INTRODUCTION: Several studies suggest that oral monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) may be more effective than serotonin reuptake inhibitors for treating treatment-resistant depression (TRD). Despite this advantage, they are now rarely prescribed due to concern over serious side effects. In contrast, selegiline transdermal system (STS) may present a safer alternative to oral MAOIs and TCAs
however, no studies have compared STS with other antidepressants. METHODS: Data from 117 patients who received STS, oral MAOIs, or TCAs for TRD were obtained from a university mood disorder clinic. Two linear regression models were created with severity and number of side effect categories endorsed as the dependent variable. Logistic regression models were created for each side effect category with presence of category as the dependent variable. In all models, antidepressant class was entered as the independent variable, with covariates. RESULTS: Although STS was less effective than oral MAOIs, it was significantly more effective than TCAs. STS treatment had significantly fewer side effect categories endorsed versus oral MAOIs and TCAs. Patients receiving STS were less likely to report gastrointestinal side effects versus TCAs and to endorse cardiovascular side effects versus oral MAOIs. In contrast, STS patients were more likely to report skin side effects versus oral MAOIs. There were no reported serious adverse events. Amongst the covariates, only the number of prior antidepressant trials predicted more side effect categories endorsed. CONCLUSIONS: Although oral MAOI therapy has been eschewed by most clinicians, STS may be better tolerated than oral MAOIs and TCAs.