Augmentation, i.e. the addition of another drug, is used to enhance the effects of standard antidepressants when two or more have successively failed to alleviate depressive symptoms despite treatment at an adequate dose for an adequate time. The therapeutic efficacy of new agents, e.g. venlafaxine, has provided clinicians with further options which now tend to be employed before augmentation but the following may be used.

The most common is augmentation is with the mood stabiliser lithium carbonate. Indeed, lithium may be effective as monotherapy for depression but is not preferred because of its adverse effect profile and need for plasma concentration monitoring. Its prescription in combination with antidepressants that have failed to produce remission is more usual and evidence suggests that up to 50% of patients who have not responded to standard antidepressants can respond after lithium augmentation. Addition of lithium requires careful titration of the plasma concentration up to the therapeutic range, with periodic checks thereafter and monitoring for toxicity (see p. 389).

Thyroid hormones also aid antidepressant action. Guidance points to the combination of tri-iodotyronine (T3) and TCAs as being most effective

(but effects of lofepramine may be augmented by levothyroxine to the extent that co-administration should be avoided). The amino acid isomer L-tryptophan, a precursor of serotonin, may also augment but such use is restricted to hospital specialists who must monitor haematological function (it is associated with an eosinophilia/ myalgia syndrome though this may have been due to an impurity rather than the L-tryptophan itself). The (3-adrenoceptor blocker pindolol can augment the action of SSRIs. Pindolol may act by binding to a serotonin autoreceptor and thus interfere with a homeostatic mechanism which acts to reduce serotonin concentrations after the initial elevation by SSRI action.

None of these augmentation strategies is ideal, since they either require plasma monitoring (lithium, tryptophan, tri-iodothyronine), expose the patient to potential toxicity (lithium, tryptophan) or have only a moderate evidence base for efficacy (triiodothyronine, pindolol).

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