Mood Stabilizers

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.

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

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

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.

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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.