The place of selective serotonin reuptake inhibitors (SSRIs) in the treatment of depressive disorders in children and adolescents. Recommendations of the Main Board of the Polish Psychiatric Association. Part 2. Pharmacological properties and safety of use

Antidepressants are generally effective and well tolerated by children, but unfortunately 31% to 48% will not respond and up to 25% of children treated with antidepressants experience physical, emotional or behavioral adverse reactions to the drug that may lead to discontinuation of treatment or require an alternative treatment. The aim of the study was to review studies evaluating the pharmacodynamic properties of selective serotonin reuptake inhibitors (SSRIs) and their safety. A different pharmacodynamic profile causes that SSRIs are characterized by a different risk of some side effects in the patient (considered common for SSRIs) and they differ in the degree of adjustment to the clinical picture of depression and co-occurring psychopathology, as well as preferences characteristic of a particular patient. SSRIs in patients <18 years of age sometimes have different pharmacokinetic parameters compared to in adults, which has a significant impact on their effectiveness and tolerance. This is related, among others, to the fact that the activity of CYP450 isoenzymes, regardless of the action of inhibitors and inducers, evolves with the patient's age and - in the case of CYP2D6, 2C9 and 2B6 - depends on genetic polymorphisms. The concentration of fluoxetine, fluvoxamine or paroxetine is about two times higher in children compared to adolescents and adults, which should be taken into account at the stage of both drug introduction and setting target doses. The T1/2 of paroxetine and sertraline at a dose of 50 mg/day (but not at higher doses) is significantly shorter in patients <18 years of age than in adults; therefore, in cases of non-optimal efficacy or the appearance of withdrawal symptoms during the day, use of them in divided doses, twice a day should be considered. In the event of significant problems with the selection of the drug and/or dose of the drug due to unsatisfactory efficacy and/or tolerance in a patient <18 years of age, examination of the dominant polymorphism for the metabolism of a given isoenzyme may be very important. This applies in particular to CYP2C19 in the case of escitalopram treatment, and to a lesser extent during treatment with sertraline, and CYP2D6 in the case of fluoxetine or paroxetine. SSRIs are generally well tolerated in patients less than 18 years of age and the majority of adverse reactions (TEAEs) during treatment are mild or moderate. In most RCTs evaluating the efficacy of SSRIs in depression in patients <18 years of age, rates of suicidal ideation or the occurrence of suicidal ideation during follow-up are comparable to placebo, suicide attempts are rare, and isolated cases occur in both the active treatment groups and the placebo arm.There was no statistically significant increased risk for antidepressants (including all SSRIs) or psychotherapy or combinations of antidepressants with psychotherapy (except venlafaxine). Only venlafaxine therapy was associated with an increased risk of suicidal behavior and/or ideation in short-term therapy compared to placebo.