The Association between Exposure to COX-2 Inhibitors and Schizophrenia Deterioration. A Nested Case-Control Study

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