Pharmacology Journal

Reports to the spontaneous reporting system in Germany have raised concerns that exposure to quinolone antibiotics may increase the risk for suicidal behaviour, i.e., suicide, suicide attempt, and suicidal ideation. Some of the case reports described suicidal behaviour in quinolone users as long as 6 months after drug exposure. The current study was designed to compare the risk of suicidal behaviours among recent quinolone users with recent users of other antibiotics and people who had not recently received any antibiotic. We report on the results of a nested case-control study of people who had suicidal behaviour and a group of controls who did not have suicidal behaviour.

The study was based on information derived from the General Practice Research Database (GPRD). Since 1987, over four million residents in the United Kingdom have been enrolled with selected general practitioners (GPs) who use office computers provided by Value Added Medical Products (VAMP Health) and have agreed to provide data for research purposes to the GPRD which is currently owned by the United Kingdom Department of Health. The GPs received 12 months of instruction on the standardized recording of medical information and they agreed to supply anonymized information to academic researchers on an ongoing basis. The information recorded includes patient characteristics, drugs dispensed, clinical diagnoses, notation of referrals to consultants, hospitalizations, certain historical information and other findings, (e.g. smoking status, blood pressure, height and weight). Referral letters from consultants and hospitalizations are kept in a manual file. The general practitioners generate prescriptions directly from the computer, and these are automatically transcribed into the patient’s computer record. The details of each prescription including dose, instructions and quantity are automatically recorded on computer and can be used to determine dose and duration of drug exposure. A modification of the Oxford Medical Information System (OXMIS) classification is used to enter medical diagnoses, and a coded drug dictionary based on the Prescription Pricing Authority’s dictionary is used for the recording of prescriptions. (OXMIS codes were mapped onto ICD codes for the purpose of this study.) Two large validation studies determined that information on all patient referrals and hospitalizations present in the manual medical records in the general practitioners’ offices was recorded on the computer over 90% of the time.

Subjects

This was a case-control study. The base population from which the data were derived was restricted to subjects who used a quinolone antibiotic (n=142 316) at some time between January 1, 1991 and April 30, 1995. The quinolones evaluated were ciprofloxacin, norfloxacin, ofloxacin, nalidixic acid, cinoxacin, enoxacin, acrosoxacin and temafloxacin. In order to be included, a subject had to have at least 18 months of information on drugs prescribed and diagnoses recorded on computer prior to the date of diagnosis. Subjects with a prior diagnosis of degenerative neurologic disease (i.e., stroke, multiple sclerosis), those with chronic liver or renal disease and those who were recorded as being drug addicts were excluded from the study.

Three groups of subjects aged 15–84 years of age were identified from the base population of quinolone users and formed the case groups: (1) persons who committed suicide (OXMIS code 3009D), (2) persons who had a diagnosis of attempted suicide (OXMIS codes L3009P, parasuicide; 9779L, drug overdose suicidal; and 3009C, attempted suicide) and (3) persons who had a diagnosis of suicidal ideation (OXMIS codes 3009BW, suicidal ideation; 3009BT, suicidal thoughts; and 3009BP, suicidal plans). If a subject had more than one of the ‘case’ diagnoses during the study period, only the first such diagnosis was considered. The index date from which exposure was determined was the date that the diagnosis was made.

Controls were derived from an initial random sample of 1000 subjects in the base population who did not have one of the ‘case’ diagnoses during the study period. The same exclusion criteria applied to cases were applied to the controls. A random index date between January 1, 1991 and April 1995 was assigned to each control subject and was considered to be the index date from which exposure was determined.

Filed under: Clinical Pharmacology