Risperidone exacerbates Psychosis: A paradoxical phenomenon?

To the Editor

Hydrocephalus manifests as abnormal accumulation of cerebrospinal fluid and dilated ventricles. These structural changes can induce psychiatric complications, including psychotic symptoms; therefore, antipsychotics are prescribed. However, treatment for hydrocephalus-induced psychosis has not been well investigated and the present choice of antipsychotics is on a case-by-case basis.

This letter reports a case of progressive psychotic symptoms concurrent with increasing risperidone dosage in a patient with hydrocephalus-induced psychosis. Following shunt surgery for hydrocephalus caused by a posterior fossa arachanoid cyst, a 22-year-old boy experienced auditory hallucinations and persecutory delusions. He had no history of psychotic symptoms or substance abuse before the surgery. We prescribed risperidone (2 mg per day) for the psychotic symptoms. After initial improvement, the symptoms gradually exacerbated 2 years later. No precipitating factor was confirmed during this period. To account for poor drug adherence, 25 mg of long-acting injectable risperidone every 2 weeks was prescribed. However, the symptoms worsened and his father attributed this to “side effects from the antipsychotics, especially the long-acting injectable one.” Therefore, acute ward admission was arranged 2 months later. Thorough physical examination including brain imaging and blood sampling revealed no active change. His psychotic symptoms with disorganized behavioral disturbance gradually subsided after reducing oral risperidone to 1 mg per day and discontinuing the injectable risperidone. Risperidone was then discontinued entirely and we prescribed flupentixol (3 mg per day) instead. This resulted in a more stable mental condition without behavioral disturbance within 45 days after admission.

Few studies directly mention that risperidone exacerbates psychotic symptoms in hydrocephalus-induced psychosis. However, D₂ receptor over-expression in the striatum could possibly be related to psychotic symptoms and behavioral disturbance (Kellendonk et al., 2006). Striatal dopamine D₂ receptors are known to be up-regulated in patients with hydrocephalus post the shunting procedure and on long-term risperidone treatment (Nakayama et al., 2007, Tarazi et al., 2001).

In conclusion, the synergistic effects of shunting surgery for hydrocephalus in combination with risperidone treatment could have upregulated the levels of striatal D₂ receptors and increased the psychosis. Although clinical confounders such as illicit drug use, poor drug adherence, or an inadequate family support system could influence the patient’s condition, the paradoxical effect of risperidone, which to our knowledge has not been reported previously, might explain the clinical presentation of our case. This effect should be considered when selecting antipsychotics for hydrocephalus in patients with psychotic symptoms, especially for long-term use and at higher doses.