SSRIs May Work More Quickly in Pediatric OCD Than You Realize
REVIEW OF: Varigonda A et al. Journal of the American Academy of Child & Adolescent Psychiatry 2016; ahead of publication.
STUDY TYPE: Systematic literature review and meta-analysis
The pharmacological treatment of obsessive-compulsive disorder (OCD) for adults is pretty well worked out. Selective serotonin reuptake inhibitors (SSRIs) are the gold-standard treatment. We have multiple randomized, placebo-controlled trials to back this up. However, we know less about medication treatment of OCD for children.
In a prior research update, we reported that SRIs and CBT are the treatments of choice for pediatric OCD (CCPR, March 2015). For this meta-analysis, researchers dug deeply into the SRI literature to answer five practical questions about the pharmacological treatment of childhood OCD: 1) How quickly do SSRIs work; 2) Are higher doses of SSRIs more effective; 3) Is one SSRI better than another; 4) Are SSRIs better than clomipramine; and 5) Are there differences between the response of children and adults to SSRIs?
To answer these questions, PubMed was mined for randomized controlled trials that compared SSRIs or clomipramine to placebo and used the Children’s YaleBrown Obsessive-Compulsive Scale as an outcome measure. Trials had to be double-blinded, and participants could not have received behavioral therapy while engaged in pharmacotherapy. Nine studies totaling 801 children were analyzed.
RESULTS: Eighty-five percent of the improvement on SSRIs occurred within the first two weeks and topped out at around week 6. Maximum dosing of SSRIs revealed no therapeutic benefit over lower doses. There were no differences between the effectiveness of fluoxetine, fluvoxamine, sertraline, and paroxetine. Clomipramine was statistically better than SSRIs. And there were no significant differences between the level of response to SSRIs in children and adults.
CCPR’S TAKE: This meta-analysis reveals some important information about treating pediatric OCD. Most notable is the relatively rapid onset of therapeutic benefit. This challenges the notion that we must wait several weeks to determine efficacy. Other findings, however, are suspect. For example, the lack of a dosing effect may be a result of limited pediatric trials with insufficient participants to adequately compare fixed doses. And, even though clomipramine fared better than the SSRIs, this could easily be because it was the first OCD medication on the market and hasn’t been put through the wringer with treatment-resistant cases, as the SSRIs have been. Also, the relative increased side effect profile of clomipramine must be balanced against possible increased benefits.
PRACTICE IMPLICATIONS: The biggest clinical takeaway is that you should be looking for improvements in your OCD pediatric patients earlier than you may previously have planned.
Metformin Use in Autistic Children Taking Atypical Antipsychotics
REVIEW OF: Anagnostou E, Aman MG, Handen BL, et al. JAMA Psychiatry 2016;73:928–937.
STUDY TYPE: Double-blind, placebo-controlled, randomized clinical trial
Atypical antipsychotics are commonly used to reduce irritability and agitation in children with autism spectrum disorder (ASD). Although effective, these medications lead to weight gain and other metabolic problems. Strategies like tailored diet plans and exercise can help, but they are often not enough. If not interrupted early, for many, continued weight gain will lead to diabetes, hypertension, and heart disease later in life.
A promising approach for managing antipsychotic-associated weight gain is metformin. Through its ability to suppress glucose production in the liver, metformin stabilizes blood sugar levels, reduces hunger, OCD and promotes fat loss. Previous studies with adults reveal that metformin can indeed stop or reverse weight gain associated with the use of atypical antipsychotics. Similar data exist for children as well, but we know little with respect to those with ASD. To explore this issue, researchers randomized 61 children with ASD between the ages of 6 and 17 to receive metformin (n = 29) or placebo (n = 32). Nearly all were on either risperidone (60%) or aripiprazole (38%). The children were tracked for 16 weeks for changes in body mass index (BMI) and adverse events. For kids between 6 and 9, metformin and placebo were initially titrated to a maximum of 500 mg twice daily (1,000 mg/d average); older children received up to 850 mg twice daily (1,587 mg/d average).
RESULTS: Metformin beat placebo, but not dramatically so. Patients on placebo had no weight loss over the 16-week trial, whereas those on metformin had an average decrease in BMI of 5%. Three of the 28 kids on metformin (11% of the sample) achieved an 8%–9% BMI reduction, but four children on metformin dropped out due to increased agitation, and one dropped out because of sedation. Gastrointestinal (GI) distress was also noted in 25% of those on metformin, versus less than 7% on placebo.
CCPR’S TAKE: These results are consistent with previous research on metformin and weight gain. It’s certainly useful to have additional data for our youngest patients with ASD. However, this is a small study, making it difficult to generalize. GI discomfort is a known side effect of metformin and is often cited as a reason for early discontinuation. It’s important to remember that children with ASD have a difficult time reporting physical discomfort: some may have suffered through 16 weeks of GI distress with no one the wiser.
PRACTICE IMPLICATIONS: Metformin may be a reasonable choice for reducing weight gain in your patients with ASD who need to be on an atypical antipsychotic, but any weight loss is likely to be rather small. If you are unsure whether metformin is appropriate for your patient, consult with an endocrinologist.