Clonazepam. Clonazepam(Drug information on clonazepam) (Klonopin) has been studied in two controlled trials. One showed equal efficacy to clomipramine(Drug information on clomipramine), while the other showed no difference from placebo (Hewlett et al., 1992; Hollander et al., 2003c). Clonazepam may have a role in patients with extreme anxiety and/or insomnia but should not be used "as needed," especially if the patient is also undergoing CBT.
Buspirone. Buspirone(Drug information on buspirone) (BuSpar), a partial 5-HT1A receptor agonist, appeared promising from case reports and open trials. One early controlled trial showed equal efficacy to clomipramine (Pato et al., 1991). However, three controlled trials have since yielded disappointing results (Grady et al., 1993; McDougle et al., 1993; Pigott et al., 1992).
Lithium. Despite promising case reports, lithium(Drug information on lithium) (Eskalith, Lithobid) did not prove to be efficacious in two double-blind, placebo-controlled trials (McDougle et al., 1991; Pigott et al., 1991). However, lithium and other mood stabilizers have a role in patients with comorbid bipolar disorder and/or who experience mood instability or hypomania as a result of SRI treatment.
Other Augmenting Agents
Oral morphine(Drug information on morphine). Preliminary results from a once-a-week, double-blind trial of this opioid receptor agonist showed modest but significant improvement in symptoms over lorazepam(Drug information on lorazepam) (Ativan) and placebo in eight patients (Franz et al., 2001).
Other augmentation strategies with medication or dietary supplements have been tried, including stimulants, L-tryptophan, pindolol(Drug information on pindolol) (Visken), oxytocin(Drug information on oxytocin) and androgen antagonists. None of these has shown sufficient promise (Altemus et al., 1999; Mundo et al., 1998; Owley et al., 2002).
If the patient has shown no response to SRIs or clomipramine, a different medication in the antidepressant class may be tried.