Jordan F. Karp

Training in Empirically Validated Treatments: What Are Clinical Psychology Students Learning?

Directors of clinical training (83%) and directors of internships with American Psychological Asso-ciation approval (55%) responded to a survey concerning empirically validated psychological treat-ments in which their students received training. Most programs provided supervised clinical experi-ence in a number of these treatments. However, over 20% of doctoral training programs failed toprovide minimal coverage of empirically validated treatments in didactic courses, and internshipprograms typically did not require that students be competent in any of these treatments beforecompletion of the program. The absence of didactic and clinical training in empirically validatedpsychodynamic therapies and interpersonal therapy was most marked. These findings suggest thatprograms need to be more attentive to teaching data-based treatments.PAUL CRITS-CHRISTOPH received his PhD in clinical psychology fromYale University in 1984. He is currently associate professor of psychol-ogy in psychiatry and director of the Center for Psychotherapy Researchat the University of Pennsylvania. At present he is studying the effects ofbrief dynamic psychotherapy and cognitive therapy for cocaine addic-tion and for generalized anxiety disorder and is examining the processof interpersonal psychotherapy and cognitive therapy for depression.ELLEN FRANK received her PhD from the University of Pittsburgh in1979. She is professor of psychiatry and psychology in the Departmentof Psychiatry at the University of Pittsburgh School of Medicine. Shedirects the Depression and Manic-Depression Prevention Program atWestern Psychiatric Institute and Clinic. Her treatment research hasfocused on the prophylaxis of recurrent mood disorders using interper-sonal psychotherapy, pharmacotherapy, and their combination.DIANNE L. CHAMBLESS received her PhD in clinical psychology fromTemple University in 1979. She is currently professor of psychology atThe American University. She conducts research on the psychopathol-ogy and cognitive-behavioral treatment of anxiety disorders and is par-ticularly interested in psychotherapy integration and the impact of in-terpersonal relationships on anxiety.CINDY BRODY received her BA in psychology from the University ofPennsylvania in 1991 and for 3 years was a research assistant at theCenter for Psychotherapy Research. She is currently a doctoral studentin clinical psychology at The American University. Her major researchinterests are in coping, interpersonal problems, and psychotherapy pro-cess and outcome.JORDAN F. KARP received his BA in psychology from Emory University in1992. He completed 2 years as a research associate in the Depression andManic-Depression Prevention Program at Western Psychiatric Instituteand Clinic. He is currently a medical student at the University ofPittsburgh.WE THANK David Barlow, Barry Wolfe, and Division 12 for assistance

Maintenance Treatment of Depression in Old Age: A Randomized, Double-blind, Placebo-Controlled Evaluation of the Efficacy and Safety of Donepezil Combined With Antidepressant Pharmacotherapy

CONTEXT Cognitive impairment in late-life depression is a core feature of the illness. OBJECTIVE To test whether donepezil hydrochloride and antidepressant therapy is superior to placebo and antidepressant therapy in improving cognitive performance and instrumental activities of daily living and in reducing recurrences of depression over 2 years of maintenance treatment. DESIGN Randomized, double-blind, placebo-controlled maintenance trial. SETTING University clinic. PARTICIPANTS One hundred thirty older adults aged 65 years and older with recently remitted major depression. INTERVENTIONS Random assignment to maintenance antidepressant pharmacotherapy and donepezil or to maintenance antidepressant pharmacotherapy and placebo. MAIN OUTCOME MEASURES Global neuropsychological performance, cognitive instrumental activities of daily living, and recurrent depression. RESULTS Donepezil and antidepressant therapy temporarily improved global cognition (treatment × time interaction, F₂,₂₁₆ = 3.78; P = .03), but effect sizes were small (Cohen d = 0.27, group difference at 1 year). A marginal benefit to cognitive instrumental activities of daily living was also observed (treatment × time interaction, F₂,₁₃₇ = 2.94; P = .06). The donepezil group was more likely than the placebo group to experience recurrent major depression (35% [95% confidence interval {CI}, 24%-46%] vs 19% [95% CI, 9%-29%], respectively; log-rank χ² = 3.97; P = .05; hazard ratio = 2.09 [95% CI, 1.00-4.41]). Post hoc subgroup analyses showed that of 57 participants with mild cognitive impairment, 3 of 30 participants (10% [95% CI, 0%-21%]) receiving donepezil and 9 of 27 participants (33% [95% CI, 16%-51%]) receiving placebo had a conversion to dementia over 2 years (Fisher exact test, P = .05). The mild cognitive impairment subgroup had recurrence rates of major depression of 44% with donepezil vs 12% with placebo (likelihood ratio = 4.91; P = .03). The subgroup with normal cognition (n = 73) showed no benefit with donepezil and no increase in recurrence of major depression. CONCLUSIONS Whether a cholinesterase inhibitor should be used as augmentation in the maintenance treatment of late-life depression depends on a careful weighing of risks and benefits in those with mild cognitive impairment. In cognitively intact patients, donepezil appears to have no clear benefit for preventing progression to mild cognitive impairment or dementia or for preventing recurrence of depression. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00177671.

fMRI Correlates of White Matter Hyperintensities in Late-Life Depression

OBJECTIVE This study tests whether or not the structural white matter lesions that are characteristic of late-life depression are associated with alterations in the functional affective circuits of late-life depression. This study used an emotional faces paradigm that has been shown to engage the affective limbic brain regions. METHOD Thirty-three elderly depressed patients and 27 nondepressed comparison subjects participated in this study. The patients were recruited through the NIMH-sponsored Advanced Center for Interventions and Services Research for the Study of Late-Life Mood Disorders at the University of Pittsburgh Center for Bioethics and Health Law. Structural and functional MRI was used to assess white matter hyperintensity (WMH) burden and functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent (BOLD) response on a facial expression affective-reactivity task in both elderly participants with nonpsychotic and nonbipolar major depression (unmedicated) and nondepressed elderly comparison subjects. RESULTS As expected, greater subgenual cingulate activity was observed in the depressed patients relative to the nondepressed comparison subjects. This same region showed greater task-related activity associated with a greater burden of cerebrovascular white matter change in the depressed group. Moreover, the depressed group showed a significantly greater interaction of WMH by fMRI activity effect than the nondepressed group. CONCLUSIONS The observation that high WMH burden in late-life depression is associated with greater BOLD response on the affective-reactivity task supports the model that white matter ischemia in elderly depressed patients disrupts brain mechanisms of affective regulation and leads to limbic hyperactivation.

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.

Body pain and treatment response in late-life depression.

OBJECTIVE The authors investigated the influence of body pain on 1) time to treatment response and 2) suicidal ideation, in late-life depression. They hypothesized that higher levels of body pain would predict a longer time to and lower likelihood of response, and increased levels of suicidal ideation. METHODS Subjects (N=187) were older adult outpatients (age > or =69 years), with current episodes of major depression, who were openly treated with paroxetine up to 40 mg daily and weekly interpersonal psychotherapy. Response was defined as 3 consecutive weeks of Hamilton Rating Scale for Depression at < or =10. Body pain was measured with the Bodily Pain Index of the SF-36 quality-of-life assessment. Authors used survival-analysis models on the responder sample to test the effect of body pain on response, after controlling for severity of depression. RESULTS Overall response rate was 75.4%. Nonresponders reported more severe pain at baseline. After covarying for severity of baseline depression, no effect was found for physical pain on time-to-response or degree of suicidality. Bodily pain remained stable during acute treatment for responders, independent of depression response to combination psychotherapy and antidepressant treatment. CONCLUSIONS Older adult patients with higher levels of physical pain can still respond to antidepressant treatment; however, reported bodily pain may be associated with a more difficult-to-treat depression.

Impact of Chronic Musculoskeletal Pathology on Older Adults: A Study of Differences between Knee OA and Low Back Pain

OBJECTIVES The study aimed to compare the psychological and physical characteristics of older adults with knee osteoarthritis (OA) vs those of adults with chronic low back pain (CLBP) and to identify psychological and physical predictors of function as measured by gait speed. DESIGN Secondary data analysis. METHOD AND PATIENTS Eighty-eight older adults with advanced knee OA and 200 with CLBP who had participated in separate randomized controlled trials were selected for this study. MEASURES Inclusion criteria for both trials included age > or =65 and pain of at least moderate intensity that occurred daily or almost every day for at least the previous 3 months. Psychological constructs (catastrophizing, fear avoidance, self-efficacy, depression, affective distress) and physical measures (comorbid medical conditions, pain duration, pain severity, pain related interference, self-rated health) were obtained. RESULTS Subjects with CLBP had slower gait (0.88 m/s vs 0.96 m/s, P = 0.002) and more comorbid conditions than subjects with knee pain (mean 3.36 vs 1.97, P < 0.001). All the psychological measures were significantly worse in the CLBP group except the Multidimensional Pain Inventory-Affective Distress score. Self-efficacy, pain severity, and medical comorbidity burden were associated with slower gait regardless of the location of the pain. CONCLUSIONS Older adults with chronic pain may have distinct psychological and physical profiles that differentially impact gait speed. These findings suggest that not all pain conditions are the same in their psychological and physical characteristics and may need to be taken into consideration when developing treatment plans.

Somatic symptoms in late-life anxiety: treatment issues.

Understanding and addressing somatic symptoms are complex in older adults, who have more comorbid medical illnesses. This article describes a systematic review of the literature on somatic symptoms in older patients with anxiety disorders. Additionally, the hypothesis was tested that somatic symptoms would respond to selective serotonin reuptake inhibitor treatment in 30 anxious patients aged 60 years and older who participated in a 32-week trial of citalopram. The literature review showed few original data articles about somatic symptoms in older patients with anxiety disorders. These articles suggest that such a relationship is common and that treatment of anxiety, or anxious depression, is associated with a reduction in somatic symptoms. In the analysis, citalopram treatment was associated with a significant decrease in several somatic symptoms from pretreatment baseline. It is concluded that somatic symptoms in older adults with anxiety disorders or anxious depression often improve with successful antidepressant treatment. However, additional treatment and integrated approaches are likely to be necessary for many such individuals.

Pain interference impacts response to treatment for anxiety disorders

Background: Anxiety disorders and pain are commonly comorbid, though little is known about the effect of pain on the course and treatment of anxiety. Methods: This is a secondary analysis of a randomized controlled trial for anxiety treatment in primary care. Participants with panic disorder (PD) and/or generalized anxiety disorder (GAD) (N=191; 81% female, mean age 44) were randomized to either their primary‐care physicians usual care or a 12‐month course of telephone‐based collaborative care. Anxiety severity, pain interference, health‐related quality of life, health services use, and employment status were assessed at baseline, and at 2‐, 4‐, 8‐, and 12‐month follow‐up. We defined response to anxiety treatment as a 40% or greater improvement from baseline on anxiety severity scales at 12‐month follow‐up. Results: The 39% who reported high pain interference at baseline had more severe anxiety (mean SIGH‐A score: 21.8 versus 18.0, P<.001), greater limitations in activities of daily living, and more work days missed in the previous month (5.8 versus 4.0 days, P=.01) than those with low pain interference. At 12‐month follow‐up, high pain interference was associated with a lower likelihood of responding to anxiety treatment (OR=.28; 95% CI=.12–.63) and higher health services use (26.1% with ≥1 hospitalization versus 12.0%, P<.001). Conclusions: Pain that interferes with daily activities is prevalent among primary care patients with PD/GAD and associated with more severe anxiety, worse daily functioning, higher health services use, and a lower likelihood of responding to treatment for PD/GAD. Depression and Anxiety, 2009.

A review of the effectiveness of antidepressant medications for depressed nursing home residents

BACKGROUND Antidepressant medications are the most common psychopharmacologic therapy used to treat depressed nursing home (NH) residents. Despite a significant increase in the rate of antidepressant prescribing over the past several decades, little is known about the effectiveness of these agents in the NH population. OBJECTIVE To conduct a systematic review of the literature to examine and compare the effectiveness of antidepressant medications for treating major depressive symptoms in elderly NH residents. METHODS The following databases were searched with searches completed prior to January 2011 and no language restriction: MEDLINE, Embase, PsycINFO, CINHAL, CENTRAL, LILACS, ClinicalTrials.gov, International Standard Randomized Controlled Trial Number Register, and the WHO International Clinical Trial Registry Platform. Additional studies were identified from citations in evidence-based guidelines and reviews as well as book chapters on geriatric depression and pharmacotherapy from several clinical references. Studies were included if they described a clinical trial that assessed the effectiveness of any currently-marketed antidepressant for adults aged 65 years or older, who resided in the NH, and were diagnosed by DSM criteria and/or standardized validated screening instruments with Major Depressive Disorder, minor depression, dysthymic disorder, or Depression in Alzheimers disease. RESULTS A total of eleven studies, including four randomized and seven non-randomized open-label trials, met all inclusion and exclusion criteria. It was not feasible to conduct a meta-analysis because the studies were heterogeneous in terms of study design, operational definitions of depression, participant characteristics, pharmacologic interventions, and outcome measures. Of the four randomized trials, two had a control group and did not demonstrate a statistically-significant benefit for antidepressant pharmacotherapy over placebo. While six of the seven non-randomized studies identified a response to an antidepressant, their results must be interpreted with caution as they lacked a comparison group. CONCLUSIONS The limited amount of evidence from randomized and non-randomized open-label trials suggests that depressed NH residents have a modest response to antidepressant medications. Further research using rigorous study designs are needed to examine the effectiveness and safety of antidepressants in depressed NH residents, and to determine the various facility, provider, and patient factors associated with response to treatment.

The impact of pain and depression on recovery after coronary artery bypass grafting.

Objective: To describe the relationship between pain and depression on recovery after coronary artery bypass grafting (CABG). Methods: A secondary data analysis on 453 depressed and nondepressed post-CABG patients enrolled in a randomized, controlled, effectiveness trial of telephone-delivered collaborative care for depression. Outcome measures were collected from March 2004 to September 2007 and included pain, physical function, and mood symptoms. Results: Depressed patients (baseline Patient Health Questionnaire-9 score ≥10) versus those without depression reported significantly worse pain scores on the 36-Item Short Form Health Survey Bodily Pain Scale at baseline and up to 12 months post-CABG, p < .05. Among patients with depression, those who received collaborative care reported significantly better pain scores at each time point between 2 and 12 months post-CABG versus depressed patients randomized to the usual care control group, p < .05. Regardless of intervention status, depressed participants with at least moderate pain at baseline reported significantly lower functional status (measured by the Duke Activity Status Index) at 8 and 12 months versus depressed patients with none or mild pain, p < .05. Depressed patients with at least moderate pain at baseline were also significantly less likely to show improvement of depressive symptoms throughout the course of follow-up versus depressed patients with little or no pain, p < .05. These findings controlled for age, gender, education, race, comorbid conditions, and baseline pain diagnosis. Conclusions: Depression and pain seem to influence functional recovery post-CABG. The relationship between these two conditions and 12-month outcomes should be considered by clinicians when planning treatment. HTN = hypertension; CVA = cerebral vascular accident; COPD = chronic obstructive pulmonary disease; CHF = chronic heart failure; PHQ = Patient Health Questionnaire; HRS-D = Hamilton Rating Scale-Depression; DASI = Duke Activity Status Index; NSAIDs = nonsteroidal antiinflammatory drug.