Lecture on Antidepressants and Anxiolytics

Overview

• Depression and anxiety are often comorbid, requiring similar treatment approaches.
• Depression is a common disorder with treatments available since the 1950s.
• Treatment has become safer with more selective and less toxic medications.
• Important to treat both depression and anxiety due to their frequent coexistence.
• Placebo effect and inter-patient variability are challenges in treatment.
• Secondary causes of depression (like hypothyroidism) should be ruled out.
• Medications like isotretinoin and corticosteroids can worsen symptoms.
• Underdiagnosis can lead to serious outcomes like suicide attempts.

Theories on Depression

• Monoamine Theory: Suggests that depression is linked to the depletion of monoamines (dopamine, norepinephrine, serotonin).
• Treatment aims to boost these neurotransmitters, though changes take weeks to manifest.
• Phases of Treatment:
  • Acute Phase: Initial treatment lasting 6-12 weeks.
  • Maintenance Phase: Focus on preventing recurrence.

Antidepressant Classes

1. Monoamine Oxidase Inhibitors (MAOIs)

   • Irreversible inhibitors affecting serotonin, norepinephrine, and dopamine.
   • Risk of hypertensive crisis with tyramine-rich foods.
   • Notable drugs: Phenelzine, Tranylcypromine.

2. Tricyclic Antidepressants (TCAs)

   • Inhibit reuptake of serotonin and norepinephrine.
   • High toxicity in overdose.
   • Used for depression, insomnia, and some pain conditions.
   • Notable drugs: Amitriptyline, Nortriptyline.

3. Selective Serotonin Reuptake Inhibitors (SSRIs)

   • Block reuptake of serotonin.
   • Considered first-line treatment.
   • Safer in overdose and more tolerable.
   • Notable drugs: Fluoxetine, Sertraline, Escitalopram.

4. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

   • Block reuptake of serotonin and norepinephrine.
   • Used for depression and neuropathic pain.
   • Notable drugs: Venlafaxine, Duloxetine.

5. Miscellaneous Antidepressants

   • Bupropion: Affects norepinephrine and dopamine; less sexual dysfunction.
   • Mirtazapine: Blocks alpha-2 receptors; causes sedation and weight gain.
   • Trazodone: Causes sedation; risk of priapism.
   • Ketamine: NMDA receptor antagonist; rapid effects for treatment-resistant depression.

Side Effects and Risks

• Risk of increased suicidality, especially in youth.
• Withdrawal symptoms with abrupt discontinuation.
• Serotonin syndrome with excessive serotonin activity.
• Important to monitor for QT prolongation, especially with citalopram.

Anxiolytics

• Anxiety disorders include generalized anxiety, social anxiety, panic disorders, etc.
• Treatment mirrors that for depression, often using SSRIs and SNRIs.
• Benzodiazepines used for acute anxiety relief.

Benzodiazepines

• Enhance GABA activity.
• Risk of dependence and withdrawal.
• Prefer "LOT" benzodiazepines in the elderly (Lorazepam, Oxazepam, Temazepam).

Other Anxiolytics

• Buspirone: Serotonin agonist; less effective than benzodiazepines.
• Beta-blockers: Used for performance anxiety.

Considerations

• Special populations: Elderly, pediatric, pregnant/lactating women.
• Non-pharmacologic treatments: Psychotherapy, TMS, ECT.
• Importance of patient education and adherence to therapy.

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Note: Always consider drug interactions and patient history when prescribing. Monitor for signs of withdrawal, suicidality, and serotonin syndrome. Use appropriate agents based on patient-specific factors and conditions.