The association between exposure to COX-2 inhibitors and schizophrenia deterioration. A nested case-control study.
BACKGROUND
COX-2 inhibitors (COX-2i) have been reported to have beneficial effects on schizophrenia. This observational study assesses the association between exposure to COX-2i or/and NSAIDs and schizophrenia deterioration.


METHODS
We conducted a case-control study within a cohort (n=3,485) of antipsychotic users with a schizophrenia diagnosis (ICD-9=295.x) in IMS-Lifelink, a US claims database. Case events indicating exacerbation of schizophrenia were: switching antipsychotic medication, starting combination therapy, using parenteral antipsychotics or an increasing dose. For each case one control was selected. Exposure to COX-2i/NSAIDs (current/recent/none) and cumulative exposure in Defined Daily Doses 90 days before the index/event date were assessed. Age, sex and co-medication were evaluated as confounders. Logistic regression analysis was used to assess the association.


RESULTS
1,443 case events occurred. For current use, no benefit on schizophrenia case events from exposure to COX-2i was found (adjusted OR 1.16; 95% CI 0.83-1.62). Instead, recent COX2i use with a duration of 0 to 93 days was associated with an increased risk for schizophrenia deterioration (adjusted OR 2.56; 95% CI 1.35-4.87). This association was strongest in rofecoxib. No relation was found for NSAIDs.


CONCLUSIONS
The use of COX-2i was not associated with a decreased risk for schizophrenia deterioration in this population.
Stolk
P
P
Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.
Souverein
P C
PC
Leufkens
H G M
HG
Weil
J G
JG
Egberts
A C G
AC
Heerdink
E R
ER
D000367:Age Factors; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D014150:Antipsychotic Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology*; D012737:Sex Factors; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014150:Antipsychotic Agents; D052246:Cyclooxygenase 2 Inhibitors