Mood Stabilizers

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Mood Stabilizers - Steadying the Swings

  • Drugs that treat/prevent mood episodes (mania/depression) without inducing the opposite pole.
  • Indications: Bipolar Disorder (acute mania, acute depression, maintenance), Schizoaffective disorder, Impulse control disorders.
  • Classification:
    • Lithium: Gold standard.
    • Anticonvulsants: Valproate, Lamotrigine, Carbamazepine.
    • Atypical Antipsychotics: Olanzapine, Risperidone, Quetiapine, Aripiprazole, Lurasidone, Cariprazine.

⭐ Lithium is the only mood stabilizer proven to reduce suicide risk in bipolar disorder patients.

Lithium - The Classic Balancer

  • MoA: Modulates G-protein signaling (↓IP3/DAG), inhibits GSK-3β.
  • Indications: Bipolar disorder (mania, maintenance), acute mania, augmentation in depression.
  • Therapeutic Range & Monitoring: Therapeutic range 0.6-1.2 mEq/L (acute 1.5; prophylaxis 0.4-0.8). Levels 12h post-dose.
  • Key Monitoring: Baseline: RFT, TFT, ECG, electrolytes, preg test. Ongoing: RFT, TFT.
  • Side Effects (SE):
    • Common: GI upset, fine tremor, polyuria/dipsia, wt gain.
    • 📌 LMNOP: Lithium, Movement (tremor), Nephrotoxicity (NDI), hypOthyroidism, Pregnancy (Ebstein's - ⚠️ avoid 1st trim).
  • Toxicity:
    • Levels: >1.5 (mild), >2.0 (mod), >2.5 mEq/L (severe).
    • Features: Coarse tremor, ataxia, confusion, seizures.
    • Rx: Stop Li, hydrate; Dialysis if severe (>2.5 or Sx).
  • Drug Interactions (↑Li): NSAIDs (not Aspirin), Thiazides, ACE-I/ARBs.

⭐ Lithium is the only mood stabilizer proven to reduce suicide risk in bipolar disorder. oka

Anticonvulsants - Versatile Mood Modulators

  • Valproate (VPA):

    • Mech: ↑GABA, Na+/Ca2+ block.
    • Uses: Acute mania, mixed episodes, maintenance.
    • S/E: Wt. gain, hepatotoxicity, pancreatitis. ⚠️ NTDs (contraindicated pregnancy unless essential; supplement folate).
    • Monitor: Levels (50-125 mcg/mL), LFTs, CBC.
  • Lamotrigine (LTG):

    • Mech: Na+ channel block, ↓glutamate release.
    • Uses: Bipolar depression (mainstay), maintenance. Not for acute mania.
    • S/E: Rash, headache. ⚠️ Stevens-Johnson Syndrome (SJS)/TEN risk (slow titration essential!).
    • Titrate: Start 25mg/day. Valproate ↑LTG levels (halve LTG dose); Carbamazepine ↓LTG levels (double LTG dose).
  • Carbamazepine (CBZ):

    • Mech: Na+ channel block.
    • Uses: Acute mania, mixed episodes (less common due to S/E profile & interactions). Trigeminal neuralgia.
    • S/E: Drowsiness, ataxia, GI upset, hyponatremia. ⚠️ Agranulocytosis, aplastic anemia, SJS (screen for HLA-B*1502 in Asians). 📌 CNS effects, Bone marrow suppression, Zzz (sedation).
    • Monitor: Levels (4-12 mcg/mL), CBC, LFTs. Potent CYP450 auto-inducer.

⭐ Lamotrigine: Slow titration (e.g., start 25mg/day, then gradual increase based on concurrent meds) is VITAL to minimize the risk of life-threatening SJS/TEN. Co-administration with Valproate (inhibits LTG metabolism) significantly ↑ SJS risk and requires even slower titration/lower LTG doses.

Urticaria from Lamotrigine

Atypicals & Treatment Strategy - Modern Approaches

Atypical antipsychotics (AAPs) are pivotal in modern bipolar disorder management, offering efficacy across various illness phases.

  • Key AAPs in Mood Stabilization:

    • Olanzapine: Acute mania, maintenance. SE: ↑Weight, metabolic syndrome.
    • Quetiapine: Acute mania & depression, maintenance. SE: Sedation, orthostasis.
    • Risperidone: Acute mania. SE: EPS, ↑prolactin.
    • Aripiprazole: Acute mania, maintenance. SE: Akathisia.
    • Lurasidone: Bipolar depression. SE: Akathisia, nausea.
  • Treatment Strategy Algorithm: Choice depends on phase, prior response, and side effects.

⭐ Quetiapine is unique among atypicals for its FDA approval and efficacy in treating both acute mania and acute bipolar depression.

  • Key Considerations:
    • Individualize: Prior response, patient preference, SE profile.
    • ⚠️ Pregnancy: Valproate contraindicated. Lamotrigine, Lithium (monitor closely), and select AAPs are options.

High‑Yield Points - ⚡ Biggest Takeaways

  • Lithium: Gold standard for bipolar disorder; narrow therapeutic index, requires renal/thyroid monitoring. Ebstein's anomaly risk in pregnancy.
  • Valproate: Effective for acute mania/mixed states; teratogenic (neural tube defects), hepatotoxicity.
  • Carbamazepine: Risk of agranulocytosis, SJS (HLA-B*1502); potent enzyme inducer.
  • Lamotrigine: For bipolar depression; slow titration crucial to prevent SJS.
  • Atypical antipsychotics (e.g., olanzapine, quetiapine) also serve as mood stabilizers, especially in acute mania.
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