Resistant Catatonia in a High-Functioning Autism Spectrum Disorder Patient Successfully Treated with Amantadine

To The Editor:

Case Report

Mr G. was a 27-year-old Caucasian with a high-functioning autism spectrum disorder (HFASD). After his twin brother left the familial home, he developed depressive-like symptoms including psychomotor retardation, deterioration of his personal hygiene, social withdrawal, and stereotypies. He was initially diagnosed with a major depressive disorder (MDD) and treated with fluoxetine 20 mg/day for 6 weeks, without efficacy. Thereafter, a diagnosis of schizophrenia was suspected and aripiprazole was prescribed up to 15 mg/day for 4 weeks, without efficacy.

He was then hospitalized in our psychiatric unit. Symptoms included verbigeration, motor stereotypies, mannerisms, ambitendency, posturing, catalepsy, waxy flexibility, and negativism. No psychotropic drug was given at admission. Blood serum screening, cerebral MRI, and electroencephalography were all normal.

The patient's Bush–Francis Catatonia Rating Scale (BFCRS) score was 46, indicating a severe catatonic syndrome.

First, we administered 10 mg of zolpidem p.o., without improvement. Thereafter, we tried lorazepam 7.5 mg/day p.o. for 72 hours without any response. After a washout period of 1 week, we used the N-Methyl-d-aspartate (NMDA) antagonist amantadine (Ene-Stroescu et al. 2014), p.o., at 200 mg/day. A dramatic improvement was observed within 2 weeks. BFCRS score decreased to 4, and no relapse was observed after 8 weeks of follow-up. No sign of MDD or schizophrenia was found after catatonia resolution.

Discussion

Catatonia pathophysiology seems to be either a γ-aminobutyric acid (GABA)_A hypoactivity and/or an NMDA hyperactivity in the loop of basal ganglia thalamocortical circuits, resulting in hypodopaminergia (Northoff 2002).

Many studies suggested an increase in glutamate level in the limbic cortex of HFASD patients (Page et al. 2006), a finding that is observed in catatonia as well. In patients with HFASD there is also a higher prevalence of catatonia (17%) (Wing and Shah 2010) than in other adult psychiatric inpatients (10%).

We can hypothesize that there are two subtypes of catatonia with two different possible pharmacological treatments. Most of the time catatonia appears to be caused by a GABA_A hypoactivity. In such cases, benzodiazepines would be most effective. In other cases, catatonia seems to be caused by NMDA hyperactivity, as we can see in HFASD. Amantadine, an NMDA antagonist and weak dopaminergic agonist, could be a logical option in such cases.

Further randomized controlled studies comparing amantadine with a benzodiazepine in HFASD catatonic patients are required.