(234) Dosing of antidepressants in relation to body weight in children and adolescents with overweight and obesity- a population-based study

Background: Medicines to children are commonly dosed according to weight or age to adjust for physiologic and pharmacokinetic differences compared to adults. Overweight and obesity could result in substantial pharmacokinetic alterations. However, paediatric recommendations regarding optimal dosing of SSRI (selective serotonin reuptake inhibitors) in individuals with elevated body weight are lacking.

Objectives: The aim of the present study was to evaluate the prescribed doses of SSRI in relation to body weight.

Methods: The population-based cohort study BMI Epidemiology Study (BEST) Gothenburg cohort has height and weight available from school health care records in the city of Gothenburg, Sweden, and information on prescription of SSRI from linkage with the National Prescribed Drug Register. We included boys and girls from the BEST Gothenburg cohort who were prescribed the antidepressants fluoxetine (n=347) or sertraline (n= 733) with a weight measurement not earlier than three months before, or later than six months after the dispensing date. We compared the outcomes dose and the dose per kg body weight for individuals with the exposures overweight and obesity versus normal weight (including underweight), using Student´s t-test (standard deviation [sd]).

Results: Individuals with overweight or obesity received slightly lower doses of fluoxetine in first prescriptions, but no significant differences were seen for iterated prescriptions. However, the mean dose per kg body weight was clearly lower in individuals with overweight or obesity compared with normal weight in first prescriptions (overweight and obesity: 0.22 mg/kg (sd =0.08); normal weight 0.34 mg/kg (sd=0.14), p< 0.001), and in iterated (overweight and obesity: 0.33 mg/kg (sd=0.15); normal weight: 0.42 mg/kg (sd=0.17), p< 0.01) prescriptions. For sertraline, there were no significant dose differences between individuals with overweight or obesity compared with normal weight. However, pronounced differences were seen in mean dose per kg body weight in first and iterated prescriptions.

Conclusions: The prescribed doses of SSRI were essentially similar in individuals with overweight or obesity compared with normal weight, but the doses per kg body weight were significantly lower. This finding suggests that children and adolescents with elevated weight could be at risk of being underdosed. Given the ongoing obesity epidemic, there is a large need for more knowledge regarding drug disposition in children and youth with obesity. High-quality clinical studies addressing pharmacodynamics, pharmacokinetics and optimal dosing in individuals with elevated body weight are warranted.