Possible Drug-drug Interaction between Pregabalin and Clozapine in Patients with Schizophrenia: Clinical Perspectives

O. Schjerning; S. Lykkegaard; P. Damkier; J. Nielsen

doi:10.1055/s-0034-1390468

Pharmacopsychiatry, Table of Contents

Pharmacopsychiatry 2015; 48(01): 15-18
DOI: 10.1055/s-0034-1390468

Original Paper

Possible Drug-drug Interaction between Pregabalin and Clozapine in Patients with Schizophrenia: Clinical Perspectives

Authors

O. Schjerning

¹Psychiatry, Aalborg University Hospital, Aalborg, Denmark

²Clinical Department of Medicine, Aalborg University, Aalborg, Denmark
S. Lykkegaard

³Mental Health Centre Copenhagen, Denmark
P. Damkier

⁴Department of Clinical Chemistry & Pharmacology, Odense University Hospital, Odense, Denmark
J. Nielsen

¹Psychiatry, Aalborg University Hospital, Aalborg, Denmark

²Clinical Department of Medicine, Aalborg University, Aalborg, Denmark

Abstract

Introduction: Pregabalin is an antiepileptic drug with anti-anxiety properties and is approved for treatment of generalized anxiety disorder. Anxiety is common in patients with schizophrenia and pregabalin has been suggested as an off-label add-on treatment.

Methods: Pregabalin was added to clozapine in 2 patients with schizophrenia, who both suffered from severe anxiety symptoms.

Results: Both patients experienced falls and consequently bone fractures. Increased plasma levels of clozapine likely contributed to the outcome. One patient had confirmed seizures whereas the mechanism in the other patient was less clear.

Discussion: This short report discusses the possible mechanism of a pregabalin-clozapine interaction.

Key words

pregabalin - clozapine - side effects - schizophrenia - anxiety

Full Text

References

References
1 Uggerby P, Nielsen RE, Correll CU et al. Characteristics and predictors of long-term institutionalization in patients with schizophrenia. Schizophr Res 2011; 131: 120-126
2 van Os J, Kapur S. Schizophrenia. Lancet 2009; 374: 635-645
3 Achim AM, Maziade M, Raymond E et al. How prevalent are anxiety disorders in schizophrenia? A meta-analysis and critical review on a significant association. Schizophr Bull 2011; 37: 811-821
4 Huppert JD, Weiss KA, Lim R et al. Quality of life in schizophrenia: Contributions of anxiety and depression. Schizophr Res 2001; 51: 171-180
5 Michail M, Birchwood M. Social anxiety disorder in first-episode psychosis: Incidence, phenomenology and relationship with paranoia. The British Journal of Psychiatry 2009; 195: 234-241
6 Braga RJ, Petrides G, Figueira I. Anxiety disorders in schizophrenia. Compr Psychiatry 2004; 45: 460-468
7 Bech P. Dose-response relationship of pregabalin in patients with generalized anxiety disorder. A pooled analysis of four placebo-controlled trials. Pharmacopsychiatry 2007; 40: 163-168
8 Schönfeldt-Lecuona C, Wolf RC, Osterfeld ND et al. Pregabalin in the treatment of schizophrenic anxiety. Pharmacopsychiatry 2009; 42: 124-125
9 Englisch S, Esser A, Enning F et al. Augmentation with pregabalin in schizophrenia. J Clin Psychopharmacol 2010; 30: 437-440
10 Nielsen J, Correll CU, Manu P et al. Termination of clozapine treatment due to medical reasons: When is it warranted and how can it be avoided?. J Clin Psychiatry 2013; 74: 603-613
11 Nielsen J, Damkier P, Lublin H et al. Optimizing clozapine treatment. Acta Psychiatr Scand 2011; 123: 411-422
12 Gahr M, Schmid MM, Schönfeldt-Lecuona C. Pregabalin-associated elevation of clozapine serum levels. Pharmacopsychiatry 2012; 45: 297-299
13 Englisch S, Alm B, Meyer-Lindenberg A et al. Pregabalin-associated increase of clozapine serum levels. J Clin Psychopharmacol 2012; 32: 127
14 Hiemke C, Baumann P, Bergemann N et al. AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: Update 2011. Pharmacopsychiatry 2011; 44: 195-235
15 Millar J, Sadasivan S, Weatherup N et al. Lyrica nights – recreational pregabalin abuse in an urban emergency department. Emergency Medicine Journal 2013; 30: 874
16 Loftus H, Wright A. Potential misuse of pregabalin and gabapentin. BMJ 2014; 348: 1290
17 Grosshans M, Lemenager T, Vollmert C et al. Pregabalin abuse among opiate addicted patients. Eur J Clin Pharmacol 2013; 69: 2021-2025
18 Grosshans MF. Pregabalin abuse, dependence, and withdrawal: A case report. Am J Psychiatry 2010; 167: 869
19 Filipetto FA, Zipp CP, Coren JS. Potential for pregabalin abuse or diversion after past drug-seeking behavior. J Am Osteopath Assoc 2010; 110: 605-607
20 Wills B, Reynolds P, Chu E et al. Clinical outcomes in newer anticonvulsant overdose: A poison center observational study. J Med Toxicol 2014;
21 Duan JZ. Applications of population pharmacokinetics in current drug labelling. J Clin Pharm Ther 2007; 32: 57-79
22 Ben-Menachem E. Pregabalin pharmacology and its relevance to clinical practice. Epilepsia 2004; 45 (Suppl. 06) 13-18
23 Maines LW, Antonetti DA, Wolpert EB et al. Evaluation of the role of p-glycoprotein in the uptake of paroxetine, clozapine, phenytoin and carbamazapine by bovine retinal endothelial cells. Neuropharmacology 2005; 49: 610-617
24 Giacomini KM, Huang S-M, Tweedie DJ et al. Membrane transporters in drug development. Nat Rev Drug Discov 2010; 9: 215-236
25 Wang M, Hou R, Jian J et al. Effects of antipsychotics on bone mineral density and prolactin levels in patients with schizophrenia: A 12-month prospective study. Human Psychopharmacology: Clinical and Experimental 2014; 29: 183-189
26 Sørensen HJ, Jensen SOW, Nielsen J. Schizophrenia, antipsychotics and risk of hip fracture: A population-based analysis. Eur Neuropsychopharmacol 2013; 23: 872-878