Successfully treating obsessive-compulsive disorder (OCD) often requires primary psychotherapeutic treatment with exposure and response prevention (ERP) and pharmacological treatment with serotonergic agents, typically beginning with SSRIs; however, for a subset of patients with OCD, SSRIs alone do not effectively manage symptoms. There are a number of augmentation strategies to consider in these cases. This blog post will focus on the strategy of adding an antipsychotic medication to an SSRI.

Some patients may feel uncomfortable with the idea of starting an antipsychotic, in part as the term “antipsychotic” is a misnomer that might imply an element of their presentation that is not entirely accurate. To this end, it may be useful to provide education that antipsychotics can be effective for conditions other than psychosis, much in the same way that antidepressants can be effective for conditions other than depression.

While guidance regarding augmentation of an SSRI with an antipsychotic is somewhat limited due to a small number of trials, the following guidelines are fairly consistent among available studies and meta-analyses:

• ERP is superior to risperidone in reducing symptoms of OCD. That is to say, if a patient is not already engaged in high-quality ERP and is not responding adequately to treatment with an SSRI, encouraging ERP is likely to be more effective and carries a less negative risk profile than starting an antipsychotic. According to one study, over half (56 percent) of patients who did not respond to placebo or risperidone were noted to have a treatment response to a course of 17 sessions of ERP (McLean).
• If a patient has a partial response to an SSRI, the best next step is likely to titrate the SSRI, as OCD often requires higher doses of SSRIs for full effect; however, if there is no response to an SSRI, the best next step may be to instead add an antipsychotic.
• Consider starting an antipsychotic for augmentation after at least twelve weeks of an adequate SSRI trial. Studies suggest that one in three patients who do not respond to SSRIs do improve with antipsychotic augmentation, and an adequate trial duration of an SSRI for OCD is at least twelve weeks.
• Increased symptom severity is correlated with decreased response to antipsychotics. Available studies have demonstrated that antipsychotics are less effective in more severe cases of OCD than in moderate cases. In other words, perhaps counterintuitively, it is not advisable to reserve antipsychotic augmentation for patients with the most severe symptoms of OCD.
• Regarding selection, the most evidence-based options are aripiprazole and risperidone. Haloperidol may also be considered, though has a side effect profile that is generally less tolerable than the second-generation options. Further, olanzapine and quetiapine have not differentiated from placebo and are not considered first-line for this purpose. Other medications in this class have not been adequately assessed.
• Use relatively low doses of antipsychotics to minimize side effects, and consider side effect profile when deciding between medications. In general, aripiprazole tends to be better tolerated than risperidone.
• Regarding dosing, low to moderate doses are typically advisable to maintain tolerability, though if a patient has a partial response and is tolerating the medication well, you may consider further titration. Here are conservative recommendations for dose ranges:
  • Aripiprazole: 5-10 mg
  • Risperidone: 1-3 mg
  • Haloperidol: 2.5-10 mg
• There is an elevated risk of QTc prolongation when combining second-generation antipsychotics with clomipramine. Exercise caution and utilize appropriate monitoring when using this combination.
• Studies demonstrate some variability regarding necessary trial duration. Generally, there will likely be some effect to measure within four weeks. If there is no response to augmentation within four weeks, the recommendation is to stop the antipsychotic.
• After achieving symptom remission with an antipsychotic, this medication should be continued for at least one year. Studies have demonstrated relapse when antipsychotics are discontinued prematurely (e.g. after three months).
• When prescribing antipsychotics for any purpose, it is important to follow guidelines for routine monitoring of weight, fasting plasma glucose, A1c, lipids, and blood pressure.

In summary, augmenting an SSRI with an antipsychotic medication can be an effective strategy that may generate a treatment response in about a third of patients who have not responded to an SSRI alone. Based on current evidence, we most strongly recommend a low to moderate dose of aripiprazole, risperidone, or haloperidol as specific agents for this purpose. Once a patient achieves a favorable effect on one of these medications, we recommend continuing the medication for at least one year to prevent early relapse. More monitoring is necessary when prescribing antipsychotics versus SSRIs or clomipramine alone.

As medication management alone is often insufficient in treating OCD, and as a fair number of patients discontinue effective medications due to adverse effects, we must also highlight the role of psychotherapy. High-quality ERP remains a top recommendation for patients with OCD. ERP has been shown to be more effective than augmentation with an antipsychotic and should be the primary recommendation for patients who have not responded to a serotonergic agent alone.

This post is presented in collaboration with ADAA's OCD and Related Disorders SIG. Learn more about the SIG.

References

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