SSRIs

• Examples:

  • Citalopram
  • Sertraline
  • Fluoxetine
  • Paroxetine
• MOA:

  • Selectively inhibits serotonin reuptake in the synaptic cleft
  • Blocks reuptake of serotonin by the presynaptic membrane
  • Results in more serotonin in the synapses throughout the central nervous system
  • Depression has been linked to low serotonin levels
• Routes of delivery:

  • PO
• Indications:

  • Depression - 1st line
  • GAD - sertraline generally first line
  • Panic disorder - citalopram
  • OCD - sertraline generally first line
  • Depressive illness in children - fluoxetine only
  • Bulimia nervosa (fluoxetine)
• Contraindications:

  • Poorly controlled epilepsy - lowers seizure threshold
  • During a manic episode
• Cautions:

  • Pregnancy - try to avoid, increased risk of PPH
  • Epilepsy
  • Cardiac disease - vasoconstriction and QT prolongation (citalopram)
  • Diabetes - can worsen
  • Receiving ECT - can cause prolonged seizures
  • Prone to acute angle-closure glaucoma
  • History of bleeding disorders - especially GI bleeding
• Interactions:

  • Alcohol - increased sedation
  • NSAIDs and aspirin - increased risk of bleeding - consider prescribing PPI
  • Anti-epileptic drugs - reduces seizure threshold
  • MAOIs - high risk of serotonin syndrome - should not be started until at least a week after an SSRI has been stopped
  • Tramadol and St. Johns Wort - increased risk of serotonin discontinuation syndrome
  • Grapefruit - CYP3A4 inhibition - increased plasma sertraline concentration
• Monitoring:

  • Review patient every 1-2 weeks for a month initially after starting an SSRI
  • Review within a week in patients aged 18-30 due to increased risk of suicide
  • Normally a noticeable response within 2-4 weeks (sometimes up to 6 weeks)
  • Continue or increase dose in cases of partial response
  • Following remission, treatment should be continued at the same dose for at least 6 months
  • Patients with a history of recurrent depression should receive maintenance treatment for at least 2 years
• Common side effects:

  • GI upset
  • Nausea
  • Dry mouth
  • Sexual dysfunction
  • Anorexia and weight loss/ abnormal appetite
  • Headache
• Less common side effects:

  • Increased risk of bleeding - significantly increased if taken alongside anticoagulant or NSAID
  • Suicidal ideation
  • Convulsions
  • QT interval prolongation - mostly citalopram
  • Serotonin syndrome
  • SSRI discontinuation syndrome - most commonly with paroxetine as has shortest half life
• Sertraline:

  • Also has helpful anti-anxiety effects
  • Considered to be one of the safest in patients with heart disease e.g. following MI or heart failure
  • Associated with a higher rate of diarrhoea
• Citalopram:

  • Can prolong the QT interval - is dose dependent
  • Can lead to torsades de pointes
  • Considered to be the least safe SSRI in patients with heart disease and arrhythmia (still a lot safer than TCAs)
• Fluoxetine:

  • Particularly long half-life of around 4-7 days
  • Usual first line choice in children and adolescents
• Paroxetine:

  • Associated with weight gain
  • More likely to cause discontinuation symptoms - shortest half life
• Triptans should be avoided in patients taking SSRI due to risk of serotonin syndrome
• SSRIs and MAOIs should never be combined due to risk of serotonin syndrome
• Paroxetine and sertraline are considered safe when breastfeeding