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.


METHODS
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.


CONCLUSIONS
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.
Frye
M A
MA
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892-1272, USA.
Ketter
T A
TA
Leverich
G S
GS
Huggins
T
T
Lantz
C
C
Denicoff
K D
KD
Post
R M
RM
D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000927:Anticonvulsants / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy / Q000523:psychology; D002985:Clinical Protocols; D015331:Cohort Studies; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006760:Hospitalization; D006801:Humans; D008094:Lithium / Q000627:therapeutic use; D008297:Male; D009315:National Institute of Mental Health (U.S.); D012189:Retrospective Studies; D016896:Treatment Outcome; D014481:United States
D000927:Anticonvulsants; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D008094:Lithium