We discuss the issue of higher-than-needed doses of antipsychotic medication for augmentation in OCD. This can cause side effects. We briefly review the evidence to support the use of Risperidone in treating OCD and look at typical doses. We go on to make some recommendations for optimum doses of Risperidone.

Background

In the last year, we have seen a number of people on high doses of antipsychotic medication prescribed as augmentation for OCD. Sometimes this is Quetiapine, but most commonly it has been Risperidone, often prescribed at doses of 6mg – 8mg per day. The people we have seen have all had side effects at these doses.

There are several problems with this:

1. It is unlikely that the individual will get any additional benefit from higher doses.
2. It is very likely that they will experience harms. At these kinds of doses, drug-induced Parkinsonism and/ or marked sedation are common, but are usually reversible. However, the likelihood of developing irreversible tardive dyskinesia due to antipsychotics being prescribed at high doses for long periods of time (more than a few months), without regular review, is significant.

There are many reasons why we think this may be happening. First, the COVID pandemic (and the shift away from face-to-face contact) has undoubtedly made it more likely that people will experience side effects without being reviewed face-to-face by a prescribing doctor or nurse. Second, there is a higher turnover of staff in many community mental health teams; particularly among medical staff. It is now more likely that someone will see a locum, or a different doctor when they visit, making it harder for the same prescriber to get a good understanding of the benefits (and harms) of any drug. Third, there is increased demand for mental health services, and when combined with the obvious workforce challenges, people are seen less frequently. By the time that someone goes back for review, it may be three months (or longer) since they started the drug. This is plenty of time to develop significant side effects.

We have seen this occurring most commonly with Risperidone, ironically because this is the drug that has the best evidence for treating OCD. However, we are not sure why such high doses are being used; particularly since doses of 6mg (and above) are rarely used in schizophrenia, let alone OCD.

What does the evidence say?

The median dose of Risperidone in published trials is shown below.

It can be seen that doses of Risperidone well in excess of 2mg/ day are simply not evidence-based. There is no evidence to support the use Risperidone in doses above 2mg. It is unlikely to be beneficial and likely to be harmful.

However, there may be some situations where slightly higher doses would be considered, and these include:

1. The patient has shown (using measures of symptom reduction and improved functioning) a clear dose-response relationship to increasing doses of Risperidone.
2. The patient has few adverse effects to their current dose or Risperidone.
3. The risks of higher doses have been discussed with the patient and they are willing to try a higher dose.
4. The trial at higher dose is time-limited, a date for review has been agreed, and (if there is no evidence of greater benefit) there is a plan to return to the current dose.

Guidance for use of antipsychotic augmentation in OCD

We have published an algorithm for treating OCD on our website. Clinicians are advised to follow the dosing guidance in the treatment algorithm. We are happy to provide advice if higher doses are being considered.

Importantly, we would like to offer some additional guidance when prescribing antipsychotics in OCD:

1. Obtain measures of OCD symptoms (e.g. self-report Y-BOCS) and functioning (e.g. WHODAS scale) before, during, and at the end of any trial. This is the only way to assess the benefits. A general impression is probably insufficient when drugs with significant side effects are being used.
2. Screen for, and measure, side effects throughout the trial. This is likely to include inquiry about appetite, measurements of weight, and questions about restlessness (akathisia), tremor, sedation (psychological and motor), and stiffness. The SAFTEE-SI is a good tool.
3. Start low, go slow, and don’t go too high. It is vital to start at a low dose. For Risperidone, it is better to start off at 0.25mg/ day and build up over 2-3 weeks, than to start at 1.5mg, find the patient cannot tolerate it, and has stopped it when they next see you.
4. Monitor regularly. Face-to-face is ideal, but videoconference is much better than telephone. You can see facial expression and look for tremor/ restlessness. However, a telephone review every two weeks as the dose is increased is probably better than a face-to-face meeting every two months; particularly if the patient is completing regular rating scales.
5. If there is no response to a reasonable dose (e.g. Risperidone 1.5mg – 2mg/ day) after 10-12 weeks, there is unlikely to be further response. Aim to reduce the dose and switch to a different drug (e.g. Aripiprazole).
6. Although drugs such as Quetiapine or Olanzapine are surprisingly popular, they lack the evidence for benefit (Dold, Aigner, Lanzenberger, et al, 2013; Veale, Miles, Smallcombe, et al, 2014), and their use should be avoided in favour of better-evidenced drugs.

References

Dold, M., Aigner, M., Lanzenberger, R., et al (2013) Antipsychotic augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a meta-analysis of double-blind, randomized, placebo-controlled trials. International Journal of Neuropsychopharmacology, 16, 557-574. http://dx.doi.org/10.1017/S1461145712000740

Erzegovesi, S., Guglielmo, E., Siliprandi, F., et al (2005) Low-dose risperidone augmentation of fluvoxamine treatment in obsessive-compulsive disorder: a double-blind, placebo-controlled study. European Neuropsychopharmacology, 15, 69-74. http://dx.doi.org/10.1016/j.euroneuro.2004.04.004

Hollander, E., Baldini Rossi, N., Sood, E., et al (2003) Risperidone augmentation in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo-controlled study. International Journal of Neuropsychopharmacology, 6, 397-401. https://doi.org/10.1017/S1461145703003730

Maina, G., Pessina, E., Albert, U., et al (2008) 8-week, single-blind, randomized trial comparing risperidone versus olanzapine augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive–compulsive disorder. European Neuropsychopharmacology, 18, 364-372. http://dx.doi.org/10.1016/j.euroneuro.2008.01.001

McDougle, C. J., Epperson, C. N., Pelton, G. H., et al (2000) A Double-blind, Placebo-Controlled Study of Risperidone Addition in Serotonin Reuptake Inhibitor-Refractory Obsessive-Compulsive Disorder. Archives of General Psychiatry, 57, 794-801. https://doi.org/10.1001/archpsyc.57.8.794

Simpson, H. B., Foa, E. B., Liebowitz, M. R., et al (2013) Cognitive-Behavioral Therapy vs Risperidone for Augmenting Serotonin Reuptake Inhibitors in Obsessive-Compulsive Disorder: A Randomized Clinical Trial. JAMA Psychiatry, 70, 1190-1199. http://dx.doi.org/10.1001/jamapsychiatry.2013.1932

Veale, D., Miles, S., Smallcombe, N., et al (2014) Atypical antipsychotic augmentation in SSRI treatment refractory obsessive-compulsive disorder: a systematic review and meta-analysis. BMC Psychiatry, 14, 317. https://doi.org/10.1186/s12888-014-0317-5