bipolar disorder

Bipolar Disorder Overview

  • Definition: A lifelong cyclic mood disorder characterized by recurrent episodes of mood and behavioral changes: mania, hypomania, euthymia, or depressive mood.

Clinical Presentation

  • Chronic Condition: Bipolar disorder is chronic and lifelong, with recurrent mood episodes.

  • Residual Symptoms: Residual (subsyndromal) symptoms may persist even with treatment.

  • Prevalence of Symptoms: Depressive symptoms predominate, accounting for approximately $ rac{1}{3}$ of illness duration.

Diagnosis

  • Initial Steps: First, rule out medications and substance-induced causes, as well as medical or psychiatric conditions.

Manic Episode Criteria

  • Observable Symptoms: Obvious to everyone around the individual.

  • Mood Changes: Characterized by abnormally and persistently increased activity or energy, expansive or persistent irritable mood.

  • Functional Impairment: Can involve quitting a job, hospitalization, or experiencing psychosis.

  • Key Mania Symptoms: Minimum of three symptoms present:

    • Grandiosity: Exaggerated achievements, a belief of being special or powerful, rules disregarded, lack of empathy, manifested as arrogance and boasting, difficulty accepting criticism.

    • Decreased Sleep: Usually the first symptom that presents; the individual feels they don’t need sleep, believing they have significant tasks to accomplish.

    • Pressured Speech: Rapid speech patterns underpinned by a sense of urgency.

    • Distractibility: Difficulty focusing, easily sidetracked by irrelevant stimuli.

    • Increased Goal-Driven Activity or Risky Behavior: Money spending, gambling, or sexual activity.

  • Duration: Symptoms must persist for greater than one week; duration does not matter if hospitalized.

Hypomanic Episode

  • Defined as mania without hospitalization, functional impairment, or psychosis.

  • Duration: Greater than four days.

Major Depressive Episode (MDE)

  • Criteria: Greater than five symptoms persisting for more than two weeks, with at least one symptom being:

    • Depressed Mood or Loss of Interest.

  • Diagnostic Mnemonic: M SIG E CAPS

    • M: Mood (depressed or irritable)

    • S: Sleep (insomnia or hypersomnia)

    • I: Interest (loss of interest in most activities)

    • G: Guilt (feelings of worthlessness or excessive guilt)

    • E: Energy (fatigue or loss of energy)

    • C: Concentration (diminished ability to think or concentrate)

    • A: Appetite (weight loss or gain unrelated to dieting)

    • P: Psychomotor Agitation or Retardation (observable by others)

    • S: Suicidal Ideation

Bipolar Disorder Types

  • Bipolar 1 Disorder:

    • Core Distinction: Must have at least one manic episode. Can also include hypomania or MDE.

    • Typical Presentation: Mania usually presents as the first episode.

  • Bipolar 2 Disorder:

    • Characterization: Associated with chronic depression.

    • Symptom Criteria: Greater than one hypomanic episode and greater than one MDE. No history of manic episodes.

    • Depressive Burden: Often more chronic with increased time spent in depressive episodes.

    • Risks: Increased risk of suicide.

  • Cyclothymic Disorder (for informational purposes):

    • Characteristics: Chronic fluctuating mood symptoms that never meet the criteria for hypomania or MDE.

Suicidal Risk in Bipolar Disorder

  • Increased Risk Factors: Bipolar 2 disorder, psychiatric hospitalization, and substance use.

Treatment Approaches

Acute Phase Treatment

  • Goals: Rapid control of mood symptoms and agitation, restore sleep, and reduce the risk of harm to oneself or others.

Continuation Phase Treatment

  • Goals: Prevent relapse and minimize adverse effects. Support adherence to treatments.

Maintenance Phase Treatment

  • Goals: Achieve mood stability for at least three months and improve functioning. Use the lowest effective number of medications.

Long-Term Treatment Strategies

Medications

  • Mood Stabilizers:

    • Lithium: Gold standard for mood stabilization.

    • Lamotrigine: Effective for maintenance treatment.

    • Carbamazepine & Divalproex: Commonly used as mood stabilizers.

  • Second-Generation Antipsychotics (SGAs):

    • Used in acute mania, bipolar depression, and for maintenance therapy.

  • Antidepressants:

    • Bupropion and SSRIs should be used with a mood stabilizer; not recommended as monotherapy due to the potential for inducing mania.

Non-Pharmacological Options

  • Lifestyle Management: Regular sleep, exercise, and nutrition.

  • Psychoeducation: Educating patients about their condition.

  • ECT: Recommended only for severe or refractory cases.

  • Neuromodulation: Bright light therapy may be beneficial for bipolar depression.

Lithium Specifics

  • FDA Approval: Approved for acute mania and maintenance treatment.

  • Characteristics: Considered the gold standard mood stabilizer; reduces suicide risk.

  • Narrow Therapeutic Index: Wrong doses can cause toxic levels.

Dosage Guidelines for Lithium

  • Starting Dose: 600-800 mg/day.

  • Maintenance Dose: 900-1200 mg/day.

  • Target Serum Levels:

    • Acute Mania: 0.8-1.2 mEq/L

    • Maintenance: 0.6-1.0 mEq/L

  • Steady State Timeframe: 5 days where the first level is recorded; lithium levels must be checked carefully.

Lithium Administration Considerations

  • Administration Instructions: Take with food if gastrointestinal upset occurs. Maintain hydration and consistent salt intake.

  • Monitoring Requirements: Regular monitoring of BMP, TSH, CBC, weight, pregnancy test, and ECG. Check lithium levels regularly.

Contraindications of Lithium

  • Warnings: #

    • Dehydration, use of diuretics, sodium depletion, renal or cardiovascular disease, pregnancy (particularly avoid in the first trimester due to cardiac malformations).

  • Toxicity Signs:

    • Levels $ ext{>}$ 1.5-2.0 mEq/L can signal gastrointestinal issues, mild ataxia, and tremors. Levels $ ext{>}$ 2.5 mEq/L may lead to severe complications including coma and cardiovascular collapse.

Drug-Drug Interactions with Lithium

  • Drugs Increasing Lithium Levels:

    • NSAIDs (except aspirin and sulindac), ACE inhibitors, ARBs, and diuretics (thiazides).

  • Drugs Decreasing Lithium Levels:

    • Caffeine and high sodium intake.

  • Serotonergic Drugs: Risk of serotonin syndrome with SSRIs, SNRIs, and Linezolid.

Divalproex Sodium

  • Indication: Monotherapy or with antipsychotics for acute manic and mixed episodes.

  • Mechanism: Increases GABA and decreases neuronal excitability.

  • Loading Strategy: 20-30 mg/kg immediate-release or 25 mg/kg extended-release.

  • Initial Titration Plan: Start with 500-750 mg at bedtime on day 1, increase by 500 mg daily, max dosage 60 mg/kg/day.

Serum Concentration for Divalproex

  • Target Range: 50-125 mcg/mL; wide therapeutic range allows flexibility, even above 126 mcg/mL being acceptable in clinical context.

Contraindications of Divalproex

  • High-Risk Groups: Hepatic disease, pregnancy, mitochondrial disorders.

  • Precautions: Hepatotoxicity, pancreatitis, hyperammonemic encephalopathy, and dose-related thrombocytopenia.

Divalproex Adverse Effects

  • Potential Side Effects: Neurologic issues (dizziness), gastrointestinal issues (diarrhea, nausea), hepatotoxicity, alopecia, rash, and thrombocytopenia.

  • Hemodialysis Consideration: Hemodialysis may be an option in severe cases of toxicity.

Monitoring Divalproex Levels

  • Timing for Checking Levels: 3-4 days after initiation or when a stable dose is achieved.

Counseling Points for Divalproex

  • Usage Guidance: Take with food to reduce gastrointestinal upset. Avoid in pregnancy unless using high doses of folic acid to reduce neural tube defect risk.