Background: Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral psychotherapy
(CBT) are first-line treatments for obsessive-compulsive disorder (OCD). However,
a significant proportion of patients do not respond satisfactorily to first-choice treatments.
Several options have been investigated for the management of resistant patients.
Objective: The aim of the present paper is to systematically review the available literature
concerning the strategies for the treatment of resistant adult patients with OCD.
Method: We first reviewed studies concerning the definition of treatment-resistant OCD;
we then analyzed results of studies evaluating several different strategies in resistant patients.
We limited our review to double-blind, placebo-controlled studies performed in
adult patients with OCD whose resistance to a first adequate (in terms of duration and
dosage) SRI trial was documented and where outcome was clearly defined in terms of decrease
in Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores and/or response/
remission rates (according to the YBOCS).
Results: We identified five strategies supported by positive results in placebo-controlled
randomized studies: 1) antipsychotic addition to SRIs (16 RCTs, of them 10 positive; 4
head-to-head RCTs); among antipsychotics, available RCTs examined the addition of
haloperidol (butyrophenone), pimozide (diphenyl-butylpiperidine), risperidone (SDA: serotonin-
dopamine antagonist), paliperidone (SDA), olanzapine (MARTA: multi-acting
receptor targeted antipsychotic), quetiapine (MARTA) and aripiprazole (partial dopamine
agonist); 2) CBT addition to medication (2 positive RCTs); 3) switch to intravenous
clomipramine (SRI) administration (2 positive RCTs); 4) switch to paroxetine (SSRI: selective
serotonin reuptake inhibitor) or venlafaxine (SNRI: serotonin-norepinephrine reuptake
inhibitor) when the first trial was negative (1 positive RCT); and 5) the addition of
medications other than an antipsychotic to SRIs (18 RCTs performed with several different
compounds, with only 4 positive studies).
Conclusion: Treatment-resistant OCD remains a significant challenge to psychiatrists. To
date, the most effective strategy is the addition of antipsychotics (aripiprazole and risperidone)
to SRIs; another effective strategy is CBT addition to medications. Other strategies,
such as the switch to another first-line treatment or the switch to intravenous administration
are promising but need further confirmation in double-blind studies. The addition of
medications other than antipsychotics remains to be studied, as several negative studies
exist and positive ones need confirmation (only 1 positive study).