Pharmacotherapy of Bipolar Disorder - Ott

What is rapid cycling characterized by?

Four or more mood episodes in 1 year

Bipolar Disorder Classification

1) Bipolar 1

2) Bipolar 2

Bipolar 1 has at least one manic episode for at least a week. Bipolar 2 has hypomaniac episodes for at least 4 days

Lithium’s narrow therapeutic index

Acute is 0.9-1.2, chronic is 0.6-0.9, toxicity 1.5 to 3.0 jump, draw trough serum concentration 72 hours after first dose and 12 hours after last dose

Lithium’s teratogenicity

avoid in first trimester

What drugs cause a decreased Li renal clearance?

ACE/Arbs, thaizide diuretics, nsaids, and dehydration

What drugs cause an increase of Lithium renal clearance

caffeine, osmotic diuretics and loop diuretics

Drugs that cause an increase in Li excretion

Sodium bicarb and high Na intake

Drugs that have toxicity related to Na depletion

thiazides

Valproate:

1) Formulation comparisons

2) Risk with certain formulations

3) Serum Concentrations

ER is less bioavailable than DR. Syrup and capsule sprinkle form has higher risk of GI ulcerations. Serum concentration 80-125 to be obtained at least 4 days after first dose or dose increase

Valproic Acid Adverse Effects

Teratogenic, PCOS, GI: anorexia, n/v/d, dyspepsia, ulcerations, Thrombocytopenia, platelet dysfunction, increased appetite leading to weight gain, and hyperammonemia

Valproate

1) monitoring parameters

2) drug interactions

Monitor for pregnancy, LFTs, CBC, and serum ammonia. Drug interaction with Lamotrigine which increases risk for SJS

Carbazepine:

1) effects

2) risks

induces nearly all CYP450 enzymes causing an increase in drugs breaking dow. Auto-induction of metabolism. Risks of thrombocytopenia/hematologic effects

Oxcarbazepine

1) effects

2) risks

CYP450 inducer but no auto-induction. Associated with hyponatremia

Lamotrigine

1) uses

2) what is NOT useful for

first line for depressive symptoms in bipolar. Not useful for acute treatment or for manic episodes

Topiramate

1) SE causes

2) Pregnancy

May cause weight loss

Treatment Considerations

1) mood stabilizers

2) monitor

Mood stabilizers are long term and considered maintenance therapy. Monitor closely for suicide attempt especially with Lithium

What bipolar drugs are known or possible teratogens?

Lithium, valproic acid, carbamazepine, and topiramate

Use of antidepressants is linked with a switch to mania. What must be done to avoid this?

Use of a maintenance mood stabilizer therapy in combo with antidepressants

Anxiety is common with bipolar. What can we use?

SSRIs

In bipolar, we prefer to use mood stablizers that target the depressive pole. What drugs do this?

Lamotrigine, lithium, lurasidone, and quetiapine