MEDICAL MALADIES
| DEPRESSION AND MEDICAL ILLNESS —Scott J. Crow, MD, Professor of Psychiatry, University of Minnesota,
Minneapolis, Medical School
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| Introduction: depression more common in medically ill than in well; lifetime prevalence in general population
8.4%, much higher in primary care clinics; some illnesses, eg, diabetes, myocardial infarction (MI), and cerebrovascular
accident (CVA), have very high rates of depression; ≈25% of people with diabetes have depression at
some point, 18% to 20% of those with MI, and up to 50% of those with CVA
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| Causes of depression in medical illness: people often say, “well, wouldn’t you be depressed too if you had this
kind of medical problem?” but that represents only one side of coin; evidence suggests that having depression increases
risk for getting certain medical illnesses
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 | Important factors: stress and loss increase risk for depression, and medical illness can represent both; iatrogenic
factors include aggressiveness of some treatment regimens (eg, implantable cardioverter defibrillators), and use
of medications (eg, β-blockers) known to cause depression; certain illnesses have direct mechanistic effect in
causing depression (eg, after CVA, depression not related to identifiable impairment but is related to location of
CVA, with left-sided cortical anterior strokes having highest risk for onset of depression soon after stroke)
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| Diagnosing depression in medical illness: difficult because symptoms of depression often same as those of medical
illness (eg, depressed mood, low energy, loss of interest, weight and/or appetite change, poor sleep, poor concentration,
irritability); depression most readily diagnosed based on cognitive symptoms; ask whether patient
enjoys things he or she usually enjoys (but not everything; medical illness may make some activities impossible),
whether he or she is looking forward to something (appropriate to situation; if patient has terminal illness, he or she
will not be looking forward to something 10 yr down road, but may eagerly anticipate something happening in
short term), and whether he or she has some degree of hopefulness; patient’s lack of hope or interest indicative of
depression
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| Does depression increase likelihood of getting certain medical illnesses? literature consistently says “yes”; in
studies, large health organizations performed certain medical measures on large number of people, then surveyed
them for depression or anxiety; patients followed for 10 to 15 yr to see whether they develop certain illnesses, eg,
hypertension or heart disease; results consistently show that those with depression but without, eg, hypertension
more likely to develop hypertension during extended follow-up; most data to date accumulated on hypertension
and heart disease and suggest that treating depression may reduce risk for them
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| In patients who already have medical illnesses, does treating depression improve outcomes? multiple studies
say “yes”; first study found that 15% to 18% of patients interviewed within 5 to 15 days after MI were depressed;
at 6-mo follow-up, their mortality rate 5 times greater than those without depression, and at 18 mo, 3.5
times greater; when reviewed for size and location of MI and New York Heart Association class, no groups distinguished,
suggesting that greatest risk factor for death was presence of depression
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| Medical illness other than heart disease: after heart disease, most data available for diabetes; in diabetics, having
depression associated with worsening glycemic control; some evidence, although “a little bit messy,” indicates that
having depression worsens outcomes after stroke, independent of location and size of lesion
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| Treatment in setting of medical illness: key to successful treatment for depression is to prepare patients adequately
(most patients not particularly well prepared); for example, provide information on duration of treatment,
advising patient that he or she probably will need antidepressants for long period, depending on his or her individual
factors; discontinuation of antidepressants “sky high” in patients with depression and medical illness, and rates
of discontinuation lower in patients educated adequately; be straightforward about possible adverse effects of medication;
shown that the earlier in course of medical illness patient seen by psychiatrist, the better the outcome; patients
seen early more likely to be compliant and to have remission of depression
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| Psychotherapy: beneficial to all patients with depression, but critical in treatment of patient with depression and
medical illness; although treatments for medical illnesses much more aggressive and stressful, support offered to
patient not increased, and psychotherapy can play important role in providing more support
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| Psychopharmacologic treatment: important in people with depression and medical illness; Enhancing Recovery
in Coronary Heart Disease (ENRICHD) trial enrolled >4000 people with depression and heart disease; initial
treatment psychotherapy, and if depression did not improve, antidepressant added, beginning with selective serotonin
reuptake inhibitor (SSRI), then moving on to other antidepressants, if necessary; group that remained depressed
but got no antidepressant did worse than groups that got any antidepressant; in groups that got
psychotherapy and antidepressant, likelihood of repeat MI or of death decreased by 40%
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| Duration of treatment: 1 yr minimum for most patients, longer if necessary; best predictor for recurrence of depression
is number of episodes of depression patient has had in past (if ≥2 episodes, risk for recurrence 90%) and
age of onset of depression (later onset increases risk)
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| Summary: depression occurs more frequently in medically ill people than in well; depression increases risk for
some medical illnesses; depression worsens outcome of some medical illnesses; treating depression may ameliorate
these risks
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| FIBROMYALGIA: EVALUATION AND TREATMENT —Lesley M. Arnold, MD, Associate Professor of Psychiatry,
University of Cincinnati College of Medicine, and Director, Women’s Health Research Program, Cincinnati
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| Introduction: although fibromyalgia recognized and called by many different names since at least 19th century, criteria
not developed until 1970s; current criteria developed by rheumatologists in 1990s; major criteria are 1)
chronic history of widespread pain present for at least 3 mo (widespread defined as pain “on right and left sides of
body and above and below waist, and axial skeletal pain”) and 2) pain on palpation at 11 of 18 tender points; all criteria
“works in progress,” and second major criterion controversial because “now it’s thought that there’s nothing
special or unique about” sites selected as tender points
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| Epidemiology: in United States, prevalence ≈2% of general population; ratio of women to men 6:1; prevalence increases
with age, and highest prevalence in women in 50s
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| Other symptoms: sex difference found in way symptoms reported, with women reporting more somatic symptoms,
including fatigue, sleep disturbance, irritable bowel syndrome, and “pain all over as if they had a flu syndrome”;
women also tend to be more sensitive to touch than men; multiple community-based studies found that about one
third of patients with fibromyalgia report current and/or past symptoms of depression and anxiety, history of treatment
for depression, and history of depression in family; in tertiary care settings, 62% to 71% of patients with fibromyalgia
reported lifetime history of depression
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| How do psychiatric symptoms affect patients with fibromyalgia? only incidence study done in Europe and
found that presence of self-assessed depression predicted onset of fibromyalgia; also, patients with comorbid depression/anxiety
and fibromyalgia “suffer a lot more,” report more physical symptoms, have greater overall ill
health, are more dissatisfied with their health, experience more interference from their pain, and have more life
stress; another study also found current and past depression associated with more physical symptoms; other studies
found that fibromyalgia patients with comorbid depression and anxiety had more disability related to their fibromyalgia
and that psychologic disturbance predicts persistent pain
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| Relationship between mood disorders and fibromyalgia: patients with fibromyalgia often reluctant to acknowledge
depression and anxiety because they do not want to be called “psychiatric,” but on questioning, “more often
than not, mood and anxiety disorders precede the development of fibromyalgia”
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| Overlap between characteristics of mood disorders and fibromyalgia: female predominance; sleep disorders;
fatigue; neuropsychiatric complaints; body aches and pains; gastrointestinal disturbances; headaches
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| Possible etiologic links: family studies suggest common heritable causal factors involved in fibromyalgia and in
mood and anxiety disorders; study underway looking at serotonin-receptor genes, because serotonin involved in
pain and mood; central monoaminergic neurotransmission involved in mood regulation and in descending pain
pathways; dysfunction of hypothalamic-pituitary-adrenal (HPA) axis may contribute to development of mood disorders
and fibromyalgia; chronic stress induces cytokine expression in brain, and cytokines may contribute to
symptoms of depression and to enhancement of pain; major classes of medications being studied include norepinephrine
and serotonin reuptake inhibitors and α2 δ ligands; tricyclic antidepressants have long history of being
used in pain disorders, and recent studies suggest their effect on pain independent of their effect on mood disorders;
some positive results using SSRIs, but results not as consistent as those using combined norepinephrine and serotonin
reuptake inhibitors
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| Tricyclic antidepressants: to date, most studied class of antidepressants in fibromyalgia; moderate overall efficacy
found; amitriptyline most common individual drug studied, but highest dose ≈50 mg, “which is a pretty low dose,”
but patients have difficulty tolerating higher dose; most consistently observed improvements related to sedative effects;
in early studies, no attempt to identify presence of comorbid psychiatric disorders, so their response to tricyclics
unknown; when psychiatric disorders present, assessment limited; no study identified predictors of response
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| Fluoxetine: earlier studies used very low doses (20 mg/day) and had negative results, so speaker’s group designed
small study that used flexible-dose design to investigate higher doses; at end of 12-wk trial, found significant improvement
in overall Fibromyalgia Impact Questionnaire (FIQ) scores and in pain scores
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| Other agents: citalopram—significant improvement in 1 secondary measure of pain and in depressive symptoms;
venlafaxine—significant improvement in all measures; mean dose 167 mg/day; duloxetine—women showed
more improvement than men, but number of men in trials small; significant reduction in pain severity and in interference
from pain; 60 mg/day seemed to work as well as 120 mg/day; milnacipran—≈37% of patients reported
50% reduction in pain (same as in duloxetine trials); twice-daily doses better tolerated than once-daily doses;
pregabalin—α2 δ ligand; similar to but more potent than gabapentin; thought to work by reducing calcium influx at
nerve terminals, thereby inhibiting release of neurotransmitters; has Food and Drug Administration (FDA) indication
for diabetic neuropathic pain and postherpetic neuralgia, now being studied for fibromyalgia; again, 30% of
patients reported 50% reduction in pain at high dose (450 mg/day); relative to duloxetine and milnacipran, tolerability
good for most patients
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| Nonpharmacologic treatment: exercise—recent study showed that 30 min/day of moderate-intensity exercise improves
mood (as well as many other aspects of health); aerobic exercise found beneficial in fibromyalgia; recommend
patient start below his or her capacity and gradually increase to goal of 30 min of moderate-intensity aerobic
exercise on most days; findings for strengthening and stretching not as consistent as those for moderate-intensity
aerobic exercise in patients with fibromyalgia; probably best for patients not to start yoga or Pilates until aerobic
capacity improved; to maximize benefits of exercise, recommend patient start with low-impact exercise (eg, walking),
then progress to other forms of exercise; acupuncture—studies using several controls for acupuncture consistently
found little or no separation of acupuncture groups from sham-acupuncture groups; however, if patients
derived comfort from acupuncture, no harm done
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Educational Objectives
| The goal of this program is to educate the listener about the relationship between depression and medical illness in
general, and between depression and fibromyalgia. After hearing and assimilating this program, the clinician will be
better able to:
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| 1. Explain the complex relationship between depression and medical illness.
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| 2. Formulate a treatment plan for patients who have depression and medical illness.
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| 3. Explore the controversy surrounding the current criteria for diagnosing fibromyalgia.
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| 4. Discuss the relationship between mood disorders and fibromyalgia.
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| 5. Discuss the treatment options for patients with fibromyalgia.
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Discussed on This Program
Amitriptyline hydrochloride [Elavil]
Citalopram hydrobromide [Celexa]
Duloxetine [Cymbalta]
Fluoxetine hydrochloride [Prozac, Sarafem]
Milnacipran [Ixel] (investigational)
Paroxetine hydrochloride [Paxil, Pexeva]
Pregabalin [Lyrica]
Venlafaxine hydrochloride [Effexor]
Suggested Reading
Aggarwal VR et al: The epidemiology of chronic syndromes that are frequently unexplained: do they have common
associated factors? Int J Epidemiol Nov 22, 2005; [Epub ahead of print]; Arnold LM et al: A double-blind,
multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major
depressive disorder. Arthritis Rheum 50:2974, 2004; Arnold LM et al: A randomized, double-blind, placebo-controlled
trial of duloxetine in the treatment of women with fibromyalgia with or without major depressive disorder.
Pain 119:5; 2005; Arnold LM et al: A randomized, placebo-controlled, double-blind, flexible-dose study of fluoxetine
in the treatment of women with fibromyalgia. Am J Med 112:191, 2002; Arnold LM et al: Family study of fibromyalgia.
Arthritis Rheum 50:944; 2004; Arnold LM, Keck PE Jr, Welge JA: Antidepressant treatment of
fibromyalgia. A meta-analysis and review. Psychosomatics 41:104, 2000; Assefi NP et al: A randomized clinical
trial of acupuncture compared with sham acupuncture in fibromyalgia. Ann Intern Med 5;143, 2005; Benoit AG et
al: Risk factors and prevalence of perioperative cognitive dysfunction in abdominal aneurysm patients. J Vasc Surg
42:884, 2005; Breuer GS et al: Perceived efficacy among patients of various methods of complementary alternative
medicine for rheumatologic diseases. Clin Exp Rheumatol 23:693, 2005; Carney RM et al: Low heart rate variability
and the effect of depression on post-myocardial infarction mortality. Arch Intern Med 165:1486, 2005; Gendreau
RM et al: Efficacy of milnacipran in patients with fibromyalgia. J Rheumatol 32:1975; 2005; Goldenberg DL,
Burckhardt C, Crofford L: Management of fibromyalgia syndrome. JAMA 292:2388, 2004; Grace SL et al: Effect
of depression on five-year mortality after an acute coronary syndrome. Am J Cardiol 96:1179, 2005; Hudson JI,
Arnold LM et al: Family study of fibromyalgia and affective spectrum disorder. Biol Psychiatry 56:884, 2004;
Janssen J et al: Late-life depression: the differences between early- and late-onset illness in a community-based
sample. Int J Geriatr Psychiatry 21:86, 2005; Joynt KE, O’Connor CM: Lessons from SADHART, ENRICHD,
and other trials. Psychosom Med 67(Suppl 1):S63; 2005; Mease P: Fibromyalgia syndrome: review of clinical presentation,
pathogenesis, outcome measures, and treatment. J Rheumatol Suppl 75:6; 2005; Mease PJ, Arnold LM,
et al: Fibromyalgia syndrome. J Rheumatol 32:2270; 2005; Powell LH et al: Depression and heart failure in patients
with a new myocardial infarction. Am Heart J 149:851, 2005; Rivard AL et al: Preoperative predictors for
postoperative problems in heart transplantation: Psychiatric and psychosocial considerations. Prog Transplant
15:276, 2005; Roundy K: Are anxiety and depression addressed in primary care patients with chronic obstructive
pulmonary disease? A chart review. Prim Care Companion J Clin Psychiatry 7:213, 2005; Salek AK et al: Effect of
aerobic exercise on patients with primary fibromyalgia syndrome. Mymensingh Med J 14:141, 2005; Shimbo D et
al: Negative impact of depression on outcomes in patients with coronary artery disease: mechanisms, treatment considerations,
and future directions. J Thromb Haemost 3:897, 2005; Sobel RM, Lotkowski S, Mandel S: Update on
depression in neurologic illness: stroke, epilepsy, and multiple sclerosis. Curr Psychiatry Rep 7:396, 2005; Staud R:
The role of acupuncture for fibromyalgia pain. More questions than answers. Curr Rheumatol Rep 7:336; 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. For this issue, Dr.
Crow disclosed that he is a consultant for Ortho/McNeil Pharmaceuticals, has received grant/research support from Eli
Lilly, GlaxoSmithKline, Ortho McNeil Pharmaceuticals, Abbott, and Pfizer, and is on the Speakers’ Bureau of Pfizer.
Dr. Arnold disclosed that she has received grants/research support from Boehringer-Ingelheim, Cypress Bioscience,
Forest, Eli Lilly, Pfizer, and Sanofi-Synthelabo, is a consultant for Cypress Bioscience, Eli Lilly, Pfizer, and Sanofi-Synthelabo,
and receives honoraria from Eli Lilly and Pfizer.
Dr. Crow spoke at “An Entertaining and Eclectic Elucidation of Psychiatric Erudition,” held September 19-20, 2005,
in Minneapolis and sponsored by the University of Minnesota, Minneapolis, Medical School. Dr. Arnold spoke at
“Golden Gleanings from Gracious, Galvanizing Gurus,” held September 30 to October 1, 2005, in Madison, Wisconsin,
and sponsored by the University of Wisconsin Medical School and the Madison Institute of Medicine, Inc. The
Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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