From the Guidelines
For treatment-resistant OCD, antipsychotic augmentation has the strongest evidence base, with risperidone and aripiprazole being the most studied options. Specifically, adding risperidone (0.5-2mg daily) or aripiprazole (5-15mg daily) to an ongoing SSRI regimen is recommended, as evidenced by a meta-analysis providing evidence of efficacy for both risperidone and aripiprazole augmentation 1. These medications should be initiated at low doses and gradually titrated based on response and tolerability. A trial of 4-8 weeks at an adequate dose is necessary to determine efficacy. Antipsychotic augmentation works by addressing dopaminergic dysfunction that may contribute to OCD symptoms resistant to serotonergic medications alone. Approximately one-third of patients with treatment-resistant OCD will respond to antipsychotic augmentation, as noted in a study published in Nature Reviews Disease Primers 1. Patients should be monitored for potential side effects including metabolic changes, sedation, and extrapyramidal symptoms.
Some key points to consider when using antipsychotic augmentation for treatment-resistant OCD include:
- The importance of gradual titration and monitoring for side effects, as highlighted in a study on the efficacy and safety of antipsychotic augmentation 1
- The potential for glutamatergic medications, such as N-acetylcysteine and memantine, to be used as alternative augmentation strategies, as suggested by several randomized controlled trials 1
- The consideration of non-pharmacological approaches, such as deep brain stimulation, for severely treatment-resistant cases, as outlined in an OCD treatment algorithm 1
- The need for ongoing monitoring of the risk-benefit ratio, particularly with regards to adverse events such as weight gain and metabolic dysregulation, as emphasized in a study on the efficacy and safety of antipsychotic augmentation 1
Overall, antipsychotic augmentation is a viable option for patients with treatment-resistant OCD, and should be considered in conjunction with other treatment modalities, such as CBT and glutamatergic medications, as part of a comprehensive treatment plan.
From the FDA Drug Label
The effectiveness of clomipramine hydrochloride for the treatment of OCD was demonstrated in multicenter, placebo-controlled, parallel-group studies, including two 10-week studies in adults and one 8-week study in children and adolescents 10 to 17 years of age Patients in all studies had moderate-to-severe OCD (DSM-III), with mean baseline ratings on the Yale-Brown Obsessive Compulsive Scale (YBOCS) ranging from 26 to 28 and a mean baseline rating of 10 on the NIMH Clinical Global Obsessive Compulsive Scale (NIMH-OC) Patients taking clomipramine experienced a mean reduction of approximately 10 on the YBOCS, representing an average improvement on this scale of 35% to 42% among adults and 37% among children and adolescents.
The augmentation strategy supported by evidence for treatment-resistant OCD is not explicitly mentioned in the provided drug label. However, clomipramine is indicated for the treatment of OCD and has shown effectiveness in reducing symptoms of OCD in clinical trials 2.
- The label does not provide information on augmentation strategies for treatment-resistant OCD.
- Clomipramine may be used as a treatment option for OCD, but its use as an augmentation strategy for treatment-resistant OCD is not directly supported by the label.
From the Research
Augmentation Strategies for Treatment-Resistant OCD
The following augmentation strategies are supported by evidence for the treatment of resistant OCD:
- Antipsychotic addition to SRIs, with risperidone and aripiprazole having the best evidence 3, 4, 5, 6
- CBT addition to medication, with two positive RCTs supporting its effectiveness 3
- Switch to intravenous clomipramine (SRI) administration, with two positive RCTs supporting its effectiveness 3
- Switch to paroxetine (SSRI) or venlafaxine (SNRI) when the first trial was negative, with one positive RCT supporting its effectiveness 3
- The addition of medications other than an antipsychotic to SRIs, although the evidence is limited and requires further confirmation 3
Specific Antipsychotics Used for Augmentation
The following antipsychotics have been studied for augmentation in treatment-resistant OCD:
- Risperidone, with positive results in several studies 3, 4, 5, 6
- Aripiprazole, with positive results in several studies 3, 5, 6
- Haloperidol, with some evidence supporting its effectiveness, although its side effect profile is a concern 3, 5, 6
- Olanzapine, quetiapine, and paliperidone, with some evidence supporting their effectiveness, although more research is needed 3