Psychiatric adverse drug reactions reported during a 10-year period in the Swedish pediatric population.

PURPOSE: Psychiatric Adverse Drug Reactions (ADRs) are frequent in the pediatric population. The aim of the present study was to analyze spontaneously reported psychiatric ADRs in children during a 10-year period. METHODS: All spontaneously reported Individual Case Safety Reports (ICSRs) concerning children (<18 years old) and psychiatric adverse reactions assessed as at least possible, registered in the Swedish Drug Information System (SWEDIS) during the period 2001-2010, were extracted and characterized. Age and sex distribution and labeling/registration status were studied. RESULTS: A total of 600 ICSRs concerning 744 psychiatric adverse reactions were identified and included in the analysis. Boys were overrepresented among included ICSRs (60.3% vs. 39.7%; p < .001). After exclusion of vaccines, the three most frequently suspected drugs were montelukast, centrally working sympathomimetic drugs, and inhaled glucocorticoids. Serious adverse reactions were reported more frequently for drugs used off-label than for drugs used according to the Swedish Physician's Desk Reference. Aggressiveness was reported more frequently for boys than for girls as were suicidal conditions. CONCLUSIONS: Psychiatric ADRs in the pediatric population have been reported for a wide range of reactions and drugs and display age and sex differences including a higher number of suicidal reactions in boys. An association was seen between serious reactions and off-label drug use. Further studies are needed to elucidate safety aspects of unlicensed drugs and drugs used off-label and whether there are differences in children's susceptibility to develop ADRs.

Effects of e-mails containing ADR information and a current case report on ADR reporting rate and quality of reports.

BACKGROUND: Spontaneous reporting of adverse drug reactions (ADRs) is one approach to increasing our knowledge on the risks of drugs in clinical practice. Under-reporting is a shortcoming of this system. OBJECTIVES: To evaluate if repeated e-mails with attachments on ADR information can affect (1) the reporting of ADRs and (2) the quality of the ADR reports. METHODS: All 117 heads of primary health care units in the region of Västra Götaland in Sweden were randomly allocated (1:1) to an intervention group or a control group. The intervention consisted of e-mails with attachments sent out to each of the 117 heads in January, May and September 2007. These e-mails included (1) the heading "Every ADR report is important", (2) a current case report of an ADR and (3) instructions on how to report. The number of reports from each primary health care unit run by the same head was registered, as was the quality of the report. The quality was defined as high if the ADR was (1) serious, (2) unexpected or (3) related to the use of new drugs and not labeled as common in the summary of product characteristics. All other reports were regarded as low-quality reports. RESULTS: The total number of reports increased from 89 in 2006 to 111 in 2007 (P = 0.037). No difference in the number of reports between intervention (n = 56) and control (n = 55) units could be detected. The proportion of high-quality reports before and after the intervention was 36 and 48%, respectively (intervention, P = 0.11) and 40 and 36%, respectively (control, P = 0.55). CONCLUSIONS: No apparent effect of repeated ADR e-mails on the reporting of ADRs could be detected, although an increase in the reporting rate in general was noted.

Montelukast and psychiatric disorders in children.

PURPOSE: A signal has been raised concerning montelukast and adverse drug reactions (ADRs) in children. The purpose of the present study was to evaluate psychiatric ADRs during treatment with montelukast in children. METHODS: We analyzed all reports of psychiatric disorders during treatment with montelukast in children (<18 years) in the Swedish ADR database SWEDIS (1998-2007). The Bayesian Confidence Propagation Neural Network (BCPNN) method was used to screen for disproportional reporting rates of these reactions. An information component (IC) with a positive 95% lower confidence limit indicates a statistically significant disproportionality between the expected and the reported rate for a drug and an ADR. RESULTS: A total of 48 reports of psychiatric disorders in children during treatment with montelukast were found in SWEDIS. Reports appeared every year after registration. Psychiatric disorders reported more than once included nightmares (n = 15), unspecified anxiety (n = 11), aggressiveness (n = 11), sleep disorders (n = 10), insomnia (n = 3), irritability (n = 3), hallucination (n = 3), hyperactivity (n = 3), and personality disorder (n = 2). In 23 reports (48%), the child experiencing psychiatric ADRs was < or = 3 years old. Time from exposure to ADR was indicated in 35 reports. In 28 of these (80%), the time from exposure to ADR was less than 1 week. A statistical signal for psychiatric disorders appeared in the fourth quarter of 1998 (three reports, IC-value: 2.34, 95% lower confidence limit: 0.62). CONCLUSIONS: Psychiatric ADRs can occur during montelukast treatment in children, indicating that attention to this is essential. Further studies are needed to establish the magnitude of the problem.

Individual case safety reports in children in commonly used drug groups - signal detection.

BACKGROUND: Due to few paediatric drug safety studies, knowledge on risks of drug treatment in children is limited. The knowledge needs to be increased to make proper risk-benefit analyses possible when treating paediatric patients with drugs. The aim of the present study was to investigate drug groups commonly used in children concerning type and frequency of individual case safety reports in children. METHODS: Number and type of individual case safety reports in the 30 groups of drugs (5th level ATC-code) most sold (number of defined daily doses) in outpatient treatment to children (<15 years old) during 2005 were obtained. Descriptive analyses of the adverse drug reactions reported in children were performed. RESULTS: The number of individual case safety reports per million defined daily doses in children varied in the groups of drug between 0 and 24. The largest number was found in the drug group R03DC, the leukotriene receptor antagonist montelukast; the majority of the children being <5 years old and experiencing psychiatric adverse drug reactions. CONCLUSION: The number of individual case safety reports per million defined daily doses varies in different groups of drugs. A possible signal for montelukast and psychiatric adverse drug reactions was found, which should be further explored.

Temporal improvement in heart failure survival related to the use of a nurse-directed clinic and recommended pharmacological treatment.

BACKGROUND: The use of recommended drugs for chronic heart failure (CHF) has been discouragingly low in clinical practice. The aim of this study was to prospectively evaluate to which extent a nurse-directed heart failure clinic could accomplish drug titration with modern heart failure treatments, with focus on beta-blockers. METHODS: Outcome of drug titration was evaluated for 418 patients referred to the nurse-run clinic from 1995 through 2001, using a prospective, open, non-randomised quality control protocol. RESULTS: Throughout the period, most of the patients were discharged on an ACE inhibitor (during 2001, 86%). The use of beta-blockers increased during the observation (from 43% to 88%). Patients started on an ACE-inhibitor treatment continued in 89% and in 95% when started on a beta-blocker. There was a significant decrease in mortality, relative risk per year 0.84 (95% CI, 0.75 to 0.94), P=0.002. Three-year mortality was reduced from 27% to 10%. In a multivariable analysis, survival was significantly associated with ejection fraction, renal function, the use of beta-blockers and ACE inhibitors, and negatively with digitalis treatment. CONCLUSIONS: The nurse-directed titration succeeded in introducing more patients on beta-blockers than on ACE-inhibitors. Mortality was reduced during the study period, associated with more use of documented therapy, beta-blockers in particular. These findings suggest that the observed signs of improvement in CHF prognosis are likely caused by more efficient medical treatment.

[Nurse-managed clinic provides a good foundation for heart failure patients]. / Sjuksköterskeledd mottagning ger goda förutsättningar för hjärtsviktspatienten.

We report one of the first analyses of modern heart failure treatment in clinical practice, using beta-blockers and ACE-inhibitors, based on computerised evaluation of a nurse-administered outpatient clinic. One hundred thirty-three patients were treated. Up-titration of an ACE-inhibitor was performed in 104 patients, 13% of whom had to discontinue treatment due to intolerance. Beta-blockers were introduced in 42 patients, and 2% had to discontinue. Of those continuing therapy 97% and 89% of the targeted dose was reached, ACE-inhibitors and beta-blockers, respectively. During the titration 52% of the patients receiving an ACE-inhibitor, and 57% of those receiving a beta-blocker, reported symptomatic improvement. In contrast to pharmaceutical studies, our patients were referred with no other selection than that applied by the patient's physician. With a nurse-monitored treatment strategy it was possible to achieve a high rate of treatment compliance with ACE-inhibitors and beta-blockers.

Rates of spontaneous reports of adverse drug reactions for drugs reported in children: a cross-sectional study with data from the Swedish adverse drug reaction database and the Swedish Prescribed Drug Register.

BACKGROUND: Knowledge of drug safety is limited in the paediatric population, especially for drugs not used as labelled. Spontaneous reporting of adverse drug reactions (ADRs) may be an important source for increased knowledge, but the extent of the overall rate of reporting in children is not known. OBJECTIVE: The main objective of the study was to determine the extent of the spontaneous reporting of ADRs in children with a focus on drugs not used as labelled; this involved investigations of reporting rates of individual case safety reports (ICSRs) per 1000 treated individuals for drugs reported in children, to compare these between drugs labelled and not labelled for use in children, and to compare the rates for children with those of adults. METHODS: ICSRs (extracted from the Swedish ADR database) and number of treated individuals (extracted from the Swedish Prescribed Drug Register) were analysed for a 2-year period (2006-7). For drugs with one or more ICSR regarding children, rates of ICSRs per 1000 treated individuals were determined and compared between children (<18 years of age) and adults (≥18 years of age). Reported drugs for which >10% of the volume was sold over-the-counter or for in-hospital use were excluded. The overall reporting ratio of aggregated ICSRs per 1000 treated individuals was calculated between drugs not labelled and drugs labelled for use in children, separately for children and adults. The overall reporting ratio was also calculated between children and adults, separately for drugs labelled and drugs not labelled for use in children. RESULTS: A total of 255 (children) and 1402 (adults) ICSRs concerning 94 drugs were included in the analysis. Seventy-four (29%) and 711 (51%) ICSRs in children and adults, respectively, were registered as serious (p < 0.00001, two-sided test of proportions). For drugs reported in three or more ICSRs regarding children, the rates of ICSRs per 1000 treated individuals varied between (range) 0.01-6.45 (children) and 0.01-6.39 (adults). For 17 of the drugs (18%) the rates of ICSRs per treated individual were significantly higher for children than for adults, and for 2 of the drugs (2%) the result was the opposite. The overall comparison of aggregated ICSRs per 1000 treated children revealed a higher reporting rate for drugs not labelled than for drugs labelled for children: rate ratio 3.44 (95% CI 2.67, 4.43); p < 0.00001. The corresponding result for adults was 1.52 (95% CI 1.37, 1.68); p < 0.00001. The overall reporting rate of aggregated ICSRs per 1000 treated individuals was higher in children than adults for drugs not labelled for children: rate ratio 2.01 (95% CI 1.61, 2.51); p < 0.00001. CONCLUSIONS: The results of the present study indicate that the extent of the reporting of ADRs is greater for drugs not labelled for children than for drugs labelled for children. For these drugs, the extent of the reporting is greater for children than for adults. Thus, healthcare personnel willingly report ADRs in children, especially ADRs for drugs used outside the terms of the product licence. The finding is reassuring since there are few other sources for knowledge of paediatric drug safety. Important limitations of the study are (i) only a few ICSRs were registered for most drugs, thus giving each ICSR a strong impact on the rates for individual drugs; and (ii) the results of the present study apply only to the drugs included in the analysis.

Reporting of adverse drug reactions may be influenced by feedback to the reporting doctor.

OBJECTIVE: The purpose of this study was to investigate two different feedback alternatives to doctors reporting adverse drug reactions (ADRs) concerning (1) effects on reporting rates and (2) doctors' opinions. METHODS: When reporting an ADR during January through March 2006, doctors in the western part of Sweden were randomised according to working address to receive feedback I or feedback II. Feedback I consisted of the conventional mode of feedback. Feedback II consisted of the contents of feedback I supplemented with information on the reported drug from the regional drug information centre. A questionnaire was administered 2 weeks after the feedback. The doctors were asked to give their opinion on the feedback concerning amount of information, quality and overall impression on a 6-point scale, where 1 corresponded to too little/very bad and 6 to too much/very good. During the inclusion period and the 6-month follow-up period, additional ADR reports originating from receivers of either feedback I or II were identified and compared. RESULTS: Sixty-six doctors received feedback I, and 49 received feedback II. The number of doctors reporting more than once was greater in the group receiving feedback II (39% vs. 22%; P = 0.039). Feedback II was judged to contain more information than feedback I (4.1 +/- 0.8 vs. 3.6 +/- 0.9; P = 0.014). No difference between the feedback alternatives concerning doctors' opinions on quality and overall impression could be detected. Sixty-five doctors (70%) stated that the content of the feedback letter could affect their willingness to report ADRs. CONCLUSION: The content of the feedback to doctors reporting ADRs may influence reporting rates.