Comparison of rapid-cycling and non-rapid-cycling bipolar I manic patients during treatment with olanzapine: analysis of pooled data.
BACKGROUND
Rapid-cycling (RC) bipolar disorder patients experience high levels of morbidity, typically respond unsatisfactorily to available treatments, and, so, require additional studies of novel treatments. We report on the first controlled study comparing acute and continuous clinical outcomes in RC and non-RC manic patients treated with olanzapine.


METHODS
We analyzed data pooled from 2 placebo-controlled, double-blind, 3- to 4-week trials of olanzapine in mania (N = 254), 1 with an open-label extension up to 1 year (N = 113) and controlled supplementation with lithium or fluoxetine as needed, to compare demographic, clinical, and outcome measures between RC and non-RC subgroups of 254 DSM-IV bipolar I manic subjects.


RESULTS
RC (N = 90, 35%) versus non-RC subjects (N = 164, 65%) were younger at intake (p = .02), less often psychotic (p < .0001), and more likely to have familial bipolar disorder (p < .0001), abused substances (p = .01), more previous hospitalizations (p = .004), and many more illness episodes (p < .001). In initial blinded trial outcomes, relative responses (> or = 50% improvement of mania) to olanzapine/placebo were similar in RC and non-RC subjects, though early responses to olanzapine favored RC over non-RC subjects (p = .003), and long-term outcomes favored non-RC subjects (p = .05). Fewer RC subjects achieved strictly defined initial symptomatic remission (p = .014) within a year; RC subjects were more likely to experience recurrences (p = .002), especially of depressive illness (< .001), and had more rehospitalizations (p = .01) and suicide attempts (p = .03).


CONCLUSIONS
RC bipolar I patients showed major initial differences and more rapid initial clinical changes, especially toward depression, with less favorable long-term outcomes than non-RC cases during treatment with olanzapine. Inclusion of RC bipolar disorder patients can complicate therapeutic trials, but these patients require further study for differential responsiveness to innovative treatments with methods of assessing clinical response that take their mood instability into account.
Vieta
Eduard
E
Bipolar Disorders Program, Department of Psychiatry, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain. evieta@clinic.ub.es
Calabrese
Joseph R
JR
Hennen
John
J
Colom
Francesc
F
Martínez-Arán
Anabel
A
Sánchez-Moreno
Jose
J
Yatham
Lakshmi N
LN
Tohen
Mauricio
M
Baldessarini
Ross J
RJ
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology*; D004354:Drug Screening Assays, Antitumor; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use; D006801:Humans; D008094:Lithium / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D015201:Meta-Analysis as Topic; D000077152:Olanzapine; D016016:Proportional Hazards Models; D011569:Psychiatric Status Rating Scales; D016019:Survival Analysis; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D005473:Fluoxetine; D001569:Benzodiazepines; D008094:Lithium; D000077152:Olanzapine