Why have early investigational therapies of obsessive-compulsive disorder failed to materialise?

The mid-1980s brought about a revolution in the way in which clinicians approached the treatment of obsessive-compulsive disorder (OCD) pharmacologically. Indeed, clinicians adopted the use of selective serotonin (5-HT) re-uptake inhibitors, as treatment options, when it was demonstrated that OCD patients responded specifically to drugs enhancing 5-HT functioning in approximately 60% of all cases. Evidence to suggest a role for serotonergic compounds in OCD was further elucidated by increasing evidence in the following years. Since then, a number of different compounds that more or less directly modulate the 5-HT system have been proposed, although other therapeutic targets have also been considered. Unfortunately, despite our advancement in the understanding of this disorder, several of the treatment proposals never reached the clinic, staying at mere suggestion or not receiving sufficient development. The aim of this paper is to reflect and comment on the possible reasons that might have led to neglect or discarding these drugs that might have been effective in treating OCD.