Careful consideration should be taken when using off-label antipsychotics in children due to limited studies on efficacy,” wrote the study team from the department of pharmacy at the University of Kansas Health System. “Future research is warranted to assess the efficacy and safety of these agents in children and adolescents.”
The report in Mental Health Clinician pointed out that depression rates in children/adolescents in the United States have increased in the past 10 years, emphasizing that fluoxetine and escitalopram are the only two antidepressants approved for the treatment of major depression disorder (MDD) in children and/or adolescents.
“In adults, some antipsychotics are approved for augmented treatment of MDD. However, there is limited research on antipsychotic augmentation in child/adolescent MDD,” according to the researchers.
A retrospective chart review evaluated antipsychotic prescribing for MDD in hospitalized patients aged 4 to 17 years to determine the frequency of prescribing antipsychotics for MDD and what factors go into the decision to add an antipsychotic. Patients at a Midwest child/adolescent psychiatric hospital from June 1, 2018, to May 31, 2021, were included if they were diagnosed with MDD and were not on an antidepressant or antipsychotic before admission.
The results showed that 6.8% of a cohort of 600 patients were prescribed an antipsychotic. “Binomial logistic regression analysis found that increased age (odds ratio [OR] 1.28; 95% CI = 1.045, 1.568; P = .017) and multiple admissions within 1 year (OR 3.277; 95% CI = 2.283, 4.705; P <.001) were associated with the use of antipsychotics in patients with MDD,” the authors wrote. “Post-traumatic stress disorder and disruptive mood dysregulation disorder were also associated with the use of antipsychotics.”
Background information in the study noted that depression rates in children/adolescents in the United States have significantly increased over the last decade. In 2020, for example, MDD affected 17% of adolescents aged 12 to 17 years, with suicide as the second leading cause of death for ages 10 to 14 years and the third leading cause for ages 15 to 24 years.
“Unfortunately, it is estimated that only 41.6% of adolescents with MDD receive treatment,” the researchers noted, adding, “Treatment of MDD in children/adolescents is limited with psychotherapy and pharmacotherapy being the main treatment options.”
Fluoxetine is FDA approved for use in patients aged 7 years or older, and escitalopram for those aged 12 years and older.
“While other antidepressants are commonly used off-label for MDD in children/adolescents, some guidelines recommend against specific antidepressants (e.g., paroxetine, venlafaxine) because of concerns for increased suicide in young adults,” the study pointed out. “In 2004, the FDA issued a black box warning for all antidepressants in youths from a meta-analysis, which revealed a 4% risk of new suicidal thinking/behaviors in youths taking an antidepressant compared with 2% in the placebo group. Moreover, studies have found venlafaxine and paroxetine to be associated with an increased risk of suicidal behavior and ideations. This black box warning has complicated treatment for children/adolescents with MDD.”
Major guidelines generally recommend psychotherapy and selective serotonin reuptake inhibitors for pharmacotherapy to treat depression, but the study authors note some gaps, explaining, “Unfortunately, these guidelines have limited recommendations for child/adolescent patients who fail to respond to antidepressants and/or psychotherapy.”
For adults, antipsychotics such as aripiprazole, brexpiprazole, cariprazine, olanzapine, and quetiapine are approved as adjunctive MDD treatment. For children, however, only the National Institute for Health and Care Excellence Guidelines recommend augmentation with a second-generation antipsychotic in psychotic depression.
The researchers of the current study note that the few studies looking at use of antipsychotics for depression in children/adolescents are limited to MDD with psychosis or bipolar depression. Yet, while there is limited research on antipsychotic augmentation in child/adolescent MDD without psychosis, it is practiced clinically.
An issue is that “the use of antipsychotics can be associated with significant adverse effects in youths, including metabolic abnormalities (diabetes mellitus or weight gain), cardiac arrhythmias, dyslipidemia, hyperprolactinemia, and extrapyramidal symptoms,” according to the authors.
The study team wrote that its results “highlight the need for further research focused on evaluating the efficacy and safety of alternative treatments for MDD in children/adolescents, especially in patients who are refractory to guideline-recommended treatment with psychotherapy and/or antidepressants. Clinicians should consider the potential risks antipsychotics pose, including metabolic effects and extrapyramidal symptoms.”
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