NEWER AND OLDER ANTIDEPRESSANTS - A COMPARATIVE REVIEW OF DRUG-INTERACTIONS

A large number of drug interactions involving antidepressants have bee n de scribed. Some of these are common to specific classes of antidepr essant drugs, while others are related to peculiar properties of indiv idual compounds and vary greatly from one compound to another within t he same drug class. In general, the broader the range of receptors and enzymes affected by a given drug, the greater the potential for pharm acodynamic interactions. Older generation monoamine oxidase inhibitors (MAOIs) are particularly likely to cause interactions. These can occu r with a wide range of compounds including tyramine-containing foods, alcohol (ethanol), opioids, sympathomimetic agents and other antidepre ssant drugs [e.g. tricyclic antidepressants (TCAs) and selective serot onin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs)]. The mor e recently developed reversible and selective inhibitors of monoamine oxidase-A, such as moclobemide, appear to carry a much lower risk of c ausing serious drug interactions. TCAs affect several neurotransmitter systems, but to differing degrees. This may result in many clinically significant pharmacodynamic interactions, including the reversal of t he hypotensive action of some centrally active antihypertensive agents and the potentiation of the effects of anticholinergic agents and CNS depressants. Important pharmacokinetic interactions with TCAs include induction of their metabolism by anticonvulsants and impairment of th eir elimination by metabolic inhibitors such as fluoxetine, fluvoxamin e, antipsychotics and quinidine. Appropriate dosage adjustments may be required to minimise the potentially adverse effects resulting from t hese interactions. Some second generation antidepressants do not diffe r greatly from TCAs in pharmacological profile and so may be involved in similar interactions. However, others have a more selective mechani sm of action and a lower potential for drug interactions. This is espe cially true for the SSRIs, which cause fewer pharmacodynamic interacti ons than MAOIs and TCAs. Nevertheless, SSRIs may interact adversely wi th drugs that also affect serotonergic transmission (including lithium ) and may inhibit selectively the hepatic enzymes involved in the meta bolism of concurrently prescribed drugs such as TCAs, antipsychotics, carbamazepine, oral anticoagulants and P-adrenoceptor blocking agents. Fluoxetine and paroxetine, in particular, appear to be powerful inhib itors of CYP2D6, whereas fluvoxamine is a more potent inhibitor of CYP 1A2. Avoidance of unnecessary polytherapy, knowledge of the interactio n potential of individual agents and careful individualisation of dosa ge based on close evaluation of clinical response are essential to min imise potentially adverse drug interactions among patients receiving a ntidepressant therapy.