Correspondence
Managing Depression in Outpatients
N Engl J Med 2001; 344:1251-1253April 19, 2001
- Article
To the Editor:
An important point in Whooley and Simon's review article on managing depression in outpatients (Dec. 28 issue)1 that needs greater emphasis is the differential diagnosis of depressive and bipolar disorders. Although most patients will truthfully admit to having had a manic episode if they are asked directly, few patients, in my experience, volunteer this information. A history of hypomania is not volunteered simply because having had periods of feeling very upbeat, having lots of energy, accomplishing a great deal, and needing less sleep than usual is unlikely to be viewed as evidence of illness. And yet bipolar II disorder is quite common, with a prevalence estimated at 1 in 200 or higher.2,3
I strongly recommend that every patient being evaluated for depression be asked two simple questions: “What are you like when you are well?” And “Have there ever been periods in your life when you seemed not to need much sleep, you got a lot of things done, and you were really energetic and upbeat?” Alternatively, the Mood Disorder Questionnaire is a simple, valid, and reliable instrument.4
Why look for bipolar II disorder? First, it is an inherently life-threatening condition. Patients with the disorder are more likely to attempt suicide than are patients with a depressive disorder or bipolar I disorder, and they are more likely to abuse substances.3 Second, it is a condition we can easily, if inadvertently, exacerbate. Whereas neglecting to treat unipolar depression prolongs unnecessary suffering, mistreating bipolar depression with antidepressant monotherapy is dangerous: it increases the risk of mania, hypomania, and cycle acceleration.5
5 ReferencesAnn-Marie Paley, M.D.
110-11 Queens Blvd., Forest Hills, NY 113751
Whooley MA ,Simon GE . Managing depression in medical outpatients. N Engl J Med 2000;343:1942-1950
Full Text | Web of Science | Medline2
Diagnostic and statistical manual of mental disorders. 4th ed. Washington, D.C.: American Psychiatric Association, 1994.
3
Angst J . The emerging epidemiology of hypomania and bipolar II disorder. J Affect Disord 1998;50:143-151
CrossRef | Web of Science | Medline4
The Mood Disorder Questionnaire. Galveston: The University of Texas Medical Branch, 2000.
5
Post RM ,Denicoff KD ,Keverich G , et al. Drug-induced switching in bi-polar disorder: epidemiology and therapeutic implications. CNS Drugs 1997;8:352-365
CrossRef | Web of Science
To the Editor:
Whooley and Simon conclude that for cases of mild depression, Hypericum perforatum (St. John's wort), an herbal remedy marketed as a dietary supplement, appears to be as effective as low-dose tricyclic antidepressants, and that “side effects are infrequent.” The use of St. John's wort has increased sharply in the United States1 and in Europe.2 Given the tendency to regard remedial herbal extracts as harmless, it is essential to be aware of the potential interactions between hypericum and various drugs. At least eight reported cases have suggested that hypericum extracts are potent inducers of hepatic enzymes. These reports are supported by strong evidence that hypericum activates hepatic cytochrome P-450, roughly doubling its metabolic activity.2 More specifically, hypericum may alter serum concentrations of commonly used drugs, such as warfarin, digoxin,3 and theophylline.4 The concomitant use of hypericum in patients being treated with serotonin-reuptake–inhibiting antidepressants (e.g., paroxetine and sertraline) has been reported to result in symptoms characteristic of the serotonin syndrome, a potentially life-threatening condition caused by excess cerebral serotonin.5 Thus, it is necessary to be aware of potential interactions with hypericum and to recognize the importance of reporting such interactions when they occur.
5 ReferencesRaz Gross, M.D.
Columbia University, New York, NY 100321
Gaster B ,Holroyd J . St John's wort for depression: a systematic review. Arch Intern Med 2000;160:152-156
CrossRef | Web of Science | Medline2
Ernst E . Second thoughts about safety of St John's wort. Lancet 1999;354:2014-2016
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Johne A ,Brockmoller J ,Bauer S ,Maurer A ,Langheinrich M ,Roots I . Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum). Clin Pharmacol Ther 1999;66:338-345
CrossRef | Web of Science | Medline4
Nebel A ,Schneider BJ ,Bake RK ,Kroll DJ . Potential metabolic interaction between St John's wort and theophylline. Ann Pharmacother 1999;33:502-502
CrossRef | Web of Science | Medline5
Fugh-Berman A . Herb-drug interactions. Lancet 2000;355:134-138[Erratum, Lancet 2000;355:1020.]
CrossRef | Web of Science | Medline
To the Editor:
Drs. Whooley and Simon state that “beta-blockers do not cause depression” and cite a study by Gerstman and colleagues.1 Although beta-blockers may not significantly increase the incidence of depression in the general population, the study by Gerstman et al. does not answer the question of whether beta-blockers increase its incidence among patients with previous episodes of major depression, or whether these drugs should be discontinued if depression develops. We are concerned that some physicians may assume that beta-blockers have been proved safe for patients with previous or ongoing major depression.
1 ReferencesSheldon E. Greisman, M.D.
University of Maryland School of Medicine, Baltimore, MD 21201Lisa A. Greisman, M.D.
University of Virginia Health System, Charlottesville, VA 229081
Gerstman BB ,Jolson HM ,Bauer M ,Cho P ,Livingston JM ,Platt R . The incidence of depression in new users of beta-blockers and selected antihypertensives. J Clin Epidemiol 1996;49:809-815
CrossRef | Web of Science | Medline
To the Editor:
I would like to call your attention to a mistake in the review by Whooley and Simon. Table 4 on page 1946 lists the antidepressant doxepin (Sinequan) as approved by the Food and Drug Administration (FDA) for alcoholism as well as for depression. In fact, one of the FDA-approved indications for doxepin is “depression and/or anxiety associated with alcoholism” — not alcoholism itself. Readers should not think that doxepin is an effective treatment for alcoholism itself.
David A. Gorelick, M.D., Ph.D.
National Institute on Drug Abuse, Baltimore, MD 21224To the Editor:
Whooley and Simon's review article on depression made me depressed. Considering depression entirely within a medical model, as one might consider, say, nephritis, sets a low standard of care. Often the most useful thing physicians can offer to a depressed patient is their caring interest. This is best indicated not only by talking and counseling, but especially by listening to the patient. In every case of depression, it is necessary to at least broach the question of what is troubling the patient. Any subsequent therapy or referral is much more likely to be successful in the context of a doctor–patient relationship in which the doctor listens to the patient.
Lawrence D. Blum, M.D.
2400 Chestnut St., Suite 2810, Philadelphia, PA 19103To the Editor:
Whooley and Simon's review did not focus on depression in patients with coexisting chronic physical illness. It may be difficult to diagnose depression in patients with symptoms of chronic illness, such as fatigue or anorexia. In such cases, the cognitive symptoms of depression, such as anhedonia, hopelessness, and a wish to die, gain relative importance in the diagnostic process. Medical staff may view depression as an expected reaction to chronic illness, which may account for the low rates of detection of depression in patients with chronic illness.1 Randomized, controlled trials have demonstrated that antidepressant medications are effective in patients with many types of chronic illnesses.2 Most physically ill patients do not tolerate the side effects of tricyclic antidepressants, so the selective serotonin-reuptake inhibitors or other, newer antidepressants should be considered the first-line drugs for such patients.3 Drug interactions may be of less concern if citalopram or venlafaxine is used to treat depressed patients taking multiple medications.
3 ReferencesJ. Robert Swenson, M.D.
Ottawa Hospital, Ottawa, ON K1H 8L6, Canada1
Perez-Stable EJ ,Miranda J ,Munoz RF ,Ying YW . Depression in medical outpatients: underrecognition and misdiagnosis. Arch Intern Med 1990;150:1083-1088
CrossRef | Web of Science | Medline2
Gill D, Hatcher S. Antidepressants for depression in people with physical illness (Cochrane Review). In: The Cochrane Library. Issue 4. Oxford, England: Update Software, 2000.
3
Beliles K ,Stoudemire A . Psychopharmacologic treatment of depression in the medically ill. Psychosomatics 1998;39:S2-S19
Web of Science | Medline
To the Editor:
The experiences of women are noticeably absent from Whooley and Simon's review. The higher suicide rate among men is emphasized, but the incidence of depression is twice as high in women as in men,1 and although men commit more suicides, women make more suicide attempts. Clinicians need guidance on how to advise women who take antidepressants and want to become pregnant, on the safety ratings for antidepressants during pregnancy, and on the postpartum depression that follows 10 to 15 percent2 of all pregnancies.
Childhood sexual abuse is a powerful predictor of depression, particularly for women.3 Physicians treating outpatients with depression must ask about such painful past experiences. By neglecting to ask, physicians reinforce the secrecy, shame, and isolation frequently associated with such victimization.4
A broader issue illustrated by this article is the way in which women's experiences, both as patients and providers, become invisible if a sex-neutral approach is taken. Female primary care physicians see more female patients than do their male counterparts5 and thus see far more women with depression.
5 ReferencesMolly Carnes, M.D.
Gloria E. Sarto, M.D., Ph.D.
Kristen Springer, M.P.H.
University of Wisconsin, Madison, WI 537051
Kessler RC ,McGonagle KA ,Zhao S , et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Arch Gen Psychiatry 1994;51:8-19
CrossRef | Web of Science | Medline2
Llewellyn AM ,Stowe ZN ,Nemeroff CB . Depression during pregnancy and the puerperium. J Clin Psychiatry 1997;15:26-323
Weiss EL ,Longhurst JG ,Mazure CM . Childhood sexual abuse as a risk factor for depression in women: psychosocial and neurobiological correlates. Am J Psychiatry 1999;156:816-828
Web of Science | Medline4
Zupancic MK ,Kreidler MC . Shame and the fear of feeling. Perspect Psychiatr Care 1999;35:29-34
CrossRef | Web of Science | Medline5
McMurray JE ,Linzer M ,Konrad TR ,Douglas J ,Shugerman R ,Nelson K . The work lives of women physicians: results from the Physician Work Life Study. J Gen Intern Med 2000;15:372-380
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: We thank Dr. Carnes et al. for their comments regarding the higher incidence of depression in women, the use of antidepressant medications during pregnancy, the prevalence of postpartum depression, and the relation between childhood sexual abuse and the risk of depression. We regret that space constraints made discussion of these and other important issues beyond the scope of our paper, but we can refer readers to comprehensive reviews of these topics.1,2
We agree with Dr. Paley that patients should be asked about a history of mania (elevated mood, increased energy, and impulsivity) whenever a diagnosis of major depression is being considered. This history taking is especially important before one prescribes antidepressant medications, which can precipitate manic episodes in patients with bipolar disorders.
Dr. Gross highlights the potential side effects and drug interactions of H. perforatum (St. John's wort). We agree that herbal remedies should never be perceived as risk-free. Recent evidence does suggest that St. John's wort may lower the concentrations of certain drugs, such as warfarin, digoxin, theophylline, cyclosporine, oral contraceptives, and human immunodeficiency virus type 1 protease inhibitors.3 In addition, at least five cases of symptoms consistent with the serotonin syndrome have been reported in elderly patients taking H. perforatum with serotonin-reuptake inhibitors (e.g., sertraline and nefazodone).4
Drs. Greisman and Greisman express concern that our statement regarding beta-blockers may cause some providers to assume that beta-blockers have been proved safe for patients with a history of depression. Since there is no clear evidence that beta-blockers are unsafe in patients with a history of depression,5 we believe it is important not to withhold these medications from any patients who might otherwise benefit from therapy (especially those with heart disease). If depression occurs after the patient starts taking a beta-blocker, it is reasonable to explore potential causality by stopping the drug. However, unless discontinuation clearly alleviates depressive symptoms, concern about the potential contribution of the beta-blocker to depression should not prevent patients from taking it again.
We thank Dr. Gorelick for pointing out that doxepin is approved by the FDA for “depression and/or anxiety associated with alcoholism” and not for alcoholism itself.
We agree with Dr. Blum about the importance of health care providers' offering depressed patients their listening ears and caring interest. Such interventions can be particularly useful as the initial treatment for patients with mild depression and as adjunct therapy for patients with more severe depression.
As Dr. Swenson points out, the detection and treatment of depression are of particular importance in patients with chronic physical illness because depression worsens the prognosis associated with such medical illnesses as cardiovascular disease. We agree that selective serotonin-reuptake inhibitors may be better tolerated than tricyclic antidepressants in many patients and that some serotonin-reuptake inhibitors may slow the metabolism of other medications, but we would not specifically endorse citalopram or venlafaxine as preferred options.
5 ReferencesMary A. Whooley, M.D.
University of California, San Francisco, CA 94143Gregory E. Simon, M.D., M.P.H.
University of Washington, Seattle, WA 981011
Weissman MM ,Olfson M . Depression in women: implications for health care research. Science 1995;269:799-801
CrossRef | Web of Science | Medline2
Wisner KL ,Zarin DA ,Holmboe ES , et al. Risk-benefit decision making for treatment of depression during pregnancy. Am J Psychiatry 2000;157:1933-1940
CrossRef | Web of Science | Medline3
Drug interactions with St John's wort. Med Lett Drugs Ther 2000;42:56-56
Medline4
Lantz MS ,Buchalter E ,Giambanco V . St John's wort and antidepressant drug interactions in the elderly. J Geriatr Psychiatry Neurol 1999;12:7-10
CrossRef | Web of Science | Medline5
Long TD ,Kathol RG . Critical review of data supporting affective disorder caused by nonpsychotropic medication. Ann Clin Psychiatry 1993;5:259-270
CrossRef | Medline
- Citing Articles (1)
Citing Articles
1
Kristen W. Springer, Jennifer Sheridan, Daphne Kuo, Molly Carnes. (2003) The Long-term Health Outcomes of Childhood Abuse. An Overview and a Call to Action. Journal of General Internal Medicine 18:10, 864-870
CrossRef
