Chronological Changes of Plasma Homovanillic Acid (HVA) and 3‐methoxy‐4‐hydroxyphenylethyleneglycol (MHPG) Levels in 4 Patients with Temporal Lobe Epilepsy who Developed Psychosis‐Like Symptoms (Hallucination and Delusion) During Zonisamide (ZNS) Administration.

Abstract

Purpose: Zonisamide (ZNS) is a relatively new antiepileptic drug with an extensive therapeutic spectrum. However, ZNS can produce psychiatric side effects. In this study, we serially measured plasma hoinovaniliic acid (HVA) and 3‐methoxy‐4‐hydroxyphenylethyleneglycol (MHPG) levels in 4 patients with epilepsy who developed psychosis‐like symptoms (hallucinations and delusions) during ZNS administration. Methods: Subjects comprised 4 patients (3 males and 1 female) with temporal lobe epilepsy ranging in age from 18 to 28 years. Intervals from the start of ZNS administration to the appearance of psychiatric symptoms ranged from 36 to 707 days. Intervals from achievement of the maximal dose to the appearance of psychiatric symptoms ranged from 2 to 240 days. In these 4 patients, the maximal doses of ZNS ranged from 300 to 600 mg/day. In 3 cases, serum ZNS levels were within the effective therapeutic concentration range wlicn syinptoms appeared. However, in 1 case, the serum ZNS level exceeded thc therapeutic level. In all cases, psychiatric symptoms disappeared after ZNS was switched to other antiepileptic drugs and anti‐psychotic agents (2‐5 mg/day of haloperidol or 10 mg/day of thioridazine) were added. In these cases, we serially measured plasma HVA and MHPG concentrations. Results: Case 1 was a 28‐year‐old male. Delusions of persecution appeared 190 days after ZNS administration was started. HVA levels at the appearance of psychiatric symptoms were 12.7 ng/ml and HVA levels at the disappearance of psychiatric symptoms were 7.4 ng/ml. MHPG levels at the appearance of psychiatric symptoms were 14.5 ng/ml and MHPG levels at the disappearance of psychiatric symptoms were 6. I ng/ml. When psychiatric symptoms appeared, the plasma HVA level was increased, whereas the MHPG level was slightly increased.Case 2 was an 18‐year‐old female. Auditory hallucinations appeared 320 days after ZNS first was administered. HVA levels at the appearance of psychiatric symptoms were 9.6‐ 10.0 nghl and HVA levels at the disappearance of psychiatric symptoms were 5.3–6.1 ng/ml. MHPG levcls at the appearance of psychiatric symptoms were 4.14.2 ng/ml and MHPG levels at the disappearance of psychiatric symptoms were 3.1 ng/ml. When psychiatric symptoms appeared, the plasma HVA level was increased, but there was no increase in MHPG.Case 3 was an 18‐year‐old male. Delusion of persecution appeared 707 days after ZNS administration was started. HVA levels at the appearance of psychiatric symptoms were 10.6 ng/ml and HVA levels at the disappearance of psychiatric symptoms were 7.2 ngiml. MHPG levels at the appearance of psychiatric symptoms were 5.3 ng/ml and MHPG levels at the disappearance of psychiatric symptoms were 3.9 ng/ml. When psychiatric symptoms appeared, plasma HVA level was increased, while the MHPG level was slightly increased.Case 4 was a 20‐year‐old male. Auditory hallucination appeared 36 days after ZNS was administered. HVA levels at the appearance of psychiatric symptoms were 13.6 ng/ml and HVA levels at the disappearance of psychiatric symptoms were 7.2 ng/ml. MHPG levels at the appearance of psychiatric symptoms were 5.4 ng/ml and MHPG levels at the disappearance of psychiatric symptoms were 6. I ng/ml. When psychiatric symptoms appeared, the plasma HVA level was increased, but there was no increase in MHPG. Conclusions: In all patients, the plasma HVA levels at the appearance of psychiatric symptoms was higher than the corresponding level at time of disappearance of psychiatric symptoms. Psychiatric symptoms may have been associated with activation of dopaniine by ZNS. MHPG levels were slightly increased in 2 cases. However, in thc other 2 cases, there were no changes in MHPG. The influence of ZNS on neurotransmitter metabolites should be further investigated in a larger nuniber of patients.