The increasing use of polypharmacotherapy for refractory mood disorders: 22 years of study

Background: Few studies have approached the subject of polypharmacotherapy systematically. This retrospective review of 178 patients with refractory b ipolar disorder or unipolar depression (Research Diagnostic Criteria or DSM -III-R criteria) discharged from the National Institute of Mental Health (N IMH) Biological Psychiatry Branch between 1974 and 1996 was conducted to as sess the degree and efficacy of "add-on" pharmacotherapy. Method: Following completion of formal structured blinded research protocol s, patients entered a treatment phase (often again on a blind basis) in whi ch all agents available in the community could be utilized. Each patient's retrospective life chart and all prospective double-blind nurse- and self-r ated NIMH data were reviewed. The overall degree of improvement at discharg e was assessed by rating on the Clinical Global Impressions scale (CGI) as modified for bipolar illness (CGI-BP). Results: A 78% improvement rate (moderate or marked on the CGI) was achieve d at the time of discharge. There was a significant relationship between nu mber of medications utilized at discharge as a function of discharge date ( r = 0.45, p < .0001). The percentages of patients discharged on treatment w ith 3 or more medications were 3.3% (1974-1979), 9.3% (1980-1984), 34.9% (1 985-1989), and 43.8% (1990-1995), No correlation was found between polyphar macy and age (r = -0.03, p = .66). Patients more recently discharged from t he NIMH had an earlier age at illness onset, more lifetime weeks depressed, and a higher rate of rapid cycling than patients in the earlier cohorts. Conclusion: Increasing numbers of medications in more recent NIMH cohorts w ere required to achieve the same degree of improvement at hospital discharg e. More systematic approaches to the complex regimens required for treatmen t of patients with refractory mood disorder are clearly needed.