Pharmacotherapy of Treatment-Resistant OCD: Augmentation Strategies

Treatment of obsessive compulsive disorder is often challenging. Treatment resistance is quite common, between 40 to 60% of patients do not show and adequate response to first-line treatments.

We invited Dr. David Veale to comment on his meta-analysis published in BMC Psychiatry : “Atypical antipsychotic augmentation in SSRI treatment refractory obsessive-compulsive disorder: a systematic review and meta-analysis”

About our guest: Dr. David Veale




Dr. Veale is consultant Psychiatrist In Cognitive Behaviour Therapy at the South London and Maudsley NHS Trust and The Priory Hospital North London. He is a Visiting Senior Lecturer at the Institute of Psychiatry, King’s College London. He specializes in obsessive compulsive disorder (OCD), body dysmorphic disorder (BDD), health anxiety, depression, and emetophobia.





Interview conducted by Flavio Guzman, MD

  • Practical definition of treatment-resistant OCD
  • Stepped-approach to pharmacotherapy
  • Efficacy of second-generation antipsychotics as augmentation strategy
    • When to use them
  • Other treatment options


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Dr. Guzman: In this episode, our guest is Dr. David Veale. He is here to discuss treatment-resistant OCD. Dr. Veale is Consultant Psychiatrist in cognitive behaviour therapy at the South London and Maudsley NHS Trust and The Priory Hospital North London. He specializes in obsessive-compulsive disorder, body dysmorphic disorder, health anxiety, depression and emetophobia.

His group published a paper in BMC Psychiatry, called Atypical Antipsychotic Augmentation in SSRI Treatment Refractory Obsessive Compulsive Disorder: A systematic review and meta-analysis.

Treatment of obsessive-compulsive disorder is often challenging. Treatment-resistance is quite common. Between 40-60 % of patients don’t show an adequate response to first-line treatments. There is an additional problem. Currently, we don’t have a standard definition of treatment resistance. So I asked Dr. Veale about a practical definition for clinicians.

Dr. Veale: Well, researchers use various criteria in terms of percentage reduction on standardized scales like the Yale-Brown Obsessive Compulsive Scale. But for clinicians, I think it’s primarily about whether your patient remains significantly distressed or handicapped interfered in their life by the symptoms of OCD.

Dr. Guzman: Now, our guest describes a stepped approach for treating OCD. This includes how to use SSRIs, the role of clomipramine, a stepped approach also for CBT, and when to use antipsychotics. He discusses the findings of his meta-analysis.

Dr. Veale: In general, we use a stepped approach in medication and so as you say, you start off with one SSRI . The problem is often is that people don’t necessarily use it at the maximum tolerated dose for at least three or four months, there is this dose-response relationship. Unless you get up to the highest tolerated dose for at least three months, then you can’t really say whether you had any benefit from this or anything.

Now, it’s true that sometimes people can’t tolerate high doses but that’s the thing to aim for. If that doesn’t work, you go on to an alternative SSRI. Again, maximum tolerated dose for at least three months.
Then you might want to consider clomipramine. Again, as you know, a little bit more difficult to use because you’re more likely to get side effects in the higher doses . But certainly, two SSRIs and clomipramine would be the pharmacological stepped approach and it often depends upon obviously the availability of CBT. But you know, CBT is also done in stepped approach because if you get more intensive CBT, then it may be a more experienced therapist or more frequent sessions and so on, so both of those can go together.

The question is then what you do if you’re still distressed and handicapped. And that’s when the antipsychotics come in, and so you’d be staying on the maximum tolerated doses of SSRI . The meta-analysis found mainly that it’s best to use probably aripiprazole or risperidone.

Aripiprazole and risperidone are probably most effective in OCD, at least that’s what the meta-analysis shows. But the key issue is that it’s not like using an antipsychotic for schizophrenia, you can use quite low doses so some of the trials found risperidone even 0.5 mg was effective. And so, an equivalent dose of aripiprazole might be 2.5 or 5 mg. So you can use quite low doses. Furthermore, you can find out whether it’s being effective or not within four weeks. So that if it really has had no benefit in four weeks at a low dose, well possibly some people might increase the dose. But it’s probably very unlikely to have any further benefit and you might well then want to discontinue. It’s not something that you just want to leave someone on for many months and years, like something you would be perhaps with an anti-psychotic in schizophrenia. If it’s not working, there’s no point in staying on it.

Dr. Guzman: What if it works?

Dr. Veale: Then you probably want to stay on it. But we don’t know is actually all these studies so far have only been done for three months or so. And no one has actually done any good studies in the long term. There’s a small study that suggests that if you are getting benefits and then you stop taking it, then you’re more likely to relapse. But there is one long-term study going on at the moment in Japan on aripiprazole , we look forward to that because people want to know how effective it is in the long term. Does the effect wear off over time or anything? We just don’t know, but the key issue is that low doses for at least a month and then you can decide whether to remain on it or not.

Dr. Guzman: Is there a symptom profile useful to identify those patients that might show response to antipsychotics?

Dr. Veale: People have looked at this. One or two trials looked at people with comorbid tics but then that didn’t come out in other trials and certain, perhaps sometimes, certain types of symptoms. It maybe if you’re highly anxious, it might just help reduce your level of arousal but there’s no good evidence really at all. No one knows. It’s just a matter of trial and error to be honest.

Dr. Guzman: What other options do we have for treatment-resistant OCD?

Dr. Veale: The only other thing to say is that there is some evidence, one or two isolated trials from mega doses of SSRIs, very high levels of SSRIs but you’d need to do ECG monitoring and serum monitoring of the particular drug. The thing, you know, if you’re going to up to sertraline 400 mg or fluoxetine 120-60 mg, these are done sometimes because there are also some patients who are rapidly metabolizers. So occasionally, that might be worth investigating.

There are one or two trials done on lamotrigine added to an SSRI and a trial on memantine added to an SSRI. So there is a sort of scraping the barrel to certain types of medications at the bottom of the barrel. But it’s tough and probably there is a group of patients who really struggle with all medications and the CBT as well. Certainly in our own unit, we have such patients in our residential units like an inpatient unit and they get intensive therapy. So you’re getting CBT 3- 4 times a week with an assistant therapist and it’s the right environment in terms of support and so.

So if that doesn’t work, then there is experimental work going on in terms of looking at deep brain stimulation. So there’s always something around the corner.

Dr. Guzman: That was Dr. David Veale on treatment-resistant OCD. For more psychopharmacology updates, visit


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