Choosing antipsychotics for children with schizophrenia: Evidence plus experience
Seeking efficacy while managing adverse effects in early-onset psychosis
DR. KOWATCH: Why do you like aripiprazole for this patient population?
DR. FRAZIER: Aripiprazole doesn’t tend to be associated with as much weight gain as olanzapine or risperidone, although I’ve had children—especially in the autism spectrum—who have gained quite a bit of weight on aripiprazole. Clinically, I’ve noticed that aripiprazole seems to brighten up children’s affect. It also seems to help many children in my practice with attentional symptoms, although that’s anecdotal.
Although we don’t have a lot of data to inform this discussion about aripiprazole, a placebo-controlled study of 302 adolescents diagnosed with schizophrenia showed that aripiprazole, 10 mg/d, targeted negative symptoms fairly well, based on changes from baseline in PANSS (Positive and Negative Syndrome Scale) total scores. This was a 6-week multicenter, double-blind, randomized, trial.2
Ultimately, cognition in patients with schizophrenia is the strongest predictor of success in the workplace and in school. We need data on what happens to neurocognitive functioning with aripiprazole—and all the other atypical agents.
DR. KOWATCH: What would be your third-line agent?
DR. FRAZIER: Well, that varies for me. I’m trying to match the medication I use with the individual patient, and at this point I prescribe based on the side-effect profile more than anything else. I also consider if the child has a family member who has suffered from a similar condition and what agents the family member responded to.
Let’s say I have a child who has tried 1 or 2 atypical antipsychotics and has not had a good response. Many times I decide to try yet another atypical, and often I will try quetiapine. But after a patient has not responded to 2 atypicals, I might start thinking about a typical agent or clozapine. I use clozapine quite a bit. I find it is the most efficacious agent available, and the data speak to this as well.3,4 It has been truly remarkable for some children in my practice.
Less than 50% chance of efficacy?
DR. KOWATCH: The TEOSS study found 50% or lower response rates across 8 weeks of antipsychotic treatment. Clinically, what kind of response rates do you see with antipsychotics in children and adolescents?
DR. FRAZIER: I probably see about a 50% response rate in my practice as well. It’s variable, and the earlier the onset of the illness, the harder it is to treat.
DR. KOWATCH: Do you ever combine a typical antipsychotic with an atypical?
DR. FRAZIER: I try not to, but a number of children in the schizophrenia spectrum have enduring positive symptoms after 2 or 3 trials of atypical antipsychotics. Sometimes adding a touch of a typical agent can improve the situation. The typicals I usually try are perphenazine (around 8 to 16 mg/d) or molin done (around 20 to 60 mg/d). Sometimes I use a very low dose of haloperidol (such as 0.5 to 2 mg/d) with an atypical agent, and it can be quite effective.
DR. KOWATCH: That has been our experience as well; sometimes combining typical and atypical agents improves response. Besides medications, what do you consider an optimal treatment plan for a child or adolescent with psychosis?
DR. FRAZIER: These children need a multi-modal approach. Pharmacotherapy is the cornerstone because you want to decrease positive symptoms of psychosis, but often these children require therapeutic school placements or residential programs. If they’re old enough, cognitive-behavioral therapy can help by teaching them skills to manage ongoing psychotic symptoms. Older teens often have comorbid substance abuse and may require substance abuse intervention.
Are antipsychotics overused?
DR. KOWATCH: Do you think antipsychotics are overused in pediatric patients with psychosis?
DR. FRAZIER: In pediatric patients with psychosis? No.
DR. KOWATCH: What about in pediatric patients with behavioral disorders?
DR. FRAZIER: We need more studies to inform our practice and to be mindful of the evidence. Most children with schizophrenia have substantial developmental challenges (Box 2).5 In the autism spectrum, often an atypical antipsychotic is the only agent that can help a patient who is aggressive, self-injurious, or agitated.
In terms of bipolar disorder in children and adolescents, it would be ideal if we had more head-to-head comparator studies to inform our prescriptive practice. For example, we need more studies comparing traditional mood stabilizers such as lithium with the atypical agents.
