Efficient prevention of adverse drug reactions (ADRs) requires knowledge about their severity and pharmacological mechanisms and is dependent on reliable data on their frequencies and possible risk factors. The study was conducted to investigate the prescribers' experience and understanding of the ADRs of psychotropic drugs, and their attitude towards reporting these. In a questionnaire, physicians treating adult psychiatric patients were asked which ADRs that they regarded bothersome for some of the most widely used antidepressants and antipsychotics. Questions about the relationship between blockade of drug receptors and ADRs, and about the physicians' personal experience of and attitudes towards reporting of ADRs were also included. In total, 70 of 91 questionnaires (78%) were returned. The mean number of ADRs regarded bothersome ranged from 2.4 to 9.3 for the various drugs/drug classes. Qualified psychiatrists stated a significantly higher number of bothersome ADRs than did the residents. The percentage of physicians associating blockade of a receptor with a specific ADR varied from 76% (histamine receptor blockade and sedation) to 37% (alpha(1)-adrenergic blockade and tachycardia). Thirty-nine per cent of the physicians had never reported an ADR to the Norwegian Medicines Agency. The number of ADRs considered bothersome was relatively high. The pattern of these ADRs generally mirrored the typical ADR profiles of the drugs. The knowledge of the underlying mechanisms of ADRs was more or less incomplete. The reporting rate of ADRs to the national regulatory authorities was low.
PURPOSE: To study the association between alopecia and selective serotonin reuptake inhibitors (SSRIs) by estimating reporting rates and by making association comparisons within databases of adverse drug reactions (ADRs). METHODS: All reports of alopecia with marketed SSRIs until the end of 2004 were identified in SWEDIS, the national Swedish database for spontaneously reported ADRs, and in Vigibase, the international ADR database of the World Health Organization. Total SSRI sales volumes in Sweden until the end of 2004 were obtained from the National Corporation of Swedish Pharmacies. The Bayes' Confidence Propagation Neural Network (BCPNN) method was used to estimate associations between alopecia and each of the SSRIs within the two databases. RESULTS: A total of 27 reports of alopecia were identified in SWEDIS. As two reports concerned the use of two SSRIs, there was a total of 29 drug-ADR combinations. All except three reports concerned women (88.9%). The reporting rate of alopecia in Sweden was significantly higher with sertraline compared with citalopram; 20.1 (95%CI 10.7-34.4) reports per million patient-years versus 4.5 (95%CI 1.8-9.3) reports per million patient-years. No significant differences in reporting rates were noted for the remaining SSRIs. Sertraline also showed a statistically significant association with alopecia in both SWEDIS and Vigibase. Citalopram was significantly associated with alopecia in Vigibase, but not in SWEDIS. No statistically significant associations were found for any of the other SSRIs. CONCLUSIONS: Alopecia appears to be a rare ADR to SSRIs. The risk of alopecia seems to vary between the different SSRIs, and might be higher in women than in men.
PURPOSE: To evaluate the frequency, severity and preventability of warfarin-induced cerebral haemorrhages due to warfarin and warfarin-drug interactions in patients living in the county of Ostergötland, Sweden. METHODS: All patients with a diagnosed cerebral haemorrhage at three hospitals during the period 2000-2002 were identified. Medical records were studied retrospectively to evaluate whether warfarin and warfarin-drug interactions could have caused the cerebral haemorrhage. The proportion of possibly avoidable cases due to drug interactions was estimated. RESULTS: Among 593 patients with cerebral haemorrhage, 59 (10%) were assessed as related to warfarin treatment. This imply an incidence of 1.7/100,000 treatment years. Of the 59 cases, 26 (44%) had a fatal outcome, compared to 136 (25%) among the non-warfarin patients (p
Rates of nonadherence during treatment with antipsychotics have been found to vary in a wide range from 20% to 90%. The aim of the present study was to investigate the influence of inpatient versus outpatient status on the adherence to treatment with olanzapine and clozapine. In the period from 1999 to 2007, olanzapine and clozapine were the 2 most frequently analyzed antipsychotics at the Department of Clinical Pharmacology at St. Olavs University Hospital, Trondheim, Norway, with more than 24,000 and more than 18,000 samples, respectively. In total, 111 patients on olanzapine and 95 patients on clozapine had provided samples in both the inpatient and outpatient settings and were included in the study. The primary outcome variable was the serum concentration-to-dose ratio (C/D ratio), that is, the serum drug concentration per milligram of drug given. For olanzapine, the C/D ratio in the outpatient setting was 10.7% lower than in the inpatient setting (P = 0.013). No such difference was found for clozapine. The difference in the olanzapine group was exclusively attributed to a lower outpatient ratio in females. For clozapine, no sex influence was found. No effect of age on the C/D ratios was found either for olanzapine or for clozapine. The lower C/D ratio in females using olanzapine in the outpatient setting might imply that they, in contrast to males, are less adherent to their medication when outside hospital. For clozapine, there were no indications of differences in adherence between inpatients and outpatients.
BACKGROUND: Medication errors can arise both during prescription and administration (dispensing and distribution) of drugs. Little is known about types of medication errors in Norwegian hospitals. MATERIAL AND METHOD: All medication errors reported at St. Olav's Hospital from 1 July 2002 to 30 June 2006 were reviewed and analysed. RESULTS: 610 reports were identified. The most common cause of reporting (39 %) was prescription of a different dose from the one prescribed. Other frequent causes were administration of a different drug than the one prescribed (17 %), inadvertent subcutaneous infusion of an intravenous drug (15 %), and that the drug was given to another patient (12 %). The errors were almost exclusively reported by nurses. In 107 cases (18 %), precautions had been taken to reduce the extent of injury after the error had been identified. The causes of errors could be classified in three main categories: Nonvigilance caused by stress, lack of appropriate routines or violation of them, and lack of appropriate skills/negligence. INTERPRETATION: Changes of routines, improved education in existing routines, and increased pharmacological competence may contribute to prevention of medication errors.
BACKGROUND: There is an increasing interest in on-site testing for drugs of abuse. METHODS: Based upon our own experience and published literature, we have reviewed advantages and disadvantages of such tests. On-site testing is also evaluated in relation to the recommendations for urinary testing of drugs of abuse from the Norwegian Health Authorities. RESULTS: The most significant advantage with on-site testing is provision of rapid results, usually within 5-10 minutes. Disadvantages are the risks of false positive and false negative results, the fact that numerous drugs cannot be tested for, and the limited possibilities to detect manipulation. According to Norwegian regulations, on-site testing can be used for medical purposes, but cannot be used as the only method if a positive result may cause sanctions such as e.g. exclusion from school, job dismissal or loss of parental rights. There are also special requirements for the organization of such testing. INTERPRETATION: Before starting on-site testing for drugs of abuse, it should be considered if such testing is allowed or discouraged in the specific case. It is mandatory to know how the specific test works and to have routines for follow-up of positive test results.
Risk factors for extrapyramidal symptoms during treatment with selective serotonin reuptake inhibitors, including cytochrome P-450 enzyme, and serotonin and dopamine transporter and receptor polymorphisms.
INTRODUCTION: Extrapyramidal symptoms (EPS) are rare adverse drug reactions to selective serotonin reuptake inhibitors (SSRIs). This study aimed to investigate the potential risk factors for EPS associated with SSRIs including polymorphisms of cytochrome P-450 isoenzymes, and serotonin and dopamine transporters and receptors. METHODS: All spontaneous adverse drug reaction reports received by the Swedish Medical Products Agency until December 1999 that were coded with EPS and judged to be at least possibly related to SSRI treatment were included in the study. Reporting physicians received a form for collection of relevant information including current and previous use of SSRIs and antipsychotics, alcohol or substance abuse, central nervous system damage, a history of epilepsy or EPS, and a family history of Parkinson disease. A blood sample was also requested for genotyping of selected cytochrome P-450, and serotonin and dopamine transporter and receptor mutations. RESULTS: A total of 64 cases of EPS were reported. Twenty-eight forms (46%) were returned, and 20 blood samples were obtained. Identified potential risk factors included age of 65 years or older and the presence of the A1 allele of the D2 dopamine receptor gene (DRD2) Taq1A polymorphism (relative risk, 2.4; 95% confidence interval, 1.2-4.5 vs literature controls). No relationship was apparent for sex, drug dose, or other genetic polymorphisms. At least 1 additional potential risk factor for EPS, such as a history of central nervous system damage, alcohol or substance abuse, epilepsy, Parkinson disease, previous or current exposure to antipsychotic drugs, concomitant treatment with other antidopaminergic or serotonergic agents, or a history of EPS, was found in 93% of the cases. CONCLUSION: The risk of EPS with SSRIs seems to increase with advanced age and with the presence of the A1 allele of DRD2 Taq1A polymorphism. Because of the small sample size of our study and the use of historical controls rather than patients who did not experience EPS during SSRIs treatment, the DRD2 finding is preliminary and needs to be replicated in other studies before firm conclusions can be drawn. At least 1 additional potential risk factor was found in almost all cases.
A compilation of therapeutic drug monitoring data for 15 antidepressant drugs in a naturalistic routine clinical setting is presented. A substantial number of serum concentrations, at different daily doses, are outlined, and the intraindividual and overall serum concentration coefficient of variation for a respective substance is presented. Also, concentration comparisons between women and men, and patients older or younger than 65 years are made. The drugs included are amitriptyline (n = 394), citalopram (n = 5457), clomipramine (n = 400), escitalopram (n = 3066), fluoxetine (n = 793), fluvoxamine (n = 165), mianserin (n = 1063), mirtazapine (n = 1427), moclobemide (n = 200), nortriptyline (n = 206), paroxetine (n = 1677), reboxetine (n = 85), sertraline (n = 2998), trimipramine (n = 158), and venlafaxine (n = 1781). Of the 9 drugs exhibiting linear (first order) kinetics, all but reboxetine gave a significant negative dose-to-dose-normalized correlation with concentrations, that is an increased clearance with higher dose. When dose was correlated to the metabolite:parent substance ratio for drugs exhibiting linear kinetics, citalopram and mianserin gave a positive slope, contrary to a negative slope shown for sertraline and venlafaxine. The intraindividual variations of the serum concentrations were lower than the overall variations, and the intraindividual variation of the metabolite:parent substance ratio was lower than the intraindividual variation of respective parent substance (except clomipramine and mianserin). Women had significantly higher serum concentrations than men (significant for citalopram, escitalopram, mianserin, mirtazapine, and venlafaxine), and patients older than 65 years had higher serum concentrations than the younger ones for all drugs except amitriptyline, moclobemide, and trimipramine. By presenting a comprehensive compilation of therapeutic drug monitoring data for each drug, a reference tool is created, in addition to improved pharmacokinetic knowledge of antidepressant drugs.
PURPOSE: One of the main methods for monitoring the safety of marketed drugs is spontaneously reporting of suspected adverse drug reactions (ADRs). The objective of this study was to describe the pattern of spontaneously reported fatal adverse drug reactions (FADRs) by analysing data from the national spontaneous reporting system in Sweden. METHODS: In Sweden it is compulsory to report all new or serious suspected ADRs to the Medical Products Agency. The information in these reports is stored in the national database SWEDIS (Swedish Drug Information System). All suspected FADRs reported to SWEDIS between 1 January 1995 and 31 December 2004 were reviewed and analysed. RESULTS: During the study period 990 reports of FADRs were found. The main distribution of suspected FADRs was: haemorrhages (n = 603; 60.9%), blood and bone marrow dysfunction (n = 71; 7.2%), sudden death (n = 38; 3.8%) and pulmonary embolism (n = 30; 3.0%). Antithrombotic agents were the drugs most frequently implicated in the FADRs (n = 605; 61.1%). Vitamin K antagonists were reported in 453 cases (45.8%) and acetylsalicylic acid in 82 cases (8.3%). Among the fatalities with blood and bone marrow dysfunction methotrexate was the most frequently reported drug. For sudden death and pulmonary embolism, antipsychotics and oestrogen containing drugs, respectively, were most commonly reported. CONCLUSIONS: Bleeding complications amounted more than half of all reports of FADRs and vitamin K antagonists were implicated in most of these reports. However, as spontaneous reporting systems are primarily set up for signalling purposes, the data must be interpreted with utmost care.