TREATMENT APPROACHES TO THERAPY-RESISTANT DEPRESSION

Resistance to antidepressant treatment is a controversial field and th erapy resistance has received a wide range of definitions. The field h as suffered from a lack of consensus on how to classify treatment resi stance and from the related failure to standardise clinical criteria i n trials of new therapeutic approaches. A significant proportion of tr icyclic antidepressant (TCA)-resistant depression results from the fai lure to sustain an adequate course of therapy. This can be due to eith er inadequate prescribing or the poor tolerability of TCAs. The majori ty of cases of treatment resistance, however, involve antidepressant t herapy at a dose and duration that would normally be expected to be ef fective. In these cases, therapy may fail for many reasons. Refractory depression may occur in patients with medical conditions such as subc linical hypothyroidism, stroke and closed head injuries. Patients with alcoholism may prove refractory to treatment, as may those receiving certain medications, notably calcium channel blockers. Certain subtype s of depression, such as rapid-cycling disorder and delusional depress ion, also appear to be more refractory to treatment. A variety of ther apeutic approaches have been applied to treatment-resistant depression but, for most of these, placebo-controlled clinical trials with subst antial numbers of patients have not been conducted. Selective serotoni n re-uptake inhibitors (SSRIs) may have a role to play in TCA-resistan t patients as a result of their superior tolerability; monoamine oxida se inhibitors (MAOIs) also have a significant therapeutic role. ECT ha s an important role to play in patients who failed to respond to succe ssive drug therapies. Of the various add-on therapies, thyroid augment ation (triiodothyronine) of antidepressant treatment has shown promise , and definite benefits have been established for lithium augmentation . Evidence has emerged to show that lithium is not only effective as a n adjunct to TCA therapy, but also to the better tolerated SSRIs. Howe ver, further trials will be necessary to determine the optimal dosage and treatment duration for lithium augmentation.