Diuretic Used to Treat Behavioral Symptoms in ASD
How could a loop diuretic potentially benefit children with autism spectrum disorder (ASD)? A case study in Pediatrics describes a 10-year-old female patient who experienced a paradoxical reaction to clobazam that led doctors to bumetanide treatment and improvements in ASD-associated symptoms. There is currently only one treatment (risperidone) approved by the Food and Drug Administration (FDA) for the treatment of specific symptoms associated with ASD in children and adolescents.
In the case report, a female patient experienced epileptic seizures starting at age 4 and received a diagnosis of focal epilepsy with right temporoparietal localization and focal seizures occurring in clusters; an MRI showed focal cortical dysplasia of the right temporal lobe. At age 8 she exhibited delay in language development, rigidity, repetitive behaviors with peculiar interests, and deficits in long-term memory performance. She was then diagnosed with ASD and genetic testing revealed 15q11.2 duplication that is commonly found in neurodevelopmental problems, but also in some healthy patients.
Treatment history for epilepsy included valproic acid, lamotrigine, and oxcarbazepine without seizure reduction and with some adverse effects. Prophylactic antiepileptic drugs were discontinued at age 6.3 and clobazam 5–10mg daily was initiated during the clustering of seizures only; this was partly successful but also led to profound restlessness, arousal, and talkativeness lasting for days. Based on the paradoxical reaction, the authors hypothesized that this could suggest depolarizing, rather than hyperpolarizing, GABA activity due to elevated levels of intraneuronal chloride. The physicians received permission to initiate a six-month trial of bumetanide, a selective chloride importer (NKCC1) antagonist, 0.5mg twice-daily. This led to declines in aberrant response to sensory stimuli (Sensory Profile) and behavioral rigidity (Repetitive Behavior Scale–Revised) from clinical to normal levels. The seizure frequency or severity did not change but the postictal symptoms were less severe, which enabled the patient to attend school during clustering of seizures.
The authors noted that bumetanide can decrease neuronal chloride concentrations and could possibly reinstate g-aminobutyric acid (GABA)-ergic inhibition in patients with neurodevelopmental disorders like ASD. This paradoxical response to GABA-enforcing drugs could support the use of bumetanide in individual cases, but other cases with paradoxical responses and larger-scale studies are still needed.
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