ABSTRACT
Title
Zopiclone and Prazepam Dependence: Role of Hair Analysis for the Monitoring of Treatment in a Migraine Patient
Authors
A. Ferrari1, I. Tiraferri1, F. Palazzoli2, M. Licata2.
1Division of Toxicology and Clinical Pharmacology, Headache Centre. 2Legal Medicine – Forensic Toxicology Lab., University of Modena and Reggio Emilia, Italy.
1Division of Toxicology and Clinical Pharmacology, Headache Centre. 2Legal Medicine – Forensic Toxicology Lab., University of Modena and Reggio Emilia, Italy.
Abstract
Zopiclone is a non-benzodiazepine hypnotic agent, indicated for short-term treatment of insomnia (max. 4 weeks) at the dose of 7.5 mg/day. It has been marketed as a drug with a lower potentiality of overuse than benzodiazepines. Prazepam, a prodrug for desmethyldiazepam, is a benzodiazepine derivative drug indicated for the treatment of anxiety at the dose of 20-40 mg/day. Its abuse liability is described as lower than other benzodiazepines, because of the slow onset and long duration of action. Insomnia and anxiety are prevalent symptoms in general population, in particular among migraine patients.Here we are going to present the case of a chronic migraine patient with zopiclone and prazepam dependence, and analgesic overuse, whose hair was analysed to detect the use of the drugs. The drugs in her hair were detected by liquid chromatography/electrospray tamdem mass spectrometry [LC/ESI-MS/MS (Agilent technology, Palo Alto, CA, USA)](Matuszewski et al., 2003).
Description of the case: 37-year-old female migraine patient, Secondary School Diploma, married. Two 7-year-old twin daughters, she runs a tobacconist shop. Smoker (15 cigarettes/day), teetotaller, she drinks 1 coffee/day. She started suffering from headache as a child. After puberty, she had perimenstrual migraines. Migraine disappeared during pregnancy, but worsened after her daughters’ birth. It has been daily and associated to severe insomnia for 3 years. In summer 2009, a psychiatrist prescribed her fluoxetine and hypnotics. The patient came to Headache Centre in January 2010. She suffered from daily headache and unbearable insomnia and every day she used at least an intramuscular injection of ketorolac (Toradol 10 mg), 20 tablets of zopiclone (Imovane 7.5 mg), 20 tablets of prazepam (Prazene 20 mg). She was admitted to day hospital to be detoxified. At admission, a sample of hair was collected for drug testing. During hospitalization, prazepam and zopiclone were gradually reduced. In order to prevent withdrawal symptoms, delorazepam (En) was administered intravenously and a prophylactic migraine treatment was started, with topiramate (Topamax) 25 mg in the evening, which was then gradually increased to 100 mg/day. At the discharge, the patient was taking 4 tablets of zopiclone and 4 of prazepam a day. The psychiatrist also recommended mirtazapine (Remeron) 30 mg/day. At two- month follow-up, the patient was taking every day: topiramate 100 mg (with good migraine improvement), 2 tablets of zopiclone, and 2 of prazepam. Another hair sample was collected.
At the admission in the proximal hair segment (recent use) fluoxetine 6.3 ng/mg, zopiclone 6.68 ng/mg, prazepam 0.67 ng/mg were detected; in the distal hair segment (previous use) fluoxetine 1.7 ng/mg, zopiclone 3.94 ng/mg, prazepam 0.92 ng/mg were detected. At two- month follow-up, in the proximal hair segment (recent use) fluoxetine 1.9 ng/mg, topiramate 6.3 ng/mg, mirtazapine 1.0 ng/mg, delorazepam 0.14 ng/mg, prazepam 0.06 ng/mg were detected and zopiclone was not detectable. Therefore hair analysis confirmed the pharmacological history of the patient.
Zopiclone and prazepam dependence had been nearly only reported in subjects with predisposition to abuse or suffering form psychiatric disorders (Cimolai, 2007). Doses were always lower than in the case that we described. In this patient, insomnia, anxiety, and the stressing family situation were, besides from migraine, the main factors which had led to an increasing use, up to 150 mg/day of zopiclone and 400 mg/day of prazepam, with consequent dependence.
Hair analysis has a long tradition in the detection of substances of abuse. However, the keratinous matrix can also be used to detect a large number of drugs. In the clinical setting, the analysis of drugs in the hair can demonstrate previous use of medications and compliance with drug therapy over time.
Cimolai (2007).Can Fam Physician. 53, 2124-2129.
Matuszewski et al. (2003). Anal Chem. 75, 3019-3030.
Description of the case: 37-year-old female migraine patient, Secondary School Diploma, married. Two 7-year-old twin daughters, she runs a tobacconist shop. Smoker (15 cigarettes/day), teetotaller, she drinks 1 coffee/day. She started suffering from headache as a child. After puberty, she had perimenstrual migraines. Migraine disappeared during pregnancy, but worsened after her daughters’ birth. It has been daily and associated to severe insomnia for 3 years. In summer 2009, a psychiatrist prescribed her fluoxetine and hypnotics. The patient came to Headache Centre in January 2010. She suffered from daily headache and unbearable insomnia and every day she used at least an intramuscular injection of ketorolac (Toradol 10 mg), 20 tablets of zopiclone (Imovane 7.5 mg), 20 tablets of prazepam (Prazene 20 mg). She was admitted to day hospital to be detoxified. At admission, a sample of hair was collected for drug testing. During hospitalization, prazepam and zopiclone were gradually reduced. In order to prevent withdrawal symptoms, delorazepam (En) was administered intravenously and a prophylactic migraine treatment was started, with topiramate (Topamax) 25 mg in the evening, which was then gradually increased to 100 mg/day. At the discharge, the patient was taking 4 tablets of zopiclone and 4 of prazepam a day. The psychiatrist also recommended mirtazapine (Remeron) 30 mg/day. At two- month follow-up, the patient was taking every day: topiramate 100 mg (with good migraine improvement), 2 tablets of zopiclone, and 2 of prazepam. Another hair sample was collected.
At the admission in the proximal hair segment (recent use) fluoxetine 6.3 ng/mg, zopiclone 6.68 ng/mg, prazepam 0.67 ng/mg were detected; in the distal hair segment (previous use) fluoxetine 1.7 ng/mg, zopiclone 3.94 ng/mg, prazepam 0.92 ng/mg were detected. At two- month follow-up, in the proximal hair segment (recent use) fluoxetine 1.9 ng/mg, topiramate 6.3 ng/mg, mirtazapine 1.0 ng/mg, delorazepam 0.14 ng/mg, prazepam 0.06 ng/mg were detected and zopiclone was not detectable. Therefore hair analysis confirmed the pharmacological history of the patient.
Zopiclone and prazepam dependence had been nearly only reported in subjects with predisposition to abuse or suffering form psychiatric disorders (Cimolai, 2007). Doses were always lower than in the case that we described. In this patient, insomnia, anxiety, and the stressing family situation were, besides from migraine, the main factors which had led to an increasing use, up to 150 mg/day of zopiclone and 400 mg/day of prazepam, with consequent dependence.
Hair analysis has a long tradition in the detection of substances of abuse. However, the keratinous matrix can also be used to detect a large number of drugs. In the clinical setting, the analysis of drugs in the hair can demonstrate previous use of medications and compliance with drug therapy over time.
Cimolai (2007).Can Fam Physician. 53, 2124-2129.
Matuszewski et al. (2003). Anal Chem. 75, 3019-3030.