Numerous positive open trials of clomipramine in OCD were followed by at least 22 controlled trials in which clomipramine was either more effective (11 trials) than placebo or tricyclic comparators or equally as effective as selective serotonin reuptake inhibitor (SSRI) comparators (5 trials) (Greist et al. 1995). Clinical opinion has generally led to dosing at the higher end of the dosing range for these agents, although fixed-dose trials, when available, have usually found a flat dose–response curve, suggesting that many patients receive more medication than necessary. Side effects of clomipramine are typical of a tricyclic antidepressant and include anticholinergic, antihistaminergic, and alpha-adrenergic blocking effects.