Venlafaxine. Several case reports and open-label studies suggest that venlafaxine (Effexor) (a serotonin and norepinephrine(Drug information on norepinephrine) reuptake inhibitor), alone or in combination with SRIs, may be helpful (Hollander et al., 2003b; Sevincok and Uygur, 2002). A single-blind comparison with clomipramine(Drug information on clomipramine) showed venlafaxine to be nearly as effective and more tolerable (Albert et al., 2002). A double-blind comparison with paroxetine(Drug information on paroxetine) (Paxil) showed both to be equally effective, with a 40% response rate (Denys et al., 2003). Venlafaxine may be a good option after failed SRI trials or as augmentation. It is relatively well-tolerated.
Monoamine oxidase inhibitors. A randomized, controlled trial comparing phenelzine(Drug information on phenelzine) (Nardil) with clomipramine found the two to be equally efficacious (Vallejo et al., 1992). However, a placebo-controlled comparison of phenelzine with fluoxetine(Drug information on fluoxetine) (Prozac) found fluoxetine to be significantly superior except for obsessions regarding symmetry, which responded well to phenelzine (Jenike et al., 1997).
For severely treatment-resistant cases, there is some evidence for the efficacy and safety of intravenous clomipramine. In a double-blind, randomized, controlled trial in treatment-refractory patients, Fallon and colleagues (1998) found that nine of 21 patients treated with 14 days of clomipramine infusions followed by seven days of oral treatment were responders, compared with none of 18 in the placebo group. Improvement was maintained by the end of blind ratings at three weeks, and the regimen was well tolerated.
Citalopram(Drug information on citalopram) has been tested intravenously in an open trial of 39 outpatients, in which 59% achieved a response by day 21 (Pallanti et al., 2002b). In both trials, the intravenous administration appeared to produce a relatively rapid effect (two to three weeks).
After pharmacologic and CBT strategies have been exhausted, nonpharmacologic somatic treatments may be considered.
Deep brain stimulation. A group of investigators treated eight patients with severe treatment-resistant OCD with stereotactically implanted quadripolar electrodes in the bilateral anterior limbs of the internal capsule (using the same targets as in capsulotomy) (Cosyns et al., 2003). Their initial report showed beneficial effects in three of the first four patients.