Safety of Off-Label Pharmacological Treatment in Pediatric Neuropsychiatric Disorders: A Global Perspective From an Observational Study at an Italian Third Level Children’s Hospital

Abstract

Background: The acquisition of proper and relevant pediatric clinical data is essential to ensure tolerable and effective pediatric drug therapies. In the field of pharmacological treatment of neuropsychiatric disorders, the lack of sufficient high quality scientific evidence for pediatric age results in the frequent need to prescribe off-label drugs. With the aim of improving knowledge about safety profile of off-label drug prescription in children and adolescent with neurological and/or psychiatric disorders, we realized a multidisciplinary pharmacovigilance study.Materials and methods: An observational retrospective study was conducted to assess the safety of off-label pharmacological therapies in patients aged 0–18 years, admitted to the Neuropsychiatry Unit of the Institute for Maternal and Child Health - IRCCS “Burlo Garofolo” between January 2016 and December 2018. Prescription patterns and adverse drug reactions were evaluated by a multidisciplinary team.Results: Overall, 230 patients were enrolled, 48% boys (N = 111), 52% girls (N = 119), average age of 10 years, and a total of 534 prescriptions was analyzed. 54.5% (N = 125) of patients had epilepsy, 37.5% (N = 86) suffered from psychiatric disorders, 8% (N = 19) had other neurological disorders. The prevalence of off-label prescriptions was 32% and 50% of the study population received at least one off-label drug. A total of 106 ADRs was detected: 57% of ADRs were due to drug-drug interactions, 30% were due to off-label prescriptions, 10% were due to overdose and 3% were due to improper use. No significant association between emerged ADRs and off label prescriptions was found (Fisher’s exact two-tailed test, p = 1.000). There was significant association between increasing number of administrated drugs and risk of ADRs (OR 1.99; IC95% 1.58–2.5; p = 0.000). Psychiatric disorders were associated with at least three times higher risk to be treated with an off-label drug (OR 3.30; IC95% 2.26–4.83; p = 0.000).Conclusions: This study shows that off-label prescribing in neuropsychiatric disorders does not pose a greater risk of ADRs than on-label prescribing and highlights unmet clinical needs in pediatric neuropsychopharmacology. The multidisciplinary approach can provide important contributions to improve therapeutic path of these already complex pathologies by careful monitoring of therapeutic appropriateness and drug interactions.

Improving Drug Safety in Pediatric and Young Adult Patients with Hemato-Oncological Diseases: A Prospective Study of Active Pharmacovigilance

“…In this way, the use of drugs beyond authorized indications represents a viable alternative in the pediatric setting. However, although the most frequent outcome also that occurred in our study was a complete resolution of ADRs, at least considering short follow-ups, once again patients and their families must be adequately informed about the risks involved in this type of prescription [ 7 , 16 ].…”

“…Based on the literature, active surveillance in this context seems to be an excellent strategy to improve therapeutic appropriateness. In fact, the active monitoring of drug prescriptions ensures that the patient takes the most appropriate drug in the correct dose, route of administration and duration of treatment, thus limiting therapeutic errors [ 3 , 4 , 5 , 6 , 7 , 8 ].…”

The Use of Psychotropic Medication in Pediatric Oncology for Acute Psychological and Psychiatric Problems: Balancing Risks and Benefits

“…Antidepressants are the first line in the treatment of major depressive disorders and anxiety disorders, as well as post-traumatic stress disorders, which are all common in children and adolescents, with a collective prevalence ranging from 15% to 30% [ 80 , 81 , 82 ].…”

“…On the contrary, the lack of labeling for a specific disorder, symptom, age group, or dosage does not automatically mean that the use of the drug is inappropriate for that particular use. Instead, it suggests that the inclusion of a specific drug on the label has not been approved by the EMA and/or FDA [ 82 , 83 , 84 , 85 ]. Thus, the responsibilities for the prescription of that therapy rely on the prescriber only.…”

Prescripciones off-label en psiquiatría infanto-juvenil. ¿Por qué, cuándo y cómo?

“…(2022). 33( 158): 89-97. pediátricos los cuales son más elevados que los desarrollados en adultos debido a la múltiple población pediátrica que hay que incluir, los retos en el reclutamiento, las dificultades en el diseño de los ensayos asociadas el pequeño número de pacientes y la falta de controles apropiados por edad (Giurin, 2022).…”