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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.


Evidence-Based Approaches to Depression and Its Physical Symptoms: Part I


GOAL
To provide primary care physicians with an update on the most current thinking regarding the treatment of depression and its physical symptoms.

TARGET AUDIENCE
This activity is designed for primary care physicians. No prerequisites required.

LEARNING OBJECTIVES
The Johns Hopkins University School of Medicine takes responsibility for the content,
quality, and scientific integrity of this CME activity. At the conclusion of this activity,
participants should be able to:

  • Understand the relationship between emotional and physical symptoms in the depressed patient.
  • Identify the available medications used for depression and major depressive disorder.
  • Evaluate existing data in the treatment of depression and its physical symptoms.
  • Describe the symptoms associated with major depressive disorder.
     

ACCREDITATION STATEMENT
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to sponsor continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for
a maximum of 2 category 1 credits toward the AMA Physician's Recognition Award.
Each physician should claim only those credits that he/she actually spent in the activity.

The estimated time to complete this educational activity: 2 hours.

Release date: December 15, 2003. Expiration date: December 15, 2005.

DISCLAIMER STATEMENT
The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of Johns Hopkins University School of Medicine name implies review
of educational format design and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an unrestricted educational grant from Eli Lilly and Company.

Advanced Studies in Medicine (ISSN-1530-3004) is published by Galen Publishing, a division of Advanced Studies in Medicine, an HMG Company. PO Box 340, Somerville, NJ 08876. (908) 253-9001. Copyright ©2003 by Galen Publishing. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. Advanced Studies in Medicine is a registered trademark of The Healthcare Media Group, LLC.

Full Disclosure Policy Affecting CME Activities:
As a sponsor accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Director and Participating Faculty reported the following:

PROGRAM DIRECTOR

    John A. Flynn, MD
    Associate Professor
    Department of Medicine
    Johns Hopkins University School of Medicine
    Baltimore, Maryland
    Dr Flynn reports having no financial or
    advisory relationships with corporate
    organizations related to this activity.


    Thomas W. Koenig, MD
    Assistant Professor
    Department of Psychiatry and
    Behavioral Sciences
    Johns Hopkins University School of Medicine
    Baltimore, Maryland
    Dr Koenig reports having no financial or
    advisory relationships with corporate
    organizations related to this activity.

PARTICIPATING FACULTY

    J. Sloan Manning, MD
    Associate Professor
    Department of Family Medicine
    Associate Professor
    College of Nursing
    University of Tennessee
    Memphis, Tennessee
    • Dr Manning reports serving as a consultant to and receiving honoraria from Eli Lilly and Company.

    Charles B. Nemeroff, MD, PhD
    Reunette W. Harris Professor and Chair
    Department of Psychiatry and
    Behavioral Sciences
    Emory University School of Medicine
    Atlanta, Georgia
    Dr Nemeroff reports receiving grant and/or research support from Abbott Laboratories, American Foundation for Suicide Prevention, AstraZeneca LP, Bristol-Myers Squibb Company, Eli Lilly and Company, Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, Merck & Co, Inc, National Alliance for Research on Schizophrenia and Depression, National Institutes for Mental Health, Pfizer, Inc, Stanley Foundation/National Alliance for the Mentally Ill, and Wyeth; serving as a consultant to Abbott Laboratories, Acadia Pharmaceuticals, AstraZeneca LP, Bristol-Myers Squibb Company, Corcept Therapeutics Inc, Cypress Biosciences Inc, Cyberonics, Eli Lilly and Company, Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, Merck & Co, Inc, Neurocrine Biosciences, Novartis Corporation, Organon, Otsuka America Pharmaceutical, Inc, Sanofi-Synthelabo Inc, Scirex, Somerset Pharmaceuticals, and Wyeth; serving on the speakers+ bureau for Abbott Laboratories, AstraZeneca LP, Bristol-Myers Squibb Company, Eli Lilly and Company, Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, Organon, Otsuka America Pharmaceutical, Inc, Pfizer, Inc, and Wyeth; and serving on the Board of Directors for the American Foundation for Suicide Prevention, Cypress Biosciences Inc, the George West Mental Health Foundation, NovaDel Pharma Inc, and the Heinz C. Prechter Fund for Manic Depression.
    Dr Nemeroff also holds stock in Corcept Therapeutics Inc and Neurocrine Biosciences; and holds the patent for the method and devices for transdermal delivery of lithium (US 6 375 990 B1) and the method to estimate serotonin and norepinephrine transporter occupancy after drug treatment using patient or animal serum (provisional filing April 2001).

Notice:
In accordance with the ACCME Standards for Commercial Support, the audience is advised that one or more articles in this continuing medical education activity may contain reference(s) to unlabeled or unapproved uses of drugs or devices.

Faculty have indicated that they have not referenced unlabeled/unapproved uses of drugs or devices.

Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

Evidence-Based Approaches to Depression and Its Physical Symptoms
John A. Flynn, MD,* and Thomas W. Koenig, MD†

Depression and anxiety are claiming greater attention in recent years, in part because of public awareness campaigns to reduce the stigma and to increase awareness that these are often treatable conditions. Currently, depression is one of the most common psychiatric illnesses treated in primary care.1 It is not only common, but also debilitating. In the US National Comorbidity Survey (a nationally representative household survey of more than 8000 persons aged 15 to 54 years), Kessler et al found that 10% of the surveyed population who had major depression suffered from work impairment for 6 or more days in the previous month, and 22.5% of those with major depression indicated severe social impairment.2 In another similar survey, the Midlife Development in the United States Survey (a nationally representative survey of more than 3000 adults aged 25 to 74 years), those results were 13.1% and 17.2%, respectively.2 A cross-sectional study of primary care facilities (nearly 26 000 patients) in 14 countries found that of patients suffering from depression, 48% had moderate-to-severe occupational dysfunction, and 58% reported physical disability. The results were consistent across measures of disability and across centers (and therefore cultures).3

As a result of its high prevalence, primary care physicians (PCPs) have frequent visits from patients with depression. Significant healthcare resources are used, not only in terms of office visits, but also laboratory tests, imaging modalities, and referrals to specialists. The causes of these mounting healthcare costs are multifactorial, involving both the patient and physician.

The physical symptoms of depression are also gaining greater recognition and appreciation as a common and an important part of depressive symptomatology. Physical symptoms are often some of the first signs of a depressive illness, are not often attributed to depression by the patient or clinician, and are frequently untreated or undertreated. Many primary care patients have been ill for a long time before seeing their physicians. Typically, they have either accepted their symptoms (emotional and/or somatic) as a part of life, or, if the connection between a physical symptom and depressed mood is made, the patient may feel ashamed for being depressed. Some patients feel more comfortable discussing their physical rather than their emotional symptoms; some patients never connect the physical and emotional symptoms. The PCP, therefore, must know what questions to ask patients in order to draw out the depressive symptoms that are not clearly evident on presentation.

Despite its high prevalence, a significant number of PCPs do not feel comfortable diagnosing or treating depressive illness. PCPs may also overlook physical symptoms, or conversely, may spend precious time and resources searching for a physical cause for the somatic symptoms of a depressive illness.

Often, remission from depression in clinical studies is defined as achieving a score of less than 7 on the Hamilton Depression Rating Scale (HAM-D). Although the HAM-D considers some somatic symptoms, these symptoms are not the prominent features being evaluated. Therefore, remission may not necessarily imply an asymptomatic state if somatic symptoms, quality of life, and psychosocial functioning are not considered. For most patients, depression is a recurring, chronic condition, and patients may remain symptomatic (emotionally or somatically) between episodes.

How does the PCP distinguish the physical symptoms of depression from those of another cause? This issue of Advanced Studies in Medicine (ASiM) focuses on the presentation and treatment of the physical symptoms of depression in primary care, the most common of which is pain. We offer 3 interviews with leading clinicians on this subject, and each presents a case study discussing different challenges associated with this disorder in a primary care setting. We also offer a review article on one of the newest antidepressants, duloxetine, and the clinical results of 6 published studies of this agent in depressed patients.

As a rheumatologist with extensive experience in treating psychiatric disorders associated with painful conditions in primary care, Dr Flynn discusses the clinical aspects of diagnosing depression in the presence of physical symptoms and the challenges faced by PCPs given their current understanding of depression. This interview and case study also underscore the importance of the PCP being alert for the possibility of an underlying psychological disorder in patients with multiple vague somatic symptoms.

Dr J. Sloan Manning is a PCP with a long-held passionate interest in the fusion of primary care and mental health. With his experience in teaching family physicians about diagnosing and managing depression, Dr Manning offers practical information on this disorder, particularly in terms of the challenges faced by PCPs-time, managed care constraints, and patient education. Dr Manning also discusses the problem of undertreatment and how it can be too easily accepted by both patients and physicians. Controlled studies show that symptom remission rates for depression are typically less than 50%, and 35% of patients in primary care discontinue treatment within the first month.4-6

Another important aspect is the role of the psychiatrist in managing depression, even in primary care. Psychiatrists have a critical role to play in complementing treatment of depression by PCPs. Dr Manning describes his experience in working with psychiatrists for consultation regarding specific patients and as a -mentoring+ relationship to learn more about depression. To illustrate, a randomized, controlled study of primary care patients with depression showed that those who received antidepressant medication with increased intensity and frequency of visits over the first 4 to 6 weeks of treatment improved their medication adherence at 90 days from 50% to 75%. The follow-up program consisted of visits 1 and 3 with a PCP and visits 2 and 4 with a psychiatrist.7

The traditional medications for treating depression have been tricyclic antidepressants (TCAs), which have largely (but not completely) been replaced by selective serotonin reuptake inhibitors (SSRIs). TCAs are very effective medications for depression, but the side effects are often considered unacceptable by patients. SSRIs offer a much improved safety profile, similar efficacy compared with TCAs, and the added benefit of almost no risk with overdose. As their name implies, SSRIs affect almost exclusively the serotonergic systems, while TCAs affect both serotonergic and noradrenergic systems, along with other types of neurotransmitters and receptors. Both serotonin and norepinephrine are important constituents in the pathways of pain perception. It is not surprising, therefore, that TCAs also have analgesic properties for chronic pain syndromes. These analgesic properties appear to be independent of their antidepressant properties.8

A new class of drugs, dual-reuptake inhibitors, increase synaptic cleft concentrations of both serotonin and norepinephrine and have shown to be effective antidepressants. Because of their dual mode of action, they are also now under closer investigation to assess their efficacy in depressed patients with pain symptoms.

Up to one half of all patients with depressive illness will require some change in therapy-switching antidepressants, adding a second antidepressant, or augmenting current treatment with another nonantidepressant; these patients are more vulnerable to relapse, impairment, and even suicide, underscoring the need for aggressive early treatment. Dr Charles B. Nemeroff, a leading psychiatrist in the fields of affective and anxiety disorders, was also interviewed for this issue of ASiM. In 2001, Dr Nemeroff participated in a roundtable meeting of experts on partial response and nonresponse to antidepressant therapy. The committee concluded, in their published review, that -simultaneous targeting of both the noradrenergic and serotonergic systems is the most effective strategy.9 Importantly, the ongoing Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study funded by the National Institutes of Mental Health will hopefully provide insight into appropriate strategies if patients fail initial treatment.10
In his interview, Dr Nemeroff discusses the psychopharmacology behind dual-reuptake inhibitors, the role of psychiatrists in managing depression in primary care, and the obstacles to including psychiatry in this treatment paradigm. As with PCPs, the barriers are many, including managed care issues, professional relationships between psychiatrists and PCPs, and patients+ reluctance to consult a psychiatrist because of the associated stigma, the perceived lack of seriousness of their problem, or healthcare insurance coverage limitations.

The case studies and interviews will highlight the issues surrounding the diagnosis and management of depression in primary care and offer ideas for overcoming the myriad barriers, so that remission rates can be improved beyond the unacceptable.
 

REFERENCES
1. Sartorius N, Ustun TB, Lecrubier Y, Wittchen HU. Depression comorbid with anxiety: results from the WHO study on psychological disorders in primary health care.
Br J Psychiatry Suppl. 1996;(30):38-43.
2. Kessler RC, DuPont RL, Berglund P, Wittchen HU. Impairment in pure and comorbid generalized anxiety disorder and major depression at 12 months in two national surveys. Am J Psychiatry. 1999;156(12):1915-1923.
3. Ormel J, VonKorff M, Ustun TB, Pini S, Korten A, Oldehinkel T. Common mental disorders and disability across cultures. Results from the WHO Collaborative Study on Psychological Problems in General Health Care. JAMA. 1994;272(22):1741-1748.
4. Entsuah AR, Huang H, Thase ME. Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo. J Clin Psychiatry. 2001;62(11):869-877.
5. Thase ME, Entsuah AR, Rudolph RL. Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry. 2001;178:234-241.
6. Simon GE, VonKorff M, Wagner EH, Barlow W. Patterns of antidepressant use in community practice. Gen Hosp Psychiatry. 1993;15(6):399-408.
7. Katon W, Von Korff M, Lin E, et al. Collaborative management to achieve treatment guidelines. Impact on depression in primary care. JAMA. 1995;273(13):1026-1031.
8. Sawynok J, Esser MJ, Reid AR. Antidepressants as analgesics: an overview of central and peripheral mechanisms of action. J Psychiatry Neurosci. 2001;26(1):21-29.
9. Hirschfeld RM, Mongtomery SA, Aguglia E, et al. Partial response and nonresponse to antidepressant therapy: current approaches and treatment options. J Clin Psychiatry. 2002;63(9):826-837.
10. Fava M, Rush AJ, Trivedi MH, et al. Background and rationale for the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Psychiatr Clin North Am. 2003;26(2):457-494.


*Associate Professor, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
áAssistant Professor, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.





Johns Hopkins Advanced Studies in Medicine (ISSN-1558-0334), is published by Galen Publishing, LLC, d/b/a ASiM, PO Box 340, Somerville, NJ 08876. (908) 253-9001. Copyright ©2012 by Galen Publishing. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. ASiM is a registered trademark of The Healthcare Media Group, LLC.