Sane is being forced to close two of its three national call centres following a £1m cut in government funding.
The closure of the centres in Bristol and Macclesfield will be accompanied by the loss of 127 trained volunteers and 13 full-time staff.
Only the London office of Saneline will continue to answer calls. The helpline takes 1,000 calls a week from people in distress and demand is such that it would cater for a further 11,000 if it had the means.
Saneline costs £1.3m to run annually and had previously been under a two-year government contract worth £1m a year, which has not been renewed.
Marjorie Wallace, chief executive of Sane, said: "We are sad and disappointed to have to take this step."