Serotonin reuptake inhibitors (SRIs), especially potent ones given at high doses 
over long periods of time, are often effective in the treatment of 
obsessive-compulsive disorder (OCD). However, a large percentage of patients do 
not respond to treatment with SRIs, and those who do respond often do not fully 
remit, which should be the standard goal of treatment in OCD. If a patient has 
been treated for several months and has not yet responded to treatment with 
several SRIs, the physician should perform a careful assessment of resistant 
and/or residual clinical symptoms and any comorbid conditions to determine which 
next-step treatment would be the most appropriate. One strategy for patients who 
have not responded to treatment with an SRI is to switch them to a 
serotonin-norepinephrine reuptake inhibitor, because some patients may respond 
better to agents that target multiple systems. Another promising approach is the 
augmentation of SRIs with neuroleptics. In addition, open trials have shown that 
intravenous (IV) clomipramine and IV citalopram may be effective in the 
treatment of resistant OCD. Novel pharmacotherapeutic treatments and 
electroconvulsive therapy have been attempted, with mixed success. Recently, 
researchers have been studying repetitive transcranial magnetic stimulation, 
vagal nerve stimulation, and neurosurgical approaches such as gamma knife 
capsulotomy and deep brain stimulation to learn if these procedures are 
effective in treating treatment-resistant OCD. Repetitive transcranial magnetic 
stimulation has possibilities not only as a therapy but also as an instrument 
that can help researchers describe the neurocircuitries involved in OCD. More 
results are needed before the effectiveness of the nonpharmacologic treatments 
for OCD can be determined.