1. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 33 Drugs for Bipolar Disorder

2. 2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Bipolar Disorder  Formerly known as manic-depressive illness  Afflicts an estimated 3.7% of the adult population  Mainstays of therapy  Lithium, valproic acid  Many also receive an antipsychotic  Chronic condition that requires lifelong treatment

3. 3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Bipolar Disorder  Definition of bipolar disorder (BPD)  Cyclic disorder  Recurrent fluctuations in mood  Episodes of mania and depression persist for months without treatment  Treatment  Drugs  Psychotherapy

4. 4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Characteristics of Bipolar Disorder  Types of mood episodes seen in bipolar disorder (BPD)  Pure manic episode (euphoric mania)  Hypomanic episode (hypomania)  Major depressive episode (depression)  Mixed episode

5. 5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Patterns of Mood Episodes  Subdivided into two major categories  Bipolar I disorder Manic or mixed episodes Manic or mixed episodes Usually depressive episodes Usually depressive episodes  Bipolar II disorder Hypomanic or depressive episodes Hypomanic or depressive episodes Not manic or mixed episodes Not manic or mixed episodes

6. 6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Treatment of Bipolar Disorder  Drug therapy  Nondrug therapy

7. 7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Drug Therapy  Types of drugs employed  Mood stabilizers (Lithium) Relieve symptoms during manic and depressive episodes Relieve symptoms during manic and depressive episodes Prevent recurrence of manic and depressive episodes Prevent recurrence of manic and depressive episodes Do not worsen symptoms of mania or depression; do not accelerate the rate of cycling Do not worsen symptoms of mania or depression; do not accelerate the rate of cycling  Antipsychotics Given during severe manic episodes Given during severe manic episodes  Antidepressants Given during depressive episodes Given during depressive episodes

8. 8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Drug Therapy  Drug selection  Short-term therapy: manic episodes  Short-term therapy: depressive episodes  Long-term preventive treatment  Promoting compliance  Short-term hospitalization  Long-term prophylactic therapy  Education for both patient and family

9. 9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Nondrug Therapy  Education  Patient and family  Psychotherapy  Individual, group, family  Electroconvulsive therapy  Last resort

10. 10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Mood-Stabilizing Drugs  Lithium  Antiepileptic drugs

11. 11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Lithium (Lithonate, Lithotabs)  Chemistry  Simple inorganic ion  Found naturally in animal tissues  Therapeutic uses  Bipolar disorder  Other uses Alcoholism Alcoholism Bulimia Bulimia Schizophrenia Schizophrenia Glucocorticoid-induced psychosis Glucocorticoid-induced psychosis

12. 12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Lithium (Lithonate, Lithotabs)  Mechanism of action  Altered distribution of certain ions  Altered synthesis and release of norepinephrine, serotonin, and dopamine  Mediates intracellular responses to neurotransmitters  Shown to facilitate regeneration of damaged optic nerves  Can increase total gray matter in regions known to atrophy in BPD

13. 13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Lithium (Lithonate, Lithotabs)  Pharmacokinetics  Absorption and distribution  Excretion Short half-life Short half-life Excreted by the kidneys Excreted by the kidneys Sodium levels: lithium excretion reduced when sodium level low Sodium levels: lithium excretion reduced when sodium level low  Plasma levels 0.8–1.4 mEq/L 0.8–1.4 mEq/L

14. 14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Lithium (Lithonate, Lithotabs)  Adverse effects  Excessive lithium levels Greater than 1.5 mEq/L Greater than 1.5 mEq/L Monitor levels q 2–3 days at initiation of therapy and then q 3–6 months Monitor levels q 2–3 days at initiation of therapy and then q 3–6 months  Therapeutic lithium levels Gastrointestinal Gastrointestinal Tremors Tremors Polyuria Polyuria Renal toxicity Renal toxicity Goiter and hypothyroidism Goiter and hypothyroidism Teratogenesis Teratogenesis

15. 15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Lithium (Lithonate, Lithotabs)  Drug interactions  Diuretics  Nonsteroidal anti-inflammatory drugs (NSAIDs)  Anticholinergic drugs  Preparations, dosage, and administration  Lithium carbonate  Lithium citrate  Dosage is highly individualized

16. 16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Antiepileptic Drugs  Divalproex sodium (Valproate)  Carbamazepine  Reduces symptoms  Protects against recurrence of mania and depression  Target trough plasma level: 4–12 mcg/mL  Lamotrigine  Indicated for long-term maintenance  Can be used alone or in combination

17. 17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Antipsychotic Drugs in BPD  Used to acutely control symptoms during manic episodes  Used long term to help stabilize mood  Benefit patients with or without psychotic symptoms  Can be combined with mood stabilizer  Five antipsychotics approved for use  Olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), aripiprazole (Abilify), and ziprasidone (Geodon)