Way to screw up irksome state (7)
I believe the answer is:
boredom
'irksome state' is the definition.
'way to screw up' is the wordplay.
'way' becomes 'mode' ('mode' can be a synonym of 'way').
'to screw' becomes 'rob' (I can't explain this - if you can you should believe this answer much more).
'up' says the letters should be written in reverse (in down clue: letters go upwards).
'mode'+'rob'='moderob'
'moderob' back-to-front is 'BOREDOM'.
(Other definitions for boredom that I've seen before include "no interest" , "Monotony" , "Ennui in bedroom" , "Feeling" , "Tedium, ennui" .)