Mood Stabilizers

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Overview & Lithium - The OG Mood Tamer

  • Mood Stabilizers: Prevent/treat mood episodes (mania/depression) in Bipolar Disorder (BPD) without switching poles. Also: schizoaffective disorder.
    • Types: Lithium, Anticonvulsants (Valproate, Lamotrigine), Atyp. Antipsychotics.
  • Lithium (Li+):
    • MOA: ↓ IP3/DAG, ↓ GSK-3β.
    • Uses: Acute mania, BPD prophylaxis, anti-suicidal.
    • PK: Oral, renal excretion (competes with Na+).
    • Range: Therapeutic 0.6-1.2 mEq/L. Toxic > 1.5 mEq/L. Severe > 2.5 mEq/L.
    • Side Effects:
      • GI (N/V/D), fine tremor (Rx: propranolol).
      • Renal: Polyuria/polydipsia (Nephrogenic Diabetes Insipidus - NDI).
      • Thyroid: Hypothyroidism, goiter.
      • Cardiac: T-wave changes.
      • Teratogenic: Ebstein's anomaly (📌 Lithium → Low Ebstein's).
    • Monitor: Li levels, RFT, TFT.
    • ↑ Li: Thiazides, NSAIDs, ACE-I.

⭐ Lithium is unique for its anti-suicidal properties in BPD and can cause Nephrogenic Diabetes Insipidus (NDI) and hypothyroidism.

Lithium: Mechanism, Indications, and Side Effects

Valproate & Lamotrigine - Seizure Stoppers, Mood Menders

Valproate (VPA):

  • Primary for: Acute mania, mixed states, prophylaxis.
  • MOA: ↑GABA effects, blocks Na+/Ca++ channels.
  • Key SE: Weight gain, tremor, alopecia, hepatotoxicity, pancreatitis.
  • ⚠️ Teratogenic (Neural Tube Defects). 📌 VPA: Very Problematic during All trimesters (pregnancy).
  • Monitoring: LFTs, CBC. Therapeutic range: 50-125 µg/mL.

Lamotrigine (LTG):

  • Primary for: Bipolar depression, maintenance therapy.
  • MOA: Blocks Na+ channels, ↓glutamate release.
  • Key SE: Rash (potential for SJS/TEN!), headache. 📌 LTG: Look for Threatening Generalized rash.
  • ⚠️ Slow titration crucial to prevent Stevens-Johnson Syndrome (SJS).

Comparison: VPA vs. LTG

FeatureValproate (VPA)Lamotrigine (LTG)
Bipolar PhaseMania, MixedDepression, Maintenance
Key SE RiskHepatotoxicity, NTDs, PancreatitisStevens-Johnson Syndrome (SJS)
TitrationStandardSlow, cautious

⭐ Valproate: High risk of Neural Tube Defects. Lamotrigine: Key for bipolar depression; ⚠️ slow titration prevents SJS.

Stevens-Johnson Syndrome Rash with Blistering and Lesions

Carbamazepine & Atypicals - The Backup Crew

Carbamazepine (CBZ):

  • Uses: Bipolar (mania, maintenance), trigeminal neuralgia, seizures.
  • MOA: Na+ channel blocker.
  • Side Effects:
    • CNS: Drowsiness, ataxia.
    • Hematologic: Agranulocytosis, aplastic anemia (monitor CBC).
    • SIADH (hyponatremia).
    • Rash, SJS/TEN (screen HLA-B*1502 in Asians).
  • Kinetics: Autoinducer (3-5 weeks); CYP450 inducer (↓ other drugs).
  • Related: Oxcarbazepine - less enzyme induction, ↓rash/hematotoxicity risk.

Atypical Antipsychotics as Mood Stabilizers:

  • Role: Acute mania, bipolar depression, maintenance.
DrugPrimary Indication (Mood)Key Metabolic Side Effect(s)
OlanzapineAcute mania, maintenance↑ Weight, dyslipidemia
RisperidoneAcute mania, mixed episodes↑ Weight, hyperprolactinemia
QuetiapineMania, bipolar depression, maint.↑ Weight, sedation
AripiprazoleAcute mania, maintenanceAkathisia, less weight gain

Clinical Use & Special Populations - Mood Navigator

  • General Principles:
    • Acute Mania: Lithium, Valproate, AAPs. ECT for severe cases.
    • Bipolar Depression: Lamotrigine, Quetiapine, Lurasidone. Avoid antidepressant monotherapy.
    • Maintenance: Lithium, Lamotrigine, Valproate, LAI AAPs.
  • Special Populations:
    • Pregnancy:

      ⭐ Lithium: Ebstein's anomaly risk (1st trimester), monitor levels. Valproate: ⚠️ High teratogenicity (NTDs, ↓IQ) - CONTRAINDICATED. Lamotrigine: Relatively safer, cleft risk, monitor levels (may ↓).

      • Carbamazepine: NTDs. Avoid.
    • Renal Impairment: Lithium (↓ dose, monitor closely, or avoid). Valproate/Lamotrigine preferred.
    • Hepatic Impairment: Valproate (⚠️ AVOID - hepatotoxicity). Lamotrigine/Lithium preferred.
    • Elderly: "Start low, go slow." ↑Sensitivity. Lithium (↑neuro/nephrotoxicity), Valproate (sedation, ataxia).

High‑Yield Points - ⚡ Biggest Takeaways

  • Lithium: Gold standard for bipolar disorder. Narrow therapeutic index; monitor renal/thyroid, levels. Risk: Ebstein's anomaly.
  • Valproate: For acute mania, rapid cycling. Risks: neural tube defects, hepatotoxicity, pancreatitis.
  • Carbamazepine: Risks: agranulocytosis, SIADH. Potent enzyme inducer (autoinduction).
  • Lamotrigine: For bipolar depression. Slow titration prevents Stevens-Johnson Syndrome (SJS).
  • Atypical antipsychotics (e.g., olanzapine, quetiapine) also used as mood stabilizers, especially in acute mania.

Practice Questions: Mood Stabilizers

Test your understanding with these related questions

A patient with depression was given Imipramine for 2 weeks. Relatives noticed increased excitement, colorful clothes, and increased talking. What is the next step in management?

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Flashcards: Mood Stabilizers

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Which second gen. antipsychotic is associated with gestational diabetes and neonatal seizures?_____

TAP TO REVEAL ANSWER

Which second gen. antipsychotic is associated with gestational diabetes and neonatal seizures?_____

Clozapine

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