Memantine for OCD

[cbrons]

What is your experience with it?
I have only used it in one very severe case (young man who was in residential ERP treatment for 2 months and refused to take SSRIs) and it worked pretty well (I think).

 

[Yoyomama88]

I really want to try it. I read that apparently ketamine can work for ocd, so the glutamate and nmda mechanism makes sense

 

[clausewitz2]

I've used it a fair amount since I treat lots of OCD. It seems about as effective as Abilify as a third line after moving through SSRIs at adequate doses (400 mg sertraline or equivalent) and clomipramine at adequate dose (250 mg). I've seen more dramatic improvement with riluzole but then memantine is so very much cheaper. I think memantine probably deserves a trial before neuroleptics for OCD these days based on evidence base.

Edit: one exception might be for young people in that OCD/Tourette's cluster with lots of symmetry, just right, and harm obsessions. Them I probably bust out neuroleptics before memantine.

 

[Stagg737]

I've used it a fair amount since I treat lots of OCD. It seems about as effective as Abilify as a third line after moving through SSRIs at adequate doses (400 mg sertraline or equivalent) and clomipramine at adequate dose (250 mg). I've seen more dramatic improvement with riluzole but then memantine is so very much cheaper. I think memantine probably deserves a trial before neuroleptics for OCD these days based on evidence base.

Edit: one exception might be for young people in that OCD/Tourette's cluster with lots of symmetry, just right, and harm obsessions. Them I probably bust out neuroleptics before memantine.

Is the bold a typo or just something I’m not understanding?

 

[clausewitz2]

Is the bold a typo or just something I’m not understanding?

100% a typo

 

[Merovinge]

I've used it a fair amount since I treat lots of OCD. It seems about as effective as Abilify as a third line after moving through SSRIs at adequate doses (400 mg sertraline or equivalent) and clomipramine at adequate dose (250 mg). I've seen more dramatic improvement with riluzole but then memantine is so very much cheaper. I think memantine probably deserves a trial before neuroleptics for OCD these days based on evidence base.

Edit: one exception might be for young people in that OCD/Tourette's cluster with lots of symmetry, just right, and harm obsessions. Them I probably bust out neuroleptics before memantine.

Are you indicating primarily using monotherapy in these cases? The few patients I have on Abilify for OCD it's being used adjunctively with high dose SSRI when the SSRI makes some improvement but remains with crippling symptoms. Would memantine be used similarly?

 

[clausewitz2]

Are you indicating primarily using monotherapy in these cases? The few patients I have on Abilify for OCD it's being used adjunctively with high dose SSRI when the SSRI makes some improvement but remains with crippling symptoms. Would memantine be used similarly?

Yes, this is basically always used as an adjunct.

 

[cbrons]

Yes, this is basically always used as an adjunct.

Always? You haven't seen people with success using it alone?

 

[clausewitz2]

Always? You haven't seen people with success using it alone?

I rarely see people with OCD on monotherapy that does not involve SRIs of some description unless they have really intolerable side effects, so hard to say. If I had to pick a most common non-SRI monotherapy I have ended up working with in OCD it'd be NAC for the 'i hate medicines but give me a nutraceutical pill' crowd.

Perhaps unsurprisingly many people with OCD have spent a lot of time researching OCD and tend to have a strong preference for the 'correct' treatments, and every website you find will mention SSRIs, so...

 

[Merovinge]

Perhaps unsurprisingly many people with OCD have spent a lot of time researching OCD and tend to have a strong preference for the 'correct' treatments, and every website you find will mention SSRIs, so...

Next your going to tell me plastic surgeons like things done a certain way. Get out of here with these ridiculous stereotypes 😆.

 

[birchswing]

I've been following a prodrug of riluzole that's supposed to have fewer side effects and may seek (receive?) approval specifically for OCD:

Pipeline | Biohaven

Our portfolio includes treatments for a range of diseases with unmet medical needs.

www.biohavenpharma.com

 

[Psychferlyfe3000]

I've used it a fair amount since I treat lots of OCD. It seems about as effective as Abilify as a third line after moving through SSRIs at adequate doses (400 mg sertraline or equivalent) and clomipramine at adequate dose (250 mg). I've seen more dramatic improvement with riluzole but then memantine is so very much cheaper. I think memantine probably deserves a trial before neuroleptics for OCD these days based on evidence base.

Edit: one exception might be for young people in that OCD/Tourette's cluster with lots of symmetry, just right, and harm obsessions. Them I probably bust out neuroleptics before memantine.

The frustrating thing about the evidence base is that it is mostly out of one region of Iran and not done using Intention to Treat analyses (ie, they are completer analyses). Clausewitz2, do you still find memantine to be roughly as effective as abilify for augmentation based on your experience?

 

[Psychferlyfe3000]

Also, for anyone else that treats a lot of OCD, I would really appreciate your input on effect size (anecdotally) of memantine vs aripiprazole for treatment-refractory OCD!

 

[mistafab]

I would say from experience the effect size of either is infinitely small. A research-level statistical phenomenon and almost nothing of clinical relevance. Doesn't mean I don't try it, but don't expect this to be meaningful in terms of treatment effect.

The most important pharmacological (not treatment) steps for OCD should be SRI (typically prozac) to max doses tolerated-> fluvox (or skip) to max tolerated-> clomipramine. The rest needs to be the exposure/OCD therapy.

Pharma can be expected AT BEST to reduce symptoms by 40-60% in OCD, even when well optimized. If you've already achieved this, then pharma is not where you should be looking for further OCD effect. Way better to do therapy (even supportive) than to push harder on the meds.

Edit: I would say from my experience working with a lot of severe OCD, that I would rather escalate care to a MAOI then waste time piddling around with augmentation strategies if someone has not achieved the 40-60% drop we expect. I have not had to utilize this given that clomipramine has worked in combination with supportive psychotherapy for refractory, severe OCD causing SI/severe depression in several cases I've had - but I definitely would use it should it be appropriate. An antipsychotic makes much more sense to me than memantine given that a majority of severe OCD cases have had (or have) concomitant MDD (I think the research estimates up to 60%?), and we know abilify augmentation does work for depression.

I am familiar with the literature and also need to say that misdiagnosis of psychosis as OCD is a frequent phenomenon in people who are not OCD experts. Given this, I think the data supporting antipsychotic augmentation in OCD is flawed due to this phenomenon (psychotic patients are called OCD, and they respond to the antipsychotic thus supporting the incorrect hypothesis).

Given that, it makes sense for providers not familiar with OCD who have not seen the expected 40-60% decrease in symptoms to trial augmentation with an antipsychotic. If the patient responds robustly, they should consider the possibility that what they thought was OCD was actually psychosis. If they don't respond, then discontinue the antipsychotic and escalate the pharma treatment for OCD.

 

[Psychferlyfe3000]

I would say from experience the effect size of either is infinitely small. A research-level statistical phenomenon and almost nothing of clinical relevance. Doesn't mean I don't try it, but don't expect this to be meaningful in terms of treatment effect.

The most important pharmacological (not treatment) steps for OCD should be SRI (typically prozac) to max doses tolerated-> fluvox (or skip) to max tolerated-> clomipramine. The rest needs to be the exposure/OCD therapy.

Pharma can be expected AT BEST to reduce symptoms by 40-60% in OCD, even when well optimized. If you've already achieved this, then pharma is not where you should be looking for further OCD effect. Way better to do therapy (even supportive) than to push harder on the meds.

Edit: I would say from my experience working with a lot of severe OCD, that I would rather escalate care to a MAOI then waste time piddling around with augmentation strategies if someone has not achieved the 40-60% drop we expect. I have not had to utilize this given that clomipramine has worked in combination with supportive psychotherapy for refractory, severe OCD causing SI/severe depression in several cases I've had - but I definitely would use it should it be appropriate. An antipsychotic makes much more sense to me than memantine given that a majority of severe OCD cases have had (or have) concomitant MDD (I think the research estimates up to 60%?), and we know abilify augmentation does work for depression.

I am familiar with the literature and also need to say that misdiagnosis of psychosis as OCD is a frequent phenomenon in people who are not OCD experts. Given this, I think the data supporting antipsychotic augmentation in OCD is flawed due to this phenomenon (psychotic patients are called OCD, and they respond to the antipsychotic thus supporting the incorrect hypothesis).

Given that, it makes sense for providers not familiar with OCD who have not seen the expected 40-60% decrease in symptoms to trial augmentation with an antipsychotic. If the patient responds robustly, they should consider the possibility that what they thought was OCD was actually psychosis. If they don't respond, then discontinue the antipsychotic and escalate the pharma treatment for OCD.

I appreciate your thoughts, Mistafab! The literature doesnt seem to suggest that clomipramine is much better than very high dose SSRI these days. Have you seen a clear difference in response with eg sertraline 400mg daily vs clomipramine? Also, which MAO-I do you tend to use for this? I do wonder at times if it is even possible to distinguish clinically between the very beginning of the psychotic spectrum or OCD. Also, for all we know, they are composed of some of the same "building blocks", which I have seen some OCD experts muse about.

 

[Psychferlyfe3000]

My patient in particular developed OCD after using a psychedelic. They perseverate on sexual impropriety, but dont have any other obsessional content or compulsions.

 

[mistafab]

My patient in particular developed OCD after using a psychedelic. They perseverate on sexual impropriety, but dont have any other obsessional content or compulsions.

Do they actually have compulsions? Are these actually obsessions? I have seen folks who become preoccupied with sexual content and display sexual impropriety from MDMA and LSD. It may be a permanent effect if that's what you're seeing, and not actually OCD.

Is it ego-syntonic? Does it cause distress to the patient (as opposed to just causing consequences)?

 

[Psychferlyfe3000]

Do they actually have compulsions? Are these actually obsessions? I have seen folks who become preoccupied with sexual content and display sexual impropriety from MDMA and LSD. It may be a permanent effect if that's what you're seeing, and not actually OCD.

Is it ego-syntonic? Does it cause distress to the patient (as opposed to just causing consequences)?

The compulsion is basically avoiding people that they feel attracted to to avoid feelings of shame or embarrassment. It is definitely ego-dystonic. Yes, highly distressing to the patient.

 

[mistafab]

I appreciate your thoughts, Mistafab! The literature doesnt seem to suggest that clomipramine is much better than very high dose SSRI these days. Have you seen a clear difference in response with eg sertraline 400mg daily vs clomipramine? Also, which MAO-I do you tend to use for this? I do wonder at times if it is even possible to distinguish clinically between the very beginning of the psychotic spectrum or OCD. Also, for all we know, they are composed of some of the same "building blocks", which I have seen some OCD experts muse about.

I think the problem is that the literature is the research was not powered to evaluate differences in efficacy between SSRIs and clomipramine. At best, we can say they they are "as good." There is a paucity in good head to head data which is common in this area. I think there was a single trial looking at a direct head to head comparison of clomipramine and paroxetine, but I don't recall any other data.

As is often the case with these types of trials, they use endpoints (like 12 weeks, for example), which would favor "effect" from medications that reach appropriate dosing faster. I.e. prozac would be at a working dose at week 1, but TCA wouldn't get up to working dose until week 3 - the 12 week time point thus would be 'equal' but clomipramine would have only had 9 weeks to work, and prozac had 11 for example. This 'effect lag' is the same reason why people feel the STAR*D trial make MAOis look less effective than we see in clinical practice - they had less than half the time to work just as well.

I have not found 400 mg sertraline significantly superior to 200-300 mg of sertraline. I have seen major changes in OCD results from inappropriate doses (25-150 mg, for example) up to appropriate doses (200 or more). I have found clomipramine to be superior to high dose monotherapy with SSRIs.

 

[tr]

Wow 400 mg sertraline equivalent? I've never tried going that high. I dip to another SSRI or clomipramine by 200-250. @clausewitz2 do you often see improvement show up in that supra-FDA range?

Memantine I have seen/used occasionally and it's been effective but I don't have the opportunity to use it often bc I see primarily reproductive and it has no pregnancy safety data.

NAC I use a lot esp for skin picking, it seems kind of binary where it works great about half the time and does absolutely nothing for the other half.

 

[clausewitz2]

Wow 400 mg sertraline equivalent? I've never tried going that high. I dip to another SSRI or clomipramine by 200-250. @clausewitz2 do you often see improvement show up in that supra-FDA range?

Memantine I have seen/used occasionally and it's been effective but I don't have the opportunity to use it often bc I see primarily reproductive and it has no pregnancy safety data.

NAC I use a lot esp for skin picking, it seems kind of binary where it works great about half the time and does absolutely nothing for the other half.

400 mg sertraline is a very typical move for me. The OCD expert I trained with tended to very aggressively up-titrate people from 200 to 400 mg after a trial of 200 (like, over the space of two weeks). He felt there was unlikely to be improvement in the middle of this range and so it was best to get to the maximally effective dose as quickly as possible. Perhaps consistent with @mistafab I have seen more of my patients get some benefit from 300 mg (often because we had to slow down the titration for a prolonged period of time due to side effects) so I am increasingly actually trying 300 deliberately before moving to 400 more often.

I continue to be unimpressed by memantine, I can think of only 2-3 cases where I am convinced it did anything positive.

Re:clomipramine, it is often enough clearly superior to the response to SSRIs that if there is data failing to show superiority, so much worse for the data. Sometimes even relatively small (~50 mg) doses of it produce surprising gains, especially when it serves to "unstick" patients who have plateau'd in E/RP. More than one person I work with sing the praises of clomipramine and want to stay on it at all costs while also experiencing fairly strong versions of the expected side effects that do genuinely bother them. That said, my clomipramine success stories tend to be closer to the 250 end of the OCD dosing range.


Neuroleptic-induced obsessive compulsive symptoms are indeed a thing, incidence appears to be related to how similar the antipsychotic in question is to clozapine (so clozapine #1, olanzapine much lower #2, everything else a distant #3). It will be interesting to see if this is observable when we have better long-term data about Cobenfy.

The MAO-I that has specific evidence for OCD is phenelzine. Definitely an option but a hard sell, many people with OCD get extremely nervous when you start talking about potentially lethal side effects. And I say this as someone who uses MAOIs significantly more than I think the average psychiatrist.

 

[clozareal]

Wow 400 mg sertraline equivalent? I've never tried going that high. I dip to another SSRI or clomipramine by 200-250. @clausewitz2 do you often see improvement show up in that supra-FDA range?

Memantine I have seen/used occasionally and it's been effective but I don't have the opportunity to use it often bc I see primarily reproductive and it has no pregnancy safety data.

NAC I use a lot esp for skin picking, it seems kind of binary where it works great about half the time and does absolutely nothing for the other half.

Off-label higher doses of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder: Safety and tolerability - PubMed

OLHD-SRIs appear to be safe and well tolerated in OCD patients in SED ≤ 650 mg/day doses and the side-effects did not differ between the three dosing groups.

pubmed.ncbi.nlm.nih.gov

Doses have been used up to 650mg sertraline, 80mg escitalopram, 120mg fluoxetine, 600mg fluvoxamine.

 

[Psychferlyfe3000]

Off-label higher doses of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder: Safety and tolerability - PubMed

OLHD-SRIs appear to be safe and well tolerated in OCD patients in SED ≤ 650 mg/day doses and the side-effects did not differ between the three dosing groups.

pubmed.ncbi.nlm.nih.gov

Doses have been used up to 650mg sertraline, 80mg escitalopram, 120mg fluoxetine, 600mg fluvoxamine.

Oh wow...Presumably with some form of EKG monitoring? Also, I wonder if the sexual dysfunction increases linearly or if it plateaus at some point.

 

[Psychferlyfe3000]

Off-label higher doses of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder: Safety and tolerability - PubMed

OLHD-SRIs appear to be safe and well tolerated in OCD patients in SED ≤ 650 mg/day doses and the side-effects did not differ between the three dosing groups.

pubmed.ncbi.nlm.nih.gov

Doses have been used up to 650mg sertraline, 80mg escitalopram, 120mg fluoxetine, 600mg fluvoxamine.

400 mg sertraline is a very typical move for me. The OCD expert I trained with tended to very aggressively up-titrate people from 200 to 400 mg after a trial of 200 (like, over the space of two weeks). He felt there was unlikely to be improvement in the middle of this range and so it was best to get to the maximally effective dose as quickly as possible. Perhaps consistent with @mistafab I have seen more of my patients get some benefit from 300 mg (often because we had to slow down the titration for a prolonged period of time due to side effects) so I am increasingly actually trying 300 deliberately before moving to 400 more often.

I continue to be unimpressed by memantine, I can think of only 2-3 cases where I am convinced it did anything positive.

Re:clomipramine, it is often enough clearly superior to the response to SSRIs that if there is data failing to show superiority, so much worse for the data. Sometimes even relatively small (~50 mg) doses of it produce surprising gains, especially when it serves to "unstick" patients who have plateau'd in E/RP. More than one person I work with sing the praises of clomipramine and want to stay on it at all costs while also experiencing fairly strong versions of the expected side effects that do genuinely bother them. That said, my clomipramine success stories tend to be closer to the 250 end of the OCD dosing range.


Neuroleptic-induced obsessive compulsive symptoms are indeed a thing, incidence appears to be related to how similar the antipsychotic in question is to clozapine (so clozapine #1, olanzapine much lower #2, everything else a distant #3). It will be interesting to see if this is observable when we have better long-term data about Cobenfy.

The MAO-I that has specific evidence for OCD is phenelzine. Definitely an option but a hard sell, many people with OCD get extremely nervous when you start talking about potentially lethal side effects. And I say this as someone who uses MAOIs significantly more than I think the average psychiatrist.

Interesting re: clomipramine. One theory as to why it may be superior is the addition of NET inhibition. It does make me wonder if atomoxetine + high-dose SSRI would be as effective but without the cholinergic side effects.

 

[Merovinge]

Interesting re: clomipramine. One theory as to why it may be superior is the addition of NET inhibition. It does make me wonder if atomoxetine + high-dose SSRI would be as effective but without the cholinergic side effects.

I don't have any sources to attribute this claim to, but I believe there's more to clomipramine than simply NET. It's not like high dosage venlafaxine or duloxetine makes waves in OCD. Certainly not an OCD expert, but I routinely find SSRIs underdosed in adolescents and I believe clomipramine is held off way too long (people treat it like it's starting clozapine...).

 

[aim-agm]

Interesting re: clomipramine. One theory as to why it may be superior is the addition of NET inhibition. It does make me wonder if atomoxetine + high-dose SSRI would be as effective but without the cholinergic side effects.

I believe I've had people on an SRI +atomoxetine or desipramine that I later switched to clomipramine for additional benefit, although I can't recall examples offhand.

I think in OCD you would want to use desipramine rather than atomoxetine - the former has more NET inhibition mg for mg than the latter, and atomoxetine is not studied above 100 mg while desipramine can go up to 300 mg.

 

[Stagg737]

Interesting re: clomipramine. One theory as to why it may be superior is the addition of NET inhibition. It does make me wonder if atomoxetine + high-dose SSRI would be as effective but without the cholinergic side effects.

I don't have any sources to attribute this claim to, but I believe there's more to clomipramine than simply NET. It's not like high dosage venlafaxine or duloxetine makes waves in OCD. Certainly not an OCD expert, but I routinely find SSRIs underdosed in adolescents and I believe clomipramine is held off way too long (people treat it like it's starting clozapine...).

Imo extra benefits from clomipramine vs SSRIs more likely comes from mechanisms other than increase in NE activity. Clomipramine is also a fairly strong alpha-1 and H1 antagonist and has a fair amount of D3 antagonism. Idk if it's one or those or some combination of that + the serotonergic effects. Even so, pharmacologic treatment is almost never "curative" and therapy is essential, which should say something about the underlying etiology of OCD.

Re:clomipramine, it is often enough clearly superior to the response to SSRIs that if there is data failing to show superiority, so much worse for the data. Sometimes even relatively small (~50 mg) doses of it produce surprising gains, especially when it serves to "unstick" patients who have plateau'd in E/RP. More than one person I work with sing the praises of clomipramine and want to stay on it at all costs while also experiencing fairly strong versions of the expected side effects that do genuinely bother them. That said, my clomipramine success stories tend to be closer to the 250 end of the OCD dosing range.

Want to add a N=1 to the bolded. I have a colleague who frequently augments SSRIs with relatively low doses of clomipramine. His anecdata is that patients do tend to get some of the benefits of high-dose clomipramine (likely from the additive/synergistic serotonergic effects of the combo) with much fewer side effects that typically come from the higher doses of clomipramine. I've only done this once or twice but those people have felt it worked really well for them. Seeing how well it's worked I've been keeping it in mind a lot more for patients on or slightly above the FDA max doses for SSRIs who still have significant symptoms as opposed to just cross-tapering to clomipramine.

 

[Psychferlyfe3000]

When you say low doses, what doses are you referring to?

 

[Stagg737]

When you say low doses, what doses are you referring to?

If you're asking me, then typically max dose SSRI + clomipramine 25-50mg. Maybe a touch higher, but just having that extra 50mg of clomipramine seems to be fantastic for some patients.