BIPOLAR DISORDER

BIPOLAR DISORDER - Susan Louisa Montauk, MD
BASICS
DESCRIPTION
• A psychiatric disorder characterized by at least one episode of mania and often involving dramatic "mood swings"; episodes of mania and/or hypomania, and major depression that cause marked impairment and/or hospitalization.
• The symptoms must not be due to a substance (e.g., drug), treatment (e.g., ECT or light therapy), a general medical condition (e.g., hyperthyroidism), or medication
ALERT
Geriatric Considerations
New onset in seniors demands a workup for organic or chemically induced pathology
Pediatric Considerations
• Signs and symptoms must be placed into a developmental context
• There is a large overlap with symptoms of Attention Deficit Hyperactivity Disorder (ADHD) and Oppositional Defiant Disorder
• Children and adolescents experience more rapid cycling and mixed states than adults
• Depression often presents as irritable mood
Pregnancy Considerations
No medications currently used for bipolar I disorder are category A or B
EPIDEMIOLOGY
Incidence
No overall incidence data have been reported.
Prevalence
1.0-1.6% (1)
RISK FACTORS
Genetics (2,3)
• Monozygotic twin concordance 40-70%
• Heritability estimate 0.93
• Several chromosomes implicated
• likely many gene set variations
PATHOPHYSIOLOGY
• Neurotransmitters known to be involved
• Serotonin
• Norepinephrine
• Dopamine
• Brain structures most involved
• MRI findings suggest that abnormalities in prefrontal cortical areas, striatum, and amygdala predate illness onset
ETIOLOGY
• Genetic predisposition (major)
• Life stressors
ASSOCIATED CONDITIONS
Substance abuse (60%) (4), ADHD, Anxiety disorders (e.g., Anorexia nervosa, Bulimia nervosa, Generalized anxiety disorder, Obsessive compulsive disorder, Panic disorder, Post-traumatic stress disorder, Social phobia)


DIAGNOSIS
DSM-IV-R CRITERIA
• Bipolar I disorder requires at least one manic or mixed episode (simultaneous mania and depression). There may be episodes of hypomania or major depression as well.
• Mania
- Distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary)
- During the period of mood disturbance, 3 or more of the DIGFAST 1 symptoms must persist (4 if the mood is only irritable) and must be present to a significant degree
• Depression
- 5 or more of the 9 symptoms (see Sns and Sxs) must have been present during the same 2-week period and represent change from previous functioning; at least 1 of the symptoms is either (1) or (2).
- Bipolar II (More common in primary care) requires a major depression and at least one hypomanic episode.
SIGNS AND SYMPTOMS
• Mania (DIGFAST)
- Distractibility (attention too easily drawn to unimportant or irrelevant external stimuli)
- Insomnia, decreased need for sleep (e.g., feels rested after only 3 hours of sleep)
- Grandiosity or inflated self-esteem
- Flight of ideas or subjective experience that thoughts are racing
- Agitation or increase in goal-directed activity (socially, at work or school, or sexually)
- Speech pressured/more talkative than usual
- Taking risks: Excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., financial or sexual)
• Hypomania
- A distinct period of persistently elevated, expansive, or irritable mood, lasting throughout at least 4 days, that is different from usual non-depressed mood but is not severe enough to cause marked impairment in social or occupational functioning
• Depression (DSM)
• Depressed mood most of the day
- Markedly diminished interest or pleasure activities most of the day
- Significant weight loss when not dieting or weight gain
- Insomnia or hypersomnia
• Psychomotor agitation or retardation
• Feel worthless
• Excessive/inappropriate guilt
• Diminished concentration; indecisiveness
• Recurring thoughts of death; suicidal ideation/plan
• Signs and Symptoms More Likely in Bipolar than in Unipolar Depression (5,6)
• Agitation
• Atypical depression symptoms (subjectively restless, leaden paralysis, hypersomnia)
• Feelings of worthlessness
• Hyperphagia
• Hypersomnia
• Melancholia
• Psychomotor retardation
• Suicidal ideation/planning
• Minimal tearfulness
History
• Collateral information makes diagnostics more complete and is often the best source for a clear history.
• HOPI (major points)
- Mood-Mood Disorder Questionnaire and an interview
- Sleep: Longest awake without stimulants and without sleepiness?
- Coexistent conditions? Psychosis?
- Suicide/violence risk
Physical Exam
Base focused exam on history and review of systems
TESTS
• Mood Disorder Questionnaire
- Sensitivity for mania/hypomania 0.73, specificity 0.90 (7)
• Child Behavior Checklist
- For Juvenile Bipolar Disorder
• "Dementia" workup if new onset in seniors
Lab
• No labs help rule in bipolar disorder
• Consider drug/alcohol screen if may help assist in future psychoeducation
• Many mood stabilizer medications must have regular blood draw monitoring
DIFFERENTIAL DIAGNOSIS
Other disorders with mania
Brain tumors
Drug intoxications
Organic mood disorders
Schizoaffective disorder
TREATMENT
PRE-HOSPITAL
• Medication
• Psychotherapy
• Psychoeducation
• Cognitive Behavioral Therapy
• Social Rhythm Therapy
STABILIZATION
Safe environment plus appropriate medication. Useful comparative studies not done
GENERAL MEASURES
Although experts agree that adopting a "healthy lifestyle" is key to better outcomes, there are few clinical trials to access specific diet or exercise effects
MEDICATION (DRUGS)
First Line
Maintenance therapy for Bipolar Disorder often consists of 3-4 of the following psychoactive medications. (8)
Antiseizure Medications
NOTE: Taper any antiseizure med discontinued for reasons other than major side effects.
• Carbamazepine (Carbatrol, Equetro, Tegretol, generic):
- FDA approval: Equetroonly for acute mania and mixed episodes
- Selected warnings: Do not use with TCA or MAOI/Caution with renal or cardiac disease. (Aplastic anemia/agranulocytosis/Preg Cat D)
- Monitoring: Baseline and q3-6 months
• Divalproex sodium (Depakote, generic)
- FDA approval: None
- Selected warnings: Do not use with hepatic or urea cycle disorders. Pancreatitis, polycystic ovary syndrome Preg Cat D. Dose-related hepatic failure and low platelets
- Monitoring: Baseline and q6 months
• Lamotrigine (Lamictal)
- FDA approval: Only for maintenance therapy
- Selected warnings: Titrate slowly (rash). Caution with renal, hepatic, or cardiac impairment. Blood dyscrasias, acute multiorgan failure, deadly hypersensitivity. Chronic ophthal. Preg Cat C.
- Monitoring: Baseline
• Oxcarbazepine (Trileptal)
- FDA approval: None
- Selected warnings: Caution if hypersensitivity to carbamazepine. Severe rash, hyponatremia/Preg Cat C adjust for CrCl.
- Monitoring: Baseline
• Topiramate (Topamax)
- FDA approval: None
- Adult dose: 25 mg/d; increase by 25-50 mg q3-14 days prn/as tolerated. Adjust for CrCl.
- Selected warnings: Possible acidosis in predisposed states. Renal stones, low serum bicarb, acute myopia, oligohidrosis. Preg Cat C.
- Monitoring: Baseline and as needed (prn)
Atypical Antipsychotics
NOTE: All of these drugs have the following possible major side effects: Orthostatic hypotension, Poor ability to reduce core body temperature, Negatively effect glucose regulation, Negatively affect lipid metabolism, Tardive dyskenesia, Increased mortality in elderly with dementia-related psychosis, Seizures, Neuroleptic malignant syndrome, Weight gain. All except aripiprazole may increase prolactin Preg Cat C.
NOTE: All of these drugs need the following
• Monitoring: Blood work and weight at baseline then 4, 8, and 12 weeks; then q3 months
• Aripiprazole (Abilify):
- FDA approval: Acute mania, mixed episodes, and maintenance
- Selected warnings: CVAs in seniors with dementia
• Olanzapine (Zyprexa)
- FDA approval: Acute mania, mixed episodes, and maintenance therapy (Zydis ODT contains phenylalanine)
- Selected warnings: CVAs in seniors with dementia
• Quetiapine (Seroquel)
- FDA approval: Acute mania
- Selected warnings: Cataracts, hypothyroidism
- Monitoring: Eye exam at baseline, then prn
• Risperidone (Risperdal)
- FDA approval: Acute mania and mixed episodes
- Selected warnings: M tabs contain phenylalanine
• Ziprasidone (Geodon)
- FDA approval: Acute mania and mixed episodes
Lithium
Lithium (Lithobid, Eskalith, generic)
FDA approval: Adult acute mania and maintenance therapy
Selected warnings: Use with caution in patients with significant renal or cardiovascular disease, in severely debilitated or dehydrated patients, and sodium-depleted patients (diuretics, Angiotensin Converting Enzyme Inhibitors (ACEIs). Toxicity can lead to diabetes insipidus, seizures, encephalopathic syndrome, arrhythmias, hypothyroidism. Preg Cat D.
Monitoring: At baseline, with dose change, then in 5 days, then q2-3 months  3, then q6-12 months
Second Line
• Antidepressants (not until mood stabilizers are on board) for some patients
• Benzodiazepines
FOLLOW-UP
DISPOSITION
Admission Criteria
Both primarily determined by safety
Issues for Referral
• Experience and comfort level of physician
• Stability of patient
PROGNOSIS
• Most untreated persons will experience manic and/or depression episodes across their lifespan
• Treatment reduces frequency and severity
COMPLICATIONS
In general, the most extreme "complication" is violence toward self or others
PATIENT MONITORING
• Careful medication monitoring
• Regularly scheduled visits to help support medication adherence and healthy lifestyle
REFERENCES
1. Kessler RC, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: Results from the National Comorbidity Study. Arch Gen Psychiatry. 1994;51:8-19.
2. Kieseppa T, et al. High concordance of bipolar I disorder in a nationwide sample of twins. Am J Psychiatry. 2004;161(10):1814-21.
3. Craddock N, Jones I. Molecular genetics of BD. Br J Psychiatry. 2001;41(suppl):128-133.
4. Rush J. Toward an Understanding of BD and Its Origin. J of Clinical Psychiatry 2003;64(suppl 6): 4-8.
5. Keck PE. Evaluating Treatment decisions in Bipolar Depression. CME. Medsacpe. www.medscape.com
6. Mitchell PB, Wilhelm K, Parker G, et al. The clinical features of bipolar depression: A comparison with matched major depressive disorder patients. J Clin Psychiatry. 2001;62:212-216.
7. Hirshfeld RM. Validation of the Mood Disorder Questionnaire Bipolar Depression Bulletin. July 2004.
8. Post RM. Practical approaches to polypharmacy in the long-term management of bipolar disorder. Drug Benefit Trends. 2004;16:329-342.
9. Ketter TA, Ed. Advances in Treatment of Bipolar Disorder. Review of Psychiatry, Vol 24 Amer Psychiatric Publishing
10. Working Group on BD. Practice guidelines for the treatment of patients with BD. Am J Psychiatry 2002;159(Suppl 4):1-50.
11. Vieta E, Goikolea JM. Atypical antipsyhotics: Newer options for mania and maintenance therapy. BD 2005;7(Suppl 4):21-33.
ADDITIONAL READING
• Hirschfeld RM, Vomik LA. Rscognition and diagnosis of bipolar disorder. J Clin Psychiatry. 2004;65(Suppl 15):5-9.
• Vieta E, Pacchiarotti I, Scott J, et al. Evidence-based research on the efficacy of psychologic interventions in bipolar disorders: a critical review. Curr Psychiatry Rep. 2005;7(6):449-455.