MOOD DISORDERS: HIGHS AND LOWS
From the 31st Semi-Annual Family Practice Review, sponsored by Temple University School of Medicine,
Philadelphia, PA, and Lancaster General Hospital, Lancaster, PA
| BIPOLAR DISORDERS —Roger J. Cadieux, MD, Clinical Professor, Department of Psychiatry, Pennsylvania State
University College of Medicine, Hershey, PA
|
| Bipolar disorder (BD) types: bipolar I—≥1 manic or mixed episodes; associated with fluctuating affect; bipolar
II—≥1 major depressive episodes, accompanied by ≥1 hypomanic episodes; presence of manic episode automatically
bipolar I; cyclothymic—uncommon (dysthymia more common); chronic fluctuating mood disturbance characterized
by hypomanic and depressive episodes; prevalence by type—classic or pure mania 40% to 60%; mixed
states of mania and depression 40%; patients with mixed states undergo 3 to 5 depressive episodes for every manic
episode; rapid cyclers (4 episodes/yr) 10%
|
| Manic and hypomanic states: defined as “distinct period of persistently elevated, expansive, or irritable mood
lasting for at least 4 days (hypomania), or at least 1 wk (mania) with 3 or more symptoms”; look for grandiosity,
decreased sleep, loquaciousness, racing thoughts, flight of ideas, distractibility, increased activity, and indiscreet
activities; manic episode should be severe enough to cause marked impairment in social and/or occupational functioning
or to necessitate hospitalization (otherwise, hypomania)
|
| Epidemiology of BD: lifetime prevalence 1% to 2% of population in United States (2-4 million people); equally distributed
between sexes; genetic heterogeneity responsible for 50% to 70% of etiology (remaining 30%-50% due to
environmental triggers); peak age of onset 15-29 yr (rare in child <10 yr of age); mean age of first treatment 22 yr;
mean age of first hospitalization 26 yr; course of illness—depression 3.5-fold more common than mania in patients
with dual affective states; lifelong chronic recurrent disorder
|
| Characteristics of BD: genetics and risk for bipolar disorder—if no family history, risk of developing disorder
1% to 7%; if one parent bipolar/unipolar, risk 27%; if one parent bipolar, risk 30%; if 2 parents bipolar, risk 74%; if
one dyzygotic twin bipolar, risk for other 15%, and if one monozygotic twin bipolar, risk for other 85%; sex
differences—bipolar I more common in men, bipolar II more common in women; mania more common in men, depression
more common in women; functional difficulties—occupational difficulties common; patients have primary
process thinking (eg, saying whatever comes to mind) that interferes with relationships; divorce 2 to 3 times
more likely
|
| Diagnosis: study data—survey of 500 patients with BD found 73% received alternative explanation of their symptoms
before accurate diagnosis; 48% consulted ≥5 health care professionals before being diagnosed; 83% ultimately
had correct diagnosis made by psychiatrist; challenges—survey of Depression and Bipolar Support
Alliance membership found 70% misdiagnosed with depressive disorder; most patients in depressed state when
seeking medical help; hypomania and mania can develop in patients with BD treated with selective serotonin reuptake
inhibitors (SSRIs) or selective norepinephrine reuptake inhibitors (SNRIs); keys to diagnosis—early-onset
depression; frequent and difficult-to-control depression; poor or idiosyncratic response to antidepressants; depressive
episode changing from retarded to irritable or agitated; depression combined with substance abuse or impulsivity;
childhood onset of mood disorder; early-onset psychosis with relatively good social functioning; family
history of mood disorder or substance abuse problems
|
| Assessment: issues of concern—presence of psychosis (especially persecutory delusions and paranoid ideation);
increased risk for suicide; cognitive impairment; potential for violence; risk-taking behaviors; sexual indiscretion;
diminished ability for self-care; childbearing status; financial resources; lack of psychosocial support system
|
 | Comorbid conditions: frequently complicate diagnosis; 65% of patients with BD have ≥1 comorbid conditions, and
25% of patients have ≥3 comorbid conditions; comorbid conditions involve substance abuse, medical illness, and
psychiatric disorders; multidimensionality of BD—associated disorders include diabetes mellitus, cardiovascular
disease, obesity, substance abuse, eating disorders, anxiety disorders, impulse control disorders, attention-
deficit/hyperactivity disorder (ADHD), personality disorders, migraine, and pain disorders; patients may present
with these other disorders, but BD core issue; comorbid disorders may resolve once BD treated; suicide—25%
to 50% of patients with BD attempt suicide at least once; suicide attempts more common with bipolar I than with
bipolar II; 10% to 20% of deaths in patients with BD due to suicide (30 times higher than general population)
|
| Treatment: nonpharmacologic treatment goals—assess and treat acute exacerbations; prevent recurrences; improve
and maintain inter-episode functioning; provide assistance, education, insight, and support to patient and
family; compliance issues—denial of BD; reluctance to give up experience of mania; cost and bother of treatment;
medication side effects
|
| Pharmacologic treatment: lithium carbonate—gold standard; other choices—valproate, carbamazepine (eg, Tegretol),
lamotrigine (Lamictal; does not help highs), and atypical antipsychotic drugs; lithium (continued)—
response rate 80%; onset of efficacy 2 wk; therapeutic range 0.6 to 1.2 mEq/mL, but most patients respond well
with therapeutic range 0.4 to 0.6 mEq/mL; used in acute illness; reduces frequency, duration, and severity of
manic and depressive episodes when used prophylactically; requires pretreatment physical examination with laboratory
tests, including complete blood cell count (CBC), serum urea nitrogen (BUN), creatinine level, pregnancy
test, thyroid function test, electrocardiography (ECG) with rhythm strip for patients ≥40 yr of age;
consider combining with antipsychotic agent if patient presents as acutely and severely manic (to decrease mania);
capsules better tolerated than tablets (generic lithium available in capsule form); mild acute adverse effects
(serum level >1 mEq/L) include nausea, tremor, diarrhea, polyuria, polydipsia, weight gain, hair loss or brittleness,
and muscle weakness; toxic level indicated by confusion, ataxia, muscle twitching, and nystagmus; chronic
adverse effects include renal impairment (eg, interstitial fibrosis, tubular atrophy, glomerular sclerosis not associated
with reduced glomerular filtration rate or renal insufficiency), thyroid dysfunction (eg, goiter-like expansion
of thyroid gland), hematopoietic effects (eg, reduction in white blood cell count [WBC]), and teratogenic
effects during first trimester of pregnancy; valproate—associated with many adverse effects; consider secondarily
to lithium; divalproex (Depakote)—effective in BD; long-term adverse effects include significant weight
gain; weight gain—associated with divalproex, olanzapine (eg, Zyprexa), and paroxetine (eg, Paxil); dosage
formulations—Depakote available in extended-release tablet, but not syrup; valproic acid (generic) available in
syrup; carbamazepine—as effective as lithium; associated with some antidepressant effects; rarely used; antidepressant
agents—dosage adjustments common; monotherapy usually contraindicated; avoid those with greater
drug interactions and protein-binding (eg, fluoxetine, paroxetine)
|
| Appropriate psychiatric referrals: patients with—delusional or psychotic behavior; recurrent, chronic, or bipolar
depression; medical and psychiatric symptoms not clarified by completion of evaluation; suicidal or violent behavior;
request for second opinion
|
| DEPRESSION —David A. Baron, DO, Professor and Chair, Department of Psychiatry and Behavioral Science,
Temple University School of Medicine, Philadelphia, PA
|
| Overview: impact on society—by 2020, unipolar major depression expected to be second leading cause of disability
worldwide; mental illnesses and alcohol and drug use disorders important causes of disability, with cost of $80
billion annually; physical and psychologic symptoms—patients with depression may present with physical or
psychologic symptoms, or both; personality or culture may play some role, eg, individuals in Asian countries tend
to present with higher number of physical symptoms, while individuals in South America present with higher number
of psychologic symptoms; comorbidity with chronic pain—depressed patients twice as likely to have chronic
pain; depression complicates disease outcomes—as independent risk factor, major depression negatively affects
patients with, eg, cardiovascular disease, diabetes, stroke; associated with significant risk for mortality
|
| Diagnosis: challenges—study found primary care physicians made accurate diagnosis of depression in 75% of patients
presenting with psychosocial complaints, but in only 20% of patients presenting with somatic symptoms;
likelihood of depression increases with number of physical symptoms; study found patients presenting with >9
physical complaints 60% more likely to have depression
|
| Recurrence and remission: treatment goals—recommend aggressive treatment to achieve remission, restore
functionality, and prevent neurodegenerative process; preventing recurrence—likelihood of depressive episode
increases with number of depressive episodes; recommend lifelong (or at least long-term) treatment with antidepressants
for patients with history of ≥3 major depressive episodes; ≥3 major depressive episodes also increases
suicide risk; study found suicide leading cause of death in women 20 to 55 yr of age, 6 mo prior to and 1 yr postpartum;
cost of treatment—study found remission of depression associated with lower cost than partial or no response
to treatment
|
| Neurobiology of depression: neurodegenerative disease processes—hypothalamic-pituitary-adrenal (“stress”)
axis produces corticotrophin-releasing factor (CRF), adrenocorticotropic hormone, and cortisol; excess cortisol
(stress hormone) reduces brain-derived neurotrophic factor and results in changes in brain structure; untreated depression
results in decreased size of left hippocampus; depression not only mood disorder, but also brain disease;
untreated chronically depressed individuals exhibit changes in neurophysiology and neuroanatomy; synaptic plasticity
down-regulated in patients with chronic depression
|
| Antidepressant therapy: norepinephrine and serotonin—newer antidepressant agents (SNRIs; eg, venlafaxine,
duloxetine) block both serotonin and norepinephrine; SNRIs more effective in patients with depression who have
pain; duloxetine approved by Food and Drug Administration (FDA) for diabetic neuropathic pain, independent of
depression; achieving complete remission—goal of antidepressant therapy; consequences of not achieving remission
include worsening and increase in number of depressive episodes, shorter time between depressive episodes,
and increased risk for suicide (risk increases with each major depressive episode); incomplete remission—patient
becomes more functional, but not “well” (eg, sleep or relationships show improvement, but not at healthy baseline);
complete remission necessary to prevent future relapses; study found asymptomatic patients showed longer duration
of improvements in mood and had significantly longer time between depressive episodes; SSRIs effective in treating
depressive symptoms and achieving sense of positive well-being, but not as effective in patients who have greater
number of somatic symptoms or pain; study found initial symptomatic relief of fatigue, stomach pain, headache,
sleep problems, and palpations with SSRIs decreases after 9 mo of therapy; consider tricyclic antidepressants (TCAs)
or SNRIs in patients with somatic complaints or pain conditions associated with depression; role in physical pain
modulation—severity of pain at baseline strong predictor of poor response to SSRI
|
| Nonpharmacologic therapy: psychotherapy—combining psychotherapy with pharmacotherapy superior to either
alone; cognitive-behavioral therapy (CBT), supportive psychotherapy, or other psychiatric or psychologic therapies
all useful adjuncts; psychotherapy often underutilized; effective alone in patients with mild-to-moderate depression,
but less effective as sole treatment as severity of depression increases; improves patient compliance with antidepressant
treatment; exercise—important treatment strategy for depression; type of exercise should be enjoyable
to individual patient
|
| QUESTIONS AND ANSWERS —Drs. Baron and Cadieux
|
| Fibromyalgia: considered musculoskeletal disorder, but high comorbidity with psychiatric disorders; patients experience
musculoskeletal symptoms and trigger point pains; labeling of disorder not as important as providing most
effective treatment strategy
|
| Issues in patients with BD: medication compliance—developing therapeutic alliance with patient helps to improve
compliance; patients must believe physician their advocate; drug combinations—recommend at least 2
types of drugs (antipsychotic agent and mood stabilizer) in manic patient; consider adding antidepressant as patient
stabilizes, and particularly if patient becomes depressed; questions to ask patients in primary care setting—ask
how they feel; determine their baseline, and whether they have lows and highs (eg, racing or colliding thoughts);
ask about past history of trouble (eg, flirtatiousness, distractibility) and family history; nephrogenic diabetes
insipidus—uncommon side effect from lithium carbonate; long-term treatment requires balance between relief of
symptoms and avoidance of side effects; follow patients closely at regular intervals (monitor, eg, blood levels, thyroid
hormone levels, renal status)
|
| Weight gain: SNRIs not associated with significant weight gain; TCAs associated with 15- to 20-lb weight gain
|
| Helping family members of patients with BD cope: individuals experiencing manic episodes often remove
themselves from family setting; patients in hypomanic state more likely to create problems within family (eg,
overspending); family members need to require individual with BD to maintain therapeutic alliance with health
care professional for that person to remain at home (placing boundaries may prove difficult if spouse has BD);
consider BD same as any medical illness (eg, diabetes) and work to make sure loved one getting appropriate
medical care
|
| Monitoring patients taking lithium for BD: start patient on 300 mg, wait 1 wk, then get therapeutic level; obtain
trough level; after first week, increase dose until desired serum level achieved, then check at 6-mo intervals; obtain
serum lithium status if signs of toxicity develop (vomiting, diarrhea, and mental status changes)
|
Suggested Reading
Berk M et al: Diagnosis and management of patients with bipolar disorder in primary care. Br J Gen Pract 55:663,
2005; Berk M et al: The management of bipolar disorder in primary care: a review of existing and emerging therapies.
Psychiatry Clin Neurosci 59:229, 2005; Bland R: Depression and its management in primary care. Can J Psychiatry
52(2):75, 2007; Conradi HJ et al: Enhanced treatment for depression in primary care: long-term outcomes
of a psycho-educational prevention program alone and enriched with psychiatric consultation or cognitive behavioral
therapy. Psychol Med 37:849, 2007; Egede LE: Failure to recognize depression in primary care: issues and challenges.
J Gen Intern Med 22:701, 2007; Gallo JJ et al: The effect of a primary care practice-based depression intervention
on mortality in older adults: a randomized trial. Ann Intern Med 146:689, 2007; Gaynes BN et al: Major
depression symptoms in primary care and psychiatric care settings: a cross-sectional analysis.Ann Fam Med 5:126,
2007; Hirschfeld RM et al: Screening for bipolar disorder in patients treated for depression in a family medicine
clinic. J Am Board Fam Pract 18:233, 2005; Kaye NS: Is your depressed patient bipolar? J Am Board Fam Pract
18:271, 2005; Muzina DJ et al: Differentiating bipolar disorder from depression in primary care. Cleve Clin J Med
74:89, 2007; Schur EA et al: Feeling bad in more ways than one: comorbidity patterns of medically unexplained and
psychiatric conditions. J Gen Intern Med 22:818, 2007.
Educational Objectives
| The goal of this program is to improve management of bipolar disorder and depression. After hearing and assimilating
this program, the clinician will be better able to:
|
| 1. Distinguish between bipolar I, bipolar II, and cyclothymic disorders.
|
| 2. Discuss the genetic risk for development of bipolar disorder (BD).
|
| 3. Recognize when to refer a patient with BD to a psychiatrist.
|
| 4. Identify the symptoms commonly associated with depression.
|
| 5. Recognize the risks associated with repeated recurrences of depression (eg, suicide), and implement treatment
strategies that incorporate pharmacologic and nonpharmacologic therapies.
|
Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose
relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any
identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary
business or commercial interest. For this program, the following has been disclosed: Dr. Baron is a consultant
for Eli Lilly, Shire Pharmaceuticals, and Pharma and is on the Speakers’ Bureau for Eli Lilly.
Acknowledgements
Drs. Cadieux and Baron spoke in Philadelphia, PA, at the 31st Semi-Annual Family Practice Review, presented
March 25-30, 2007, by Temple University School of Medicine and Lancaster General Hospital. The Audio-Digest
Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
|
