Differences in generic sertraline for children: real or artefact from cost containing to clinical quality of generics use

Abstract

The safety and efficacy of antidepressant drugs in children have been widely debated in the last few years, especially after suicide-related behaviours (suicide attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour, and anger) were more frequently observed in clinical trials in children and adolescents treated with selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) [1, 2]. Several regulatory agencies issued “Dear Doctor” letters to warn doctors about this risk and to strengthen the use of these drugs’ contraindications in treating paediatric depression [3–5]. The Food and Drug Administration advised manufacturers to insert a “black box warning” antidepressant labelling [6], and the European Medicines Agency (EMEA) indicated that SSRIs should not be used in treating children and adolescents less than 18 years old, except for patients with approved indications [7]. In such a context, controversy over the safety of antidepressants has shaken public confidence, and regulators’ evaluations and decisions have been questioned [8]. Sertraline is the most frequently prescribed antidepressant in children in Italy [9] and the UK [10], with a prevalence of 5 per 10,000 children and adolescents. Sertraline and fluvoxamine are the only SSRIs licensed in Europe for the treatment of obsessive compulsive disorder (OCD), but only in children >6 years old. At the end of 2005, several sertraline-containing generic drugs were licensed for the European market with different Summary of Product Characteristics (SPCs), especially concerning paediatric use, which led to doubts by many health professionals. The characteristics (dosage, formulation, therapeutic indications, age range for administration) of the SPCs of the licensed Italian products, requested from the manufacturers, were analysed. In addition, the information on the products licensed in four other European countries was obtained, by consulting the British National Formulary for the UK, the Dictionaire Vidal for France, FASS (the Swedish catalogue of medical products) for Sweden, and the National Drug Regulatory Agency website for Spain. The sertraline brand name drug marketed in Italy, France, and Sweden as Zoloft, in Spain as Besitran, and in the UK as Lustral (produced by Pfizer in all cases), is licensed everywhere for the treatment of depressive illness symptoms, including accompanying adult anxiety symptoms and OCD in patients over 6 years of age. Formulations are available as 50/100 mg film-coated scored tablets or capsules, 25 mg film-coated scored tablets or capsules (available only in France) and 20 mg/ml oral solution (not available in France). Sertraline-containing generic medicines are not available in the UK, while a total of 49 are licensed in the other four European countries considered, 9 of which are licensed in more than one country and 3 (Merck Generics, Ratiopharm, Sandoz) in all four. The formulations and dosages are the same as the brand name drug, except for the oral solution, which could be particularly useful for paediatric patients, but is not available as a generic. Major depression in adults is an indication reported in all the SPCs of these drugs, while differences exist concerning the indication for OCD treatment: in Spain and France, all sertraline-containing generic drugs have indications for Eur J Clin Pharmacol DOI 10.1007/s00228-006-0207-y