To assess the frequency of adverse drug reaction in patients with fibromyalgia in relation to medications prescribed for this condition. To evaluate the potential role of the P450IID6 phenotype in the pathogenesis of these adverse drug reactions.
Thirty-five patients with fibromyalgia were assessed using a structured questionnaire with demographic and clinical data and perceived adverse drug reactions. A sample of 60 patients with rheumatoid arthritis and 62 patients with localized back pain served as controls. The P450IID6 phenotype was determined for each of the fibromyalgia patients.
Overall, 141 patients had used NSAID and 79 (56%) of them reported adverse effects. Antidepressant drugs were used by 68 patients and 35 (51%) patients had adverse effects. Muscle relaxant drugs were used by 48 patients and 15 (31%) of them reported side effects. Analgesics were used by 122 patients and 22 (18%) had experienced adverse effects. Statistical differences in the frequency of adverse effects were found with antidepressant drugs in the fibromyalgia group, compared with rheumatoid arthritis (p=0.01) and back pain (p=0.02). Four of the 35 patients (11.4%) had a metabolic ratio (M.R.) greater than 0.30 (log M.R.= -0.52) indicative of the poor metabolizers (PM) phenotype. M.R. varied from 0.005 (log M.R. = -2.30) to 4.99 (log M.R. = 0.70).
The problem of adverse drug reactions in fibromyalgia patients does not appear to correlate with the PM phenotype of the P450IID6 oxidative enzyme. It also is unlikely that altered xenobiotic detoxification attributable to this PM phenotype would have a significant role in the development of fibromyalgia.
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.
To compare the rates of low birth weight, preterm delivery and small for gestational age (SGA), in pregnancy outcomes among women who were exposed and nonexposed to antidepressants during pregnancy.
At The Motherisk Program, we analyzed pregnancy outcomes of 1,243 women in our database who took various antidepressants during their pregnancy. Nine hundred and twenty-eight of these women and 928 nonexposed women who delivered a live born infant were matched for age, (+/-2 years), smoking and alcohol use and specific pregnancy outcomes were compared between the two groups.
There were 82 (8.8%) preterm deliveries in the antidepressant group and 50 (5.4%) in the comparison group. OR: 1.7 (95% CI: 1.18-2.45). There were 89 (9.6%) in the antidepressant group and 76 (8.2%) in the comparison group who delivered babies evaluated as SGA; OR: 1.19 (95% CI: 0.86-1.64). The mean birth weight in the antidepressant group was 3,449+/-591 g and 3,455+/-515 g in the comparison group (P=.8).
The use of antidepressants in pregnancy appears to be associated with a small, but statistically significant increased rate in the incidence of preterm births, confirming results from several other studies. It is difficult to ascertain whether this small increased rate of preterm births is confounded by depression, antidepressants, or both. However, we did not find a statistically significant difference in the incidence of SGA or lower birth weight. This information adds to limited data available in the literature regarding these outcomes following the use of antidepressants in pregnancy.
Alcohol and drugs are important risk factors for traffic injuries, a major health problem worldwide. This prospective study investigated the epidemiology and the presence of alcohol and drugs in fatally and hospitalized non-fatally injured drivers of motor vehicles in northern Sweden. During a 2-year study period, blood from fatally and hospitalized non-fatally injured drivers was tested for alcohol and drugs. The study subjects were recruited from well-defined geographical areas with known demographics. Autopsy reports, medical journals, police reports, and toxicological analyses were evaluated. Of the fatally injured, 38% tested positive for alcohol and of the non-fatally 21% tested positive; 7% and 13%, respectively, tested positive for pharmaceuticals with a warning for impaired driving; 9% and 4%, respectively, tested positive for illicit drugs. The most frequently detected pharmaceuticals were benzodiazepines, opiates, and antidepressants. Tetrahydrocannabinol was the most frequently detected illicit substance. No fatally injured women had illegal blood alcohol concentration. The relative proportion of positively tested drivers has increased and was higher than in a similar study 14 years earlier. This finding indicates that alcohol and drugs merit more attention in future traffic safety work.
Antidepressants appear to promote tumor growth in experimental studies; however, results from epidemiologic studies are inconclusive. We used a population-based cohort study to estimate the incidence of cancer after antidepressant treatment in 39,807 adult users of antidepressants identified in the Prescription Database of the County of North Jutland, Denmark between January 1, 1989 and December 31, 1995. Information on cancer occurrence was obtained from the Danish Cancer Registry. We categorized exposure according to use of tricyclic antidepressants, tetracyclic antidepressants, selective serotonin reuptake inhibitors, or monoamine oxidase inhibitors. In the follow-up period beginning 1 year after first known prescription, there were 966 cancers among users of antidepressants; our population estimate suggested an expected number of 946 for an overall standardized incidence ratio of 1.0 (95% confidence interval = 1.0-1.1). Users of tricyclic antidepressants had an excess of non-Hodgkin's lymphoma, with the risk increasing with the number of prescriptions of tricyclic antidepressants. The standardized incidence ratio was 2.5 (95% confidence interval, 1.4-4.2) for those with five or more prescriptions. Our results provide little evidence that antidepressants promote cancer at other sites, except for a possible effect of tricyclic antidepressants and tetracyclic antidepressants on non-Hodgkin's lymphoma.
Experimental and epidemiologic studies suggest that antidepressant medication use may be associated with breast cancer risk. This hypothesis was investigated using a population-based case-control study; cases diagnosed in 1995-1996 were identified using the Ontario Cancer Registry, and controls were randomly sampled from an Ontario Ministry of Finance database. Data were collected using a self-administered questionnaire, and multivariate logistic regression was used to estimate odds ratios and 95% confidence intervals. Adjusted odds ratio estimates ranged from 0.7 to 0.8 and were not statistically significant for "ever" use of antidepressants, tricyclics, and selective serotonin reuptake inhibitors. Compared with no antidepressant use, use of tricyclic antidepressants for greater than 2 years' duration was associated with an elevated risk of breast cancer (odds ratio (OR) = 2.1, 95% confidence interval (CI): 0.9, 5.0). Of the six most commonly reported antidepressant medications, only paroxetine use was associated with an increase in breast cancer risk (OR = 7.2, 95% CI: 0.9, 58.3). Results from this study do not support the hypothesis that "ever" use of any antidepressant medications is associated with breast cancer risk. Use of tricyclic medications for greater than 2 years, however, may be associated with a twofold elevation, and use of paroxetine may be associated with a substantial increase in breast cancer risk.
Comment In: Am J Epidemiol. 2000 Dec 1;152(11):1104-511117620
Comment In: Am J Epidemiol. 2000 Dec 1;152(11):1104; author reply 110511117621
Animal and human studies have reported an association between antidepressant (AD) medication use and breast cancer risk. A population-based case-control study was designed specifically to examine this association among women in Ontario, Canada.
The Ontario Cancer Registry (OCR) identified women diagnosed with primary breast cancer. Controls, randomly sampled from the female population of Ontario, were frequency matched by 5-year age groups. A mailed self-administered questionnaire included questions about lifetime use of AD and potential confounders. Multivariate logistic regression yielded odds ratio estimates.
'Ever' use of AD was reported by 14% (441/3077) cases versus 12% (372/2994) controls. The age-adjusted odds ratio (AOR) for 'ever' use was 1.17, (95% CI: 1.01, 1.36). An increased risk was also observed for selective serotonin reuptake inhibitors = 1.33 (95% CI: 1.07, 1.66), Sertraline = 1.58 (95% CI: 1.03, 2.41), and Paroxetine = 1.55 (95% CI: 1.00, 2.40). None of the 30 variables assessed for confounding altered the risk estimate by more than 10%. Multivariate adjustment including all possible breast cancer risk factors yielded an unchanged, but not significant, point estimate (MVOR = 1.2, 95% CI: 0.96, 1.51). No relationship was observed for duration or timing of AD use.
A modest association between 'ever' use of AD and breast cancer was found using the most parsimonious multivariate model. OR estimates did not change, but CI were widened and statistical significance lost, after adjustment for factors associated with breast cancer risk.
Comment In: Int J Epidemiol. 2003 Dec;32(6):966-714681257
Animal and human studies have suggested that antidepressant medications may be associated with several cancers. The authors evaluated the association between antidepressant medication use and the risk of non-Hodgkin's lymphoma using a Canadian population-based case-control study, the National Enhanced Cancer Surveillance Study. Non-Hodgkin's lymphoma cases (n=638) diagnosed in 1995-1996 were identified using the Ontario Cancer Registry, and controls (n=1,930) were identified from the Ontario Ministry of Finance Property Assessment Database. Antidepressant medication use was ascertained using a self-administered questionnaire. Multivariate logistic regression was used to estimate odds ratios. "Ever" use of antidepressant medications was not associated with non-Hodgkin's lymphoma risk. The odds ratio for non-Hodgkin's lymphoma with 25 or more months of tricyclic antidepressant medication use was 1.6; however, this was nonsignificant. Duration or history of use or individual types of antidepressant medications were not associated with non-Hodgkin's lymphoma risk. These findings do not support an increased risk of non-Hodgkin's lymphoma with antidepressant medication use.