Mood Stabilizers

Drug Therapy of BD

Mood Stabilizers are key!!!!!

• Lithium

• Carbamazepine

Antipsychotics

• Given during severe manic episodes

Antidepressants

• Given during depressive episodes

Mood Stabilizer Functions

• Relieve symptoms during 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

BD Treatment: Acute

• Acute Therapy: Manic episode

  • Lithum

  • Valproic Acid

  • If needed: Antipsychotic or antidepressant

BD Treatment: Long-term

One or more mood stabilizers and other drugs that are needed acutely (lithium and valproic acid) 

Lithium

MOA: Not clear

• Effective for both the manic AND depressive components

• PREFERRED FOR PT WITH CLASSIC (euphoric) MANIA (pure mania)

Lithium Onset

Anti-manic effect begins 5-7 days after onset of tx. Takes 2-3 weeks to see full lithium effects 

• Renal excretion of lithium AFFECTED BY BLOOD LEVELS OF SODIUM

• When Na levels are inadequate it retains lithium in an attempt to compenstate. In the presence of hyponatremia, lithium toxicity can occur

Lithium Considerations

• NTI: Monitor!!!!!!!!!!!!

• Cleared by kidneys and anything that creates sodium reeks havoc

  • *If body is in stage of hyponatremia, kidneys are highly efficient to hold onto Na and because Na and lithium are SO CLOSE ON PERIODIC TABLE, it will hold on to lithium!!!!

  • Maintain Na levels!!!

• Teratogenic in FIRST TRIMESTER (L for Little Bundle of Joy)

Lithium AE

Therapeutic levels:

• GI effects- nausea, diarrhea, abdominal bloating)

• Tremor (Parkinsonian-like)

• Polyuria

• Renal toxicity

• Goiter and hypothyroidism: CAUSES HYPER AND HYPOTHYROIDISM

• Teratogensis

• Leukocytosis

Lithium Mild Toxicity Range

1.3-1.4 mEq/L

Lithium Mild Toxicity S/S

• apathy

• irritability

• lethargy

• muscle weakness

• nausea

Lithium Mild Toxicity Treatment

Hold lithum!!! Supprotive 

Lithium Moderate Toxicity Range

1.5 - 2.5 mEq/L

Lithium Moderate Toxicity S/S

• Blurred vision

• confusion

• diarrhea

• marked tremor

• vertigo

• increased deep tendon reflexes

Lithium Moderate Toxicity Tx

Hold Lithium; Supportive

Lithium Severe Toxicity Range

> 2.5 mEq/L

Lithium Severe Toxicity S/S

• cardiac dysrhythmia

• coma

• renal failure

• seizures

• stupor

Lithium Severe Toxicity Tx

Hold Lithium; Hemodialysis

Lithium Monitoring

• Lithium Levels: 0.6 - 1.2 mEq/L TYPICAL LEVEL FOR MAINTENANCE

• I&O: Encourage fluid intake of at least 2000-3000 ml/day to prevent drug toxicity due to side effect of polyuria

• Renal function: Cleared by kidneys so look at creatinine and BUN

• Thyroid function tests: Cause hyper and hypothyroidism

• Urinalysis: q6-12 months

• CBC: Leukocytosis!!!!

NO LFTS

Influences on Lithium Concentrations: NTI - Increased

Agents Responsible

ACE inhibitors Dehydration ↓GFR Lisinopril  NSAIDs Sodium intake (decreased) Thiazide diuretics

NSAIDs and Diuretics should NOT be given due to Na increase and this increases Na levels!!!

Influences on Lithium Concentrations: NTI - Decreased

Agents Responsible

Caffeine ^ GFR Sodium Intake increased

Take lithium and woman starts taking salt away from everything to be healthy: This can lead to Na toxicity!!!! Maintain sodium intake!!!

Selection of Mood Stabilizer: Carbamazepine (Anti-seizure med)

Responders: 3rd line agent; Head injury

Nonresponders: Rapid Cycling > 10 year history of illness

Selection of Mood Stabilizer: Lamotrigine (anti-seizure med)

Responders: Bipolar Depression

Non-responders: Less effective for manic phase

Selection of Mood Stabilizer: Lithium

Responders:

• Elated mania (pure)

• Previous response to lithium 

• Few episodes of illness

• Suicidal ideation

Nonresponders:

• Repeated non-adherence

Mood Stabilizing Anticonvulsants

• Valoroic Acid: Strong inhibitor of metabolism

• Alters GABA mediated transmission

• Rapid-cycling bipolar disorders

• Target plasma levels 50-125 ug/mL

• Adverse Effects:

  • Thrombocytopenia

  • Liver failure

Lithium: Superior in preventing relapse and reducing suicidal ideation

Carbamazepine (Anticonvulsant)

Often added to lithium!!!!!

• Reduces symptoms

• Given with lithium

• Rapidly cycling disorders

• Target trough plasma level 6 to 12 µg/ml

• Mechanism unknown

• Adverse effects

  • Neurological effects

  • Hematological effects

  • Leukopenia

  • Anemia

  • Thrombocytopenia

Carbamazepine (Anticonvulsant): Metabolism

Very Strong Metabolism Inducer

• BAM I DID IT MYSELF

Lamotrigine: Alternative

Long term maintenance of depression!!!!

• Well tolerated, but dosed too fast = SJS

• Common regimen is valproic acid + Lamotrigine and together these can cause SJS, so monitor and REDUCE LAMOTRIGINE BY 40% AND MONITOR MORE

ISBD Guidlines for Antidepressants

• Treatment-emergent mania

• Do not use as monotherapy in type I

• Type I > Type II

• Risk dependent on Class?

• Highest Risk: TCAs

• SNRIs, particularly venlafaxine, carry higher risk

• Low risk: SSRIs and bupropion

• Mood stabilizers may not entirely mitigate effects

• Data for efficacy weak

• Be selective