Tricyclic Antidepressants

Dr Tom Leach

8 years ago

Contents

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

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 Hypotension – due to α blockade
Epileptic fits – even in those with no history of the condition
Weight gain – due to appetite stimulation
Hyponatraemia – due 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

Alcohol – together 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