The TCAs are a heterogeneous group of drugs in terms of their pharmacological actions; they are only similar in structure. Although the structural similarity of drugs is close their pharmacological actions are very different. For instance, clomipramine is a very close structural analogue of chlorpromazine, but their effects could hardly be more different.
Any discussion that says 'the tricyclics ...' is certain to be an imprecise generalisation.
Gillman's maxim No. 5
"A generalisation about a 'class' of drugs may tell us more about the (restricted) knowledge of the speaker/author than it does about the properties of drugs in question."
Several currently widely marketed TCAs could be withdrawn without being missed, or used only as cheap anti-histamines / sedatives (trimipramine, doxepin and probably dothiepin).
It is logical to select four of the TCAs for antidepressant treatment and master the safe use of those. Look at the notes on 'receptor affinities' and 'toxicity' in the full version of 'Psychopharmacology Update Notes'; they will substantiate/demonstrate the rationale for the following preferences.
- clomipramine:-- is probably still be the best and cheapest serotonin and noradrenalin reuptake inhibitor (SNRI).
- nortriptyline:-- potent as an noradrenalin reuptake inhibitor, modest but useful sedative effect, linear pharmacokinetics, dirt cheap, no active metabolites, no significant inhibition of cytochrome P450 enzymes.
- amitriptyline:-- probably has the best evidence for superior efficacy in severe depression of any drug (but from my experience clomipramine is more potent as an antidepressant).
- desipramine:-- best side effect vs potency profile, particularly the least like to cause postural hypotension or anti-muscarinic side effects (note lofepramine is similar and is metabolised into desipramine). But ... it is very potent and the usually recommended dose range is very probably much too high.
