Bipolar Meds

Bipolar Disorder Treatment Overview

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

    • Mood Stabilizers

    • Antipsychotics

    • Antidepressants

Mood Stabilizers

  • Definition: Drugs that help in managing bipolar disorder by relieving symptoms during manic and depressive episodes, preventing recurrence of these episodes, and ensuring that symptoms do not worsen or accelerate cycles.

  • Major Mood Stabilizers:

    • Lithium

    • Divalproex sodium (Valproate)

    • Carbamazepine

Antidepressants

  • Usage: Generally prescribed in conjunction with mood stabilizers to mitigate the risk of triggering hypomania or manic episodes due to elevated mood.

  • Common Antidepressants Used:

    • Bupropion (Wellbutrin)

    • Venlafaxine (Effexor XR)

    • SSRIs (Selective Serotonin Reuptake Inhibitors) such as Fluoxetine (Prozac) or Sertraline (Zoloft)

Acute Therapy

Manic Episodes

  • First-line treatments: Lithium and Valproate.

    • Choice Determinants:

    • Clinical presentation helps determine treatment.

    • Valproate is preferred when classic euphoric mania is not present.

    • Lithium is preferred for classic euphoric mania.

  • Psychotic symptoms: If present, second-generation antipsychotics such as Risperidone (Risperdal) or Olanzapine (Zyprexa) can be added.

  • Combination of mood stabilizers is acceptable; takes 2 or more weeks to achieve mood stabilization.

  • Adjuvant Therapy: Antipsychotics or benzodiazepines may be utilized to manage insomnia, anxiety, and agitation until the mood stabilizer fully acts.

Depressive Episodes

  • Treatment Options: As with manic episodes, mood stabilizers can be used alone or an antidepressant may be added, but it is crucial to avoid using antidepressants alone to prevent possible hypomania or mania.

  • Preferred Antidepressants: Again include bupropion, venlafaxine, or SSRIs.

Long-term Preventive Treatment

  • Strategy: Utilize one or more mood stabilizers based on what was effective during acute therapy.

  • Electroconvulsive Therapy (ECT): Reserved as a treatment option for patients unresponsive to medications. Indications include:

    • Psychotic depression

    • Severe non-psychotic depression

    • Severe mania

    • Rapid cycling Bipolar disorder

Lithium

  • Nature: An inorganic ion with a single positive charge, belonging to the same group as potassium and sodium. It has no known physiological function but is found in animal tissues.

  • Antimanic Effects: Begin within 5-7 days; full effect may take 2-3 weeks.

  • Preferred Use: Mainly for classic (euphoric) mania, with Valproate being more suitable for other forms of mania.

  • Research Findings: Recent studies suggest Lithium may be superior to Valproate in reducing suicide risk and may enhance grey matter in specific brain regions with atrophy in bipolar disorder (e.g., prefrontal cortex, hippocampus, caudate nucleus).

  • Administration: Due to its short half-life and toxicity, Lithium is administered in divided daily doses. Monitoring of sodium is critical, as low sodium can elevate Lithium levels and lead to toxicity.

Lithium Safety and Toxicity

  • Monitoring Guidelines:

    • Therapeutic Levels: Maintain below 1.5 mEq/L; initial range during acute episodes should be 0.8-1.4 mEq/L; after stabilization, aim for 0.4-1 mEq/L.

    • Testing: Blood levels should be drawn in the AM, 12 hours after the last evening dose and monitored every 3-6 months during maintenance.

  • Signs of Toxicity:

    • Mild (1-1.5 mEq/L): Hand tremors, GI upset, thirst, muscle weakness.

    • Moderate (1.5-2 mEq/L): Persistent GI discomfort, coarse hand tremors, confusion, sedation, muscle irritability, ECG changes.

    • Severe (2.0-2.5 mEq/L): Ataxia, giddiness, excessive urination, serious ECG changes, seizures, stupor, hypotension, coma, and potential death.

    • Toxicity Symptoms Above 2.5 mEq/L: General convulsions, oliguria, and death.

  • Polyuria: Occurs in 50-70% of chronic users, can lead to daily urine outputs exceeding 3 L.

  • Hydration Advice: Patients should be instructed to drink 8-12 glasses of fluid daily to avoid dehydration.

  • Litigation and Emergency Treatment: Gastric lavage or treatment with urea, mannitol, and aminophylline can hasten lithium excretion. Hemodialysis is effective in lithium removal.

Laboratory and Drug Interaction Monitoring

  • Annual Tests: Sodium, T3, T4, TSH, and CBC should be checked.

  • Drug Interaction Risks:

    • Diuretics: Can cause sodium depletion, thereby increasing lithium toxicity.

    • NSAIDs: Can elevate lithium levels by suppressing renal prostaglandin synthesis (up to 60%).

    • Aspirin (ASA): Does not affect Lithium levels and is acceptable for pain management.

    • Anticholinergics: May lead to urinary retention, particularly problematic for patients experiencing lithium-induced polyuria.

  • Contraindications: Lithium therapy is usually contraindicated in patients with cardiovascular disease, brain injuries, renal diseases, thyroid disorders, myasthenia gravis, pregnancy, breastfeeding, or those under 12 years of age.

Antiepileptic Drugs (AEDs)

  • Three Major Antiepileptic Medications:

    • Divalproex Sodium (Valproate)

    • Carbamazepine

    • Lamotrigine

  • Divalproex Sodium (Valproate):

    • Indication: First anti-seizure medication approved for bipolar disorder. Effective in acute mania and preventing manic relapses, though less effective with depressive episodes.

    • Mechanism of Action: Neuropathic and neuroprotective effects similar to lithium.

    • Dosage Range: Target plasma level is 50-120 mcg/ml.

  • Common Side Effects: Serious adverse effects can include thrombocytopenia, pancreatitis, and liver failure. Not recommended for pregnant patients due to teratogenic risks. Gastrointestinal disturbances and weight gain are frequent.

  • Carbamazepine:

    • Use: Approved for treating and preventing manic episodes. Less effective for depression, but has neurological side effects such as visual disturbances and neurologic unsteadiness.

    • Hematologic Effects: Can include leukopenia, anemia, thrombocytopenia, or aplastic anemia.

    • Metabolic Effects: Induces cytochrome P450 enzymes, may speed up its own metabolism and affect concurrent medications (e.g., oral contraceptives and warfarin).

  • Lamotrigine (Lamictal):

    • Indication: Long-term maintenance therapy of bipolar disorder to prevent affective relapses into mania or depression. Can be used alone or with other mood stabilizers.

    • Side Effects: Common side effects include headache, dizziness, double vision, and the rare but severe risk of skin rashes (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis).

Antipsychotic Drugs

  • Purpose: Used in acute manic episodes to control symptoms and long-term to stabilize mood.

  • Applications: Effective for patients with or without psychotic symptoms; typically used in conjunction with mood stabilizers (lithium or valproate).

  • Atypical (Second-Generation) Antipsychotics: Preferred due to lower risks of extrapyramidal side effects, including tardive dyskinesia.

    • Examples of Atypical Antipsychotics Used in Mania:

    1. Olanzapine (Zyprexa)

    2. Quetiapine (Seroquel)

    3. Risperidone (Risperdal)

    4. Aripiprazole (Abilify)

    5. Ziprasidone (Geodon)

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

    1. Aripiprazole

    2. Olanzapine

    3. Ziprasidone

Antianxiety Agents

  • Medications: Clonazepam (Klonopin) and Lorazepam (Ativan) used for acute mania in patients resistant to other treatments.

  • Effectiveness: Also effective for managing psychomotor agitation associated with mania.

  • Caution: Avoid in individuals with a history of substance abuse.