SSRIs – Selective Serotonin Reuptake Inhibitors
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Selective Serotonin Re-uptake Inhibitors (SSRIs) e.g. fluoxetine, paroxetine, sertraline, citalopram

These are the most common used antidepressant. They are:
  • Just as effective as TCAs in mild / moderate depression
  • Less effective than TCAs in severe depression
  • Also used in OCD
  • Not recommended in those under 18, efficacy is not proven, except for fluoxitine – but if used proceed with caution
  • Should take them first thing in the morning – they disrupt the sleep pattern if you give them at night

Mechanism of action

Reduced neuronal reuptake of serotonin – but very little effect on noradrenaline
Have low affinity for muscarinic, histaminergic, and adrenergic receptors – and as a result have fewer side effects than the TCAs. They are also less dangerous in overdose than TCAs

SSRIs cause:

  • An initial increase in the concentration of serotonin around the somatodendritic and axon terminal areas. This results in a decrease in the number of 5-HT inhibitory receptors
  • As a result of the downregulation of receptors, more 5-HT is then released from the axon terminal. This effect is more long-term, and results in even more 5-HT downregulation


  • Well absorbed from gut
  • Have long(ish) half lives – generally around 24 hours
  • Beware the long half lives when giving MAOIs after a course of SSRIs. Recommended wait 5 weeks after fluoxetine and 2 weeks after other SSRIs. Also, you should not start an SSRI within a week of stopping an MOAI
  • They take 2-4 weeks before clinical benefit is seen
  • Paroxetine and fluoxetine should not be used in conjunction with TCAs because they can alter the hepatic metabolism of TCAs and lead to toxicity
  • Should be taken in the morning to avoid sleep disturbance

Side effects

  • Increased anxiousness
  • Feeling of ‘emotional numbness’
  • Headache
  • Nausea
  • Dry mouth / constipation (paroxetine)
  • Weight loss / anorexia
  • May also cause increased appetite and weight gain.
  • Vomiting
  • Insomnia
  • Loss of libido / inability to achieve orgasm
  • There is a small but real risk of increased suicidal and self harm thoughts – especially in children
  • Hypersensitivity


  • Can impair skilled tasks – e.g. driving
  • Caution in those with epilepsy, and undergoing ECT, as they can prolong a seizure.
  • Can impair hepatic metabolism of other drugs


MAOIs – used in conjunction with these, they can cause serotonin syndromewhich may involve tremor, hyperthermia, cardiovascular sx (potentially fatal!)
**SSRIs should not be used in bipolar disorder, and immediately discontinued if the patient enters a manic phase**


This is debated. Although it is not thought there is ‘addiction’ in the true sense, withdrawal symptoms can occur, and the drug dose should be gradually reduced to avoid these. Symptoms can include:
  • GI disturbance
  • Headaches
  • Anxiety
  • Dizziness
  • Parasthesia
  • Sleep problems
  • General fatigue / flu-like symptoms
  • Sweating


  • Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
  • Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.
  • Beers, MH., Porter RS., Jones, TV., Kaplan JL., Berkwits, M. The Merck Manual of Diagnosis and Therapy

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Dr Tom Leach

Dr Tom Leach MBChB DCH EMCert(ACEM) FRACGP currently works as a GP and an Emergency Department CMO in Australia. He is also a Clinical Associate Lecturer at the Australian National University, and is studying for a Masters of Sports Medicine at the University of Queensland. After graduating from his medical degree at the University of Manchester in 2011, Tom completed his Foundation Training at Bolton Royal Hospital, before moving to Australia in 2013. He started almostadoctor whilst a third year medical student in 2009. Read full bio

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