DSA14 - Mood Stabilizers

What should be given to control Manic episodes/Sx in Bipolar Disorder (aka for RAPID control of Sx)?

Anti-mania (Lithium) Agent/Antiseizure Agent + Antipsychotic Agent

Lithium MoA

Natural Salt (substitutes for Na in generating APs AND in Na/K exchange across membrane) --> 2-3 wks = Effects on neurotransmitter systems; Therapeutic level of 0.9-1.4 mEq/L for Acute Mania

Lithium Tx

Prophylaxis of Mania (5-7 days) AND Depressive Sx of Bipolar Depression + REDUCES SUICIDE ATTEMPTS, esp good for COMPROMISED LIVER; Maintain levels > 0.5-0.7 mEq/L; Given TWICE daily, in ER form

How much Lithium should be given in Acute Bipolar Episodes?

1-1.5 mEq/L

How much Lithium should be given in Bipolar maintenance?

0.6-1.2 mEq/L

Lithium S/E

FINE TREMOR (even in Therapeutic dose range); Thirst, Polyuria/Polydipsia (Renal Dysfunction), Diarrhea, WT GAIN, Edema --> Hypothyroidism; Elevated Ca + Lethargy, Dysphoria, Ataxia; Hyponatremia (avoid thiazides & NSAIDs); Reversible Leukocytosis; Mild Cognitive Impairment; Transient acne; Gastric Distress

Lithium C/I

Renal Disease, Post MI 10-14 days ("Sick Sinus Syndrome" - depresses sinus node), Diuretics Use/NSAID Use, Use of Older Antipsychotic Drugs, MG, DM2, UC, Psoriasis, Senile Cataracts, First Trimester Preg, Breastfeeding

Given that Lithium has a narrow therapeutic window (toxic > 2.0 mEq/L), what should be done during treatment?

Monitor Li plasma levels

What can be done if a Lithium O/D occurs?

Dialysis

Why should Diuretics and NSAIDs NOT be used while taking Lithium?

Reduces Lithium Clearance

Why is Lithium C/I with use of older antipsychotic drugs (more potent D2 blockers)?

Worsens EPS S/Es

What are examples of Renal Dysfunction (Polyuria, Polydipsia) in which pts should NOT take Lithium?

-Less ability to to conserve H2O in CD w/ presence of ADH (NPI) --> May be irreversible

-Chronic Interstitial Nephritis

-Minimal change glomerulopathy

What is the first sign of Polyuria/Polydispisa?

Nocturia

Why is Lithium C/I in pregnancy?

-Renal clearance increases then drops to normal after

-Becomes present in breast milk

-Class D Teratogen

Divalproex Sodium (Valproic Acid + Sodium Valproate) MoA

Anti-convulsant - increases GABA levels

What is the therapeutic level for Divalproex Sodium?

50-125 mg/ml

Divalproex Sodium (Valproic Acid + Sodium Valproate) Tx

FIRST LINE (faster onset, 4-5 days); Acute Mania/Irritability, ER = Acute Mania or Mixed States, Long Term Maintain Bipolar Disorder

Divalproex Sodium (Valproic Acid + Sodium Valproate) S/E

Mild GI Sx, Rashes, Hematological Abns, Hair Loss, ALCs w/ heavy EtOH use, Fatal Hepatotoxicity, NTDs, Inc appetite & WEIGHT GAIN (tears your stomach up, less so than JUST Valproate alone)

Divalproex Sodium (Valproic Acid + Sodium Valproate) C/I

Liver Issues (metabolized by Liver), Avoid in Pregnancy (NTDs), PCOS

Carbamazepine MoA

Anti-convulsant - acts through blockage of voltage dependent sodium channels; Therapeutic at 8-12 mg/ml

Carbamazepine Tx

Acute Mania, Bipolar Maintain, Manic/Mixed States (5-7 days for efficacy/More effective in rapid cycles > 4 eps/yr)

Carbamazepine S/E

Transient Skin Rashes (Aplastic Anemia (rare), Agranulocytosis), Impaired Coordination, Drowsiness, Dizziness, Ataxia, Transient Leukopenia, Hyponatremia, Diplopia, GI S/Es, Sedation, Wt Gain

Why should Carbamezapine be started LOW and be titrated up SLOWLY?

To avoid AEs

How should Carbamazepine be started and adjusted?

•Start 200 twice daily and increase to three times a day after 3 to 5 days (Most require 600 - 1600)

•Monitor levels as it induces own metabolism and may require further dosage increase after initially achieving therapeutic level

•Monitor CBC, liver function, and levels q 3 months

Why should Carbamazepine levels be monitored?

Can induce its own metabolism

Oxcarbazepine MoA

Anti-convulsant - acts through blockage of voltage dependent sodium channels; Therapeutic at 8-12 mg/ml; BETTER THAN CARBA

Oxcarbazepine Tx

Acute Mania, Bipolar Maintain, Manic/Mixed States (5-7 days for efficacy/More effective in rapid cycles > 4 eps/yr)

Oxcarbazepine S/E

Impaired Coordination, Drowsiness, Dizziness, Ataxia, Transient Leukopenia, Hyponatremia, Diplopia, GI S/Es, Sedation, Wt Gain

Lamotrigine MoA

Anticonvulsant - blocks Na and/or Ca channels inhibiting glutamate and GABA

Lamotrigine Tx

Maintain Tx of Bipolar (esp for Depression) - can be used in pregnancy Category C; Potentiating agent for antidepressants

What is the target dose for Lamotrigine? How does slow titration get us to this target dose?

200 mg/d; 25 mg/d for 2 weeks --> 50 mg/d for 2 weeks --> 100 mg/d for 1 week, then 200 mg/d

How is the Lamotrigine metabolized?

By liver

Lamotrigine S/E

Stevens Johnson Syndrome (why dose should be raised SLOWLY), Toxic Epidermal Necrolysis

What Antipsychotics can be used for Acute Mania/in Long Term Therapy + Li or Anti-seizure agents?

Olanzapine, chlorpromazine, quetiapine, haloperidol, risperidone, and lurasidone

Lurasidone MoA

Antipsychotic (Atypical Antipsychotic - block D2 receptors BUT block 5HT2 receptors MORE)

Lurasidone Tx

Bipolar Disorder (Mania & Depression)

Lurasidone S/E

MORE EPS S/Es, less wt gain

What Benzodiazepines can be given to control acute mania (adjunct to antipsych med + mood stabilizing drug)?

Clonazepam, Lorazepam