Antipsychotics:  Olanzepine (Zyprexa) and Quetiapine (Seroquel)

Two newer atypical antipsychotics, olanzepine (Zyprexa) and quetiapine (Seroquel), have a similar safety profile to risperidone, but pediatric experience with their use is limited, particularly in developmental disabilities (Aman and Madrid 1999; Findling et al. 1998). Six of eight patients with autism or PDD responded clinically to olanzepine, with improvements in several behavioral areas, including socialization, in an open trial (Potenza et al. 1999). McConville et al. (2000) found that quetiapine was well tolerated and effective in an open trial in 10 adolescents with psychosis. However, in an open trial of 6 children and adolescents with autism, quetiapine was found to be helpful in only 2, and side effects such as sedation and behavioral activation were common (Martin et al. 1999). In our experience quetiapine has often been helpful in treating adolescents and adults with FXS who did not respond well to risperidone.

Antipsychotics:  Side Effects

The most common side effect of risperidone and olanzapine is weight gain, which for many patients can lead to significant obesity. These medications cause a drug-induced satiety dysregulation (Findling et al. 1998), which may be less severe with quetiapine. The increase in weight can lead to a fatty liver or steatohepatitis (Kumra et al. 1997), so liver function studies should be followed in patients treated with atypicals, particularly if weight gain is seen. Sedation is common unless the atypical is given at bedtime. A slow increase in dose will reduce the chance of EPS, although they occasionally occur and necessitate lowering of the dose (Findling et al. 1998). Acute dystonic reactions are treated with diphenhydramine or benzotropine. Parkinsonism may respond to amantadine, and akathesia may improve with propranolol or clonazepam if benzotropine is not helpful (Findling et al. 1998). Another side effect of risperidone is prolactin elevation, which can cause breast tenderness, enlargement, and even galactorrhea in females and gynecomastia and sexual dysfunction in males (Findling et al. 1998). Olanzepine and quetiapine do not lead to substantial prolactin elevation, so they are good alternatives if these symptoms become significant. This seems to be a significant problem in less than 10% of the patients treated with risperidone (Findling et al. 1998). Cataracts have been reported occasionally in patients treated with quetiapine, so ophthalmoscopy is recommended at six-month intervals with quetiapine treatment (Findling et al 1998).

This article is not intended to give medical advice for individual cases.  Any change in medical treatment should be done in consultation with appropriate medical personnel.  This article is written for medical professionals.  Some of the terms will be unfamiliar to those who are not trained in medical fields. *This article is from the chapter on treatment in the 3rd edition of Fragile X Syndrome: Diagnosis, Treatment, and Research edited by Randi Jenssen Hagerman, M.D. and Paul Hagerman, M.D., Ph.D., to be published May 2002.  It is included with permission from The Johns Hopkins University Press. References to other chapters refer to chapters in the book which are not included as part of this website. The complete 3rd edition of Fragile X Syndrome: Diagnosis, Treatment, and Research can be ordered from the National Fragile X Foundation by calling 1-800-688-8765 or from The Johns Hopkins University Press at 1-800-537-5487.

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