Otto Krüger, 67, was granted permission to temporarily leave his ward at 1:45pm on Sunday but he failed to return to the facility at the agreed time.
Now police are warning the public not to approach the man, who is dependent on medication and can be “very aggressive”.
It is thought he could be in or around the cities of Cologne and Bonn in North Rhine-Westphalia.
In 1998 the man kicked his 78-year-old neighbour to death in Bad Godesberg, south of Bonn. The following year he was placed in a closed psychiatric ward by a Bonn court.
The man had previously gone missing in December 2014 during an accompanied visit to a Christmas market. RP Online reported that he was on the run for two weeks but was caught after witnesses spotted him in a bistro.
Police have asked anyone with information on Krüger's whereabouts to contact them.