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 bipolar
disorder or unipolar depression (Research Diagnostic Criteria or
DSM-III-R criteria) discharged from the National Institute of
Mental Health (NIMH) Biological Psychiatry Branch between 1974
and 1996 was conducted to assess the degree and efficacy of
“add-on” pharmacotherapy.

Method: Following completion of formal
structured blinded research protocols, patients entered a
treatment phase (often again on a blind basis) in which all
agents available in the community could be utilized. Each
patient’s retrospective life chart and all prospective
double-blind nurse- and self-rated NIMH data were reviewed. The
overall degree of improvement at discharge 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 achieved at the time of discharge. There
was a significant relationship between number of medications
utilized at discharge as a function of discharge date (r = 0.45,
p < .0001). The percentages of patients discharged on
treatment with 3 or more medications were 3.3% (1974-1979), 9.3%
(1980-1984), 34.9% (1985-1989), and 43.8% (1990-1995). No
correlation was found between polypharmacy and age (r = -0.03, p
= .66). Patients more recently discharged from the 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 were required to achieve the same degree
of improvement at hospital discharge. More systematic approaches
to the complex regimens required for treatment of patients with
refractory mood disorder are clearly needed.