Impact of real-world ziprasidone dosing on treatment discontinuation rates in patients with schizophrenia or bipolar disorder.
BACKGROUND
The purpose of this study is to evaluate the relationship between maximum dose of ziprasidone and time to discontinuation in the treatment of schizophrenia/schizoaffective disorder and bipolar disorder in clinical practice.


METHODS
The 2001-2006 MarketScan Commercial and Medicare Databases were analyzed for maximum ziprasidone doses achieved in patients with schizophrenia/schizoaffective disorder or bipolar disorder. Ziprasidone maximum-dose groups were defined as low (20-60 mg/d), medium (61-119 mg/d), or high (120-160 mg/d). Patients receiving >160 mg/d were excluded. Mean time to discontinuation was evaluated across propensity score-matched dosing groups. Cox proportional hazard models were used to adjust for confounding when comparing the high- and medium-dose groups with the low-dose group.


RESULTS
Data were available for 33,340 patients with schizophrenia/schizoaffective disorder, of whom 16.6% received low dose of ziprasidone, 22.0% medium dose, and 61.4% high dose. Of those subjects with bipolar disorder (n=27,751), 26.1% were receiving a low dose of ziprasidone, 25.7% a medium dose, and 48.3% a high dose. Among the propensity score-matched dosing groups, the respective mean time to discontinuation for low, medium, and high doses was 90.5, 117.2, and 201.6d within the schizophrenia/schizoaffective disorder cohort and 84.6, 110.7, and 173.2d within the bipolar cohort (p<0.0001 for all comparisons). The hazard ratios for discontinuing therapy were significantly lower for the medium- (0.84, 0.84) and high-dose (0.57, 0.60) groups relative to the low-dose group in schizophrenia/schizoaffective disorder and bipolar disorder, respectively.


CONCLUSIONS
Patients with schizophrenia/schizoaffective or bipolar disorders receiving ziprasidone 120-160 mg/d experienced a statistically significant lower discontinuation rate compared with those receiving lower doses.
Citrome
Leslie
L
Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA. citrome@nki.rfmh.org
Reist
Christopher
C
Palmer
Liisa
L
Montejano
Leslie B
LB
Lenhart
Gregory
G
Cuffel
Brian
B
Harnett
James
J
Sanders
Kafi N
KN
D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D001714:Bipolar Disorder / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D016208:Databases, Factual / Q000706:statistics & numerical data; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D038801:International Classification of Diseases / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D011336:Probability; D057216:Propensity Score; D016016:Proportional Hazards Models; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D012559:Schizophrenia / Q000188:drug therapy*; D013844:Thiazoles / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone