[Selective serotonin reuptake inhibitors in major depressive disorder in children and adolescents (ratio of benefits/risks)]

L Hjalmarsson, M Corcos, Ph Jeammet
L'Encéphale 2005, 31 (3): 309-16

UNLABELLED: Major depressive disorder in children and adolescents is associated with high risk of suicide and persistent functional impairment. While psychological treatments are used as a first line treatment in mild and moderately severe depression in this age group, the number of prescriptions for antidepressant medication (SSRI) has grown in recent years. Recently, FDA and MHRA advised that most of SSRI should not be used to treat MDD under the age of 18 years. They may increase the risk of suicidal thoughts and self harm. We reviewed the recent literature on efficacy and suicide risks of SSRI in depressed young people. Conflicting findings of SSRI efficacy have been reported in clinical studies. The discrepancies could be related to the heterogeneous samples and the absence of a standard definition of treatment effectiveness. In randomised placebo-controlled antidepressant clinical trials (RCT), the assessment of treatment effectiveness is commonly made with the CDRS-R (improvement of 20% or 30% or 40%) and CGI. SSRI demonstrated significantly, but modest, improvement compared with placebo in CGI score of 1 or 2: 10% more for sertraline, 16.8% more for paroxetine and between 16 to 24% more for fluoxetine. In adults, RCT studies have shown placebo response rates of 30% to 50%, drug response rates of 45% to 50% and drug-placebo differences of 18% to 25%. The highest placebo response rates, in young people, may be related to the highly selected group not representative of the general population of depressed patients and/or to the high youths' sensibility of psychotherapy. Patients participating in antidepressant clinical trials have a low BDI and CDI in Emslie's study for example (2002). In adults, previous reports suggest that SSRI use is associated with increased suicidal risk. But the analyse of 48 277 depressed patients participating in RCT for nine FDA approved antidepressants fail to support an overall difference in suicide risk between antidepressants (SSRI) and placebo treated subjects. An inverse relationship between regional change in use of antidepressants (increased) and suicide (decreased) is found in young -people in United States from 1990 and 2000. We can not draw a conclusion from few studies with few -participants. None suicide have been reported in pharmacological studies. And the link between "suicidality" and MDD can not be excluded. The instruments of assessment in depressed young patients are based on extensions of adult procedures. Whereas clinical picture of MDD in children, adolescents and adults have some differences. Depressed youngsters have more pronounced mood lability. Depressed adolescents have more anhedonia than depressed children. Future investigations into the efficacy and safety of treatments for children and adolescents depression should use specific instruments directly built on phenomenological and clinical picture of depressed children and adolescents. Comparison studies of pharmacotherapy, specific psychotherapies (not only CBT) and combined therapies are necessary to identify the adolescents who will benefit the most from specific or combined therapies. Further studies into the factors that influence treatment outcome including clinical picture (clinical dimensions, severity, duration, co morbidity), genetic factor, age, and i-llness course may help identify appropriate treatments for children and adolescents with MDD. Studies should include patients more severely ill, with associated psychiatric troubles, treatment resistance, history of relapses... In clinical studies, the link between "suicidality" and some clinical dimensions (which take part in clinical picture or not) must be analysed by assessing anhedonia, hopelessness feel, impulsive trait, borderline personality, familial inter-action, biological indices. New treatment should be expand and their efficacy and safety must be study: St John's worth, Bright light therapy, Trans-cranial Magnetic Stimulation.

IN PRACTICE: suicide and MDD have a strongest relation and it must be investigate syste-matically during the course of MDD. The suicide risk increases in the context of past history of suicide attempts, hopelessness, psychosis, impulsivity traits, substance abuse, familial dysfunction, life events, open access of arms. The use of SSRI in depressed children and adolescents is also the question of the quality and the support of the consultant and the mode of the prescription.

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