NADD Bulletin Volume I Number 3 Article 3

Complete listing

Serotonin Reuptake Inhibitors and Atypical Antipsychotics: Implication for Use

Judy L. Curtis, Pharm.D. Stanley R. Platman, M.D.

The selective serotonin reuptake inhibitors (SSRIs) are a relatively new group of antidepressants. Included in this class of medications are fluoxetine, paroxetine, sertraline, fluvoxamine and clomipramine. These drugs have different side effects and indications than the traditional tricyclic antidepressants or monoamine oxidase inhibitors. The exception to side effect differences is clomipramine, which carries all the warnings and adverse drug reactions of the tricyclic antidepressants. Unlike traditional antidepressants some of these drugs are indicated by the FDA for panic disorder and obsessive compulsive disorder.

These drugs have been used in people with developmental disabilities to treat symptoms of depression and obsessive compulsive disorders. Case reports and an open trial describe the use of the SSRIs in those exhibiting self-injury or aggression. (Sovner, et al., 1993; Ricketts, et al., 1993; Markowitz, 1992; Sread, Boon, Presberg 1994 & Campbell, Duffy, 1995) Fluoxetine, sertraline and paroxetine have been reported to decrease frequency of self injury or aggression in people with developmental disabilities. Unfortunately, there are no controlled trials of these drugs in people with developmental disabilities in the literature.

There are two reports of the use of fluoxetine in people with autism and developmental disabilities. (Cook, et al., 1995 & Ghaziuddin, Isai, Ghaziuddin, 1991) The results of these reports are mixed. Some individuals had improvement on the Clinical Global Impression scale. However, several people experienced a worsening of behavior demonstrated by an increase in irritability or agitation. Compulsive rituals associated with autism did not appear to respond to fluoxetine.

Our experience treating individuals with autistic symptoms and ritualistic behavior with the SSRIs mimic these results. The ritualistic behavior did not decrease when these individuals were treated with the SSRIs and irritability and agitation appeared to increase. We have, however, successfully treated two individuals with what appears to be obsessive compulsive behavior with these drugs.

The "atypical" antipsychotic medications have provided the clinician with a different type of medication to consider for treating individuals with developmental disabilities who have psychotic disorders. These drugs include clozapine, risperidone and olanzapine. Sertindole and quetiapine are also atypical antipsychotic drugs and are due to be released this year. These drugs are considered atypical due to dramatic differences from the traditional agents such as chlorpromazine, haloperidol and thioridazine. Their side effect profile, clinical effects and cost are very different from traditional agents. The atypical agents have several advantages. They are much less likely than traditional agents to cause extrapyramidal side effects such as Parkinsonism akathisia and acute dystonic reactions. They also appear to treat some individuals whose psychosis was unresponsive to traditional agents.

The use of these agents in people with developmental disabilities consists primarily of case reports. (Rubin, Langa, 1994, Towbin, Dykens, Pugliese, 1994, Pary, 1994 & Safatovic, et al., 1994) Clozapine has been reported to reduce aggression, self-injury and psychotic symptoms in people with developmental disabilities and schizophrenia, bipolar disorder and autism. Clozapine also improved socialization, self care skills and cooperation in these individuals. Clozapine's use is limited however, to individuals that do not respond the traditional agents or other atypical antipsychotic medications due to its very serious side effect profile. Agranulocytosis has occurred in people receiving this drug and close monitoring of the blood count is mandatory. Additionally, clozapine causes a lowering of the seizure threshold, sedation and weight gain. Our experience with this drug is similar to what has been reported.

Risperidone has also been used to treat individuals with developmental disabilities. Vanden Borre and colleagues (1993) conducted a double blind crossover study adding risperidone or placebo to existing regimens of 37 people with mental retardation. Their results showed an improvement in behavior in people receiving risperidone based on scores obtained from the Aberrant Behavior Checklist. Unfortunately, the study did not report changes in specific target symptoms. Purdon and colleagues (1994) report two cases of improvement in stereotypies, autistic behaviors, social reasoning and memory in two individuals diagnosed with pervasive developmental disorder. Again, our experience with risperidone is similar. We find that individuals with autistic symptoms show a decrease in stereotypical and ritualistic behavior and increase in social skills. Risperidone is, however, not without side effects. Extrapyramidal symptoms such as a tremor may occur especially when the dose is increased to 6mg daily or higher. Weight gain can also be a significant side effect. We have also found that using low doses of risperidone, 0.5mg to 4mg a day is more beneficial that increasing the dose to 6mg a day or higher.

There are currently no published reports on the other atypical antipsychotic medications in people with developmental disabilities.

These drugs are not useful in treating acute or episodic treatment of specific symptoms. None of these drugs are available in injectable form and only risperidone is marketed as a liquid. These drugs need to be increased slowly, especially clozapine. Clozapine must be given in divided doses and high peak levels should be avoided due to the potential to reduce the seizure threshold. These drugs do not cause the rigidity and parkinsonian akinesia of the traditional agents. Therefore, individuals receiving them may "wake up" and be much more active. Care givers that expect these drugs to "control" behavior will need education and retraining to deal with someone who is a more alert and active person.

The SSRIs and atypical agents are still relatively new medications. Their place in therapy is not yet completely defined. They do, however, offer new types of medications for individuals that have been refractory to traditional treatments. They are not without side effects and need to be used appropriately for best results.

References

Campbell JJ, Duffy JD (1995). Sertraline treatment of aggression in a developmentally disabled patient. Journal of Clinical Psychiatry, 56:123-124.

Cook EH, Rowlett R. Jaselskis C, Leventhal BL (1992). Fluoxetine treatment of children and adults with autistic disorder and mental retardation. Journal of the American Academy of Child and Adolescent Psychiatrw, 31 :739-745.

Ghaziuddin, M., Isai, L., Ghaziuddin N (1991). Fluoxetine in Autism with depression. Journal of the American Academy of Child and Adolescent Psychiatry, 30:508 - 9.

Markowitz P (1992). Effect of fluoxetine on self injurious behavior in the developmentally disabled a preliminary study. Journal of Clinical Psychopharmacology, 12: 27 - 31.

Pary RJ (1994). Clozapine in three individuals with mild mental retardation and treatmentrefractory psychiatric disorders. Mental Retardation, 32:323-327.

Purdon SE, Wilson L, Labelle A, Jones BDW (1994). Risperidone in the treatment of pervasive developmental disorder. Canadian Journal of Psychiatry, 39:400-404.

Ricketts RW, Goza AB, Ellis CR, Singh YN, Singh NN, Cooke JC (1993). Fluoxetine treatment of severe self-injury in young adults with mental retardation. Journal of the American Academy of Child and Adolescent Psychiatry, 32:865-869.

Rubin M, Langa, (1995). A: Clozapine, mental retardation, and severe psychiatric illness: clinical response in the first year. Harvard Review of Psychiatry, 3 :293-294.

Sajatovic M, Ramirez LF, Kenny JT, Meltzer HY (1994). The use of clozapine in borderlineintellectual-functioning and mentally retarded schizophrenic patients. Comprehensive Psychiatry, 35:29-33.

Sovner R. Fox CJ, Lowny M J. Lowry MA (1993). Fluoxetine treatment of depression and associated self injury in two adults with mental retardation. Journal of Intellectual Disability Research, 37: 301 - 311.

Sread RW, Boon F. Presberg J (1994). Paroxetine for self-injurious behavior. Journal of the American Academy of Child and Adolescent Psychiatry, 33:909-910.

Towbin KE, Dykens EM, Pugliese RG (1994). Clozapine for early developmetnal delays with childhood-onset schizophrenia: protocol and 15-month outcome. Journal of the American Academy of Child and Adolescent Psychiatry, 33, 5:651-657.

Vanden Borre R, Vermote R, Nuttiens M, et al. (1993). Risperidone as add-on therapy in behavioural disturbances in mental retardation: a double-blind placebo-contolled cross-over study. Acta Psychiatric Scandiavia, 87:167-171.

For more information contact:

Judy L. Curtis, Pharm.D.
Director
Clinical Pharmacy Services
Rosewood Center
Rosewood Lane
Owings Mill, MD 21117