Trajectories of suicidal ideation in depressed older adults undergoing antidepressant treatment.

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.

Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial.

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.

Advancing the screening of fibromyalgia in late-life depression: practical implications for psychiatric settings.

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.

Neuropsychological functioning in the acute and remitted States of late-life depression.

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.

Safety, tolerability, and clinical effect of low-dose buprenorphine for treatment-resistant depression in midlife and older adults.

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.

Dynamic prediction of treatment response in late-life depression.

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.

Shiftworkers report worse sleep than day workers, even in retirement.

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.

Memantine for late-life depression and apathy after a disabling medical event: a 12-week, double-blind placebo-controlled pilot study.

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.

A community-academic partnership develops a more responsive model to providing depression care to disadvantaged adults in the US.

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.

Changes in neuropsychological functioning following treatment for late-life generalised anxiety disorder.

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.

Effects of a two-hour change in bedtime on the sleep of healthy seniors.

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.

High worry severity is associated with poorer acute and maintenance efficacy of antidepressants in late-life depression.

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.

Salivary cortisol is associated with diagnosis and severity of late-life generalized anxiety disorder.

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.

Sleep and circadian rhythms in spousally bereaved seniors.

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.

Cognitive impairment in late-life generalized anxiety disorder.

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.

Effect of comorbid anxiety on treatment response and relapse risk in late-life depression: controlled study.

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.

Relapse during continuation pharmacotherapy after acute response to ECT: a comparison of usual care versus protocolized treatment.

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."

Use of OSWALD for analyzing longitudinal data with informative dropout.

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.

Statistical analysis of longitudinal psychiatric data with dropouts.

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.

The relationship between pain and mental flexibility in older adult pain clinic patients.

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.