Bipolar Meds

Bipolar Disorder Treatment Overview

  • Bipolar Disorder is treated with three major groups of drugs:

    • Mood stabilizers

    • Antipsychotics

    • Antidepressants

Mood Stabilizers

  • Definition: Mood stabilizers are drugs that serve multiple functions:

    1. Relieve symptoms during manic and depressive episodes.

    2. Prevent recurrence of manic and depressive episodes.

    3. Do not worsen symptoms of mania or depression, or accelerate the rate of cycling.

  • Common Mood Stabilizers:

    1. Lithium

    2. Divalproex sodium (Valproate)

    3. Carbamazepine

Antidepressants

  • Usage: Antidepressants are usually given in conjunction with a mood stabilizer due to long-held belief that they may elevate mood excessively and lead to hypomania or manic episodes.

  • Commonly used Antidepressants:

    • Bupropion (Wellbutrin)

    • Venlafaxine (Effexor XR)

    • SSRIs: such as Fluoxetine (Prozac) or Sertraline (Zoloft)

Acute Therapy: Manic Episodes

  • Preferred Medications:

    • Lithium and Valproate are the preferred treatments.

    • The choice between Lithium and Valproate is determined by clinical presentation:

    • Valproate is preferred in most cases except classic euphoric mania.

    • Lithium is the treatment of choice for classic euphoric mania.

  • Psychotic Features: If psychosis is present, a second-generation antipsychotic (e.g., Risperidone (Risperdal) or Olanzapine (Zyprexa)) may be added to treatment.

  • Combination Use: Mood stabilizers can be used together.

  • Timeline: Stabilization may take 2 or more weeks.

  • Adjuvant Therapy: Antipsychotics or benzodiazepines may be added to alleviate insomnia, anxiety, and agitation until the mood stabilizer is effective.

Acute Therapy: Depressive Episodes

  • Treatment options include:

    • Mood stabilizers alone, or

    • Addition of an antidepressant (never use an antidepressant alone due to risk of inducing hypomania or mania).

  • Preferred Antidepressants: Include Bupropion, Venlafaxine, or an SSRI.

Long-term Preventive Treatment

  • Long-term treatment typically involves one or more mood stabilizers, often utilizing the medication that was effective acutely.

  • Electroconvulsive Therapy (ECT): Not a first-line choice. Reserved for patients who have not responded adequately to pharmacotherapy. Indications include:

    • Psychotic depression

    • Severe nonpsychotic depression

    • Severe mania

    • Rapid cycling Bipolar Disorder

Lithium

  • Chemical Information: Lithium is a simple inorganic ion, carrying a single positive charge. It is found in the same group as potassium and sodium but has no known physiological function.

  • Onset of Action:

    • Antimanic effects typically begin within 5-7 days.

    • Full therapeutic benefits may take 2-3 weeks.

  • Indications: Primarily used for classic (euphoric) mania, while Valproate is generally preferred for other presentations.

  • Recent Findings:

    • Lithium may be superior to Valproate at preventing suicide, leading to an increased likelihood of its use.

    • Lithium has been shown to increase total grey matter in regions affected by Bipolar disorder, which includes the prefrontal cortex, hippocampus, and caudate nucleus, suggesting neuroprotective effects.

  • Pharmacokinetics:

    • Lithium is excreted rapidly by the kidneys, which necessitates divided daily doses due to its short half-life and high toxicity potential.

    • Sodium levels must remain normal, as low sodium can cause lithium retention and toxic levels.

  • Monitoring Levels:

    • Therapeutic lithium levels should be below 1.5 mEq/L.

    • Initial therapy during a manic episode requires levels between 0.8-1.4 mEq/L.

    • After stabilization, maintenance levels are reduced to 0.4-1 mEq/L.

  • Blood Testing Protocol: Blood should be drawn in the morning, 12 hours post-evening dose.

    • Perform tests every 3-6 months during maintenance therapy.

  • Toxicity Levels:

    • Mild Toxicity (Fine tremor, GI upset, thirst, muscle weakness): Occurs at levels within therapeutic range

    • Moderate Toxicity (Persistent GI upset, coarse tremor, confusion): At 1.5-2 mEq/L

    • Severe Toxicity (Ataxia, seizures, vegetative state): At 2.0-2.5 mEq/L

    • Critical Toxicity (Convulsions, oliguria): Above 2.5 mEq/L

  • Polyuria: Occurrence in 50-70% of patients on chronic lithium, which can exceed 3 L/day. This is due to lithium’s antagonistic effects on antidiuretic hormone.

  • Hydration Recommendations: Patients should drink 8-12 glasses of fluid daily to maintain hydration.

  • Lithium Excretion Measures: Gastric lavage and specific treatments can enhance lithium clearance, including urea, mannitol, and aminophylline. Both renal clearance (dialysis) and hemodyalysis are viable for lithium overdose.

Laboratory Monitoring

  • Annual assessments for:

    • Sodium

    • T3

    • T4

    • TSH

    • Complete Blood Count (CBC)

Drug Interactions

  • Diuretics: Use with caution due to the risk of sodium loss.

  • NSAIDs: Can increase lithium levels significantly by about 60% due to suppression of prostaglandin synthesis and increased renal reabsorption of lithium. Aspirin (ASA) does not elevate lithium levels and can be used.

  • Anticholinergics: May cause urinary hesitancy, and when combined with lithium-induced polyuria, this can lead to discomfort. Patients should avoid drugs with significant anticholinergic properties such as antihistamines and phenothiazines.

  • Contraindications:

    • Patients with cardiovascular disease, brain damage, renal disease, thyroid disease, myasthenia gravis

    • Not recommended for use during pregnancy or while breastfeeding.

    • Not to be prescribed for children under 12 years of age.

Antiepileptic Drugs

  • List of Antiepileptic Drugs Utilized:

    1. Divalproex sodium (Valproate)

    2. Carbamazepine

    3. Lamotrigine

  • Mechanism of Action: These drugs can help in managing symptoms of mania and depression while stabilizing mood in patients with Bipolar Disorder.

  • Divalproex Sodium Information:

    • First anti-seizure agent approved for treating Bipolar Disorder, particularly acute mania.

    • Weaker at preventing depressive episodes; appears to have neuroprotective properties similar to Lithium.

    • Acts faster than Lithium, has a high therapeutic index, and offers a more favorable side effect profile.

    • Target plasma level: 50-120 mcg/ml but can cause serious toxicity (thrombocytopenia, pancreatitis, liver failure).

  • Carbamazepine (Tegretol):

    • Approved for treatment and prevention of manic episodes but less effective for depression.

    • Common neurologic side effects include visual disturbances and ataxia, generally resolve with continued treatment.

    • Hematologic effects include leukopenia and thrombocytopenia; monitor CBC and platelet counts initially and periodically throughout treatment.

  • Lamotrigine (Lamictal):

    • Indicated for long-term maintenance therapy of Bipolar Disorder.

    • Aims to prevent affective relapses into mania or depression; can be used alone or with other mood stabilizers.

    • Side effects to monitor include headache, dizziness, and potential for life-threatening rashes (Stevens-Johnson syndrome).

Antipsychotic Drugs

  • Usage: Antipsychotic medications are used in acute settings to control symptoms during manic episodes and in long-term management to help stabilize mood. Beneficial effects are observed in patients with or without psychotic features.

  • Combination Therapy: Often administered alongside mood stabilizers such as Lithium or Valproate.

  • Atypical Antipsychotics: Preferable due to lower risk of extrapyramidal side effects (including tardive dyskinesia). Five atypical agents approved for treating manic episodes include:

    1. Olanzapine (Zyprexa)

    2. Quetiapine (Seroquel)

    3. Risperidone (Risperdal)

    4. Aripiprazole (Abilify)

    5. Ziprasidone (Geodon)

  • Long-term Use of Atypicals: Currently, only three atypical agents are approved for long-term prevention of mood episodes:

    1. Aripiprazole

    2. Olanzapine

    3. Ziprasidone

Antianxiety Agents

  • Medications: Clonazepam (Klonopin) and Lorazepam (Ativan) are antianxiety medications that can be beneficial for treating acute mania, especially in patients resistant to other treatments.

  • Indication: Also effective in managing psychomotor agitation associated with mania.

  • Caution: Should be avoided in individuals with a history of substance abuse.