Lithium is among the most classically recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with lithium requires achieving plasma levels above 0.5 mEq/L. Mood-stabilizing antiepileptic drugs such as carbamazepine, valproate derivatives or lamotrigine have not demonstrated conclusive therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Thyroid hormones are considered among the currently recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with thyroid hormones requires achieving plasma concentration of TSH close to the lower limits at the normal range (0.4 μUI/L) or even below it. Second-generation antipsychotics such as aripiprazole or quetiapine have consistently demonstrated significant therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Second-generation antipsychotics however require the careful monitoring of both cardiovascular and metabolic adverse effects.
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