Tricyclic Antidepressants
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Tricyclic Antidepressants e.g. Amitriptyline, imipramine, lofepramine
There are also related compounds, that are not technically tricyclics, but that we will consider as the same here: amoxapine, maprotiline


  • They inhibit the uptake of monoamines into the pre-synaptic neuron, by competitively binding to the ATPase monamine pump in the cell membrane
  • Some drugs are non-selective between monoamines whilst other are selective (e.g. 5-HT over NA) – However – selectivity does NOT influence efficacy
  • Many of the drugs also affect post-synaptic membranes and can block receptors for other substances, such as histamine and α-adrenoceptors. This characteristic can lead to many of the side effects of TCAs


  • True TCAs undergo first pass metabolism, other drugs don’t
  • There doesn’t appear to be a true dose relationship – although the dose is related to the severity of unwanted effects
  • Most of the drugs have active metabolites
  • Dose titration is usually necessary to get the optimal dose – this should be performed over 1-2 weeks

Unwanted Effects

  • Cardiotoxicity – this usually only occurs in overdose
  • Sedation due to H1 and α-adrenoceptor blockade, this effect may be useful in some patients to help their sleep pattern, but can be troublesome during the day
  • Antomuscarinic effects –e.g. dry mouth, constipation, urinary retention, impotence, visual disturbance
  • Tremor and sweating
  • Postural Hypotensiondue to α blockade
  • Epileptic fits – even in those with no history of the condition
  • Weight gain – due to appetite stimulation
  • Hyponatraemiadue to inappropriate ADH secretion – this can cause drowsiness, confusion and convulsions
  • WITHDRAWAL – sudden withdrawal should be avoided, and the dose should be gradually reduced over 4 weeks. Symptoms of withdrawal include; agitation, sweating, headache, malaise, GI upset


  • Alcoholtogether these have an exaggerated depressive effect
  • MAOIs – so never give these drugs together! MOAIs also have a long duration of action (up to two weeks) so be aware of this when prescribing
  • Arrhythmia when given with a Q-T prolonging drug


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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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