Abstract
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.
Conclusion: The use of COX-2i was not associated with a decreased risk for schizophrenia deterioration in this population.
Key words
schizophrenia - COX-2 inhibitors - pharmacoepidemiology
References
-
1
Akhondzadeh S, Tabatabaee M, Amini H, Ahmadi Abhari SA, Abbasi SH, Behnam B.
Celecoxib as adjunctive therapy in schizophrenia: A double-blind, randomized and placebo-controlled trial.
Schizophr Res.
2007;
90
179-185
-
2
Bresee CJ, Delrahim K, Maddux RE, Dolnak D, Ahmadpour O, Rapaport MH.
The effects of celecoxib augmentation on cytokine levels in schizophrenia.
Int J Neuropsychopharmacol.
2006;
9
343-348
-
3
Doux JD, Bazar KA, Lee PY, Yun AJ.
Can chronic use of anti-inflammatory agents paradoxically promote chronic inflammation through compensatory host response.
Med Hypotheses.
2005;
65
389-391
-
4
Hoffman C.
COX-2 in brain and spinal cord - implications for therapeutic use.
Curr Med Chem.
2000;
7
1113-1120
-
5
Hugenholtz GW, Heerdink ER, Meijer WE, Stolker JJ, Egberts AC, Nolen WA.
Reasons for switching between antipsychotics in daily clinical practice.
Pharmacopsychiatry.
2005;
38
122-124
-
6
Müller N, Riedel M, Scheppach C, Brandstätter B, Sokullu S, Krampe K. et al .
Beneficial antipsychotic effects of celecoxib add-on therapy compared to risperidone alone in schizophrenia.
Am J Psychiatry.
2002;
159
1029-1034
-
7
Müller N, Riedel M, Schwarz MJ.
Psychotropic effects of COX-2 inhibitors - possible new approach for the treatment of psychiatric disorders.
Pharmacopsychiatry.
2004;
37
266-269
-
8
Müller N, Riedel M, Schwarz MJ, Engel RR.
Clinical effects of COX-2 inhibitors on cognition in schizophrenia.
Eur Arch Psychiatry Clin Neurosci.
2005;
255
149-151
-
9
Müller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Muller B. et al .
The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine.
Mol Psychiatry.
2006;
11
680-684
-
10
Müller N, Ulmschneider M, Scheppach C, Schwarz MJ, Ackeheil M, Möller, Gruber R, Riedel M.
COX-2 inhibition as a treatment approach in schizophrenia: immunological considerations and clinical effects of celecoxib add-on therapy.
Eur Arch Clin Neurosci.
2004;
254
14-22
-
11
Onder G, Pellicciotti F, Gambassi G, Bernabei R.
NSAID-related psychiatric adverse events: who is at risk?.
Drugs.
2004;
64
2619-2627
-
12
Rapaport MH, Delrahim KK, Bresee CJ, Maddux RE, Ahmadpour O, Dolnak D.
Celecoxib augmentation of continuously ill patients with schizophrenia.
Biol Psychiatry.
2005;
57
1594-1596
-
13
Riedel M, Strassnig M, Schwarz MJ, Mueller N.
COX-2 inhibitors as adjunctive therapy in schozphrenia - rationale for use and evidence to date.
CNS Drugs.
2005;
19
805-819
Correspondence
Dr. E. R. Heerdink
Division of Pharmacoepidemiology and Pharmacotherapy
Utrecht Institute for Pharmaceutical Sciences
P.O. Box 80082
3508 TB Utrecht
The Netherlands
Phone: +31/30/253 73 24
Fax: +31/30/253 91 66
Email: E.R.HEERDINK@UU.NL