Elevated Prolactin in Pediatric Patients on Typical and Atypical Antipsychotics

Abstract

As part of systematic treatment trials of haloperidol, clozapine, and olanzapine with a total of 35 children and adolescents with early onset psychosis, prolactin was measured at baseline and week 6 of treatment. The National Institute of Mental Health patients--13 females, 22 males (mean age, 14.1+/-2.3 years; range, 9.1-19 years) with childhood onset schizophrenia (n = 32), or Psychotic Disorder not otherwise specified (NOS) (n = 3) with onset of psychosis before age 13--were recruited for open or double-blind trials of haloperidol, clozapine, or olanzapine. Baseline serum prolactin was measured after a 3-week washout period and after 6 weeks of treatment. Mean prolactin concentration after 6 weeks of treatment was significantly elevated on all three drugs; however, on clozapine, mean prolactin remained within the normal range. Prolactin was increased above the upper limit of normal for 100% of 10 patients on haloperidol, 70% of 10 patients on olanzapine, and 0% of 15 patients on clozapine (chi2 analyses: H > C, p = 0.004; O > C, p = 0.001). Given the potential endocrine and possible cardiac correlates of hyperprolactinemia, these more robust prolactin elevations in pediatric patients after short-term exposure to olanzapine than those reported for adults justify longer observation intervals with bigger samples to establish treatment safety of atypical antipsychotics in adolescents.

The Differential Effects of Atypical Antipsychotics on Prolactin Elevation Are Explained by Their Differential Blood-Brain Disposition: A Pharmacological Analysis in Rats

“…Intriguingly, age may also have an effect on the relative prolactin-sparing effects of different atypicals after sustained use. In a pediatric population, clozapine was found to have prolactin-sparing effects similar to those in the adult population, whereas olanzapine had a significantly greater effect on prolactin release, albeit lower than that of haloperidol (Wudarsky et al, 1999). However, with the prolactin-sparing antipsychotics, this increase does not last until the next dose, and therefore, there is no cumulating prolactin elevation over time (Movin-Osswald et al, 1995;Turrone et al, 2002).…”

Atypical antipsychotics in the treatment of pathological aggression in children and adolescents: literature review and clinical recommendations

“…Still according to the TRAAY Part II recommendations, vital signs, weight, prolactin levels and metabolic changes should be constantly monitored, and ECG should be used to monitor patients at regular intervals during dose adjustment, because cardiac changes are dosedependent. 13,32 In the analysis of metabolic changes (weight gain, risk of diabetes and dyslipidemia), studies with adults found that there are differences between the several AAP medications, although results are still relatively discordant, according to Table 3. 26…”

“…[27][28][29]66 Studies that analyzed metabolic changes, such as weight gain, dyslipidemia and the risk of diabetes, have recommended that these medications should be used carefully, and that a proactive attitude should be adopted, with systematic monitoring using laboratory tests, weight control and nutritional interventions. 13,14,29,32 Studies about the treatment of pathological aggression, particularly severe or extreme forms of it, in children and adolescents, remain limited. Therefore, there are no solid scientific bases for clinical decisions at a higher degree of safety.…”

“…After six weeks of treatment, all ten patients receiving haloperidol had increases above the normal limits, and seven of the ten using olanzapine had similar increases, but none of the 15 patients using clozapine had increases above the normal range. 32 According to current TRAAY recommendations, if all other treatment options fail to control severe aggression, the use of clozapine should be considered in cases of schizophrenia and bipolar disorder in children and adolescents, despite the fact that clozapine has not yet been approved by FDA for use in these two age groups.…”

A Pilot Study of Risperidone, Olanzapine, and Haloperidol in Psychotic Youth: A Double-Blind, Randomized, 8-Week Trial

“…Study of a broad sample of children whose psychotic symptoms occur in multiple diagnostic contexts may increase the generalizability of results. In addition, it is important to determine the safety and tolerability of relatively high doses of the newer medications in the pediatric population, given the growing awareness of the increased risk of atypical antipsychoticassociated diabetes in adults (Henderson, 2002;Newcomer et al, 2002;Sernyak et al, 2002;Wirshing et al, 1998), case reports describing significant side effects when atypicals are used in children and adolescents (Selva and Scott, 2001;Buitelaar et al, 2001;Kelly et al, 1998;Martin et al, 2000;Ratzoni et al, 2002;Malone et al, 1999;Buitelaar and Willemsen-Swinkels, 2000;Wudarsky et al, 1999), welldocumented developmental differences in the side effect profiles of medications, and the likelihood that children with psychosis will remain on antipsychotics for years.…”