Examining the efficacy of antidepressant pharmacotherapy for interpersonal sensitivity in patients with depressive disorders

Interpersonal sensitivity is a transdiagnostic trait vulnerability factor for several psychiatric conditions, most notably atypical depression. Surprisingly little research attention has been devoted to pharmacotherapy for interpersonal sensitivity. We conducted a literature review of randomized controlled trials conducted over five decades to determine which antidepressant medications have demonstrated efficacy on the Hopkins Symptom Checklist interpersonal sensitivity factors. Our search focused on adult samples with unipolar depressive disorders. Compared to placebo, we found consistent evidence for the superiority of selective serotonin reuptake inhibitors and imipramine, as well as monoamine oxidase inhibitors (mainly phenelzine) specifically for patients with atypical or anxious depression. Mianserin did not appear to be effective in two trials. Phenelzine was superior to imipramine, but only for patients with atypical features, mirroring the trends observed for depression treatment effects in those trials. There was inconsistent evidence for the superiority of selective serotonin reuptake inhibitors over tricyclics (mainly imipramine), but no studies reported the converse. Some trials were underpowered with small sample sizes, or did not adequately report statistics. There was a notable absence of studies with newer antidepressants. Although interpersonal sensitivity clearly responds to serotonergic antidepressants, it is not clear from the existing literature if these are more effective than medications lacking such properties. Future research will need to carefully choose pharmacologic agents with nonoverlapping mechanisms to answer this question.