Therapeutic drug monitoring use in clinical practice of a mental health service

Introduction: Second-generation antipsychotics (SGAs), clozapine, risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, indicated for the treatment of schizophrenia and some of these for the treatment of bipolar disorder, are metabolized in the liver by the cytochrome P450 (CYP) system, a superfamily of isoenzymes. CYP450 enzyme activity is different among people. Different groups are classified as poor metabolizers (PMs), intermediate metabolizers (IMs), extensive metabolizers (EMs), ultra rapid metabolizers (UMs) [1]. Drug interaction with other psychotropic (selective serotonin reuptake inhibitors, mood stabilizers) or somatic (antibiotics, beta-blockers) medication, trough inhibition or induction of CYP450 activity, also affect SGAs metabolism speed, plasma levels, therapeutic effect and toxicity [2]. In clinical practice Therapeutic Drug Monitoring (TDM) is an established procedure for lithium, carbamazepine and valproate treatment. TDM is suggested during SGAs treatment if there is lack of clinical response or a suspect of poor compliance or toxic events at therapeutic doses, or side effects with subtherapeutic doses, drug-drug interactions, liver impairment, suspect of CYP450 polymorphism (PMs or UMs) or in elderly patients [3–5]. Materials and Methods: In the Mental Health Service of ASL Biella TDM has been carried out in collaboration with pharmaco-toxicological analysis laboratories of the universities of Bologna, Messina and Milan. Results: In 15 patients in drug treatment with SGAs, TDM was carried out to prevent toxic events of augmentation, when antidepressant (SSRI) are coadministrated, in some cases [6]. To understand the lack of clinical outcome in other cases [7]; in three cases TDM showed a clear non compliance of the patients to drug treatment; in one case TDM showed a very high plasma level of SGA and permitted a early discontinuation of SSRI, to avoid serious toxic events to the patient [8]. In eleven cases TDM showed a good compliance of patients to drug treatment and no risk of toxic events. Conclusion: Safety and efficacy are two key elements in clinical practice and TDM may contribute to both. TDM might become a helpful tool in a modern approach to drug therapy in psychiatry and guidelines to optimise its use [4,9] are welcome. References: [1] Wilkinson GR, (2003), Farmacocinetica. In: Hardman JG, Limbird LE, Goodman Gilman A (eds), “Le basi farmacologiche della terapia”, 3–29, McGraw-Hill [2] Spina E. & Leon J. de, (2007), Metabolic Drug Interactions with Newer Antipsychotics: A Comparative Review, Basic & Clinical Pharmacology & Toxicology, 100: 4–22. [3] Raggi MA, (2002), Therapeutic drug monitoring: chemical-clinical correlations of atypical antipsychotic drugs. Current Medicinal Chemistry, 9: 1397–1409. [4] Baumann P, Hiemke C, Ulrich S, Eckermann G, Gaertner I, Gerlach M, Kuss HL, Laux G, Mueller-Oerlingenhausen B, Rao ML, Riederer P, Zernig G; Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) – Therapeutic Drug Monitoring (TDM), (2004) The AGNP-TDM Expert Group Consensus Guidelines: Therapeutic Drug Monitoring in Psychiatry. Pharmacopsychiatry. 37, 6: 243–65. [5] Spina E, Scordo MG, D'Arrigo C, (2003), Metabolic Drug Interactions with new antipsychotic agents. Fundamental and Clinical Pharmacology, 17, 5: 517–538. [6] Saracino MA, Mercolini L, Flotta G, Albers LJ, Merli R, Raggi MA, (2006), Simultaneous determination of fluvoxamine isomers and quetiapine in human plasma by means of high-performance liquid chromatography. Journal of Chromatography B. 843, 2: 227–233 [7] Migliardi G., D'Arrigo C., Santoro V., Bruno A., Cambria R., Haefele E., Merli R., Spina E. (Messina) (2006), Monitoraggio terapeutico delle concentrazioni plasmatiche di olanzapina: fattori di variabilità, Proceedings of the XV National Congress of Neuropsychopharmacology, Genoa, 696–697. [8] Haefele E, Merli R (2008), Pharmacological Interaction between Antipsychotic and Antidepressant Drugs, Proceedings of the Meeting “Therapeutic and Toxic Effects of Central Nervous System Drugs: the Importance of Drug Monitoring”, Bologna [9] Bondy B, Spellmann I, (2007), Pharmacogenetics of Antipsychotics: Useful For the Clinician? Current Opinion in Psychiatry. 20, 1: 126–130.