BERLIN – When prescribing atypical antipsychotic drugs to children with major psychiatric disorders, physicians “can't be guided by scientific data alone because there are just not enough from properly conducted trials,” Stanley Kutcher, M.D., advised.
Clinicians need to proceed with caution and “consider the symptoms, adverse effects, function, and evidence associated with each of the drugs relative to the symptoms they're being used to treat,” he said at the 16th World Congress of the International Association for Child and Adolescent Psychiatry and Allied Professions.
The literature on atypical antipsychotics in pediatric patients is limited. With the exception of a small number of controlled studies, “most of the published data come from anecdotal case reports and small open-label trials,” said Dr. Kutcher of Dalhousie University, Halifax, N.S.
“You can't determine the efficacy and tolerability of any medication from open-label studies or case series, regardless of the number of participants, and while there have been some acute, controlled studies, data from these cannot be extrapolated to the long term. There can be a loss of efficacy over time, and there can be problems with side effects that don't show up in the first few months of treatment, but emerge later,” he explained.
What little evidence does exist–mostly from adult studies–suggests that the atypical, or second-generation, antipsychotics are at least as effective as first-generation compounds and have a lower incidence of extrapyramidal symptoms such as dystonia, parkinsonism, and akathisia. Anecdotally, the atypical drugs have been linked to favorable outcomes in children with psychotic disorders, which in turn has evoked interest in their use for other psychiatric conditions, including bipolar disorder, autism-spectrum disorders, aggression and disruptive behavior disorders, and tic disorders, Dr. Kutcher noted.
A review of the literature on the use of atypical antipsychotics showed 2 double-blind randomized control trials, 22 open-label studies, 10 retrospective investigations, and 14 published reviews. “Basically, it looks like there are more people reviewing what's out there than writing anything new,” Dr. Kutcher joked. And even the two randomized control trials looked only at short-term results (6 and 8 weeks) and examined the effects of very different dosages, making it impossible to extract definitive guidelines, he said.
The dearth of scientifically based treatment guidelines has many pediatric and adolescent psychiatrists walking a tightrope without a net. “The incentive to use the newer antipsychotics is there because of their efficacy in reducing acute psychiatric symptoms, but caution must be exercised, particularly in the face of the false security brought on by a quick, dramatic response,” he said.
Physicians must be aware that the drugs described as atypical antipsychotics–clozapine (Clozaril), risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), and aripiprazole (Abilify)–are not interchangeable. Each has a unique pharmacologic profile and may be associated with a range of different adverse events that can drive treatment decisions. “For example, some drugs may be more likely than others to induce akathisia. To those not aware of this, the effect can be misinterpreted as an increase in psychosis, leading clinicians to increase the medication dose when it should be decreased,” Dr. Kutcher noted.
Careful consideration of the drugs' actions and side effects can help mitigate potential problems, Dr. Kutcher said.
Dosing Recommendations for Atypicals
Dosage determination is critical when prescribing atypical antipsychotics to children. Current dosage recommendations have been extrapolated from adult studies, typically relying on body weight and proportionately reducing an adult dosage. This approach is problematic, though, because the different pharmacokinetics in children and adolescents could make the resulting plasma concentration either subtherapeutic or toxic, Dr. Kutcher said.
To minimize the risk of adverse events and maximize the potential for therapeutic effect, children and adolescents should always be started on the lowest possible dose with any of the antipsychotic agents. Gradual increases should be guided by clinical response. Because there are also insufficient data to support hard and fast recommendations for medication duration, these decisions must be guided by clinical instinct as well.
Toward that end, Dr. Kutcher made the following recommendations:
▸ When a minimal therapeutic dose is established, maintain the pediatric patient on this dose for 1 year, carefully monitoring the patient for changes and potential adverse events.
▸ After 1 year of stable treatment, partner with the patient and parents to discuss medication withdrawal.
▸ Choose the correct time to make a change. Any changes should not be implemented during a critical or stressful period in the child's life.
▸ Devise a slow discontinuation schedule, monitoring the child carefully for symptoms.
▸ If symptoms recur, return to the therapeutic dose of the medication.