Bipolar I Disorder – Causes, Symptoms, Diagnosis, Treatment and Ongoing care
- Bipolar I (BP-I) is a mood disorder characterized by at least 1 manic or mixed episode, often alternating with episodes of major depression, that causes marked impairment and/or hospitalization.
- Symptoms are not caused by a substance (e.g., drug), a general medical condition, or a medication.
New onset in older patients (>50 years of age) requires a workup for organic or chemically induced pathology.
There is overlap with symptoms of attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). Children and adolescents experience more rapid cycling and mixed states. Depression often presents as irritable mood.
- Potential teratogenic effects of commonly used medications (e.g., lithium, valproic acid)
- Symptoms may be exacerbated in the postpartum period.
- Most common onset is between 15 and 30 years of age.
- More common in single and divorced persons
- Less common in college graduates
- Higher than average incidence in higher socioeconomic groups
- 1.0–1.6% lifetime prevalence
- Equal among men and women (manic episodes more common in men; depressive episodes more common in women)
- Women are more likely to be rapid cyclers (4 or more mood episodes per year)
- Equal among races; however, clinicians tend to misdiagnose schizophrenia in African-American patients with BP-I.
Genetics, major life stressors (especially loss of parent or spouse), or substance abuse
- Monozygotic twin concordance 40–70%
- Dizygotic twin concordance 5–25%
- 50% of patients have at least one parent with a mood disorder.
- 1st-degree relatives of people with BP-I are approximately 7× more likely to develop BP-I than the general population.
Treatment adherence and education can help to prevent relapses.
Dysregulation of biogenic amines or neurotransmitters (particularly serotonin, norepinephrine, and dopamine). MRI findings suggest abnormalities in prefrontal cortical areas, striatum, and amygdala that predate illness onset (1).
Genetic predisposition and major life stressors can trigger initial and subsequent episodes.
Commonly Associated Conditions
Substance abuse (60%), ADHD, anxiety disorders, and eating disorders
- The diagnosis of BP-I requires at least 1 manic or mixed episode (simultaneous mania and depression). Although a depressive episode is not necessary for the diagnosis, 80–90% of people with BP-I also experience depression.
- Manic episode, DSM-IV-TR criteria:
- 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 “DIG FAST” symptoms must persist (4 if the mood is only irritable) and must be present to a significant degree:
- 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)
- Major depressive episode: See “Bipolar II Disorder” for DSM-IV-TR criteria (Note: A depressive episode is not necessary for the diagnosis of BP-I.)
- Mixed episode: Criteria are met for both a manic and major depressive episode nearly every day during at least a 1-week period, and the mood disturbance causes significant impairment in functioning.
- Signs and symptoms more likely in bipolar than in unipolar depression (2): Agitation/restlessness, suicidal ideation/planning, increased frequency of depressive episodes, melancholia, psychomotor retardation, younger age of onset, hyperphagia, hypersomnia, family history of bipolar disorder, subsyndromal hypomanic symptoms (particularly increased goal-directed activity)
- Collateral information makes diagnostics more complete and is often necessary for a clear history.
- History: Safety concerns (e.g., Suicide/homicide ideation? Safety plan? Psychosis present?); Physical well-being (e.g., Number of hours of sleep? Appetite? Substance abuse?); Personal history (e.g., Told life of the party? Talkative? Speeding? Spending sprees or donations? Credit-card or gambling debt? Promiscuous? Other risk-taking behavior? Legal trouble? Religious infatuation?)
- Mental status exam in acute mania:
- General appearance: Bright clothing, excessive makeup, disorganized or discombobulated, psychomotor agitation
- Speech: Pressured, difficult to interrupt
- Mood/affect: Euphoria, irritability/expansive, labile
- Thought process: Flight of ideas (streams of thought occur to patient at rapid rate), easily distracted
- Thought content: Grandiosity, paranoia, hyperreligious
- Perceptual abnormalities: 3/4 of manic patients experience delusions, grandiose or paranoid
- Suicidal/homicidal ideation: Irritability or delusions may lead to aggression toward self or others; suicidal ideation is common with mixed episode.
- Insight/judgment: Poor/impaired
- See “Bipolar II Disorder” for an example of a mental status exam in depression.
- With mixed episodes, patients may exhibit a combination of manic and depressive mental states.
Diagnostic Tests & Interpretation
- BP-I is a clinical diagnosis.
- Mood Disorder Questionnaire is a self-assessment screen for bipolar disorders (sensitivity 73%, specificity 90%) (3).
- Patient Health Questionnaire-9 helps to determine the presence and severity of a depressive episode.
- Thyroid-stimulating hormone (TSH), complete blood count (CBC), CMP, liver function tests (LFTs), antinuclear antibody, RPR, human immunodeficiency virus, erythrocyte sedimentation rate, UDS
- Drug/alcohol screen with each presentation
- Dementia workup if new onset in seniors (e.g., TSH, RPR, vitamin B12, brain imaging)
Consider brain imaging (CT scan, MRI) with initial onset of mania to rule out organic cause (e.g., tumor, infection, or stroke), especially with onset in elderly and if psychosis is present.
Consider electroencephalogram if presentation suggests temporal lobe epilepsy (hyperreligiosity, hypergraphia).
- Other psychiatric considerations: Unipolar depression ± psychotic features, schizophrenia, schizoaffective disorder, personality disorders (particularly antisocial, borderline, histrionic, and narcissistic), attention-deficit disorder ± hyperactivity, substance-induced mood disorder
- Medical considerations: Epilepsy (e.g., temporal lobe), brain tumor, infection (e.g., AIDS, syphilis), stroke, endocrine (e.g., thyroid disease), multiple sclerosis
- In children, consider ADHD and ODD
- Ensure safety
- Medication management
- Psychotherapy (e.g., cognitive-behavioral therapy, social rhythm therapy)
- Stress reduction
- Patient and family education
- Treatment may consist of 1–4 of the following mood stabilizers or other psychotropic medications. When combining these agents, consider adding different classes (e.g., an atypical antipsychotic and/or an antiseizure medication and/or lithium).
- Lithium (Lithobid, Eskalith, generic): Dosing: 600–1,200 mg/day divided bid–qid; start 600 mg PO tid in acute mania, and titrate based on blood levels. Warning: Use caution in kidney and heart disease; use can lead to diabetes insipidus, thyroid disease. Use caution in sodium-depleted patients (e.g., those using diuretics or ACE inhibitors); dehydration can lead to toxicity (seizures, encephalopathy, arrhythmias). Pregnancy category D (Ebstein anomaly). Monitor: Check electrocardiogram (ECG) >40 years, TSH, blood urea nitrogen, creatine, lytes at baseline and every 6 months; check level 5 days after initiation or dose change, then every 1–2 weeks ×3, then every 2–3 months (Goal: 0.8–1.2 mmol/L).
- Antiseizure medications:
- Divalproex sodium, valproic acid (Depakote, Depakene, generic): Dosing: Start 250–500 mg bid–tid; maximum 60 mg/kg/day. Black box warnings: Hepatotoxicity, pancreatitis, thrombocytopenia, pregnancy category D (neural tube defects). Monitor: CBC, LFTs at baseline and every 6 months; check VPA level 5 days after initiation and dose changes (Goal: 50–125 µg/mL).
- Carbamazepine (Carbatrol, Equetro, Tegretol, generic): Dosing: 800–1,200 mg/day PO divided bid–qid; start 100–200 mg PO bid and titrate to lowest effective dose. Warning: Do not use with tricyclic acid or within 14 days of a monoamine oxidase inhibitor. Use caution with kidney/heart disease; risk of aplastic anemia/agranulocytosis, enzyme inducer; pregnancy category D. Monitor: CBC, LFTs at baseline and every 3–6 months; check level 4–5 days after initiation and dose changes (Goal: 4–12 µg/mL).
- Lamotrigine (Lamictal): Dosing: 200 mg/day; start 25 mg/day × 2 weeks, then 50 mg/day × 2 weeks, then 100 mg/day × 1 week (Note: Use different dosing if adjunct to valproate). Warning: Titrate slowly (risk of Stevens-Johnson syndrome); use caution with kidney/liver/heart disease; pregnancy category C.
- Oxcarbmazepine (Trileptal), gabapentin (Neurontin), and topiramate (Topamax) are also used in BP-I but are not approved by the Food and Drug Administration (FDA).
- Atypical antipsychotics (AAs):
- Side effects of AAs: Orthostatic hypotension, metabolic side effects (glucose and lipid dysregulation, weight gain), tardive dyskinesia, NMS, prolactinemia (except Abilify), increased risk of death in elderly with dementia-related psychosis, pregnancy category C
- Monitor: LFTs, lipids, glucose at baseline, 3 months, and annually; check for EPS with AIMS and assess weight (with abdominal circumference) at baseline, at 4, 8, and 12 weeks, and then every 3–6 months; monitor for orthostatic hypotension 3–5 days after starting or changing dose.
- Aripiprazole (Abilify): Dosing: 15 mg/day, max. 30 mg/day; less likely to cause metabolic side effects
- Olanzapine (Zyprexa, Zydis): Dosing: 5–20 mg/day; most likely to cause metabolic side effects (weight gain, diabetes)
- Symbyax (olanzapine + fluoxetine): Dosing: 6/25 mg, FDA approved for BP depression
- Quetiapine (Seroquel): Dosing: In mania, 200–400 mg bid; in bipolar depression, 50–300 mg qhs. Caution: Cataracts
- Risperidone (Risperdal): Dosing: 1–6 mg/day divided qid–bid. Generic and every 2 weeks IM preparations available
- Ziprasidone (Geodon): Dosing: 40–80 mg bid; less likely to cause metabolic side effects. Caution: QTc prolongation (>500 ms) has been a/w use (0.06%). Consider ECG at baseline.
- Antidepressants (in addition to mood stabilizers)
- Benzodiazepines (for acute agitation with mania, associated anxiety)
- Sleep medications
- Psychotherapy (e.g., cognitive-behavioral therapy, social rhythm therapy) in conjunction with medications is key (4).
- Regular exercise, a healthy diet, and sobriety have been shown to help prevent worsening of symptoms.
Issues for Referral
Comfort level of doctor, stability of patient, patients benefit from a multidisciplinary team, including a primary care physician and a psychiatrist.
- Electroconvulsive therapy can be helpful in acute mania and depression.
- Light therapy for seasonal component to depressive episodes (use with caution because it can precipitate manic episode)
Complementary and Alternative Medicine
Omega-3 fatty acids may help.
Admit if acutely dangerous to self or others.
To admit a patient (>18 years of age) to a psychiatric unit involuntarily, the patient must have a psychiatric diagnosis (e.g., BP-I) or present a danger to him- or herself or others, or their mental disease must be inhibiting them from obtaining their basic needs (e.g., food, clothing, etc.).
Alert staff to potentially dangerous or agitated patients. Acute suicidal threats need continuous observation.
Determined by safety
- Regularly scheduled visits support adherence with treatment.
- Frequent communication among primary care doctor, psychiatrist, and therapist
Mood charts are helpful to monitor symptoms.
National Alliance on Mental Illness (NAMI): http://www.nami.org/
- Frequency and severity of episodes are related to medication adherence, consistency with therapy, amount of sleep, and support systems.
- 40–50% of patients experience another manic episode within 2 years of the 1st episode.
- 25–50% attempt suicide, and 15% die.
- Substance abuse, unemployment, psychosis, depression, and male sex are associated with a worse prognosis.
1. Fornito A, Yücel M, Wood SJ, et al. Anterior cingulate cortex abnormalities associated with a first psychotic episode in bipolar disorder. Br J Psychiatry. 2009;194:426–33.
2. Perlis RH, Brown E, Baker RW, et al. Clinical features of bipolar depression versus major depressive disorder in large multicenter trials. Am J Psychiatry. 2006;163:225–31.
3. Hirschfeld RM, Holzer C, Calabrese JR, et al. Validity of the mood disorder questionnaire: a general population study. Am J Psychiatry. 2003;160:178–80.
4. Depp CA, Moore DJ, Patterson TL, et al. Psychosocial interventions and medication adherence in bipolar disorder. Dialogues Clin Neurosci. 2008;10:239–50.
American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry. 2002;159:1–50.
McAllister-Williams RH. Relapse prevention in bipolar disorder: a critical review of current guidelines. Psychopharmacol. 2006;20(2 Suppl):12–6.
See Also (Topic, Algorithm, Electronic Media Element)
Algorithm: Depression, Adult
- 296.40 Bipolar affective disorder, manic, unspecified degree
- 296.50 Bipolar affective disorder, depressed, unspecified degree
- 296.7 Bipolar I disorder, most recent episode (or current) unspecified
- 296.60 Bipolar affective disorder, mixed, unspecified degree
- 371596008 Bipolar I disorder (disorder)
- 191618007 bipolar affective disorder, current episode manic (disorder)
- 191627008 bipolar affective disorder, current episode depression (disorder)
- 16506000 mixed bipolar I disorder (disorder)
- Bipolar I is characterized by at least 1 manic or mixed episode, often alternating with episodes of major depression, that causes marked impairment.
- 25–50% of BP-I patients attempt suicide, and 15% die by suicide.
- There is no way to prevent the onset of BP-I, but treatment adherence and education can help to prevent further episodes.