Jordan Karp

Interests

Teaching

medical student educationpsychiatric graduate medical education and trainingtraining colleagues from nursing, rehabilitation science, and other disciplines about prevention and management of psychiatric illness

Research

depressiontreatment resistant depressiondementiapragmatic clinical trialsnovel mechanism agents to treat psychiatric diseases

Courses

Scholarly Contributions

Journals/Publications

• Behlke, L. M., Lenze, E. J., Pham, V., Miller, J. P., Smith, T. W., Saade, Y., Karp, J. F., Reynolds, C. F., Blumberger, D. M., Stefan, C., & Mulsant, B. H. (2021). The Effect of Venlafaxine on Electrocardiogram Intervals During Treatment for Depression in Older Adults. Journal of clinical psychopharmacology, 40(6), 553-559.
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  Venlafaxine is a commonly used antidepressant with both serotonergic and noradrenergic activity. There are concerns that it may prolong the corrected QT interval (QTc), and older adults may be at higher risk for this adverse effect, especially at higher dosages of the medication.
• Benrimoh, D., Tanguay-Sela, M., Perlman, K., Israel, S., Mehltretter, J., Armstrong, C., Fratila, R., Parikh, S. V., Karp, J. F., Heller, K., Vahia, I. V., Blumberger, D. M., Karama, S., Vigod, S. N., Myhr, G., Martins, R., Rollins, C., Popescu, C., Lundrigan, E., , Snook, E., et al. (2021). Using a simulation centre to evaluate preliminary acceptability and impact of an artificial intelligence-powered clinical decision support system for depression treatment on the physician-patient interaction. BJPsych open, 7(1), e22.
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  Recently, artificial intelligence-powered devices have been put forward as potentially powerful tools for the improvement of mental healthcare. An important question is how these devices impact the physician-patient interaction.
• Herbeck Belnap, B., Anderson, A., Abebe, K. Z., Ramani, R., Muldoon, M. F., Karp, J. F., & Rollman, B. L. (2021). Blended Collaborative Care to Treat Heart Failure and Comorbid Depression: Rationale and Study Design of the Hopeful Heart Trial. Psychosomatic medicine, 81(6), 495-505.
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  Despite numerous improvements in care, morbidity from heart failure (HF) has remained essentially unchanged in recent years. One potential reason is that depression, which is comorbid in approximately 40% of hospitalized HF patients and associated with adverse HF outcomes, often goes unrecognized and untreated. The Hopeful Heart Trial is the first study to evaluate whether a widely generalizable telephone-delivered collaborative care program for treating depression in HF patients improves clinical outcomes.
• Karp, J. F., Reynolds, C. F., Butters, M. A., Dew, M. A., Mazumdar, S., Begley, A. E., Lenze, E., & Weiner, D. K. (2021). The relationship between pain and mental flexibility in older adult pain clinic patients. Pain medicine (Malden, Mass.), 7(5), 444-52.
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  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.
• Karp, J. F., Rudy, T., & Weiner, D. K. (2021). Persistent pain biases item response on the Geriatric Depression Scale (GDS): preliminary evidence for validity of the GDS-PAIN. Pain medicine (Malden, Mass.), 9(1), 33-43.
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  Differential item functioning (DIF) assesses the consistency of items on a metric across clinical samples in relation to the attribute being measured. We hypothesized that in older adults with persistent pain, items of the Geriatric Depression Scale (GDS) would evidence DIF based on presence or intensity of pain.
• Lissemore, J. I., Mulsant, B. H., Rajji, T. K., Karp, J. F., Reynolds, C. F., Lenze, E. J., Downar, J., Chen, R., Daskalakis, Z. J., & Blumberger, D. M. (2021). Cortical inhibition, facilitation and plasticity in late-life depression: effects of venlafaxine pharmacotherapy. Journal of psychiatry & neuroscience : JPN, 46(1), E88-E96.
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  Late-life depression is often associated with non-response or relapse following conventional antidepressant treatment. The pathophysiology of late-life depression likely involves a complex interplay between aging and depression, and may include abnormalities in cortical inhibition and plasticity. However, the extent to which these cortical processes are modifiable by antidepressant pharmacotherapy is unknown.
• Morone, N. E., Karp, J. F., Lynch, C. S., Bost, J. E., El Khoudary, S. R., & Weiner, D. K. (2021). Impact of chronic musculoskeletal pathology on older adults: a study of differences between knee OA and low back pain. Pain medicine (Malden, Mass.), 10(4), 693-701.
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  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.
• Stahl, S. T., Altmann, H. M., Dew, M. A., Albert, S. M., Butters, M., Gildengers, A., Reynolds, C. F., & Karp, J. F. (2021). The Effects of Gait Speed and Psychomotor Speed on Risk for Depression and Anxiety in Older Adults with Medical Comorbidities. Journal of the American Geriatrics Society.
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  Gait speed and psychomotor speed slow with age and may predict neuropsychiatric disease such as depression and anxiety. We explored the relative predictive values of gait speed, psychomotor slowing, and a composite index of these two measures on time to new episode depression or anxiety in older adults at risk for these common psychiatric conditions.
• Tal, I., Mauro, C., Reynolds, C. F., Shear, M. K., Simon, N., Lebowitz, B., Skritskaya, N., Wang, Y., Qiu, X., Iglewicz, A., Glorioso, D., Avanzino, J., Wetherell, J. L., Karp, J. F., Robinaugh, D., & Zisook, S. (2021). Complicated grief after suicide bereavement and other causes of death. Death studies, 41(5), 267-275.
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  The authors compared baseline demographic characteristics, clinical features, and grief-related thoughts, feelings, and behaviors of individuals bereaved by suicide, accident/homicide and natural causes participating in a complicated grief (CG) treatment clinical trial. Severity of CG and depression and current depression diagnosis did not vary by loss type. After adjusting for baseline demographic features, time since death and relationship to the deceased, those with CG after suicide had the highest rates of lifetime depression, preloss passive suicidal ideation, self-blaming thoughts, and impaired work and social adjustment. Even among this treatment-seeking sample of research participants with CG, suicide survivors may face unique challenges.
• Wu, C. Y., Rodakowski, J., Terhorst, L., Dew, M. A., Butters, M., Karp, J. F., Albert, S. M., Gildengers, A. G., Reynolds, C. F., & Skidmore, E. R. (2021). Frequency of But Not Capacity for Participation in Everyday Activities Is Associated With Cognitive Impairment in Late Life. Journal of applied gerontology : the official journal of the Southern Gerontological Society, 733464820984283.
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  We examined features of everyday activities (capacity and frequency) between older adults with and without cognitive impairment over 12 months. Participants aged ≥60 years and at risk for depression were included (n = 260); 26% ( = 69) had an acquired cognitive impairment at baseline. Cognitive impairment was defined as one standard deviation below norms on the Repeatable Battery for the Assessment of Neuropsychological Status. Features of everyday activities were measured by a computerized adaptive test version of Late-Life Function and Disability Instrument (LLFDI) at six time points (baseline, 6 weeks, 3, 6, 9, 12 months). There were significant between-group differences in activity frequency ( = .04), but not activity capacity ( = .05). The group difference in activity frequency exceeded minimal detectable changes (MDC = 3.7) and reached moderate clinical meaningfulness (∆ at six time points = 3.7-4.7). Generalized linear mixed models revealed no Group × Time interactions on activity capacity and frequency ( = .65 and = .98). Practitioners may assess changes in activity frequency to monitor cognitive status of clients even when there is no loss of activity capacity.
• Altmann, H., Stahl, S. T., Gebara, M. A., Lenze, E. J., Mulsant, B. H., Blumberger, D. M., Reynolds, C. F., & Karp, J. F. (2020). Coprescribed Benzodiazepines in Older Adults Receiving Antidepressants for Anxiety and Depressive Disorders: Association With Treatment Outcomes. The Journal of clinical psychiatry, 81(6).
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  There is a paucity of data on the effects of coprescribed benzodiazepines on treatment response variability and adherence to antidepressant pharmacotherapy for depression and anxiety in late life. The objective of this transdiagnostic analysis was to examine the effect of benzodiazepines on treatment outcomes in older patients with generalized anxiety disorder (GAD) or major depressive disorder (MDD).
• Conlon, M., Tew, J., Solai, L. K., Gopalan, P., Azzam, P., & Karp, J. F. (2020). Care Transitions in the Psychiatric Hospital: Focus on Older Adults. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 28(3), 368-377.
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  Patients undergoing a care transition are vulnerable to duplication of services, conflicting care recommendations, and errors in medication reconciliation. Older adults may be more vulnerable to care transitions given their relatively higher medical burden, cognitive impairment, and frequent polypharmacy. In this Treatment in Geriatric Mental Health: Research in Action article, we first present the results of a quality improvement study examining the frequency of care transitions to and from the medical hospital among patients admitted to a university-affiliated psychiatric hospital. Among a sample of 50 geriatric adults and 50 nongeriatric adults admitted to the psychiatric hospital, we tallied the number of care transitions to and from the medical hospital. We found that the geriatric cohort was significantly more likely to experience this type of care transition (p = 0.012, Fisher's exact test) compared to the nongeriatric cohort. In the second part of this article, we use a clinical vignette to illustrate the types of medical errors that can occur as a vulnerable and frail older adult moves between acute psychiatric and medical settings. Finally, we list provider-level and systems-level evidence-based recommendations for how care of the patient in the vignette could be improved. The quality improvement study and clinical vignette demonstrate how older adults are at greater risk for care transitions to and from the acute medical setting during psychiatric hospitalization, and that creative solutions are required to improve outcomes.
• Diniz, B. S., Lavretsky, H., Karp, J. F., Rutherford, B., Mulsant, B., & Lenze, E. (2020). Mood Disorders and Dementia: Time for Action. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 28(5), 542-544.
• Gebara, M. A., & Karp, J. F. (2020). Sleep disturbances are among the risk factors associated with cognitive impairment. International psychogeriatrics, 32(7), 791-792.
• Gebara, M. A., DiNapoli, E., Hamm, M. E., Rodriguez, K. L., Kasckow, J. W., Lederer, L. G., Bramoweth, A. D., & Karp, J. F. (2020). Illness narratives and preferences for treatment among older veterans living with treatment-resistant depression and insomnia. Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists, 32(2), 81-89.
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  Despite the prevalence of comorbid late-life treatmentresistant depression (LLTRD) and insomnia in older adults, there is a gap in the literature describing patient factors, such as patients' beliefs about their illnesses and preferences for treatment, that can facilitate recovery. Therefore, we explored the perceptions and treatment preferences of older veterans with LLTRD and insomnia.
• Gillman, A., Zhang, D., Jarquin, S., Karp, J. F., Jeong, J. H., & Wasan, A. D. (2020). Comparative Effectiveness of Embedded Mental Health Services in Pain Management Clinics vs Standard Care. Pain medicine (Malden, Mass.), 21(5), 978-991.
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  Embedded behavioral medicine services are a common component of multidisciplinary chronic pain treatment programs. However, few studies have studied whether these services are associated with improved treatment outcomes.
• Hamm, M. E., Brown, P. J., Karp, J. F., Lenard, E., Cameron, F., Dawdani, A., Lavretsky, H., Miller, J. P., Mulsant, B. H., Pham, V. T., Reynolds, C. F., Roose, S. P., & Lenze, E. J. (2020). Experiences of American Older Adults with Pre-existing Depression During the Beginnings of the COVID-19 Pandemic: A Multicity, Mixed-Methods Study. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 28(9), 924-932.
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  To determine the effect of the COVID-19 pandemic on the mental health of older adults with pre-existing major depressive disorder (MDD).
• Jonassaint, C. R., Belnap, B. H., Huang, Y., Karp, J. F., Abebe, K. Z., & Rollman, B. L. (2020). Racial Differences in the Effectiveness of Internet-Delivered Mental Health Care. Journal of general internal medicine, 35(2), 490-497.
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  Computerized cognitive behavioral therapy (cCBT) can improve mental health outcomes in White populations; however, it is unknown whether racial and ethnic minority populations receive clinical benefits from cCBT.
• Kratter, I. H., Karp, J. F., Chang, Y. F., Whiteman, A. C., Feyder, M. T., Jorge, A., Richardson, R. M., & Henry, L. C. (2020). Association of Preoperative Visual Hallucinations With Cognitive Decline After Deep Brain Stimulation for Parkinson's Disease. The Journal of neuropsychiatry and clinical neurosciences, appineuropsych20040077.
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  Deep brain stimulation (DBS) is effective for the motor symptoms of Parkinson's disease (PD). Although most patients benefit with minimal cognitive side effects, cognitive decline is a risk, and there is little available evidence to guide preoperative risk assessment. Visual illusions or visual hallucinations (VHs) and impulse-control behaviors (ICBs) are relatively common complications of PD and its treatment and may be a marker of more advanced disease, but their relationship with postoperative cognition has not been established. The authors aimed to determine whether any preoperative history of VHs or ICBs is associated with cognitive change after DBS.
• Lobo, C. P., Cochran, G., Chang, C. H., Gellad, W. F., Gordon, A. J., Jalal, H., Lo-Ciganic, W. H., Karp, J. F., Kelley, D., & Donohue, J. M. (2020). Associations Between the Specialty of Opioid Prescribers and Opioid Addiction, Misuse, and Overdose Outcomes. Pain medicine (Malden, Mass.), 21(9), 1871-1890.
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  To examine associations between opioid prescriber specialty and patient likelihood of opioid use disorder (OUD), opioid misuse, and opioid overdose.
• Marshe, V. S., Islam, F., Maciukiewicz, M., Fiori, L. M., Yerko, V., Yang, J., Turecki, G., Foster, J. A., Kennedy, S. H., Blumberger, D. M., Karp, J. F., Kennedy, J. L., Mulsant, B. H., Reynolds, C. F., Lenze, E. J., & Müller, D. J. (2020). Validation study of microRNAs previously associated with antidepressant response in older adults treated for late-life depression with venlafaxine. Progress in neuro-psychopharmacology & biological psychiatry, 100, 109867.
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  MicroRNAs (miRNAs) are small 22 nucleotides long, non-coding RNAs that are potential biomarkers for antidepressant treatment response. We aimed to replicate previous associations of miRNAs with antidepressant treatment response in a sample of older adults diagnosed with late-life depression.
• Newmark, J., Gebara, M. A., Aizenstein, H., & Karp, J. F. (2020). Engaging in Late-Life Mental Health Research: a Narrative Review of Challenges to Participation. Current treatment options in psychiatry, 1-20.
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  This narrative review seeks to ascertain the challenges older patients face with participation in mental health clinical research studies and suggests creative strategies to minimize these obstacles.
• Nicol, G. E., Karp, J. F., Reiersen, A. M., Zorumski, C. F., & Lenze, E. J. (2020). "What Were You Before the War?" Repurposing Psychiatry During the COVID-19 Pandemic. The Journal of clinical psychiatry, 81(3).
• Stahl, S. T., Jung, C., Weiner, D. K., Peciña, M., & Karp, J. F. (2020). Opioid Exposure Negatively Affects Antidepressant Response to Venlafaxine in Older Adults with Chronic Low Back Pain and Depression. Pain medicine (Malden, Mass.), 21(8), 1538-1545.
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  Serotonin norepinephrine reuptake inhibitors (SNRIs) are commonly co-prescribed with opioids for chronic pain. The purpose of this study was to describe pain and mood response to venlafaxine among older adults with chronic low back pain (CLBP) and depression relative to opioid exposure.
• Stahl, S. T., Smagula, S. F., Rodakowski, J., Dew, M. A., Karp, J. F., Albert, S. M., Butters, M., Gildengers, A., & Reynolds, C. F. (2020). Subjective Sleep Quality and Trajectories of Interleukin-6 in Older Adults. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.
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  We aimed to identify trajectories of inflammation in older adults at elevated risk for syndromal depression and anxiety and to determine whether baseline physical, cognitive, and psychosocial factors could distinguish 15-month longitudinal trajectories.
• Vahia, I. V., Blazer, D. G., Smith, G. S., Karp, J. F., Steffens, D. C., Forester, B. P., Tampi, R., Agronin, M., Jeste, D. V., & Reynolds, C. F. (2020). COVID-19, Mental Health and Aging: A Need for New Knowledge to Bridge Science and Service. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 28(7), 695-697.
• Ward, M. J., Karim, H. T., Jessen, Z. F., Ghuman, A. S., Richardson, R. M., Reynolds, C. F., & Karp, J. F. (2020). Association between increased theta cordance and early response to ECT in late-life depression. International journal of geriatric psychiatry, 35(2), 147-152.
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  More than half of patients with major depression who do not respond to initial antidepressants become treatment resistant (TRD), and while electroconvulsive therapy (ECT) is effective, it involves anesthesia and other medical risks that are of concern in geriatric patients. Past studies have suggested that theta cordance (TC), a correlate of cerebral metabolism measured by electroencephalography, could guide treatment decisions related to patient selection and engagement of the therapeutic target.
• Waterman, L. A., Belnap, B. H., Gebara, M. A., Huang, Y., Abebe, K. Z., Rollman, B. L., & Karp, J. F. (2020). Bypassing the blues: Insomnia in the depressed post-CABG population. Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists, 32(1), 17-26.
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  BACKGROUND: Recovery from coronary artery bypass graft (CABG) surgery often is complicated by depression and insomnia, resulting in poorer health-related quality of life and clinical outcomes. We explored the relationships among depression, insomnia, quality of life, and the impact of a collaborative care strategy on reducing insomnia in patients after CABG surgery.
• Wathra, R., Mulsant, B. H., Thomson, L., Goldberger, K. W., Lenze, E. J., Karp, J. F., Sanches, M., Reynolds, C. F., & Blumberger, D. M. (2020). Hypertension and orthostatic hypotension with venlafaxine treatment in depressed older adults. Journal of psychopharmacology (Oxford, England), 34(10), 1112-1118.
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  Venlafaxine, a serotonin-norepinephrine reuptake inhibitor, is often used as first- or second-line therapy for depression in older adults. It can be associated with adverse blood pressure (BP) effects.
• Wu, C. Y., Rodakowski, J. L., Terhorst, L., Karp, J. F., Fields, B., & Skidmore, E. R. (2020). A Scoping Review of Nonpharmacological Interventions to Reduce Disability in Older Adults. The Gerontologist, 60(1), e52-e65.
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  Minimizing disability is critical to reduce the costly health care associated with disability and maintain quality of life into old age. We examined the effect sizes of nonpharmacological intervention studies in reducing disability and explored the active ingredients of interventions.
• Albert, S. M., King, J., Anderson, S., Dew, M. A., Zhang, J., Stahl, S. T., Karp, J. F., Gildengers, A. G., Butters, M. A., & Reynolds Iii, C. F. (2019). Depression Agency-Based Collaborative: Effect of Problem-Solving Therapy on Risk of Common Mental Disorders in Older Adults With Home Care Needs. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 27(6), 619-624.
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  Interventions to prevent depression in older adults have mainly focused on young-old ambulatory adults, not on the old-old with disabilities who receive supportive services in their homes.
• Buchalter, E. L., Oughli, H. A., Lenze, E. J., Dixon, D., Miller, J. P., Blumberger, D. M., Karp, J. F., Reynolds, C. F., & Mulsant, B. H. (2019). Predicting Remission in Late-Life Major Depression: A Clinical Algorithm Based Upon Past Treatment History. The Journal of clinical psychiatry, 80(6).
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  To determine the likelihood of antidepressant response in older adults with major depression as a function of their prior antidepressant trials.
• Cristancho, P., Lenard, E., Lenze, E. J., Miller, J. P., Brown, P. J., Roose, S. P., Montes-Garcia, C., Blumberger, D. M., Mulsant, B. H., Lavretsky, H., Rollman, B. L., Reynolds, C. F., & Karp, J. F. (2019). Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM): Study Design and Treatment Characteristics of the First 396 Participants Randomized. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 27(10), 1138-1152.
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  Evidence from clinical trials comparing effectiveness and safety of pharmacological strategies in older adults unresponsive to first-line antidepressants is limited. The study, Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM), tests three hypotheses concerning pharmacotherapy strategies for treatment-resistant late-life depression: 1) augmentation strategies will provide greater improvement than switching monotherapies; 2) augmentation strategies will have lower tolerability and more safety concerns than switching monotherapies; and 3) age will moderate the effectiveness and safety differences between treatment strategies. The authors describe the methodology, processes for stakeholder engagement, challenges, and lessons learned in the early phases of OPTIMUM.
• Gebara, M. A., DiNapoli, E. A., Lederer, L. G., Bramoweth, A. D., Germain, A., Kasckow, J. W., & Karp, J. F. (2019). Brief behavioral treatment for insomnia in older adults with late-life treatment-resistant depression and insomnia: a pilot study. Sleep and biological rhythms, 17(3), 287-295.
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  Brief Behavioral Treatment for Insomnia (BBTI) is an efficacious treatment of insomnia in older adults. Behavioral treatments for insomnia can also improve depression. However, it is unknown if BBTI is feasible or has an effect in patients with insomnia and late-life treatment resistant depression (LLTRD). The aims of this study were two-fold, to test: 1) the feasibility (defined by acceptability and retention rates) of BBTI and 2) the therapeutic potency of BBTI on symptoms of insomnia and depression.
• Gujral, S., Aizenstein, H., Reynolds, C. F., Butters, M. A., Grove, G., Karp, J. F., & Erickson, K. I. (2019). Exercise for Depression: A Feasibility Trial Exploring Neural Mechanisms. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 27(6), 611-616.
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  The aim of this study was to test the feasibility of an exercise augmentation to pharmacotherapy in depressed younger and older adults while exploring neural mechanisms.
• Karp, J. F. (2019). Resident Mental Health: Time for Action. Anesthesiology, 131(3), 464-466.
• Karp, J. F., Zhang, J., Wahed, A. S., Anderson, S., Dew, M. A., Fitzgerald, G. K., Weiner, D. K., Albert, S., Gildengers, A., Butters, M., & Reynolds, C. F. (2019). Improving Patient Reported Outcomes and Preventing Depression and Anxiety in Older Adults With Knee Osteoarthritis: Results of a Sequenced Multiple Assignment Randomized Trial (SMART) Study. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 27(10), 1035-1045.
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  Older adults with knee osteoarthritis (OA) and comorbid subsyndromal depressive symptoms are at elevated risk for incidental major depression or anxiety disorders. Using an indicated prevention paradigm, the authors conducted a sequenced multiple assignment randomized trial (SMART) to: 1) evaluate the effect of cognitive behavioral therapy (CBT) and physical therapy (PT), together with the temporal ordering of these interventions, on patient-reported global impression of change (P-GIC), mood, anxiety, and pain; and 2) compare the strategies' impact on incidence of common psychiatric disorders over 12-months.
• Lin, C., Karim, H. T., Pecina, M., Aizenstein, H. J., Lenze, E. J., Blumberger, D. M., Mulsant, B. H., Kharasch, E. D., Reynolds Iii, C. F., & Karp, J. F. (2019). Low-dose augmentation with buprenorphine increases emotional reactivity but not reward activity in treatment resistant mid- and late-life depression. NeuroImage. Clinical, 21, 101679.
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  Buprenorphine is currently being studied for treatment-resistant depression because of its rapid effect, relative safety, and unique pharmacodynamics. To understand the neural impact of buprenorphine in depression, we examined acute limbic and reward circuit changes during an intervention with low-dose buprenorphine augmentation pharmacotherapy. Mid and late-life adults with major depression (N = 31) who did not completely respond to an adequate trial of venlafaxine were randomized to augmentation with low-dose buprenorphine or matching placebo. We investigated early neural changes using functional magnetic resonance imaging (fMRI) from pre-randomization to 3 weeks using both an emotional reactivity task and a gambling task. We tested if: 1) there were significant neural changes acutely per intervention group, and 2) if acute neural changes were associated with depressive symptom change over 8 weeks using both the total score and the dysphoria subscale of the Montgomery Asberg Depression Rating Scale. Participants in both the buprenorphine and placebo groups showed similar changes in depressive symptoms. Neither the emotional reactivity nor gambling task resulted in significant neural activation changes from pre-randomization to 3-weeks. In both groups, increases in rostral anterior cingulate (rACC) and ventromedial prefrontal cortex (vmPFC) activation during the emotional reactivity task were associated with overall symptom improvement. In the buprenorphine but not the placebo group, increased activation in left anterior insula (aINS) and bilateral middle frontal gyrus (MFG) was associated with improvement on the dysphoria subscale. Activation changes in the reward task were not associated with buprenorphine. This is the first study to show an association between acute neural changes during emotion reactivity and changes in depression severity with buprenorphine treatment.
• Lissemore, J. I., Shanks, H. R., Butters, M. A., Bhandari, A., Zomorrodi, R., Rajji, T. K., Karp, J. F., Reynolds, C. F., Lenze, E. J., Daskalakis, Z. J., Mulsant, B. H., & Blumberger, D. M. (2019). An inverse relationship between cortical plasticity and cognitive inhibition in late-life depression. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 44(9), 1659-1666.
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  Executive dysfunction is a common and disabling component of late-life depression (LLD), yet its neural mechanisms remain unclear. In particular, it is not yet known how executive functioning in LLD relates to measures of cortical physiology that may change with age and illness, namely cortical inhibition/excitation and plasticity. Here, we used transcranial magnetic stimulation (TMS) to measure cortical inhibition/excitation (n = 51), and the potentiation of cortical activity following paired associative stimulation, which is thought to reflect long-term potentiation (LTP)-like cortical plasticity (n = 32). We assessed the correlation between these measures of cortical physiology and two measures of executive functioning: cognitive inhibition, assessed using the Delis-Kaplan Executive Function System Color-Word Interference ["Stroop"] Test, and cognitive flexibility, assessed using the Trail Making Test. Correlations with recall memory and processing speed were also performed to assess the specificity of any associations to executive functioning. A significant correlation was found between greater LTP-like cortical plasticity and poorer cognitive inhibition, a core executive function (r = -0.56, p 
• Peciña, M., Karp, J. F., Mathew, S., Todtenkopf, M. S., Ehrich, E. W., & Zubieta, J. K. (2019). Endogenous opioid system dysregulation in depression: implications for new therapeutic approaches. Molecular psychiatry, 24(4), 576-587.
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  The United States is in the midst of an opioid addiction and overdose crisis precipitated and exacerbated by use of prescription opioid medicines. The majority of opioid prescriptions are dispensed to patients with comorbid mood disorders including major depressive disorder (MDD). A growing body of research indicates that the endogenous opioid system is directly involved in the regulation of mood and is dysregulated in MDD. This involvement of the endogenous opioid system may underlie the disproportionate use of opioids among patients with mood disorders. Emerging approaches to address endogenous opioid dysregulation in MDD may yield novel therapeutics that have a low or absent risk of abuse and addiction relative to µ-opioid agonists. Moreover, agents targeting the endogenous opioid system would be expected to yield clinical benefits qualitatively different from conventional monaminergic antidepressants. The development of safe and effective agents to treat MDD-associated endogenous opioid dysregulation may represent a distinct and currently underappreciated means of addressing treatment resistant depression with the potential to attenuate the on-going opioid crisis.
• Bhandari, A., Lissemore, J. I., Rajji, T. K., Mulsant, B. H., Cash, R. F., Noda, Y., Zomorrodi, R., Karp, J. F., Lenze, E. J., Reynolds, C. F., Daskalakis, Z. J., & Blumberger, D. M. (2018). Assessment of neuroplasticity in late-life depression with transcranial magnetic stimulation. Journal of psychiatric research, 105, 63-70.
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  Studies using Transcranial Magnetic Stimulation (TMS), a non-invasive method of brain stimulation, have implicated impaired neuroplasticity in the pathophysiology of depression in younger adults. The role of neuroplasticity in late-life depression (LLD) has not yet been explored using TMS.
• Gebara, M. A., DiNapoli, E. A., Kasckow, J., Karp, J. F., Blumberger, D. M., Lenze, E. J., Mulsant, B. H., & Reynolds, C. F. (2018). Specific depressive symptoms predict remission to aripiprazole augmentation in late-life treatment resistant depression. International journal of geriatric psychiatry, 33(2), e330-e335.
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  To identify which specific depressive symptoms predict remission to aripiprazole augmentation in late-life treatment resistant depression.
• Gebara, M. A., Kasckow, J., Smagula, S. F., DiNapoli, E. A., Karp, J. F., Lenze, E. J., Mulsant, B. H., & Reynolds, C. F. (2018). The role of late life depressive symptoms on the trajectories of insomnia symptoms during antidepressant treatment. Journal of psychiatric research, 96, 162-166.
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  Sleep disturbances are common in late life depression; however, changes in insomnia symptoms during antidepressant treatment need to be characterized further. The objective of this study was two-fold: 1) to describe longitudinal trajectories of insomnia symptoms in older adults receiving antidepressant treatment and 2) to examine whether baseline depressive symptoms were associated with trajectories of sleep over time.
• Gebara, M. A., Siripong, N., DiNapoli, E. A., Maree, R. D., Germain, A., Reynolds, C. F., Kasckow, J. W., Weiss, P. M., & Karp, J. F. (2018). Effect of insomnia treatments on depression: A systematic review and meta-analysis. Depression and anxiety, 35(8), 717-731.
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  Insomnia is frequently co-morbid with depression, with a bidirectional relationship between these disorders. There is evidence that insomnia-specific interventions, such as cognitive behavioral therapy for insomnia, may lead to improvements in depression. The purpose of this systematic review and meta-analysis is to determine whether treatment of insomnia leads to improved depression outcomes in individuals with both insomnia and depression.
• Hsu, J. H., Mulsant, B. H., Lenze, E. J., Sanches, M., Karp, J. F., Reynolds, C. F., & Blumberger, D. M. (2018). Clinical Predictors of Extrapyramidal Symptoms Associated With Aripiprazole Augmentation for the Treatment of Late-Life Depression in a Randomized Controlled Trial. The Journal of clinical psychiatry, 79(4).
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  Augmentation with aripiprazole is an effective pharmacotherapy for treatment-resistant late-life depression (LLD). However, aripiprazole can cause extrapyramidal symptoms (EPS) such as akathisia and parkinsonism; these symptoms are distressing and can contribute to treatment discontinuation. We investigated the clinical trajectories and predictors of akathisia and parkinsonism in older patients receiving aripiprazole augmentation for treatment-resistant LLD.
• Karim, H. T., Wang, M., Andreescu, C., Tudorascu, D., Butters, M. A., Karp, J. F., Reynolds, C. F., & Aizenstein, H. J. (2018). Acute trajectories of neural activation predict remission to pharmacotherapy in late-life depression. NeuroImage. Clinical, 19, 831-839.
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  Pharmacological treatment of major depressive disorder (MDD) typically involves a lengthy trial and error process to identify an effective intervention. This lengthy period prolongs suffering and worsens all-cause mortality, including from suicide, and is typically longer in late-life depression (LLD). Our group has recently demonstrated that during an open-label venlafaxine (serotonin-norepinephrine reuptake inhibitor) trial, significant changes in functional resting state connectivity occurred following a single dose of treatment, which persisted until the end of the trial. In this work, we propose an analysis framework to translate these perturbations in functional networks into predictors of clinical remission. Participants with LLD (N = 49) completed 12-weeks of treatment with venlafaxine and underwent functional magnetic resonance imaging (fMRI) at baseline and a day following a single dose of venlafaxine. Data was collected at rest as well as during an emotion reactivity task and an emotion regulation task. Remission was defined as a Montgomery-Asberg Depression Rating Scale (MADRS) ≤10 for two weeks. We computed eigenvector centrality (whole brain connectivity) and activation during the emotion regulation and emotion reactivity tasks. We employed principal components analysis, Tikhonov-regularized logistic classification, and least angle regression feature selection to predict remission by the end of the 12-week trial. We utilized ten-fold cross-validation and Receiver Operator Curves (ROC) curve analysis. To determine task-region pairs that significantly contributed to the algorithm's ability to predict remission, we used permutation testing. Using the fMRI data at both baseline and after the first dose of treatment yielded a sensitivity of 72% and a specificity of 68% (AUC = 0.77), a 15% increase in accuracy over baseline MADRS. In general, the accuracy at baseline was further improved by using the change in activation following a single dose. Activation of the frontal cortex, hippocampus, parahippocampus, caudate, thalamus, medial temporal cortex, middle cingulate, and visual cortex predicted treatment remission. Acute, dynamic trajectories of functional imaging metrics in response to a pharmacological intervention are a valuable tool for predicting treatment response in late-life depression and elucidating the mechanism of pharmacological therapies in the context of the brain's functional architecture.
• Karp, J. F., & Levine, A. S. (2018). Mental Health Services for Medical Students - Time to Act. The New England journal of medicine, 379(13), 1196-1198.
• Karp, J. F., Gao, X., Wahed, A. S., Morse, J. Q., Rollman, B. L., Weiner, D. K., & Reynolds, C. F. (2018). Effect of Problem-Solving Therapy Versus Supportive Management in Older Adults with Low Back Pain and Depression While on Antidepressant Pharmacotherapy. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 26(7), 765-777.
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  Testing stepped-care approaches that address both depression and low back pain are needed to optimize outcomes in older adults.
• Lenze, E. J., Voineskos, A. N., Butters, M. A., Karp, J. F., & , O. a. (2018). Stopping Cognitive Decline in Patients With Late-Life Depression: A New Front in the Fight Against Dementia. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 26(8), 828-834.
• Lissemore, J. I., Bhandari, A., Mulsant, B. H., Lenze, E. J., Reynolds, C. F., Karp, J. F., Rajji, T. K., Noda, Y., Zomorrodi, R., Sibille, E., Daskalakis, Z. J., & Blumberger, D. M. (2018). Reduced GABAergic cortical inhibition in aging and depression. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 43(11), 2277-2284.
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  The neurobiology underlying depression in older adults is less extensively evaluated than in younger adults, despite the putative influence of aging on depression neuropathology. Studies using transcranial magnetic stimulation (TMS), a neurophysiological tool capable of probing inhibitory and excitatory cortical neurotransmission, have identified dysfunctional GABAergic inhibitory activity in younger adults with depression. However, GABAergic and glutamatergic cortical neurotransmission have not yet been studied in late-life depression (LLD). Here, we used single- and paired-pulse TMS to measure cortical inhibition and excitation in 92 LLD patients and 41 age-matched healthy controls. To differentiate the influence of age and depression, we also compared these TMS indices to those of 30 younger depressed adults and 30 age- and sex-matched younger healthy adults. LLD patients, older healthy adults, and younger depressed adults demonstrated significantly lower GABA receptor-mediated cortical inhibition than younger healthy controls. By contrast, no significant differences in cortical inhibition were observed between older adults with and without depression. No significant differences in GABA receptor-mediated inhibition or cortical excitation were found between the groups. Altogether, these findings suggest that reduced cortical inhibition may be associated with both advancing age and depression, which (i) supports the model of depression as a disease of accelerated aging, and (ii) prompts future investigation into diminished GABAergic neurotransmission in late-life as a biological predisposing factor to the development of depression. Given that cortical neurophysiology was similar in depressed and healthy older adults, future prospective studies need to establish the relative influence of age and depression on cortical inhibition deficits.
• Rollman, B. L., Herbeck Belnap, B., Abebe, K. Z., Spring, M. B., Rotondi, A. J., Rothenberger, S. D., & Karp, J. F. (2018). Effectiveness of Online Collaborative Care for Treating Mood and Anxiety Disorders in Primary Care: A Randomized Clinical Trial. JAMA psychiatry, 75(1), 56-64.
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  Collaborative care for depression and anxiety is superior to usual care from primary care physicians for these conditions; however, challenges limit its provision in routine practice and at scale. Advances in technology may overcome these barriers but have yet to be tested.
• Wei, W., Karim, H. T., Lin, C., Mizuno, A., Andreescu, C., Karp, J. F., Reynolds, C. F., & Aizenstein, H. J. (2018). Trajectories in Cerebral Blood Flow Following Antidepressant Treatment in Late-Life Depression: Support for the Vascular Depression Hypothesis. The Journal of clinical psychiatry, 79(6).
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  Studies have identified longitudinally that there exists an association between depression, cerebral blood flow (CBF), and white matter hyperintensities that are thought to be due to vascular pathologies in the brain. However, the changes in CBF, a measure that reflects cerebrovascular integrity, following pharmacotherapy are not well understood. In this study, we investigated the dynamic CBF changes over the course of antidepressant treatment and the association of these changes with depressive symptoms.
• Wu, C. Y., Terhorst, L., Karp, J. F., Skidmore, E. R., & Rodakowski, J. (2018). Trajectory of Disability in Older Adults With Newly Diagnosed Diabetes: Role of Elevated Depressive Symptoms. Diabetes care, 41(10), 2072-2078.
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  We examined whether the trajectory of disability differed between older adults with and without elevated depressive symptoms before and after the onset of diabetes mellitus (DM) over 10 years (2004-2014) and explored difficulties in basic and instrumental activities of daily living between the two groups.
• DiNapoli, E. A., Gebara, M. A., Kho, T., Butters, M. A., Gildengers, A. G., Albert, S. M., Dew, M. A., Erickson, K. I., Reynolds, C. F., & Karp, J. F. (2017). Subjective-Objective Sleep Discrepancy in Older Adults With MCI and Subsyndromal Depression. Journal of geriatric psychiatry and neurology, 30(6), 316-323.
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  We investigated the prevalence and correlates of discrepancies between self-reported sleep quality (Pittsburgh Sleep Quality Index) and objective sleep efficiency (actigraphy) in older adults with mild cognitive impairment (MCI) and subsyndromal depression.
• Jonassaint, C. R., Gibbs, P., Belnap, B. H., Karp, J. F., Abebe, K. K., & Rollman, B. L. (2017). Engagement and outcomes for a computerised cognitive-behavioural therapy intervention for anxiety and depression in African Americans. BJPsych open, 3(1), 1-5.
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  Computerised cognitive-behavioural therapy (CCBT) helps improve mental health outcomes in White populations. However, no studies have examined whether CCBT is acceptable and beneficial for African Americans.
• Karp, J. F. (2017). Depression is Contagious: Dyadic Interventions May Reduce Infection. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 25(4), 396.
• Karp, J. F. (2017). Providing High-Quality Pain Care for Veterans Means Considering Gender Effects. Pain medicine (Malden, Mass.), 18(9), 1625-1626.
• Marshe, V. S., Maciukiewicz, M., Rej, S., Tiwari, A. K., Sibille, E., Blumberger, D. M., Karp, J. F., Lenze, E. J., Reynolds, C. F., Kennedy, J. L., Mulsant, B. H., & Müller, D. J. (2017). Norepinephrine Transporter Gene Variants and Remission From Depression With Venlafaxine Treatment in Older Adults. The American journal of psychiatry, 174(5), 468-475.
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  The primary objective of this study was to investigate five putatively functional variants of the norepinephrine transporter (SLC6A2, NET) and serotonin transporter (SLC6A4, SERT) genes and remission in depressed older adults treated with venlafaxine. A secondary objective was to analyze 17 other variants in serotonergic system genes (HTR1A, HTR2A, HTR1B, HTR2C, TPH1, TPH2) potentially involved in the mechanism of action of venlafaxine.
• Mulvahill, J. S., Nicol, G. E., Dixon, D., Lenze, E. J., Karp, J. F., Reynolds, C. F., Blumberger, D. M., & Mulsant, B. H. (2017). Effect of Metabolic Syndrome on Late-Life Depression: Associations with Disease Severity and Treatment Resistance. Journal of the American Geriatrics Society, 65(12), 2651-2658.
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  Metabolic syndrome (MetS) is the co-occurrence of obesity and metabolic derangements. Prior research implicates MetS in prolongation of the course of depression in older adults, but its effect on antidepressant response is unknown in this population. The objective was to determine whether MetS and related metabolic dyscrasias are associated with decreased rate of remission from depression in older adults treated pharmacologically for depression.
• Rollman, B. L., Belnap, B. H., Mazumdar, S., Abebe, K. Z., Karp, J. F., Lenze, E. J., & Schulberg, H. C. (2017). Telephone-Delivered Stepped Collaborative Care for Treating Anxiety in Primary Care: A Randomized Controlled Trial. Journal of general internal medicine, 32(3), 245-255.
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  Collaborative care for depression is more effective in improving treatment outcomes than primary care physicians' (PCPs) usual care (UC). However, few trials of collaborative care have targeted anxiety.
• Stahl, S. T., Albert, S. M., Dew, M. A., Anderson, S., Karp, J. F., Gildengers, A. G., Butters, M. A., & Reynolds, C. F. (2017). Measuring Participant Effort in a Depression Prevention Trial: Who Engages in Problem-Solving Therapy?. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 25(8), 909-916.
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  To determine the acceptability of clinical interventions for depression prevention, identification of clinical characteristics associated with intervention engagement is needed. The purpose of this study is to describe levels and correlates of participant engagement in Problem Solving Therapy (PST) in adults 60 and older with subthreshold depression.
• Boyce, R. D., Handler, S. M., Karp, J. F., Perera, S., & Reynolds, C. F. (2016). Preparing Nursing Home Data from Multiple Sites for Clinical Research - A Case Study Using Observational Health Data Sciences and Informatics. EGEMS (Washington, DC), 4(1), 1252.
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  A potential barrier to nursing home research is the limited availability of research quality data in electronic form. We describe a case study of converting electronic health data from five skilled nursing facilities to a research quality longitudinal dataset by means of open-source tools produced by the Observational Health Data Sciences and Informatics (OHDSI) collaborative.
• Gildengers, A. G., Butters, M. A., Albert, S. M., Anderson, S. J., Dew, M. A., Erickson, K., Garand, L., Karp, J. F., Lockovich, M. H., Morse, J., & Reynolds, C. F. (2016). Design and Implementation of an Intervention Development Study: Retaining Cognition While Avoiding Late-Life Depression (ReCALL). The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 24(6), 444-54.
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  To discuss the design, rationale, and implementation of an intervention development study addressing indicated and selective prevention of depression and anxiety in individuals 60 years and older with mild cognitive impairment (MCI) and in their caregivers.
• Gujral, S., Ogbagaber, S., Dombrovski, A. Y., Butters, M. A., Karp, J. F., & Szanto, K. (2016). Course of cognitive impairment following attempted suicide in older adults. International journal of geriatric psychiatry, 31(6), 592-600.
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  Cognitive impairment has been associated with late-life suicidal behavior. Without longitudinal data it is unclear whether these are transient features of a depressive state or stable impairments. We examined longitudinally the course of cognitive impairment in older adults with depression and a history of suicide attempt.
• Hsu, J. H., Mulsant, B. H., Lenze, E. J., Karp, J. F., Lavretsky, H., Roose, S. P., Reynolds, C. F., & Blumberger, D. M. (2016). Impact of Prior Treatment on Remission of Late-Life Depression with Venlafaxine and Subsequent Aripiprazole or Placebo Augmentation. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 24(10), 918-22.
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  Treatment history can inform clinical decisions about subsequent treatment choices. The authors examined the impact of prior antidepressant treatment on treatment outcomes with venlafaxine only and then with augmentation with aripiprazole or placebo in depressed older adults.
• Kaneriya, S. H., Robbins-Welty, G. A., Smagula, S. F., Karp, J. F., Butters, M. A., Lenze, E. J., Mulsant, B. H., Blumberger, D., Anderson, S. J., Dew, M. A., Lotrich, F., Aizenstein, H. J., Diniz, B. S., & Reynolds, C. F. (2016). Predictors and Moderators of Remission With Aripiprazole Augmentation in Treatment-Resistant Late-Life Depression: An Analysis of the IRL-GRey Randomized Clinical Trial. JAMA psychiatry, 73(4), 329-36.
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  Safe, efficacious, second-line pharmacological treatment options exist for the large portion of older adults with major depressive disorder who do not respond to first-line pharmacotherapy. However, limited evidence exists to aid clinical decision making regarding which patients will benefit from which second-line treatments.
• Karp, J. F., Dew, M. A., Wahed, A. S., Fitzgerald, K., Bolon, C. A., Weiner, D. K., Morse, J. Q., Albert, S., Butters, M., Gildengers, A., & Reynolds, C. F. (2016). Challenges and Solutions for Depression Prevention Research: Methodology for a Depression Prevention Trial for Older Adults with Knee Arthritis and Emotional Distress. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 24(6), 433-43.
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  To describe the methodology, challenges, and baseline characteristics of a prevention development trial entitled "Reducing Pain, Preventing Depression."
• Karp, J. F., DiNapoli, E. A., Wetherell, J., Bolon, C., Rodriguez, E., Shega, J., & Weiner, D. K. (2016). Deconstructing Chronic Low Back Pain in the Older Adult-Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment: Part IX: Anxiety. Pain medicine (Malden, Mass.), 17(8), 1423-35.
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  As a part of a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults, this article focuses on anxiety-a significant contributor of reduced health-related quality of life, increased use of medical services, and heightened disability in older adults with CLBP.
• Karp, J. F., McGovern, J., Marron, M. M., Gerszten, P., Weiner, D. K., Okonkwo, D., & Kanter, A. S. (2016). Clinical and neuropsychiatric correlates of lumbar spinal surgery in older adults: results of a pilot study. Pain management, 6(6), 543-552.
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  To improve selection of older lumbar surgical candidates, we surveyed correlates of functioning and satisfaction with surgery.
• Maree, R. D., Marcum, Z. A., Saghafi, E., Weiner, D. K., & Karp, J. F. (2016). A Systematic Review of Opioid and Benzodiazepine Misuse in Older Adults. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 24(11), 949-963.
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  The authors assessed the prevalence of opioid and benzodiazepine prescription drug misuse in older adults, the risk factors associated with misuse, and age-appropriate interventions.
• Smagula, S. F., Wallace, M. L., Anderson, S. J., Karp, J. F., Lenze, E. J., Mulsant, B. H., Butters, M. A., Blumberger, D. M., Diniz, B. S., Lotrich, F. E., Dew, M. A., & Reynolds, C. F. (2016). Combining moderators to identify clinical profiles of patients who will, and will not, benefit from aripiprazole augmentation for treatment resistant late-life major depressive disorder. Journal of psychiatric research, 81, 112-8.
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  Personalizing treatment for late-life depression requires identifying and integrating information from multiple factors that influence treatment efficacy (moderators). We performed exploratory moderator analyses using data from a multi-site, randomized, placebo-controlled, double-blind trial of aripiprazole augmentation. Patients (n = 159) aged ≥60 years had major depressive disorder that failed to remit with venlafaxine monotherapy. We examined effect sizes of 39 potential moderators of aripiprazole (vs. placebo) augmentation efficacy using the outcome of percentage reduction in depressive symptom after 12 weeks. We then incorporated information from the individually relevant variables in combined moderators. A larger aripiprazole treatment effect was related to: white race, better physical function, better performance on Trail-Making, attention, immediate, and delayed memory tests, greater psychomotor agitation and suicidality symptoms, and a history of adequate antidepressant pharmacotherapy. A smaller aripiprazole treatment effect was observed in patients with: more pain and more work/activity impairment and libido symptoms. Combining information from race and Trail-Making test performance (base combined moderator (Mb*)) produced a larger effect size (Spearman effect size = 0.29 (95% confidence interval (CI): 0.15, 0.42)) than any individual moderator. Adding other individually relevant moderators in the full combined moderator (Mf*) further improved effect size (Spearman effect size = 0.39 (95% CI: 0.25, 0.52)) and identified a sub-group benefiting more from placebo plus continuation venlafaxine monotherapy than adjunctive aripiprazole. Combining moderators can help clinicians personalize depression treatment. We found the majority of our patients benefited from adjunctive aripiprazole, but a smaller subgroup that is identifiable using clinical measures appeared to benefit more from continuation venlafaxine plus placebo.
• Waterman, L., Stahl, S. T., Buysse, D. J., Lenze, E. J., Blumberger, D., Mulsant, B., Butters, M., Gebara, M. A., Reynolds, C. F., & Karp, J. F. (2016). Self-reported obstructive sleep apnea is associated with nonresponse to antidepressant pharmacotherapy in late-life depression. Depression and anxiety, 33(12), 1107-1113.
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  Obstructive sleep apnea (OSA) is frequently comorbid with late-life depression. The purpose of this project was to determine, using a sample of older adults with major depressive disorder, whether patient-reported diagnosis of OSA was associated with rate of response to venlafaxine.
• Agudelo, C., Aizenstein, H. J., Karp, J. F., & Reynolds, C. F. (2015). Applications of magnetic resonance imaging for treatment-resistant late-life depression. Dialogues in clinical neuroscience, 17(2), 151-69.
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  Late-life depression (LLD) is a growing public and global health concern with diverse clinical manifestations and etiology. This literature review summarizes neuroimaging findings associated with depression in older adults and treatment-response variability. LLD has been associated with cerebral atrophy, diminished myelin integrity, and cerebral lesions in frontostriatal-limbic regions. These associations help explain the depression-executive dysfunction syndrome observed in LLD, and support cerebrovascular burden as a pathogenic mechanism. Furthermore, this review suggests that neuroimaging determinants of treatment resistance also reflect cerebrovascular burden. Of the theoretical etiologies of LLD, cerebrovascular burden may mediate treatment resistance. This review proposes that neuroimaging has the potential for clinical translation. Controlled trials may identify neuroimaging biomarkers that may inform treatment by identifying depressed adults likely to remit with pharmacotherapy, identifying individualized therapeutic dose, and facilitating earlier treatment response measures. Neuroimaging also has the potential to similarly inform treatment response variability from treatment with aripiprazole (dopamine modulator) and buprenorphine (opiate modulator).
• Alhourani, A., McDowell, M. M., Randazzo, M. J., Wozny, T. A., Kondylis, E. D., Lipski, W. J., Beck, S., Karp, J. F., Ghuman, A. S., & Richardson, R. M. (2015). Network effects of deep brain stimulation. Journal of neurophysiology, 114(4), 2105-17.
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  The ability to differentially alter specific brain functions via deep brain stimulation (DBS) represents a monumental advance in clinical neuroscience, as well as within medicine as a whole. Despite the efficacy of DBS in the treatment of movement disorders, for which it is often the gold-standard therapy when medical management becomes inadequate, the mechanisms through which DBS in various brain targets produces therapeutic effects is still not well understood. This limited knowledge is a barrier to improving efficacy and reducing side effects in clinical brain stimulation. A field of study related to assessing the network effects of DBS is gradually emerging that promises to reveal aspects of the underlying pathophysiology of various brain disorders and their response to DBS that will be critical to advancing the field. This review summarizes the nascent literature related to network effects of DBS measured by cerebral blood flow and metabolic imaging, functional imaging, and electrophysiology (scalp and intracranial electroencephalography and magnetoencephalography) in order to establish a framework for future studies.
• Carley, J. A., Karp, J. F., Gentili, A., Marcum, Z. A., Reid, M. C., Rodriguez, E., Rossi, M. I., Shega, J., Thielke, S., & Weiner, D. K. (2015). Deconstructing Chronic Low Back Pain in the Older Adult: Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment: Part IV: Depression. Pain medicine (Malden, Mass.), 16(11), 2098-108.
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  To present the fourth in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. The series presents CLBP as a syndrome, a final common pathway for the expression of multiple contributors rather than a disease localized exclusively to the lumbosacral spine. Each article addresses one of twelve important contributors to pain and disability in older adults with CLBP. This article focuses on depression.
• Fatemi, G., Fang, M. A., Breuer, P., Cherniak, P. E., Gentili, A., Hanlon, J. T., Karp, J. F., Morone, N. E., Rodriguez, E., Rossi, M. I., Schmader, K., & Weiner, D. K. (2015). Deconstructing chronic low back pain in the older adult--Step by step evidence and expert-based recommendations for evaluation and treatment part III: Fibromyalgia syndrome. Pain medicine (Malden, Mass.), 16(9), 1709-19.
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  To present the third in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. The series presents CLBP as a syndrome, a final common pathway for the expression of multiple contributors rather than a disease localized exclusively to the lumbosacral spine. Each article addresses one of 12 important contributors to pain and disability in older adults with CLBP. This article focuses on fibromyalgia syndrome (FMS).
• Gebara, M. A., Lipsey, K. L., Karp, J. F., Nash, M. C., Iaboni, A., & Lenze, E. J. (2015). Cause or Effect? Selective Serotonin Reuptake Inhibitors and Falls in Older Adults: A Systematic Review. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 23(10), 1016-28.
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  A 2012 update of the Beers criteria categorizes selective serotonin reuptake inhibitors (SSRIs) as potentially inappropriate medications in all older adults based on fall risk. The application of these recommendations, not only to frail nursing home residents, but to all older adults, may lead to changes in health policy or clinical practice with harmful consequences. A systematic review of studies on the association between SSRIs and falls in older adults was conducted to examine the evidence for causation. Twenty-six studies met the inclusion criteria. The majority of studies were observational and suggest an association between SSRIs and falls. The direction of the relationship--causation or effect--cannot be discerned from this type of study. Standardized techniques for determining likely causation were then used to see if there was support for the hypothesis that SSRIs lead to falls. This analysis did not suggest causation was likely. There is no Level 1 evidence that SSRIs cause falls. Therefore, changes in the current treatment guidelines or policies on the use of SSRIs in older adults based on fall risk may not be justified at this time given the lack of an established evidence base. Given its significance to public health, well-designed experimental studies are required to address this question definitively.
• Jochum, J. R., Begley, A. E., Dew, M. A., Weiner, D. K., & Karp, J. F. (2015). Advancing the screening of fibromyalgia in late-life depression: practical implications for psychiatric settings. International psychogeriatrics, 27(9), 1513-21.
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  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.
• Lenze, E. J., Mulsant, B. H., Blumberger, D. M., Karp, J. F., Newcomer, J. W., Anderson, S. J., Dew, M. A., Butters, M. A., Stack, J. A., Begley, A. E., & Reynolds, C. F. (2015). Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial. Lancet (London, England), 386(10011), 2404-12.
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  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.
• Richardson, R. M., Ghuman, A. S., & Karp, J. F. (2015). Results of the First Randomized Controlled Trial of Deep Brain Stimulation in Treatment-Resistant Depression. Neurosurgery, 77(2), N23-4.
• Karp, J. F. (2014). Preventing pain requires translating biology into social change. Pain medicine (Malden, Mass.), 15(5), 728-9.
• Karp, J. F., Butters, M. A., Begley, A. E., Miller, M. D., Lenze, E. J., Blumberger, D. M., Mulsant, B. H., & Reynolds, C. F. (2014). Safety, tolerability, and clinical effect of low-dose buprenorphine for treatment-resistant depression in midlife and older adults. The Journal of clinical psychiatry, 75(8), e785-93.
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  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.
• Karp, J. F., Yu, L., Friedly, J., Amtmann, D., & Pilkonis, P. A. (2014). Negative affect and sleep disturbance may be associated with response to epidural steroid injections for spine-related pain. Archives of physical medicine and rehabilitation, 95(2), 309-15.
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  To describe whether negative affect and sleep impairment are associated with the clinical effect of epidural steroid injections (ESIs) for low back pain.
• Lenze, E. J., Hershey, T., Newcomer, J. W., Karp, J. F., Blumberger, D., Anger, J., Doré, P., & Dixon, D. (2014). Antiglucocorticoid therapy for older adults with anxiety and co-occurring cognitive dysfunction: results from a pilot study with mifepristone. International journal of geriatric psychiatry, 29(9), 962-9.
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  In older adults with anxiety disorders, chronically elevated cortisol may contribute to cognitive impairment and elevated anxiety. We conducted a pilot study with mifepristone, a glucocorticoid receptor antagonist, as a potential treatment for late-life anxiety disorders and co-occurring cognitive dysfunction.
• Rej, S., Dew, M. A., & Karp, J. F. (2014). Treating concurrent chronic low back pain and depression with low-dose venlafaxine: an initial identification of "easy-to-use" clinical predictors of early response. Pain medicine (Malden, Mass.), 15(7), 1154-62.
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  Depression and chronic low back pain (CLBP) are both frequent and commonly comorbid in older adults seeking primary care. Serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine may be effective in treating comorbid depression and CLBP. For patients with comorbid depression and CLBP, our goal was to identify "easy-to-use" early clinical variables associated with response to 6 weeks of low-dose venlafaxine pharmacotherapy that could be used to construct a clinically useful predictive model in future studies.
• Reynolds, C. F., Thomas, S. B., Morse, J. Q., Anderson, S. J., Albert, S., Dew, M. A., Begley, A., Karp, J. F., Gildengers, A., Butters, M. A., Stack, J. A., Kasckow, J., Miller, M. D., & Quinn, S. C. (2014). Early intervention to preempt major depression among older black and white adults. Psychiatric services (Washington, D.C.), 65(6), 765-73.
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  The study objective was to assess the efficacy of problem-solving therapy for primary care (PST-PC) for preventing episodes of major depression and mitigating depressive symptoms of older black and white adults. The comparison group received dietary coaching.
• Weiner, D. K., Morone, N. E., Spallek, H., Karp, J. F., Schneider, M., Washburn, C., Dziabiak, M. P., Hennon, J. G., Elnicki, D. M., & , U. o. (2014). E-learning module on chronic low back pain in older adults: evidence of effect on medical student objective structured clinical examination performance. Journal of the American Geriatrics Society, 62(6), 1161-7.
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  The Institute of Medicine has highlighted the urgent need to close undergraduate and graduate educational gaps in treating pain. Chronic low back pain (CLBP) is one of the most common pain conditions, and older adults are particularly vulnerable to potential morbidities associated with misinformed treatment. An e-learning case-based interactive module was developed at the University of Pittsburgh Center of Excellence in Pain Education, one of 12 National Institutes of Health-designated centers, to teach students important principles for evaluating and managing CLBP in older adults. A team of six experts in education, information technology, pain management, and geriatrics developed the module. Teaching focused on common errors, interactivity, and expert modeling and feedback. The module mimicked a patient encounter using a standardized patient (the older adult with CLBP) and a pain expert (the patient provider). Twenty-eight medical students were not exposed to the module (Group 1) and 27 were exposed (Group 2). Their clinical skills in evaluating CLBP were assessed using an objective structured clinical examination (OSCE). Mean scores were 62.0 ± 8.6 for Group 1 and 79.5 ± 10.4 for Group 2 (P < .001). Using an OSCE pass-fail cutoff score of 60%, 17 of 28 Group 1 students (60.7%) and 26 of 27 Group 2 students (96.3%) passed. The CLBP OSCE was one of 10 OSCE stations in which students were tested at the end of a Combined Ambulatory Medicine and Pediatrics Clerkship. There were no between-group differences in performance on eight of the other nine OSCE stations. This module significantly improved medical student clinical skills in evaluating CLBP. Additional research is needed to ascertain the effect of e-learning modules on more-advanced learners and on improving the care of older adults with CLBP.
• Andreescu, C., Tudorascu, D. L., Butters, M. A., Tamburo, E., Patel, M., Price, J., Karp, J. F., Reynolds, C. F., & Aizenstein, H. (2013). Resting state functional connectivity and treatment response in late-life depression. Psychiatry research, 214(3), 313-21.
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  Indices of functional connectivity in the default mode network (DMN) are promising neural markers of treatment response in late-life depression. We examined the differences in DMN functional connectivity between treatment-responsive and treatment-resistant depressed older adults. Forty-seven depressed older adults underwent MRI scanning pre- and post-pharmacotherapy. Forty-six never depressed older adults underwent MR scanning as comparison subjects. Treatment response was defined as achieving a Hamilton Depression Rating Scale of 10 or less post-treatment. We analyzed resting state functional connectivity using the posterior cingulate cortex as the seed region-of-interest. The resulting correlation maps were employed to investigate between-group differences. Additionally we examined the association between white matter hyperintensity burden and functional connectivity results. Comparison of pre- and post-treatment scans of depressed participants revealed greater post-treatment functional connectivity in the frontal precentral gyrus. Relative to treatment-responsive participants, treatment-resistant participants had increased functional connectivity in the left striatum. When adjusting for white matter hyperintensity burden, the observed differences lost significance for the PCC-prefrontal functional connectivity, but not for the PCC-striatum functional connectivity. The post-treatment "frontalization" of the DMN connectivity suggests a normalizing effect of antidepressant treatment. Moreover, our study confirms the central role of white matter lesions in disrupting brain functional connectivity.
• Karp, J. F., Lee, C. W., McGovern, J., Stoehr, G., Chang, C. C., & Ganguli, M. (2013). Clinical and demographic covariates of chronic opioid and non-opioid analgesic use in rural-dwelling older adults: the MoVIES project. International psychogeriatrics, 25(11), 1801-10.
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  To describe covariates and patterns of late-life analgesic use in the rural, population-based MoVIES cohort from 1989 to 2002.
• Boyce, R. D., Handler, S. M., Karp, J. F., & Hanlon, J. T. (2012). Age-related changes in antidepressant pharmacokinetics and potential drug-drug interactions: a comparison of evidence-based literature and package insert information. The American journal of geriatric pharmacotherapy, 10(2), 139-50.
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  Antidepressants are among the most commonly prescribed psychotropic agents for older patients. Little is known about the best source of pharmacotherapy information to consult about key factors necessary to safely prescribe these medications to older patients.
• Boyce, R. D., Hanlon, J. T., Karp, J. F., Kloke, J., Saleh, A., & Handler, S. M. (2012). A review of the effectiveness of antidepressant medications for depressed nursing home residents. Journal of the American Medical Directors Association, 13(4), 326-31.
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  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.
• Karp, J. F. (2012). Pain medicine fellows need explicit training in engaging patients in patient-centered pain management. Pain medicine (Malden, Mass.), 13(8), 985-6.
• Karp, J. F., & Whyte, E. M. (2012). Depression treatment for patients with complex conditions. JAMA, 308(9), 860-1; author reply 861.
• Karp, J. F., Rollman, B. L., Reynolds, C. F., Morse, J. Q., Lotrich, F., Mazumdar, S., Morone, N., & Weiner, D. K. (2012). Addressing both depression and pain in late life: the methodology of the ADAPT study. Pain medicine (Malden, Mass.), 13(3), 405-18.
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  To describe the methodology of the first NIH-funded clinical trial for seniors with comorbid depression and chronic low back pain.
• Reynolds, C. F., Butters, M. A., Lopez, O., Pollock, B. G., Dew, M. A., Mulsant, B. H., Lenze, E. J., Holm, M., Rogers, J. C., Mazumdar, S., Houck, P. R., Begley, A., Anderson, S., Karp, J. F., Miller, M. D., Whyte, E. M., Stack, J., Gildengers, A., Szanto, K., , Bensasi, S., et al. (2011). 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. Archives of general psychiatry, 68(1), 51-60.
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  Cognitive impairment in late-life depression is a core feature of the illness.
• Greenlee, A., Karp, J. F., Dew, M. A., Houck, P., Andreescu, C., & Reynolds, C. F. (2010). Anxiety impairs depression remission in partial responders during extended treatment in late-life. Depression and anxiety, 27(5), 451-6.
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  More than half of older adults with major depressive disorder require extended treatment because of incomplete response during acute treatment. This study characterizes the effect of anxiety on remission during extended treatment for partial responders.
• Karp, J. F., Weiner, D. K., Dew, M. A., Begley, A., Miller, M. D., & Reynolds, C. F. (2010). Duloxetine and care management treatment of older adults with comorbid major depressive disorder and chronic low back pain: results of an open-label pilot study. International journal of geriatric psychiatry, 25(6), 633-42.
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  In older adults, major depressive disorder (MDD) and chronic low back pain (CLBP) are common and mutually exacerbating. We predicted that duloxetine pharmacotherapy and Depression and Pain Care Management (DPCM) would result in (1) significant improvement in MDD and CLBP and (2) significant improvements in health-related quality of life, anxiety, disability, self-efficacy, and sleep quality.
• Martire, L. M., Schulz, R., Reynolds, C. F., Karp, J. F., Gildengers, A. G., & Whyte, E. M. (2010). Treatment of late-life depression alleviates caregiver burden. Journal of the American Geriatrics Society, 58(1), 23-9.
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  To describe the burden experienced by family caregivers of older adults with depression and to examine the positive effects on caregivers of treating late-life depression.
• Morone, N. E., Weiner, D. K., Belnap, B. H., Karp, J. F., Mazumdar, S., Houck, P. R., He, F., & Rollman, B. L. (2010). The impact of pain and depression on recovery after coronary artery bypass grafting. Psychosomatic medicine, 72(7), 620-5.
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  To describe the relationship between pain and depression on recovery after coronary artery bypass grafting (CABG).
• Reynolds, C. F., Dew, M. A., Martire, L. M., Miller, M. D., Cyranowski, J. M., Lenze, E., Whyte, E. M., Mulsant, B. H., Pollock, B. G., Karp, J. F., Gildengers, A., Szanto, K., Dombrovski, A. Y., Andreescu, C., Butters, M. A., Morse, J. Q., Houck, P. R., Bensasi, S., Mazumdar, S., , Stack, J. A., et al. (2010). Treating depression to remission in older adults: a controlled evaluation of combined escitalopram with interpersonal psychotherapy versus escitalopram with depression care management. International journal of geriatric psychiatry, 25(11), 1134-41.
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  More than half of the older adults respond only partially to first-line antidepressant pharmacotherapy. Our objective was to test the hypothesis that a depression-specific psychotherapy, Interpersonal Psychotherapy (IPT), when used adjunctively with escitalopram, would lead to a higher rate of remission and faster resolution of symptoms in partial responders than escitalopram with depression care management (DCM).
• Sriwattanakomen, R., McPherron, J., Chatman, J., Morse, J. Q., Martire, L. M., Karp, J. F., Houck, P. R., Bensasi, S., Houle, J., Stack, J. A., Woods, M., Block, B., Thomas, S. B., Quinn, S., & Reynolds, C. F. (2010). A comparison of the frequencies of risk factors for depression in older black and white participants in a study of indicated prevention. International psychogeriatrics, 22(8), 1240-7.
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  To compare the frequencies of risk factors, we describe risks for depression as a function of race among consecutively admitted participants in a randomized clinical trial of indicated depression prevention in later life.
• Goldstein, B. I., Houck, P. R., & Karp, J. F. (2009). Factors associated with pain interference in an epidemiologic sample of adults with bipolar I disorder. Journal of affective disorders, 117(3), 151-6.
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  Epidemiologic studies have found that major depressive disorder (MDD) and anxiety disorders are associated with pain. However, little is known regarding the prevalence and correlates of pain in bipolar I disorder (BD).
• Karp, J. F., & Meeks, T. W. (2009). Psychiatric aspects of nonpsychiatric disorders in older adults. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 17(4), 265-8.
• Karp, J. F., Skidmore, E., Lotz, M., Lenze, E., Dew, M. A., & Reynolds, C. F. (2009). Use of the late-life function and disability instrument to assess disability in major depression. Journal of the American Geriatrics Society, 57(9), 1612-9.
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  To determine whether there was greater disability in subjects with depression than in those without, the correlation between disability and depression severity and quality of life, and whether improvement in disability after antidepressant pharmacotherapy was greater in those who responded to antidepressant treatment.
• Porensky, E. K., Dew, M. A., Karp, J. F., Skidmore, E., Rollman, B. L., Shear, M. K., & Lenze, E. J. (2009). The burden of late-life generalized anxiety disorder: effects on disability, health-related quality of life, and healthcare utilization. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 17(6), 473-82.
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  To describe the burden of Generalized Anxiety Disorder (GAD), a common anxiety disorder in older adults.
• Teh, C. F., Karp, J. F., Kleinman, A., Reynolds Iii, C. F., Weiner, D. K., & Cleary, P. D. (2009). Older people's experiences of patient-centered treatment for chronic pain: a qualitative study. Pain medicine (Malden, Mass.), 10(3), 521-30.
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  Older adults with chronic pain who seek treatment often are in a health care environment that emphasizes patient-directed care, a change from the patriarchal model of care to which many older adults are accustomed.
• Teh, C. F., Morone, N. E., Karp, J. F., Belnap, B. H., Zhu, F., Weiner, D. K., & Rollman, B. L. (2009). Pain interference impacts response to treatment for anxiety disorders. Depression and anxiety, 26(3), 222-8.
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  Anxiety disorders and pain are commonly comorbid, though little is known about the effect of pain on the course and treatment of anxiety.
• Karp, J. F., Whyte, E. M., Lenze, E. J., Dew, M. A., Begley, A., Miller, M. D., & Reynolds, C. F. (2008). Rescue pharmacotherapy with duloxetine for selective serotonin reuptake inhibitor nonresponders in late-life depression: outcome and tolerability. The Journal of clinical psychiatry, 69(3), 457-63.
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  Up to 50% of depressed older adults either do not adequately respond to or are unable to tolerate treatment with a serotonin-specific reuptake inhibitor. On the basis of previous experience with serotonin-norepinephrine reuptake inhibitors, we predicted at least a 50% response rate to open-label treatment with duloxetine in subjects who were resistant to treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram.
• Driscoll, H. C., Karp, J. F., Dew, M. A., & Reynolds, C. F. (2007). Getting better, getting well: understanding and managing partial and non-response to pharmacological treatment of non-psychotic major depression in old age. Drugs & aging, 24(10), 801-14.
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  In general, the pharmacological treatment of non-psychotic major depressive disorder in old age is only partially successful, with only approximately 50% of older depressed adults improving with initial antidepressant monotherapy. Many factors may predict a more difficult-to-treat depression, including coexisting anxiety, low self-esteem, poor sleep and a high coexisting medical burden. Being aware of these and other predictors of a difficult-to-treat depression gives the clinician more reasonable expectations about a patient's likely treatment course. If an initial antidepressant trial fails, the clinician has two pharmacological options: switch or augment/combine antidepressant therapies. About 50% of patients who do not improve after initial antidepressant therapy will respond to either strategy. Switching has several advantages including fewer adverse effects, improved treatment adherence and reduced expense. However, as a general guideline, if patients are partial responders at 6 weeks, they will likely be full responders by 12 weeks. Thus, changing medication is not indicated in this context. However, if patients are partial responders at 12 weeks, switching to a new agent is advised. If the clinician treats vigorously and if the patient and clinician persevere, up to 90% of older depressed patients will respond to pharmacological treatment. Furthermore, electroconvulsive therapy is a safe and effective non-pharmacological strategy for non-psychotic major depression that fails to respond to pharmacotherapy. Getting well and staying well is the goal; thus, clinicians should treat to remission, not merely to response. Subsequently, maintenance treatment with the same regimen that has been successful in relieving the depression strongly improves the patient's chances of remaining depression free.
• Saghafi, R., Brown, C., Butters, M. A., Cyranowski, J., Dew, M. A., Frank, E., Gildengers, A., Karp, J. F., Lenze, E. J., Lotrich, F., Martire, L., Mazumdar, S., Miller, M. D., Mulsant, B. H., Weber, E., Whyte, E., Morse, J., Stack, J., Houck, P. R., , Bensasi, S., et al. (2007). Predicting 6-week treatment response to escitalopram pharmacotherapy in late-life major depressive disorder. International journal of geriatric psychiatry, 22(11), 1141-6.
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  Approximately half of older patients treated for major depressive disorder (MDD) do not achieve symptomatic remission and functional recovery with first-line pharmacotherapy. This study aims to characterize sociodemographic, clinical, and neuropsychologic correlates of full, partial, and non-response to escitalopram monotherapy of unipolar MDD in later life.
• Shega, J., Emanuel, L., Vargish, L., Levine, S. K., Bursch, H., Herr, K., Karp, J. F., & Weiner, D. K. (2007). Pain in persons with dementia: complex, common, and challenging. The journal of pain, 8(5), 373-8.
• Blank, S., Lenze, E. J., Mulsant, B. H., Dew, M. A., Karp, J. F., Shear, M. K., Houck, P. R., Miller, M. D., Pollock, B. G., Tracey, B., & Reynolds, C. F. (2006). Outcomes of late-life anxiety disorders during 32 weeks of citalopram treatment. The Journal of clinical psychiatry, 67(3), 468-72.
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  Anxiety disorders are common in later life, but little is known about the long-term benefits and risks of pharmacotherapy.
• DeLuca, A. K., Lenze, E. J., Mulsant, B. H., Butters, M. A., Karp, J. F., Dew, M. A., Pollock, B. G., Shear, M. K., Houck, P. R., & Reynolds, C. F. (2005). Comorbid anxiety disorder in late life depression: association with memory decline over four years. International journal of geriatric psychiatry, 20(9), 848-54.
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  In elderly persons with Major Depressive Disorder (MDD), coexisting Generalized Anxiety Disorder (GAD) or Panic Disorder (PD) is associated with more severe symptoms and poorer short-term treatment outcomes. The purpose of this study was to determine whether comorbid GAD or PD was associated with poorer long-term outcomes of late-life MDD, in terms of symptoms, functional disability, and cognitive status.
• Drayer, R. A., Mulsant, B. H., Lenze, E. J., Rollman, B. L., Dew, M. A., Kelleher, K., Karp, J. F., Begley, A., Schulberg, H. C., & Reynolds, C. F. (2005). Somatic symptoms of depression in elderly patients with medical comorbidities. International journal of geriatric psychiatry, 20(10), 973-82.
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  Somatic symptoms of depression such as fatigue create a diagnostic dilemma when assessing an older patient with medical comorbidities, since chronic medical illnesses may produce similar symptoms. Alternatively, somatic symptoms attributed to medical illness may actually be caused by depression. These analyses were designed to determine if somatic symptoms in older patients are more strongly associated with chronic physical problems or with depression.
• Karp, J. F., Scott, J., Houck, P., Reynolds, C. F., Kupfer, D. J., & Frank, E. (2005). Pain predicts longer time to remission during treatment of recurrent depression. The Journal of clinical psychiatry, 66(5), 591-7.
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  Pain and depression are mutually exacerbating. We know that both of these syndromes predict the future occurrence of the other. It has not been shown, however, whether the presence of pain slows the effect of treatment for depression. We hypothesized that greater pain and somatic scores prior to treatment with imipramine and interpersonal psychotherapy would predict a slowed time to remission from depression.
• Karp, J. F., Weiner, D., Seligman, K., Butters, M., Miller, M., Frank, E., Stack, J., Mulsant, B. H., Pollock, B., Dew, M. A., Kupfer, D. J., & Reynolds, C. F. (2005). Body pain and treatment response in late-life depression. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 13(3), 188-94.
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  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.
• Lenze, E. J., Karp, J. F., Mulsant, B. H., Blank, S., Shear, M. K., Houck, P. R., & Reynolds, C. F. (2005). Somatic symptoms in late-life anxiety: treatment issues. Journal of geriatric psychiatry and neurology, 18(2), 89-96.
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  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.
• Karp, J. F. (2004). Venlafaxine XR and chronic pelvic pain syndrome. The Journal of clinical psychiatry, 65(6), 880-1.
• Karp, J. F., Buysse, D. J., Houck, P. R., Cherry, C., Kupfer, D. J., & Frank, E. (2004). Relationship of variability in residual symptoms with recurrence of major depressive disorder during maintenance treatment. The American journal of psychiatry, 161(10), 1877-84.
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  To investigate how residual symptoms from an index episode of major depressive disorder may be associated with recurrence, the authors conducted a trial involving four maintenance treatment approaches and examined 1) whether the level and variability of residual symptoms differed among the maintenance treatment conditions and 2) whether greater symptom variability is associated with a higher likelihood of recurrence and more rapid recurrence.
• Mulsant, B. H., Whyte, E., Lenze, E. J., Lotrich, F., Karp, J. F., Pollock, B. G., & Reynolds, C. F. (2003). Achieving long-term optimal outcomes in geriatric depression and anxiety. CNS spectrums, 8(12 Suppl 3), 27-34.
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  Depression and anxiety disorders are very common in the elderly. Data accumulated over the past 2 decades have shown that most older patients can tolerate and respond to acute treatment with serotonergic antidepressants, other psychotropic agents, or manual-based psychotherapy. However, outcomes under usual-care conditions remain poor. This review proposes that clinicians may significantly improve the long-term outcomes of their older patients with depression and anxiety by focusing on four key factors: (1) identification and treatment of comorbid conditions; (2) full remission of acute symptoms; (3) education of patients, families, and professional colleagues about the need for long-term treatment; and (4) prevention and management of medication side-effects.