Selective Serotonin Reuptake Inhibitors (SSRI)

SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI)


SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI)

MOA:

  • Inhibits 5-HT only (not NA).
  • Lack anticholinergic and α-blocking properties.

Drugs: Paroxetine, Sertraline, Citalopram,  Fluoxetine, Fluvoxamine & Escitalopram

Uses:

  • DOC for depression, phobias, OCD, PTSD, bulimia, premenstrual tension syndrome, sustained treatment of generalized anxiety disorders & panic attacks.

Advantages over TCAs:

  • No anticholinergic adverse effects.
  • No sedation or weight gain.
  • No propensity to cause seizures or arrhythmias.

1. Depression:

  • Mild to moderate – Fluoxetine.

2. Panic disorder:

  • Sustained treatment – Sertraline.

3. Neurotic disorders:

  • Obsessive compulsive disorder – Fluoxetine.
  • Post-traumatic stress disorder – Sertraline/paroxetine.
  • Bulimia – Fluoxetine.
  • Phobia – Sertraline.
  • Impulse-control disorders – Fluoxetine.

4. GAD (generalized anxiety disorders):

  • Paroxetine & venlafaxine – Indicated for chronic GAD treatment.

5. Severe premenstrual tension syndrome (PMS):

  • Fluoxetine & sertraline.
  • Effective as continuous treatment for 2 weeks out of a month in luteal phase.
  • Associated with rapid increases in pregnenolone levels.

General adverse effects:

  • Most common adverse effects:
    • Nausea –> Anxiety –> Diarrhea
    • Due to 5-HT 3 receptor stimulation in CNS & periphery.
  • Abnormal bleeding – 
    • Due to disturbance in platelet serotonin levels.
  • Insomnia, anxiety, irritability, akathisia & decreased libido
    • Due to excessive stimulation of brain 5-HT2 receptors.
  • Sexual side effects including erectile dysfunction, anorgasmia, ejaculation inhibition & ejaculatory delay (Mainly paroxetine) –
    • Due to excessive activity at spinal 5-HT2 receptors.
  • Serotonin syndrome (Coadministration of SSRIs & MAO-inhibitors).

Individual drugs:

1. Fluoxetine:

  • Prototype SSRI.
  • Prodrug
  • Longest-acting & metabolized to nor-fluoxetine retaining anti-depressant activity.
  • Hence, anti-depressant drug of SSRI.

2. Fluvoxamine:

  • Shortest-acting SSRI.

3. Escitalopram:

  • Most specific SSRI.

4. Paroxetine:

  • Most teratogenic among SSRIs.
  • Increased risk of congenital cardiac malformations.
  • More prominent sexual side effects (erectile dysfunction, anorgasmia, ejaculation inhibition & ejaculatory delay).

6. Sertraline & citalopram:

  • Safest SSRIs for combination with warfarin.

Discontinuation syndrome of SSRI’s:

  • Withdrawal symptoms include dizziness, headache, nervousness, nausea & insomnia.
  • Paroxetine (More intense) – Due to relatively short-acting nature.
  • Fluoxetine – Safer in this regard due to very long-acting metabolite. 

Exam Important

  • (SSRI) Selective Serotonin Reuptake Inhibitors inhibits 5-HT only (not NA).
  • SSRI lack anticholinergic and α-blocking properties.
  • Paroxetine, Sertraline, Citalopram,  Fluoxetine, Fluvoxamine, Escitalopram, Duloxetine are all SSRI’s.
  • SSRI are DOC for depression, phobias, OCD, PTSD, bulimia, premenstrual tension syndrome, sustained treatment of generalized anxiety disorders & panic attacks.
  • Fluoxetine is DOC for mild to moderate depression, obsessive compulsive disorder, impulse-control disorders, bulimia & also for severe premenstrual tension syndrome (PMS).
  • Sertraline is DOC for sustained treatment of panic disorder, post-traumatic stress disorder, phobia & severe PMS.
  • Paroxetine & venlafaxine are indicated for chronic GAD treatment.
  • Most common adverse effects include Nausea –> Anxiety –> Diarrhea (in order), which occur mainly due to 5-HT 3 receptor stimulation in CNS & periphery.
  • Abnormal bleeding is reported with SSRI due to disturbance in platelet serotonin levels.
  • Insomnia, anxiety, irritability, akathisia & decreased libido are seen with SSRI, due to excessive stimulation of brain 5-HT2 receptors.
  • Sexual side effects including erectile dysfunction, anorgasmia, ejaculation inhibition & ejaculatory delay (Mainly paroxetine) are seen with SSRI, due to excessive activity at spinal 5-HT2 receptors.
  • On coadministration of SSRIs & MAO-inhibitors, serotonin syndrome occurs.
  • Fluoxetine is a prototype SSRI, longest-acting prodrug & metabolized to nor-fluoxetine retaining anti-depressant activity, hence anti-depressant drug of SSRI.
  • Fluvoxamine is shortest-acting SSRI.
  • Escitalopram is the most specific SSRI.
  • Paroxetine is most teratogenic among SSRIs with increased risk of congenital cardiac malformations & more prominent sexual side effects (erectile dysfunction, anorgasmia, ejaculation inhibition & ejaculatory delay).
  • Sertraline & citalopram are safest SSRIs for combination with warfarin.
  • Discontinuation syndrome of SSRI’s produces withdrawal symptoms including dizziness, headache, nervousness, nausea & insomnia.
  • More intensive discontinuation syndrome is seen with Paroxetine, due to their relatively short-acting nature.
  • Fluoxetine is safer without discontinuation syndrome, due to their very long-acting metabolite. 
Don’t Forget to Solve all the previous Year Question asked on SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI)

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