Currently, there is no known cure for STXBP1-E. If seizures occur, seizure control is the most important aspect. Many patients, especially in the initial phase, suffer from refractory epilepsy and need multiple anti-epileptic drugs to control the seizures. Over time, some patients do become seizure-free. Beneficial effects of specific antiepileptic drugs such as vigabatrin, valproic acid and levetiracetam have been reported, but the numbers are too small to reach consensus treatment protocols. In rare cases, epilepsy surgery has been applied as the treatment of choice.

Apart from seizure control, it is important to assess and assist developmental abilities by physical and occupational therapy. Early intervention is recommended to maximize the developmental potential. If needed, behavioral therapy can be introduced to manage behavioral issues and neurological movement disorders can be treated with corresponding drugs. Patients with severe feeding difficulties can be treated symptomatically or may require G-tube placement.

Potential future therapeutic approaches include gene-replacement therapy or upregulation of gene expression. However, extensive research is needed to study the possible mechanisms, effects and clinical applicability of such treatment.