Emilio J. Sanz

Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis

BACKGROUND Selective serotonin reuptake inhibitors (SSRIs) have been associated with withdrawal symptoms. We investigated whether use of these drugs in pregnant women might cause neonatal withdrawal syndrome. METHODS An association between paroxetine and neonatal convulsions was identified in December, 2001, by the data mining method routinely used to screen the WHO database of adverse drug reactions. An information component (IC) measure was used to screen for unexpected adverse reactions relative to the information in the database. We then assessed cases of neonatal convulsions and neonatal withdrawal syndrome associated with drugs included in the anatomical therapeutic chemical groups N06AB and N06AX. FINDINGS By November, 2003, a total of 93 suspected cases of SSRI-induced neonatal withdrawal syndrome had been reported, and were regarded as enough information to confirm a possible causal relation. 64 of the cases were associated with paroxetine, 14 with fluoxetine, nine with sertraline, and seven with citalopram. The IC-2 SD for the group became greater than 0 in the first quarter of 1991, and the IC increased to 2.68 (IC-2 SD 0.32) by the second quarter of 2003. For each individual compound, the IC-2 SD was greater than 0. INTERPRETATION SSRIs, especially paroxetine, should be cautiously managed in the treatment of pregnant women with a psychiatric disorder.

Perception of teratogenic risk of common medicines.

OBJECTIVE To assess the perception of the teratogenic risk of common medication by professionals and lay people. STUDY DESIGN A visual-analogue scale was used to measure the perceived percentage of mothers who will deliver a child with a malformation, including those exposed to a list of drugs. Fifteen general practitioners, 10 gynaecologists, 106 pre-clinical students, 150 students in their clinical training, 81 pregnant women and 63 non-pregnant women were interviewed. RESULTS The perception of the teratogenic risk related to medication used in pregnancy was higher than the recognised risk in all groups, and for all drugs. The risk associated with safe medications was perceived to be higher by non-pregnant women as compared with the pregnant women. Pregnant women perceived the medication associated risk to be higher than physicians did for all drugs included in the questionnaire. CONCLUSIONS The high and unrealistic perception of teratogenic risk amongst women and health professionals may lead to abortions of otherwise wanted and healthy children.

Drug prescribing for children in general practice

The renewal of the pursuit for a more appropriate use of drugs has special relevance for the pharmaceutical care of children. This care is distinct for a number of reasons. First, pharmacokinetics and pharmacodynamics in children are different from those in adults, even more so according to developmental stage, and there is a lack of controlled clinical trials which sufficiently evaluate the efficacy and safety of most drugs in children (1); this facilitates the off-label use of drugs for children. Secondly, children are the third partner in the doctor–patient relationship, with their parents (mostly their mothers) acting as the interface between the clinician and the treatment. This creates difficulties in recognizing and describing symptoms and arriving at the correct diagnosis, apart from the issue of the ‘‘maternal transferred self-medication’’, which is all too common (2). For the same reason, the use of medication must take into account, not only the clinical value and parental convenience, but children’s preferences as well (route, taste, etc.). Finally, children are normally seen as passive recipients of clinical care and not expected (or demanded) to intervene in the control of their own medications, even when they become older. This situation makes the need for further studies clear. From one viewpoint we need more clinical and research data. Clinical trials are very seldom performed in children, mainly owing to issues of costs and responsibilities, and to regulations which frequently result in major obstacles. The new FDA regulation promoting research in children (3) is to be encouraged and imitated. Clinical trials in children must be supported by paying particular attention to the ethical issues, the methodological problems and the relevance of the knowledge to be obtained. The N-of-1 trials (4) are probably a reliable alternative, especially in the first stages of developing a new drug. There is a need for knowledge about how medicines for children are actually used/prescribed in various settings, an area that has not been widely researched until recently. The work of Straand et al. (5) is a good example of research that addresses this need. Using a comprehensive study design, they reviewed all contact with children from 150 GPs in a Norwegian county, and described a pattern that is consistent with other countries. Their study population used 245 different substances, only 33% of those available in the total Norwegian market, and the 20 most commonly used ones accounted for 75% of all prescriptions. This is encouraging news for those who think that the range of different therapeutic substances that a GP (and indeed also a specialist) can master is limited. The findings show that medications were not prescribed in 40% of the consultations, and that when they were prescribed, their average number was low (1.2 prescriptions per consultation). These figures can be explained by a number of factors, one of which could be that children using outpatient care facilities usually have non-serious and self-limiting ailments. The study also revealed local peculiarities in paediatric precribing by GPs, for example the use of alimenazine for sleeping disturbances, a pattern that is uncommon in other European regions The overall prescribing pattern in the above study is similar to the one described for other European locations during the same period of time (6). At that time, the WHO Drug Utilization Research Group (DURG) was active in the promotion of comparative studies on drug use in children by organizing an international symposium in Novi Sad in 1988 (7) and maintaining the topic in the agendas of other meetings (8). The results of a comparative study conducted in Tenerife (Spain) and Sweden (9), presented at the 1988 meeting, showed that the 10 most frequent diagnoses accounted for 74.1% of all diagnosis in Spain and 68.7% in Sweden (20 first diagnoses accounted for 81% in this study), and the 10 most frequently prescribed pharmaceutical specialities accounted for 32.2% of all prescriptions in Spain and 63.7% in Sweden. Even if these data are not c mpletely comparable (the previous study measured percentage ofspecialities, whereas this study describes the 20 most commonsubstances , which encompassed 75% of all prescriptions), the reduced number of different medicines used seems to agree. The percentage of antibiotic prescriptions (one-third in the study) is in agreement with similar published at that time (8): in all locations studied (Norway, Spain, Sweden, UK and USA) the percentage of all children’s prescriptions being for antibiotics was between 24% and 36.6%. Published recommendations consider these percentages as high, thus more research carefully using controlled methods and outcome-oriented study designs are needed to confirm these figures. Prescribing patterns have changed with time. More than 10 y after the earlier (WHO-DURG) comparative studies, the EURO-DURG, a newly formed scientific society derived of the WHO-DURG, is currently coordinating a new observational, cross-sectional study of drug use in paediatric outpatient clinics. To date, 20 locations (in different countries) are involved in the study and new participants are more than welcome. Preliminary data from Spain suggest that along with unplanned differences in health settings and conditions change with time, drug-prescribing Acta Pædiatr 87: 489–90. 1998

Paediatric drug prescribing. A comparison of Tenerife (Canary Islands, Spain) and Sweden

SummaryThe prescribing of medicines for ambulant children below 14 years of age has been compared between Tenerife (Spain) and Sweden. Data obtained from a random sample of 1327 children in a prospective study in Tenerife were compared with data from 3901 children in a Swedish survey linking diagnosis and therapy.Upper respiratory tract infection was the main diagnosis in both countries and antibiotics was the most frequently prescribed drug group (28.2% in Tenerife and 28.8% in Sweden). Half of the children in Sweden did not receive any medication, but only 10% of those in Tenerife did not receive a prescription.Children who received a prescription on average got 1.4 drugs in Sweden and 2.3 in Spain. Amongst the ten most commonly prescribed products in Sweden there were 11 active pharmacological principles as compared to 25 in Spain. These most frequently used preparations accounted for two thirds of all the prescriptions for children in Sweden and one third in Tenerife.In conclusion, drugs were significantly more often used to treat paediatric outpatients in Tenerife than in Sweden. The prescribing physician in Spain also chose a wider variety of drugs and more commonly used fixed combination products.

Polypharmacy in psychiatric practice in the Canary Islands

BackgroundPolypharmacy with psychoactive drugs is an increasingly common and debatable contemporary practice in clinical psychiatry based more upon experience than evidence. The objective of this study was to evaluate the prevalence and conditioners of polypharmacy in psychiatric patients.MethodA cross-sectional survey was carried out using the Canary Islands Health Service Clinical Records Database. A representative sample (n = 2,647) of patients with mental disorders receiving psychotropic medication was studied.ResultsThe mean number of psychoactive drugs prescribed was 1.63 ± 0.93 (range 1–7). The rate of polypharmacy was 41.9%, with 27.8% of patients receiving two drugs, 9.1% receiving three, 3.2% receiving four, and 1.8% of the patients receiving five or more psychotropic drugs. Multiple regression analysis shows that variables sex and diagnosis have a predictive value with regard to the number of psychotropic drug used, being men and schizophrenic patients the most predisposed. Benzodiazepines were the more prevalent drugs in monotherapy, while anticonvulsants and antipsychotics were the more used in combination with other treatment. A questionable very high degree of same-class polypharmacy was evidenced, while multi-class, adjunctive and augmentation polypharmacy seem to be more appropriate.ConclusionsAlmost half of the psychiatric patients are treated with several psychotropics. Polypharmacy is common and seems to be problematic, especially when same class of drugs are prescribed together. Some diagnoses, such as schizophrenia, are associated with an increase risk of Polypharmacy but there is a lack of evidence based indicators that allows for quality evaluation on this practice.

Should medical students learn to develop a personal formulary? An international, multicentre, randomised controlled study

ObjectiveThis study was performed to determine whether students who are trained in developing a personal formulary become more competent in rational prescribing than students who have only learned to use existing formularies.MethodsThis was a multicentre, randomised, controlled study conducted in eight universities in India, Indonesia, the Netherlands, the Russian Federation, Slovakia, South Africa, Spain and Yemen. Five hundred and eighty-three medical students were randomised into three groups: the personal formulary group (PF; 94), the existing formulary group (EF; 98) and the control group (C; 191). The PF group was taught how to develop and use a personal formulary, whereas e the EF group was taught how to review and use an existing formulary. The C group received no additional training and participated only in the tests. Student’s prescribing skills were measured by scoring their treatment plans for written patient cases.ResultsThe mean PF group score increased by 23% compared with 19% for the EF group (p < 0.05) and 6% for controls (p < 0.05). The positive effect of PF training was only significant in universities that had a mainly classic curriculum.ConclusionTraining in development and use of a personal formulary was particularly effective in universities with a classic curriculum and with traditional pharmacology teaching. In universities with a general problem-based curriculum, pharmacotherapy teaching can be based on either existing or personal formularies.

Drug utilisation in outpatient children. A comparison among Tenerife, Valencia, and Barcelona (Spain), Toulouse (France), Sofia (Bulgaria), Bratislava (Slovakia) and Smolensk (Russia)

IntroductionScarce information about comparative diagnostic and therapeutic patterns in paediatric outpatients of different countries is found in the literature.ObjectiveTo describe the similarities and differences observed in diagnosis and therapeutic patterns of paediatric patients of seven locations in different countries.DesignCross-sectional, prospective, international comparative, descriptive study.Patients and methodsA randomly selected sample of 12,264 paediatric outpatients seen in consultation rooms of urban and rural areas and attended by paediatricians or general practitioners of the participating locations. Data on patient demographic information, diagnosis and pharmacological treatment were collected using pre-designed forms. Diagnoses were coded using the ICD-9 and drugs according to the ATC classification.ResultsAmong the ten most common diagnoses, upper respiratory tract infections are in the first position in all locations; asthma prevalence is highest in Tenerife (8.4%). Tonsillitis, otitis, bronchitis and dermatological affections are the most common diagnoses in all locations. Pneumonia is only reported in Sofia (3.8%) and Smolensk (2.3%). The average number of drugs prescribed per child varied from 1.3 in Barcelona to 2.9 in Smolensk. There are no great differences in the profile of pharmacological groups prescribed, but a considerable range of variations in antibiotic therapy is observed: prescription of cephalosporins is low in Smolensk (0.7%) and higher in the other locations, from 16.5% (Bratislava) to 28% (Tenerife). Macrolides prescriptions range from 12.6% (Toulouse) to 24.7% (Smolensk), except in Sofia where they drop to 5.6%. Trimethoprim and its combinations are used in Smolensk (23.3%), Sofia (11.8%) and Bratislava (8.7%). Check-up consultations are not recorded in Smolensk and Bratislava, whereas in Toulouse these visits account for 16.2% of all consultations and in the other locations the percentage varies from 6.1% (Tenerife) to 1.9% (Sofia). Homeopathic treatments are registered only in Toulouse.ConclusionExcept in asthma prevalence, there are no great differences in diagnostic maps among locations. Significant variations in the number of drugs prescribed per child and antibiotic therapies are observed. Areas for improvement have been identified.

Drug utilization by children in Tenerife Island

SummaryDrug utilization was studied in children below 14 years of age in Tenerife, Canary Islands, who were seen as outpatients by 15 paediatricians and 10 general practitioners. Data on diagnosis, previous drug exposure and prescriptions were collected from a random sample of 1327 children.Nose and throat infections (40.1%), respiratory diseases (10.2%) and miscellaneous symptoms, namely common cold, influenza or nasal congestion (10.5%), were the most frequent reasons for visiting a physician. Antibiotics represented 28.5% of the prescriptions. The youngest group (0–2 years) received more drugs than the other two groups (2–6 and 6–14 years), and 8.4% of the children did not receive any drug.Only 358 (5.1%) of the 7,000 pharmaceutical specialities available were used, and the 10 most frequently prescribed drug products constituted more than 30% of all prescriptions. Combination drugs accounted for 42.4% of the prescribed items. Healthy children presenting only for check up were frequently treated with drugs.

Prescribed daily doses and 'risk factors' associated with the use of benzodiazepines in primary care.

To assess the extent, characteristics and determinants of benzodiazepine prescription in outpatient Primary Health Care.

Psychomotor performance and fitness to drive: The influence of psychiatric disease and its pharmacological treatment

Both psychiatric disorders and psychiatric drug treatments produce changes of psychomotor performance which can disturb and/or interfere with the ability to drive safely. We studied the influence of current psychiatric drug treatments on psychomotor functions and on driving performance of 77 consecutive psychiatric outpatients in two different clinical situations: at admission, when patients are destabilized and their mental disorders untreated, and after 6 weeks of pertinent psychotropic treatment. Fitness to drive and psychomotor performance were assessed using the electronic LNDETER 100 battery. Treatment effects on global functioning were assessed using the Clinical Global Impression of Change (CGIC) scale. One-way repeated measures analysis of variance and post hoc comparisons with the Bonferroni correction were performed. At the time of diagnosis, 90% of the patients failed to achieve scores sufficient to renew their driving licenses. After 6 weeks of adequate treatment, 83% improved their mental condition, and 17% either remained unchanged or deteriorated. Of those who improved, 25% had scores sufficiently high for them to drive legally, and the rest improved their performance from baseline assessment. Three of the four sub-tests were able to discriminate between patients with different clinical conditions. The study clearly suggests that medical treatment of psychiatric problems has a positive effect on driving tests.