Rating Scale, Global Assessment Scale, and the Mini-Mental State Exam, and 87% were able to be discharged to settings no more restrictive than those at admission.

A program package RRAP: Random Regression Residual Analysis Program using SAS [1] and S-PLUS [2] is available for performing random regression residual analysis. The PROCEDURE MIXED from SAS is used for statistical inference. Both elementary-level and individual-level residuals are used. The S-PLUS programs provide: (1) a transformation to orthogonalize the elementary-level correlated residuals for standard regression residual analyses; and (2) several statistics and plots for checking model assumptions, assessing model fitting and detecting outlying individuals. RRRAP starts with a SAS Macro RRRAPMAC on the data followed by a S-PLUS Program DoRRRAP on a UNIX system.

Background: We compared pretreatment subjective and electroencephalographic sleep measures among depressed patients who remitted with psychotherapy alone and those who did not remit., Methods: Patients were 111 midlife women with recurrent major depressive disorder. Baseline psychiatric ratings and sleep studies were conducted prior to treatment with weekly interpersonal psychotherapy. Remission was defined as a score of < or = 7 for 3 consecutive weeks on the Hamilton Depression Rating Scale. Clinical and sleep measures were compared between remitters (n = 62) and nonremitters (n = 49) using t tests and random regression. Linear discriminant function analyses were used to categorize remitters and nonremitters on the basis of sleep measures., Results: Treatment nonremitters had significantly worse subjective sleep quality and significantly elevated phasic REM sleep as measured by multivariate and univariate analyses. The linear accumulation of REM activity during sleep occurred at a significantly higher rate in nonremitters than in remitters. Linear discriminant function analyses based on subjective sleep quality and REM activity correctly identified 68.3% of nonremitters and 68.5% of remitters., Conclusions: These findings highlight the role of subjective and REM sleep measures as correlates of short-term psychotherapy treatment response in major depressive disorder. Disturbed sleep may be a physiological indicator of increased limbic and brain stem arousal.

The aim of this study was to identify elderly depressed patients who can remain well on maintenance Interpersonal Psychotherapy (IPT) alone, after discontinuation of antidepressant medication. Using Cox proportional hazards models, increased severity of depression at pretreatment was associated with increased recurrence rates, to an extent greater in patients maintained on monthly IPT than in those maintained on nortriptyline. The long-term response to maintenance IPT was correctly identified in 20/25 cases by a pretreatment Hamilton score of > or = 20. Fourteen of sixteen patients with pretreatment scores of > or = 20 experienced recurrence of major depression on maintenance IPT, while 6/9 patients with pretreatment scores of less than 20 did not. (Fisher exact P = .01). The same pattern of recurrence in relation to severity was not evident in maintenance placebo, nortriptyline, or combination treatment. In addition, Hamilton scores during continuation treatment were lower (< or = 7) among those who remained well on maintenance IPT than among those who had recurrences. Elderly patients whose depressions are milder at baseline and who show excellent symptomatic remission during acute and continuation therapy may be good candidates for monthly maintenance IPT after initial successful treatment with antidepressant medication and psychotherapy.

Objective: To determine whether a high level of hopelessness after treatment of a depressive episode is an indicator of a history of lifetime suicide attempts in older people., Design: Groups of suicide attempters, suicidal ideators, and nonsuicidal patients were compared via analysis of variance with respect to levels of hopelessness, depression, anxiety, and global functioning before and after treatment of depression., Setting: An outpatient research clinic providing two treatment protocols of late-life mood disorders., Participants: A total of 107 consecutive outpatients (mean age 67) with major depression who responded to treatment., Measurements: Levels of hopelessness, severity of depression, anxiety, and global functioning were compared across the three groups at the beginning of treatment and at remission., Results: After remission there were no differences between the three groups in depression severity, anxiety, and global functioning. Hopelessness remained significantly higher in the attempter group than among ideators or nonsuicidal patients., Conclusions: Suicide attempts, the most important risk factor for subsequent suicide, are associated with persistent, high levels of hopelessness following remission of depression in late-life patients. These findings suggest that treatments designed specifically to lower hopelessness (such as cognitive, behavioral or interpersonal therapy) may be effective in reducing suicide risk.

Objective: The authors' goal was to compare serum anticholinergicity of 61 elderly depressed patients randomly assigned to double-blind treatment with paroxetine (N=31) or nortriptyline (N=30)., Method: Both antidepressants were titrated in a standardized manner, and plasma was sampled weekly for measurement of paroxetine and nortriptyline and its hydroxy metabolite concentrations. Serum anticholinergicity was measured at baseline and after 1, 4, and 6 weeks of treatment. Side effects were assessed by using a validated scale., Results: After correcting for pretreatment anticholinergicity, the authors found that mean serum anticholinergicity for the nortriptyline-treated patients was significantly greater than that for the paroxetine group at all weeks assessed. Serum anticholinergicity was significantly correlated with nortriptyline but not with paroxetine plasma levels. Complaints of dry mouth and tachycardia were significantly more frequent and severe in the nortriptyline group., Conclusions: These findings suggest that, at therapeutic plasma concentrations, paroxetine has approximately one-fifth the anticholinergic potential of nortriptyline in older patients.