Best Dx/Best Rx: Bipolar Disorder and = Depression

From: Subject: Best Dx/Best Rx: Bipolar Disorder and Depression Date: Wed, 3 Jun 2009 23:03:25 -0700 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0092_01C9E49F.7FE2E900" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_0092_01C9E49F.7FE2E900 Content-Type: text/html; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Content-Location: mhtml:file://C:\pocketnotes\bipolar2004.mht Best Dx/Best Rx: Bipolar Disorder and = Depression

Bipol= ar=20 Disorder

Depre= ssion=20

Bipolar=20 Disorder

Michael T. Compton, M.D., M.P.H.

Charles B. Nemeroff, M.D., Ph.D.
Emory = University=20 School of Medicine

Defin= ition/Key=20 Clinical Features
Diffe= rential=20 Diagnosis
Best = Tests
Best = Therapy
Best = References

Definition/Key Clinical=20 Features

Onset usually in late adolescence or early=20 adulthood=20
Not caused by a substance or a general medical = condition=20
Bipolar I disorder: one or more manic or mixed = episodes,=20 often alternating with major depressive episodes=20
Bipolar II disorder: recurrent major = depressive episodes=20 with hypomanic episodes=20
Cyclothymic disorder: at least 2 yr of = fluctuating mood=20 disturbance involving numerous periods of hypomanic symptoms and = numerous=20 periods of depressive symptoms=20
Rapid cycling bipolar disorder:≥ 4 = episodes within 1=20 yr=20
- Typically develops late in the course of=20 illness=20
- More common in women
Manic episode=20
- Distinct period of abnormally elevated, = expansive, or=20 irritable mood lasting at least 1 wk=20
- Includes≥ 3 of these symptoms (4 if = mood is only=20 irritable):=20
  - Inflated self-esteem or grandiosity =
  - Decreased need for sleep=20
  - Being more talkative than usual or feeling = need to=20 keep talking=20
  - Flight of ideas or sense that thoughts are = racing=20
  - Distractibility=20
  - Increased goal-directed activity or = psychomotor=20 agitation=20
  - Excessive involvement in pleasurable = activities that=20 have a high potential for painful consequences
- About half of manic episodes include = psychotic=20 features (e.g., grandiose delusions or auditory = hallucinations)=20
- About a quarter of manic patients have=20 hallucinations
Hypomanic episode=20
- Distinct period of elevated, expansive, or = irritable=20 mood lasting at least 4 days=20
- Includes≥ 3 symptoms of a manic = episode (4 if the mood=20 is only irritable)=20
- No psychotic features are present =
Mixed episode=20
- Major depressive episode and manic episode=20 simultaneously within 1 wk
- Patients are dysphoric but hyperactive, = agitated, and=20 unable to sleep

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Differential = Diagnosis

Other psychiatric conditions=20
- Schizophrenia
- Schizoaffective disorder=20
  - A primary psychotic disorder in which a = major=20 depressive episode, a manic episode, or a mixed episode occurs and = psychotic symptoms are present for at least 2 wk in the absence of = prominent mood symptoms
- Personality disorders=20
  - Certain personality disorders are = characterized by=20 chronic and pervasive rapidly fluctuating affective = lability=20
  - Many patients with cluster B personality = disorders=20 (e.g., borderline personality disorder) may also meet DSM-IV = criteria for=20 dysthymic disorder, bipolar II disorder, or cyclothymic = disorder=20
- Drug abuse=20
  - Alcohol=20
  - Amphetamines=20
  - Hallucinogens=20
  - Cocaine=20
  - Urine or blood toxicologic screens = necessary to=20 differentiate primary mania from a substance-induced mood disorder = with=20 manic features=20
    - Because comorbidity is common, a = positive urine=20 drug screen does not exclude a primary bipolar disorder=20
- Delirium, dementia, and medical illnesses, = especially=20 in elderly patients

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Best=20 Tests

Thorough Medical and = Psychiatric=20 Evaluation=20

Medical history and physical = examination=20
Detailed substance-use history
Thorough mental status examination findings = may include=20 the following:=20
- Eccentric dress, brightly colored clothing, = excessive=20 make-up, or multiple pieces of jewelry=20
- Euphoria, excitement, intrusiveness, or=20 irritability=20
- Psychomotor agitation and an increase in = goal-directed=20 activity=20
- Increased rate and rhythm of speech=20
- Flight of ideas/racing thoughts=20
- Elevated self-worth, grandiosity, = mood-congruent=20 psychotic features
Cognitive assessment may show the = following:=20
- Memory impairment=20
- Difficulties with attention and = concentration=20
Risk assessment for self-care and = suicidality=20

Laboratory Tests=20

Urine drug screen=20
Blood chemistries=20
Thyroid function studies=20
Syphilis serology

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Best=20 Therapy

Hospitalization for acute mania=20
Drug treatment for bipolar disorder=20
- Combination therapy often necessary=20
- Lithium: gold standard=20
  - Assess renal and thyroid function before=20 initiating=20
  - ECG before initiating=20
  - Avoid NSAIDs and diuretics=20
  - Maintain uniform salt intake=20
  - Monitor serum levels periodically=20
    - Measure 10=9612 hr after last = dose=20
    - Measure 4=965 days after last dosage = change=20
  - Monitor BUN, serum creatinine, TSH every 6 = mo=20
  - Side effects: cognitive slowing, nausea, = diarrhea,=20 polyuria, polydipsia, weight gain, tremor, metallic taste in the=20 mouth=20
  - Dose: lithium carbonate=20
    - Initial: 300 mg t.i.d. or 450 mg = b.i.d.=20
    - Maintenance: 900=961,800 mg/day=20
    - Therapeutic blood level: 0.8=961.2 = mEq/L=20
  - Cost/mo: $38
- Anticonvulsants=20
  - Valproic acid or divalproex sodium: more = effective=20 for manias that are dysphoric or mixed and for rapid = cycling=20
    - Assess CBC and liver function before=20 starting=20
    - Take with food=20
    - Dose: initial, 250 mg b.i.d.; = maintenance,=20 750=962,000 mg/day=20
    - Therapeutic blood level: 100=96125 = mg/L=20
    - Cost/mo: $72
  - Carbamazepine: not approved for = mania=20
    - Assess CBC and liver function before=20 starting=20
    - Monitor for drug-drug interactions and=20 autoinduction=20
    - Dose: initial, 100=96200 mg b.i.d.; = maintenance,=20 400=96600 mg/day=20
    - Therapeutic blood level: 6=9610 = =B5g/ml=20
    - Cost/mo: $17
  - Lamotrigine: for the maintenance treatment = of adults=20 with bipolar I disorder to delay the time to occurrence of mood = episodes=20 (depression, mania, hypomania, mixed episodes) in patients treated = for=20 acute mood episodes with standard therapy (more robust in bipolar=20 depression than mania)=20
    - Dose: 25 mg/day for 2 weeks; 50 mg/day = for 2=20 weeks; 100 mg/day for week 5; 200 mg/day for week 6=20
    - Slower titrations are required for = patients taking=20 carbamazepine, phenytoin, phenobarbital, primidone, rifampin, or = valproate because of risk of severe rash=20
    - Cost/mo: $720
  - Atypical antipsychotics=20
    - Risperidone=20
      - Dose: initial, 1=962 mg/day; = maintenance, 2=966=20 mg/day=20
      - Cost/mo: $394
    - Olanzapine=20
      - Dose: initial, 5=9610 mg/day; = maintenance, 10=9620=20 mg/day=20
      - Cost/mo: $640
    - Quetiapine=20
      - Dose: initial, 100=96200 mg/day; = maintenance,=20 400=96800 mg/day=20
      - Cost/mo: $668
    - Ziprasidone=20
      - Dose: initial, 20 mg b.i.d.; = maintenance, 40=9680=20 mg b.i.d.=20
      - Cost/mo: $162
    - Aripiprazole=20
      - Dose: initial, 5=9615 mg/day; = maintenance, 15=9630=20 mg/day=20
      - Cost/mo: $445=20
Drug treatment for depression associated with = bipolar=20 disorder=20
Drug treatment for psychotic symptoms = associated with a=20 manic episode=20
Psychotherapy: useful as adjunctive = treatment=20

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Best References

American Psychiatric Association: Am J Psychiatry = 159(suppl):1, 2002 [PMID 11958165]

Bearden CE, et al: Bipolar Disorders 3:106, 2001 = [PMID=20 11465675]

Bowden CL: J Clin Psychiatry 66(suppl 1):3, 2005 = [PMID=20 15693745]

De Leon OA: Harv Rev Psychiatry 9:209, 2001 [PMID = 11553525]

January=20 2007

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Depression

Michael T. Compton, M.D., M.P.H.
Emory University School of Medicine

Charles B. Nemeroff, M.D., Ph.D.
Emory = University=20 School of Medicine

Defin= ition/Key=20 Clinical Features
Diffe= rential=20 Diagnosis
Best = Tests
Best = Therapy
Best= =20 References

Definition/Key Clinical=20 Features

Distinguished from normal sadness and grief by = severity,=20 pervasiveness, and duration of mood disturbance and by presence of=20 neurovegetative abnormalities and other symptoms=20
Neurovegetative abnormalities=20
- Sleep disturbance (most often insomnia with=20 early-morning awakening)=20
- Change in appetite (usually anorexia) =
- Decreased energy=20
- Psychomotor abnormalities (slowed = thinking/movement=20 and speech or agitation)=20
- Diurnal variation in mood (typically worse = in=20 morning)
Other symptoms=20
- Depressed mood (may be irritability or loss = of=20 interest)=20
- Loss of enjoyment of usual activities (e.g., = eating,=20 work, sex, hobbies, time with family and friends)=20
- Loss of hope=20
- Diminished self-esteem=20
- Difficulty concentrating=20
- Poor memory=20
- Ruminations and excessive or inappropriate=20 guilt=20
- Suicidal thoughts or recurrent thoughts of=20 death

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Differential = Diagnosis

Most common causes of secondary = depression:=20
- Alcohol abuse or dependence=20
- Alzheimer=92s disease=20
- Substance abuse or dependence=20
- Parkinson=92s disease=20
- Serious medical illness=20
- Stroke

Red Flags

Post-MI patients: 1-yr mortality higher with=20 depression=20
Women > 67 yr: overall mortality higher = with more=20 depressive symptoms; risk of falls and fractures greater with=20 depression=20
Elderly patients: suicide is major risk in the = depressed=20
Adolescents and young adults 15=9624 yr old: = suicide is=20 third leading cause of death

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Best=20 Tests

No definitive biologic marker=20
Clinical observation (DSM-IV)=20
Brief questionnaires=20
- Two-question test=20
- Center for Epidemiologic Studies Depression=20 Questionnaire (CES-D) (10-item self-assessment)=20
- Geriatric Depression Scale (GDS) (15-item=20 self-assessment) (for patients > 60 yr)
- Primary Care Evaluation of Mental Disorders = Patient=20 Health Questionnaire (PRIME-MD PHQ) (nine-item = self-assessment)=20

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Best=20 Therapy

Psychotherapy

Cognitive-behavioral therapy effective in = acute=20 treatment of major depression and dysthymic disorder of mild to = moderate=20 severity=20
Combination of psychotherapy and medication = may be more=20 effective than either alone

Electroconvulsive Therapy

Single most effective therapy for acute = treatment of=20 serious major depression=20
Often indicated for treatment of depression = associated=20 with the following=20
- Medication resistance or intolerance=20
- Psychotic symptoms=20
- Catatonia=20
- Medical illness that contraindicates drug=20 treatment=20
- Acute mania=20
- Active suicidal ideation (short-term = protective=20 effect)
Contraindicated in presence of increased = cranial=20 pressure

Antidepressants

Selective serotonin reuptake inhibitors =
- Citalopram: 20 mg/day initially, then = typically=20 doubled in 1 wk in cases of severe or recurrent depression; =
  up to 60 mg/day in event of nonresponse=20
  - Dose: 40 mg/day (20=9660 mg/day)=20
  - Cost/mo: $195
- Escitalopram: 10 mg/day initially=20
  - Dose: 10 mg/day (10=9630 mg/day)=20
  - Cost/mo: $176
- Fluoxetine: 20 mg/day q.a.m. initially; = reduce to 10=20 mg/day for patients with side effects=20
  - Dose: 20 mg/day (10=9680 mg/day)=20
  - Cost/mo: $92
- Fluvoxamine: 50 mg/day initially, with = target dosage=20 of 150=96250 mg/day=20
  - Dose: 200 mg/day (50-300 mg/day)=20
  - Cost/mo: $176
- Paroxetine: 20 mg initially in morning or = evening; 10=20 mg/day in elderly or patients with hepatic or renal dysfunction or = in=20 patients who do not tolerate 20 mg/day dosage; increase in 10 mg = increments=20 up to 50 mg/day in healthy adults (40 mg/day in the elderly) who do = not=20 respond after 4 wk=20
  - Dose: 20 mg/day (10-50 mg/day)=20
  - Cost/mo: $143
- Sertraline: 50 mg/day initially, with target = dosage of=20 100=96150 mg/day in healthy adults=20
  - Dose: 100-150 mg/day (50-200 = mg/day)=20
  - Cost/mo: $148
Other New Antidepressants
- Mirtazapine (α₂ blocker, = 5-HT₂=20 blocker, 5-HT₃ blocker)=20
  - Dose: 30 mg/day=20
  - Cost/mo: $43
- Bupropion SR: start treatment at 100 mg = b.i.d. and=20 increase to 100 mg t.i.d. on fourth day of treatment; may increase = to=20 maximum of 450 mg/day=20
  - Dose: 300-400 mg/day=20
  - Cost/mo: $214
- Reboxetine: not available in U.S.=20
  - Dose: 8-10 mg/day
- Nefazodone=20
  - Dose: 150-400 mg/day=20
  - Cost/mo: $46
- Trazodone=20
  - Dose: 150-400 mg/day=20
  - Cost/mo: $19
- Venlafaxine XR=20
  - Dose: 75-225 mg/day=20
  - Cost/mo: $185
Tricyclic antidepressants and related agents: = Use as=20 second- or third-line pharmacotherapy when insufficient response to = SSRI or=20 other antidepressant; increase dosage gradually (e.g., by 25=9650 = mg/wk) until=20 achieving therapeutic dose=20
- Amitriptyline=20
  - Dose (range): 150-200 mg/day (75-300 = mg/day)=20
  - Cost/mo: $7
- Amoxapine=20
  - Dose (range): 150-200 mg/day (75-300 = mg/day)=20
  - Cost/mo: $91
- Clomipramine=20
  - Dose (range): 150-200 mg/day (75-250 = mg/day)=20
  - Cost/mo: $81
- Desipramine=20
  - Dose (range): 150-200 mg/day (75-300 = mg/day)=20
  - Cost/mo: $44
- Doxepine=20
  - Dose (range): 150-200 mg/day (75-300 = mg/day)=20
  - Cost/mo: $20
- Imipramine=20
  - Dose (range): 150-200 mg/day (75-300 = mg/day)=20
  - Cost/mo: $40
- Maprotiline=20
  - Dose (range): 150-200 mg/day (75-225 = mg/day)=20
  - Cost/mo: $50
- Nortriptyline: more potent than other TCAs; = begin at=20 10-25 mg/day=20
  - Dose (range): 75-100 mg/day (40-150 = mg/day)=20
  - Cost/mo: $26
- Protriptyline: more potent than other TCAs; = begin at=20 10-25 mg/day=20
  - Dose (range): 30 mg/day (15-60 = mg/day)=20
  - Cost/mo: $235
- Trimipramine: more potent than other TCAs; = begin at=20 10-25 mg/day=20
  - Dose (range): 150-200 mg/day (75-300 = mg/day)=20
  - Cost/mo: $171
Monoamine oxidase inhibitors: Patients taking=20 nonselective MAOIs must avoid foods or meds that contain tyramine or = other=20 pressor amines; interactions with SSRIs may also occur=20
- Isocarboxazid=20
  - Dose: 30 mg/day; range, 20-60 = mg/day=20
  - Cost/mo: $128
- Phenelzine: If no improvement in 3-4 wk, = dosage may=20 increase to as high as 90 mg/day.=20
  - Dose: 60-75 mg/day; range, 60-90 = mg/day=20
- Tranylcypromine=20
  - Dose: 30 mg/day; range, 20-90 = mg/day=20
  - Cost/mo: $210 =

Treatment-Resistant Depression

Experienced by up to 30% of patients=20
If initial antidepressant drug has been given = at full=20 therapeutic dose with no improvement after 4-6 wk, change drug=20
If initial antidepressant drug has caused = partial=20 response, augment with lithium, 300 mg t.i.d.=20
If SSRIs are ineffective, alternative is to = add=20 bupropion, 150-300 mg/day, or another newer agent, or TCA=20
Consider electroconvulsive therapy early in = course of=20 treatment

Pregnancy and Postpartum = Depression

Many antidepressant drugs are relatively safe = for=20 pregnant woman and fetus=20
Limited courses of fluoxetine or = cognitive-behavioral=20 therapy are effective in treating postpartum depression =

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Best = References

Davis: Essent Psychopharmacol 2:309, = 1998

Keller, et al: JAMA 280:1665, 1998

Silverstone, et al: J Clin Psychiatry 60:22,=20 1999

October=20 2004

Michael T. Compton, M.D., M.P.H, has = received=20 research grants from the Emory Medical Care Foundation and has been a = consultant=20 for AstraZeneca and Medscape. Charles B. Nemeroff, M.D., Ph.D., holds = stock in=20 Corcept Therapeutics, Inc. and Neurocrine Biosciences, Inc., and has = received=20 grants for clinical research from, served as consultant for, or been a = member of=20 the speakers=92 bureaus of the following companies and organizations: = Abbott=20 Laboratories; Acadia Pharmaceuticals, Inc.; the American Foundation for = Suicide=20 Prevention; AstraZeneca Pharmaceuticals LP; Bristol-Myers Squibb Co.; = Corcept=20 Therapeutics, Inc.; Cypress Bioscience, Inc.; Cyberonics, Inc.; Eli = Lilly and=20 Company; Forest Pharmaceuticals, Inc.; GlaxoSmithKline; Janssen = Pharmaceutica=20 Products, LP; Merck & Co., Inc.; the National Alliance for Research = on=20 Schizophrenia and Depression; the National Institute of Mental Health;=20 Neurocrine Biosciences, Inc.; Novartis Pharmaceuticals Corp.; Organon=20 International, Inc.; Otsuka America, Ltd.; Pfizer, Inc.; Sanofi-Aventis; = SCIREX;=20 Somerset Pharmaceuticals, Inc.; Stanley Foundation/NAMI Research = Institute; and=20 Wyeth.

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