Pharmacotherapy of Mood Disorders

Pharmacotherapy of Mood Disorders

Pharmacotherapy of Mood Disorders

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Antidepressants - Happy Pills Parade

  • SSRIs (Selective Serotonin Reuptake Inhibitors): Fluoxetine, Sertraline.
    • Mech: Block SERT → ↑ Serotonin.
    • SE: GI upset, sexual dysfunction. 📌 SE: Stomach upset, Sexual dysfunction, Restlessness, Insomnia.
    • Fluoxetine: Longest t½.
  • SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors): Venlafaxine, Duloxetine.
    • Mech: Block SERT & NET → ↑ Serotonin & NE.
    • SE: Hypertension. Duloxetine: also for neuropathic pain.
  • TCAs (Tricyclic Antidepressants): Amitriptyline, Imipramine.
    • Mech: Block SERT, NET; also H1, M1, α1 receptors.
    • SE: Cardiotoxicity (QRS prolongation), anticholinergic. 📌 Three Cs: Cardiotoxicity, Convulsions, Coma.
  • MAOIs (Monoamine Oxidase Inhibitors): Phenelzine, Moclobemide (RIMA).
    • Mech: Inhibit MAO → ↑ Serotonin, NE, Dopamine.
    • SE: Hypertensive crisis with tyramine-rich foods (cheese reaction).
  • Atypical Antidepressants:
    • Bupropion: NDRI; for smoking cessation; ↓ seizure threshold.
    • Mirtazapine: α2 antagonist; sedation (H1 block), weight gain.
    • Trazodone: SARI; priapism (rare), sedation.

⭐ Serotonin syndrome: triad of altered mental status, autonomic hyperactivity (fever, tachycardia), neuromuscular abnormalities (clonus, hyperreflexia). High risk with SSRI/SNRI + MAOI combination.

Mood Stabilizers - Even Keel Crew

  • Lithium (Li+):
    • Gold standard: Bipolar disorder (mania, maintenance).
    • MOA: ↓ IP3 & DAG, GSK-3β inhibition.
    • Therapeutic window: 0.6-1.2 mEq/L.
    • Toxicity: Tremor, ataxia, confusion. Monitor renal, thyroid.
    • 📌 LITH: Levels (0.6-1.2), Insipidus (nephrogenic DI), Teratogenic (Ebstein's anomaly), Hypothyroidism.
  • Valproate (VPA):
    • Broad spectrum: Acute mania, mixed states, maintenance.
    • MOA: ↑ GABA, blocks Na+ channels.
    • SE: GI upset, weight gain, hepatotoxicity. ⚠️ Teratogenic (neural tube defects).
  • Lamotrigine (LTG):
    • Bipolar depression, maintenance.
    • MOA: Blocks Na+ channels, ↓ glutamate release.
    • Slow titration: Risk of Stevens-Johnson Syndrome (SJS).
  • Carbamazepine (CBZ):
    • Acute mania, maintenance.
    • MOA: Blocks Na+ channels.
    • SE: Agranulocytosis, aplastic anemia, SIADH, P450 inducer.
  • Atypical Antipsychotics: Olanzapine, Risperidone, Quetiapine, Aripiprazole also used as mood stabilizers, especially in acute mania.

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

Adjunctive & Special Use - Tricky Mood Tactics

  • Treatment-Resistant Depression (TRD): Failure of ≥2 adequate antidepressant trials.
    • Augmentation: Lithium, Atypical Antipsychotics (e.g., aripiprazole, quetiapine), T3.
    • Other options: Esketamine nasal spray, ECT.
  • Antipsychotics in Mood Disorders:
    • Bipolar Depression: Quetiapine, lurasidone, olanzapine-fluoxetine combination (OFC).
    • Acute Mania: Most atypicals (e.g., risperidone, olanzapine), haloperidol.
  • Special Populations:
    • Pregnancy:
      • Antidepressants: Sertraline often preferred. Avoid paroxetine (1st trimester).
      • Mood Stabilizers: Lamotrigine (relatively safer). ⚠️ Valproate (high NTD risk), Carbamazepine (NTD risk). Lithium (monitor closely; Ebstein's anomaly risk).
      • ECT is a safe option.
    • Elderly: "Start low, go slow."
      • SSRIs (e.g., sertraline, escitalopram). Avoid fluoxetine (long $t_{1/2}$), paroxetine (anticholinergic).

⭐ Lithium augmentation can convert non-responders to responders in TRD for about 50% of cases.

Rapid & Novel Agents - Speedy Mood Rescuers

  • Ketamine & Esketamine
    • Mechanism: NMDA antagonist.
    • Uses: Treatment-Resistant Depression (TRD), rapid ↓ suicidal thoughts.
    • Onset: Hours.
    • Ketamine: 0.5 mg/kg IV over 40 min.
    • Esketamine (Spravato): Intranasal 56mg/84mg; REMS program, monitor BP.
    • SE: Dissociation, ↑BP, abuse potential.
  • Electroconvulsive Therapy (ECT)
    • Indications: Severe/psychotic depression, TRD, catatonia, acute suicidality, mania. Safe in pregnancy.
    • Mechanism: Generalized seizure induction.
    • Regimen: 2-3x/week; 6-12 sessions.
    • SE: Headache, memory loss (transient).

    ⭐ ECT is considered the most effective acute treatment for severe major depression.

  • Brexanolone (Zulresso)
    • Mechanism: Allosteric modulator of GABA-A receptors.
    • Use: Postpartum depression (IV, 60-hour infusion).

High‑Yield Points - ⚡ Biggest Takeaways

  • SSRIs (e.g., Fluoxetine) are first-line for depression; monitor for serotonin syndrome.
  • Lithium is gold standard for bipolar disorder; requires therapeutic drug monitoring (TDM).
  • Valproate is a mood stabilizer, but teratogenic; Lamotrigine risks Stevens-Johnson Syndrome (SJS).
  • TCAs carry risks of cardiotoxicity and anticholinergic effects.
  • MAOIs necessitate tyramine-free diet to prevent hypertensive crisis.
  • Atypical antipsychotics (e.g., Olanzapine) are used for acute mania and as adjuncts.
  • Esketamine for treatment-resistant depression (TRD).

Practice Questions: Pharmacotherapy of Mood Disorders

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A 72 year old lady is severely depressed. For the past 2 days she has suicidal thoughts with an actual intent to die. Which of the following is best suitable to alleviate the symptoms?

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Flashcards: Pharmacotherapy of Mood Disorders

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Drug of choice for prophylaxis of mania is:

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Drug of choice for prophylaxis of mania is:

Lithium

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