'antsiest' (via 'antsy') originates from American English, specifically from the colloquial phrase 'ants in one's pants', where 'ants' referred to the insects that would make someone fidget.

'antsy' changed from the phrase 'ants in one's pants' (informal expression) and eventually became the single-word adjective 'antsy'; regular adjective inflections produced comparative 'antsier' and superlative 'antsiest'.

Initially it referred to the literal idea of having ants (or feeling as if ants were causing movement); over time it evolved to the figurative meaning 'restless or impatient', so 'antsiest' now means 'most restless or nervous'.