The research gap in chronic paediatric pain: A systematic review of randomised controlled trials

Background and Objective: Chronic pain is associated with significant functional and social impairment. The objective of this review was to assess the characteristics and quality of randomized controlled trials (RCTs) evaluating pain management interventions in children and adolescents with chronic pain. Methods: We performed a systematic search of PubMed, Embase and the Cochrane Library up to July 2017. We included RCTs that involved children and adolescents (3 months-18 years) and evaluated the use of pharmacological or non-pharmacological intervention(s) in the context of pain persisting or re-occurring for more than 3 months. Methodological quality was evaluated using the Cochrane Risk of Bias (ROB) Tool. Results: A total of 58 RCTs were identified and numbers steadily increased over time. The majority were conducted in single hospital institutions, with no information on study funding. Median sample size was 47.5 participants (Q1,Q3: 32, 70). Forty-five percent of RCTs included both adults and children and the median of the mean ages at inclusion was 12.9 years (Q1,Q3: 11, 15). Testing of non-pharmacological interventions was predominant and only 5 RCTs evaluated analgesics or co-analgesics. Abdominal pain, headache/migraine and musculoskeletal pain were the most common types of chronic pain among participants. Methodological quality was poor with 90% of RCTs presenting a high or unclear ROB. Conclusions: Evaluation of analgesics targeting chronic pain relief in children and adolescents through RCTs is marginal. Infants and children with long-lasting painful conditions are insufficiently represented in RCTs. We discuss possible research constraints and challenges as well as methodologies to circumvent them. Significance: There is a substantial research gap regarding analgesic interventions for children and adolescents with chronic pain. Most clinical trials in the field focus on the evaluation of non-pharmacological interventions and are of low methodological quality. There is also a specific lack of trials involving infants and children and adolescents with long-lasting diseases

Low-dose amitriptyline-induced acute dystonia in a patient with metachromatic leukodystrophy.

Acute dystonia is an abrupt event mainly related to toxicity of drugs such as antiemetics, antipsychotics, anti-acids, and, more rarely, tricyclic antidepressants. Use of amitriptyline in metachromatic leukodystrophy (MLD), a lysosomal storage disorder (LSD) due to arylsulfatase A deficiency, is suggested to control neurological pain and irritability. We describe a patient with MLD who experienced acute dystonia as a side effect of low dosage of amitriptyline. The distribution of psychotropic drugs, including antidepressants, depends upon lysosomal trapping which is inefficient in LSD. The defective lysosomal depot might raise cerebral levels of amitriptyline, thus enhancing its adverse effects. Physicians caring for children with MLD treated with psychotropic drugs should be aware of such adverse events which are potentially related to lysosomal dysfunction. This experience raises a potential concern about the appropriate dose of amitriptyline in patients with MLD

Low-Dose Amitriptyline-Induced Acute Dystonia in a Patient with Metachromatic Leukodystrophy

Acute dystonia is an abrupt event mainly related to toxicity of drugs such as antiemetics, antipsychotics, anti-acids, and, more rarely, tricyclic antidepressants. Use of amitriptyline in metachromatic leukodystrophy (MLD), a lysosomal storage disorder (LSD) due to arylsulfatase A deficiency, is suggested to control neurological pain and irritability. We describe a patient with MLD who experienced acute dystonia as a side effect of low dosage of amitriptyline. The distribution of psychotropic drugs, including antidepressants, depends upon lysosomal trapping which is inefficient in LSD. The defective lysosomal depot might raise cerebral levels of amitriptyline, thus enhancing its adverse effects. Physicians caring for children with MLD treated with psychotropic drugs should be aware of such adverse events which are potentially related to lysosomal dysfunction. This experience raises a potential concern about the appropriate dose of amitriptyline in patients with MLD