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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