DEPRESSION, DYSTHYMIA AND BIPOLAR AFFECTIVE DISORDER

Epidemiology of Depression
Definition of Depression vs. Dysthymia
Differential diagnosis
Clinical evaluation of patients presenting with symptoms of depression
Treatment-General Approach
Antidepressant Pharmacotherapy
Bipolar Affective Disorder

I. Epidemiology of Depression

  1. 5% prevalence among American adults
  2. 30% lifetime incidence
  3. Mean age at onset 40y; 10% occur after age 60
  4. 2-3x higher incidence among women
  5. No racial predisposition
  6. Slightly higher risk among poor
  7. Family history is associated with increased risk
  8. 15% eventually commit suicide
  9. Untreated, usually lasts about 10mos; 75% have recurrence
  10. About 85% can be treated successfully with current treatment
  11. Low dietary intake of omega-3 fatty acids are associated with depression

II. Definition of Depression vs. Dysthymia

  1. Depression
    1. At least five of the following for at least 2wks including either 1) or 2)
    1. Depressed mood (or irritable mood in kids/adolescents
    2. Anhedonia
    3. Sig. change in weight or appetite
    4. Sleep disturbance
    5. Psychomotor agitation/retrdation
    6. Fatigue/loss of energy
    7. Feeling worthless/guilty
    8. Difficulty concentrating/indecisiveness
    9. Thoughts of death/suicide
    1. Not due to organic cause or grief
    2. No delusion/hallucination without mood sx
    3. Quick 2-question method to diagnose depression
    1. "During the past month, have you often been bothered by feeling down, depressed, or hopeless?"
    2. "During the past month, have you often been bothered by little interest or pleasure in doing things?"
    3. The above 2 questions found to be 96% sensitive and 57% specific in identifying pts w/depression c/w various NIMH "Quick Diagnostic Interview Schedule" in a study of VA patients (97% male) (J. Gen. Int. Med. 12:439, 1997-abst)
  1. Dysthymia
    1. At least two of the following for most of the day, more days than not, for > 2y:
      1. Poor appetite or overeating
      2. Insomnia or hypersomnia
      3. Low energy/fatigue
      4. Low self-esteem
      5. Poor concentration or difficulty making decisions
      6. Feelings of hopelessness
    2. Less likely to resolve spontaneously or improve with  psychotherapy or meds than major depressive disorder, but does respond to meds and cognitive therapy in some cases
    3. Some studies suggest benefit from low-dose amisulpride (Solian), an antipsychotic
    4. Exercise may be helpful
    5. 15% of pts also have some form of substance abuse or dependence

III. Differential diagnosis

  1. Schizoprenia
  2. Medication side effect (list below is not complete):
    1. Beta-blockers
    2. Alphamethyldopa
    3. Procainamide
    4. Digitalis
    5. Griseofulvin
    6. Isotretinoin
    7. Opiates
    8. Benzodiazepines
    9. Barbiturates
    10. Clonidine
    11. Guanethedine
    12. Amantadine
    13. Reserpine
    14. Baclofen
    15. Levodopa
  1. Substance abuse
  2. Endocrinopathies
    1. Diabetes
    2. Hypothyroidism
    3. Hyperparathyroidism
    4. Addison's
    5. Cushing's
    6. Hypogonadism in men (J. Clin. Endo. Metab. 84:573, 1999--JW)
  3. Anemia
  4. Sleep apnea
  5. Neurologic disease
    1. Huntington's
    2. Parkinson's
    3. Dementias
    4. Hydrocephalus
    5. Subacute infections (e.g. HIV encephalopathy and neurosyphili)
    6. Right-sided CVA
  6. Chronic fatigue syndrome
  7. Porphyrias

IV. Clinical evaluation of patients presenting with symptoms of depression

  1. History
    1. Evaluate current medications (esp. in elderly)
    2. Family psychiatric history
    3. Past psychiatric history
    4. Past and present psychosocial traumas and stressors
    5. "Vegetative signs": fatiguability, loss of libido, weight/appetite change, insomnia esp. early morning awakening
    6. Association with menstrual cycle (if patient female)
    7. Social withdrawal
    8. Performance problems: procrastination, low motivation, low frustration tolerance
    9. Tearfulness
    10. Hopefulness about future
    11. Suicidality
    12. Substance use
    13. Support system
    14. Dietary intake of omega-3 fatty acids
  2. Mental status exam
  1. Psychomotor retardation or agitation
  2. Sad or flat affect
  3. Slow, soft, monotone speech
  4. Distractibility or difficulty concentrating, esp. in elderly
  1. Lab workup-To rule out the secondary causes mentioned above

V. Management-General Approach

  1. Assess suicidality-Risk factors include:
    1. Native American or Latino ethnicity
    2. Male gender
    3. Late teens
    4. History of being abused
    5. School failure
    6. Homelessness
    7. Lack of family or other psychosocial support
    8. Previous suicide attempt
    9. Family history of suicide
    10. Suicidal thoughts with specific plan
    11. Availability of means
    12. Comorbid schizophrenia, substance abuse, personality disorder, or conduct disorder
  2. Consider referral for counseling-counseling + antidepressants is more effective than antidepressants alone
    1. Cognitive behavioral therapy every 2wks x 20wks at onset of pharcologic tx increased remission and decreased relapse rates over 2y of f/u (Arch. Gen. Psych. 55:816, 1998--AFP)
    2. Response rate was sig. higher with combination of cognitive-behavioral psychotherapy + nefazodone (titrated to 600mg/d) vs. either alone (73%, 48%, and 48% respectively) in a 12wk randomized trial of 681 adults with chronic major depression (NEJM 342:1462, 2000--JW)
  1. Frequent visits
  2. Review support system and crisis plan
  3. Exercise
    1. 30min of aerobic exercise 3x/wk shown to augment effects of Sertraline in a 16wk trial of 133 pts > 50yo with major depressive disorder; exercise alone ass'd with nearly the same results at 16wks c/w sertraline alone; at 6mo f/u, relapse rate in exercise-only group had sig. lower depression scores than either the sertraline-only or the sertaline-plus-exercise groups! (Psychosom. Med. 62:633, 2000--FP News 2/1/01)
  4. Electroconvulsive therapy (ECT) if unresponsive or psychotic features
  5. Light therapy for seasonal affective disorder
    1. Morning more effective than evening (3 studies published in Arch. Gen. Psychiat. Oct. 1998--JW)
    2. In a study in 96 adults with moderate-to-severe seasonal affective disorder randomized to light therapy (10k-lux 30min QD) vs. fluoxetine 20mg/d x 8wks, 8wk response rates were not sig. diff. ("Can-SAD" Study; Am. J. Psych. 163:805, 2006--JW)
  6. Hormonal therapy for menopausal women with depression
    1. 50 women 40-55yo with menopause and depressive disorders (major depressive disorder, dysthymia, or minor depression) randomized to transdermal 17-beta-estradiol 100ug/d vs. placebo x 12wks; the active tx group had sig. greater improvements in depression sx than the placebo group (Arch. Gen. Psych. 58:529, 2001--JW--Note that prior studies using conjugated equine estrogens have NOT shown a similar benefit)
    2. In a study in 72 postmenopausal women with major depression randomized to venlafaxine along vs. venlafaxine + various hormonal treatments, one of which was methyltestosterone, x 24wks. Only women receiving venlafaxine + methyltestosterone had sig. improvement in mood sx c/w venlafaxine alone (Menopause 13:202, 2006--JW)
  7. Antidepressant pharmacotherapy
  8. Fish oil/Omega-3 fatty acids to augment antidepressants
    1. Low dietary intake of omega-3 fatty acids are associated with depression
    2. Augmentation of antidepressant pharmacotherapy with omega-3 fatty acids has been shown to improve response rates in pts with depression in placebo-controlled trials, e.g. Eicosapentaenoic acid (EPA)  at doses of 1-2g/d (Am. J. Psychiat. 159:477, 2002; Arch. Gen. Psychiat 59:913, 2002).  In these studies, the EPA was derived from fish oil.

VI. Bipolar Affective Disorder

  1. Characterized by symptoms of depression and (at different times) symptoms of mania (racing thoughts, psychomotor agitation, tangential thinking manifested during conversation, insomnia, abnormal gregariousness, impulsivity, and/or irritability)
  2. Pharmacologic treatment options
    1. Lithium
    2. Anticonvulsant medications, particularly valproic acid
    3. 2nd-generation antipsychotics
    4. In a non-blinded study in 110 pts with chronic bipolar disorder randomized to (lithium + valproic acid) vs. (lithium alone) vs. (valproic acid alone) x 2y for prevention of relapse, the incidence of new mood disorder-related episodes was sig. lower for combination group than the valproate-only group, but there was no sig. diff. between combination group and the lithium-only group, and was sig. lower for lithium-only pts than valproate-only pts ("Bipolar Affective Disorder: Lithium/Anticonvulsant Evaluation Study" ("BALANCE"); Lancet 375:385, 2010-AFP)