Lamictal augmentation for unipolar depression

[Stagg737]

What are your top 7 ssri augmentation agents

Kind of weird to me that we're discussing this as if augmentation is the preferred method as I generally like to avoid polypharmacy as much as possible. If we're talking depression I will often switch to another agent like SNRI, TCA, or others before augmenting if there's not an adequate response or patients have notable side effects.

For actual depression augmentation: therapy, wellbutrin, mirtazapine, trazodone (I also like nefazodone, but don't use it much), lithium/abilify/other SGA (preferably a partial agonist). If mild to moderate depression I also strongly emphasize regular physical activity. After that it's a crap shoot and we can throw in lamotrigine, high doses of buspar, thyroid hormone, low dose stimulants/modafinil, phototherapy, or even some supplements/vitamins (vit d, n-acetylcysteine, omega-3's, etc). I wish amisulpride was available in the US, as that would be a potential option in a lot of cases (depression or otherwise).

Like most other psych conditions, I may choose to utilize some options before others if there's other indications for one over another and trying to boil down psychiatry to some kind of cook-book algorithm based on a DSM diagnosis is only helpful for relatively basic cases where formulation isn't really all that necessary. By the time we're getting to "treatment resistant depression" (I mean real TRD, not the insurance definition of 'has failed 3 meds') it gets too complex to stick to a script of medications for longer-term treatment. I also prefer options that have stronger evidence of decent effect sizes than options with weaker evidence for most patients.

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[TheRightMedication]

Can we claim you for team lamictal-is-a-second-rate-augmentation-agent then?

Your point is well taken about using things like TCA's before getting to augmentation, though.

 

[tr]

Kind of weird to me that we're discussing this as if augmentation is the preferred method as I generally like to avoid polypharmacy as much as possible. If we're talking depression I will often switch to another agent like SNRI, TCA, or others before augmenting if there's not an adequate response or patients have notable side effects.

This. My main takeaway from Star*D was that generally, switch is as effective as augment, so you might as well avoid the pileup of side effects and potential interactions by d/c'ing the drug that didn't work before moving on.

After three failed trials of individual medications, rather than blindly adding another med I usually get a Genomind report and refer for TMS.

 

[TheRightMedication]

After three failed trials of individual medications, rather than blindly adding another med I usually get a Genomind report and refer for TMS.

Wait what?

Edit- I mean, why TMS over ECT, and what's a genetic profile going to help with?

 

[tr]

Wait what?

Edit- I mean, why TMS over ECT, and what's a genetic profile going to help with?

Genetic profiling lets me know if people are rapid metabolizers who need above usual dosing range, or if they are SLC6A4 s/s who have poor response to meds that work on the serotonin transporter, or if they have MTHFR mutations and would benefit from L-methylfolate.

TMS because it's more accessible than ECT and with a much better side effect profile. Efficacy not quite as good as ECT but still fine, similar to meds anyway, and accessibility and tolerability way better.

 

[hamstergang]

or if they have MTHFR mutations and would benefit from L-methylfolate.

I was with you up until this point. I believe this has been discussed before but I forget how the conversation went. My understanding is that the evidence for l-methylfolate antidepressant augmentation showed good response independent of MTHFR alleles. Therefore, it should be an option regardless of what the genes show.

 

[littlefred]

Genetic profiling lets me know if people are rapid metabolizers who need above usual dosing range, or if they are SLC6A4 s/s who have poor response to meds that work on the serotonin transporter, or if they have MTHFR mutations and would benefit from L-methylfolate.

TMS because it's more accessible than ECT and with a much better side effect profile. Efficacy not quite as good as ECT but still fine, similar to meds anyway, and accessibility and tolerability way better.

Wouldn't you make the clinical call to increase the dose with regards to how the patient is responding to the treatment?

Also L-methylfolate is OTC, why not recommend patients to take it without the test? I also recommend patients taking Vitamin D3 and other supplements if they are inclined to take them.

 

[Stagg737]

Can we claim you for team lamictal-is-a-second-rate-augmentation-agent then?

Your point is well taken about using things like TCA's before getting to augmentation, though.

This. My main takeaway from Star*D was that generally, switch is as effective as augment, so you might as well avoid the pileup of side effects and potential interactions by d/c'ing the drug that didn't work before moving on.

Lol, yep. It's a viable option for the right patients, but I generally don't use it for unipolar depression augmentation unless there's another indication for it. I've also found that stopping medications and limiting polypharmacy is as effective for some patients as starting more meds and any time I'm seeing 3+ meds for more than one indication or significant crossover with multiple meds, I'm talking to my patients about simplifying. Imo, the less meds the better.

After three failed trials of individual medications, rather than blindly adding another med I usually get a Genomind report and refer for TMS.

This is where we'll disagree. The idea that failing 3 meds is TRD/warrants more thorough medical testing/follow-up is premature imo. If we know the receptor profile of meds and how the patient reacted, we should be able to get a decent idea of what's going on at a more molecular/metabolic level without needing testing. I'm not against genetic testing in the right situation, but I wouldn't pull the trigger that quickly.

 

[tr]

I was with you up until this point. I believe this has been discussed before but I forget how the conversation went. My understanding is that the evidence for l-methylfolate antidepressant augmentation showed good response independent of MTHFR alleles. Therefore, it should be an option regardless of what the genes show.

Um no? I haven't seen that? Just looked quickly and most of what I'm finding indicates clearly better response to Deplin in groups with alternate MTHFR alleles. Which is very logical.

Effect of Adjunctive l-Methylfolate 15 mg Among Inadequate Responders to SSRIs in Depressed Patients Who Were Stratified by Biomarker Levels and Genotype: Results From a Randomized Clinical Trial

Article Abstract Objective: Specific genetic or biological markers may predict inadequate response to therapy for major depressive disorder (MDD). The objective of the current post hoc analysis was to evaluate the effect of specific biological and genetic markers on the antidepressant efficacy...

www.psychiatrist.com

P255. L-Methylfolate Supplementation in Patients With MTHFR Polymorphisms in Major Depressive Disorder and Treatment Resistant Depression

Major depressive disorder is a debilitating disorder affecting nearly 280 million people worldwide (∼3.8% of the population). While there are numerous treatments available for the disease, approximately 30 – 40% of patients are unresponsive to treatment and deemed treatment resistant. Over the...

www.biologicalpsychiatryjournal.com

Effect of L-methylfolate on Depressive Symptoms in Patients with MTHFR Mutations (P3.9-057)

Objective: This study aims to determine the efficacy of L-methylfolate for treatment of depressive symptoms and the roles of C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) mutations. Background: Folate deficiency is implicated as a risk factor for MDD and is also associated with...

n.neurology.org

Also, unimpressive results in a random group of nonresponders without genetic testing:

https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2012.11071114

 

[tr]

Wouldn't you make the clinical call to increase the dose with regards to how the patient is responding to the treatment?

Also L-methylfolate is OTC, why not recommend patients to take it without the test? I also recommend patients taking Vitamin D3 and other supplements if they are inclined to take them.

Definitely not. I usually stick to FDA maximum doses unless treating OCD or have evidence for rapid metabolism.

I do recommend D3 often but only after blood test, for people with demonstrated deficiency.

Random supplementation of D3 for depression without establishing deficiency has had disappointing results in clinical trials, and tarnished the literature for quite a while.

Throwing random micronutrients at people without regard to their individual needs is pretty low yield IMO.

 

[littlefred]

Definitely not. I usually stick to FDA maximum doses unless treating OCD or have evidence for rapid metabolism.

I do recommend D3 often but only after blood test, for people with demonstrated deficiency.

Random supplementation of D3 for depression without establishing deficiency has had disappointing results in clinical trials, and tarnished the literature for quite a while.

Throwing random micronutrients at people without regard to their individual needs is pretty low yield IMO.

Fair enough, you should've made your point on the original post about considering going above FDA recommended doses and the need for genetic test to confirm that clinical decision. OTC supplements are not regulated with the same rigors as FDA meds (which are surprisingly a joke if you look into how meds get FDA indication, but that's beside the point) so endorsing them isn't doing any harm.

 

[TheRightMedication]

Genetic profiling lets me know if people are rapid metabolizers who need above usual dosing range, or if they are SLC6A4 s/s who have poor response to meds that work on the serotonin transporter, or if they have MTHFR mutations and would benefit from L-methylfolate.

TMS because it's more accessible than ECT and with a much better side effect profile. Efficacy not quite as good as ECT but still fine, similar to meds anyway, and accessibility and tolerability way better.

I strongly agree with the sentiment in other posts about titrating meds to response and tolerabity and not cytochrome expression. I suppose some of the other tests could be helpful.

Until there's more SAINT style results putting points on the board, I'm against TMS when it's used instead of ECT.

I'm due for a review on the supplements, so thanks for the article links.

 

[hamstergang]

Um no? I haven't seen that? Just looked quickly and most of what I'm finding indicates clearly better response to Deplin in groups with alternate MTHFR alleles. Which is very logical.

Effect of Adjunctive l-Methylfolate 15 mg Among Inadequate Responders to SSRIs in Depressed Patients Who Were Stratified by Biomarker Levels and Genotype: Results From a Randomized Clinical Trial

Article Abstract Objective: Specific genetic or biological markers may predict inadequate response to therapy for major depressive disorder (MDD). The objective of the current post hoc analysis was to evaluate the effect of specific biological and genetic markers on the antidepressant efficacy...

www.psychiatrist.com

P255. L-Methylfolate Supplementation in Patients With MTHFR Polymorphisms in Major Depressive Disorder and Treatment Resistant Depression

Major depressive disorder is a debilitating disorder affecting nearly 280 million people worldwide (∼3.8% of the population). While there are numerous treatments available for the disease, approximately 30 – 40% of patients are unresponsive to treatment and deemed treatment resistant. Over the...

www.biologicalpsychiatryjournal.com

Effect of L-methylfolate on Depressive Symptoms in Patients with MTHFR Mutations (P3.9-057)

Objective: This study aims to determine the efficacy of L-methylfolate for treatment of depressive symptoms and the roles of C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) mutations. Background: Folate deficiency is implicated as a risk factor for MDD and is also associated with...

n.neurology.org

Also, unimpressive results in a random group of nonresponders without genetic testing:

https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2012.11071114

I really want to look more into this as i find it very interesting but have to see a patient now. I was able to find the full article of your first link, but as I'm rushing I could only skim it. While it does find more benefits of l-methylfolate with certain genes and biomarkers, it says:
"Pooled mean change from baseline on the HDRS-28 with l-methylfolate versus placebo was ...not significantly greater for the MTHFR 677 CT/TT or MTHFR 1298 AC/CC genotypes compared to the respective homozygous dominant genotypes."

 

[ObsequiousAplomb]

Genetic profiling lets me know if people are rapid metabolizers who need above usual dosing range, or if they are SLC6A4 s/s who have poor response to meds that work on the serotonin transporter, or if they have MTHFR mutations and would benefit from L-methylfolate.

TMS because it's more accessible than ECT and with a much better side effect profile. Efficacy not quite as good as ECT but still fine, similar to meds anyway, and accessibility and tolerability way better.

I thought most of the meta analyses showed that ECT and TMS had similar adverse effect profiles.

 

[tr]

I thought most of the meta analyses showed that ECT and TMS had similar adverse effect profiles.

What the heck? What kind of literature are you guys reading?

The first result on a Google Scholar search for 'ECT vs TMS acceptability tolerability" is the following meta-analysis:

Comparative efficacy and acceptability of electroconvulsive therapy versus repetitive transcranial magnetic stimulation for major depression: A systematic review and multiple-treatments meta-analysis

The effects of electroconvulsive therapy (ECT) and bilateral, left prefrontal, and right prefrontal repetitive transcranial magnetic stimulation (rTMS…

www.sciencedirect.com

"ECT was the most efficacious, but least tolerated, treatment, while R-rTMS was the best tolerated treatment for MDD. B-rTMS appears to have the most favorable balance between efficacy and acceptability."

Also, have you ever seen anyone with near-global memory loss from TMS?? The worst they ever get is like a minor headache.

 

[tr]

I strongly agree with the sentiment in other posts about titrating meds to response and tolerabity and not cytochrome expression. I suppose some of the other tests could be helpful.

OK but where do you draw the line? How far over the FDA max are you comfortable going if someone is tolerating the medication but seeing no benefit? I feel like at some point you have to call it that the med is not working. I call it at FDA max for most patients. If you feel comfortable with some arbitrarily higher threshold, OK. The point is once you've titrated three meds to their max doses and they haven't worked, it's useful to start poking around to figure out why that might be.

This is where we'll disagree. The idea that failing 3 meds is TRD/warrants more thorough medical testing/follow-up is premature imo. If we know the receptor profile of meds and how the patient reacted, we should be able to get a decent idea of what's going on at a more molecular/metabolic level without needing testing. I'm not against genetic testing in the right situation, but I wouldn't pull the trigger that quickly.

To some extent, but by the time someone has tried three meds, I feel like they are getting kind of frustrated and I don't really feel like putting them through multiple additional blind trials. If they're SLC6A4 short/short, I'd rather know that up front since a lot of the available options work on that same receptor.

Until there's more SAINT style results putting points on the board, I'm against TMS when it's used instead of ECT.

I'm due for a review on the supplements, so thanks for the article links.

What do you mean 'instead of'? TMS and ECT seem to me to be useful for totally different populations. I wouldn't really consider them as alternatives to each other for the same patient.

The risk profile of ECT is such that to me, I would only recommend it for people with severe, treatment-resistant depression, meaning at least one hospitalization and failure of multiple medications.

TMS is very well tolerated. It works a fair amount of the time. If it doesn't work, you haven't lost much. I feel very comfortable referring regular, moderate-severity outpatients with depression or OCD for TMS.

 

[tr]

I really want to look more into this as i find it very interesting but have to see a patient now. I was able to find the full article of your first link, but as I'm rushing I could only skim it. While it does find more benefits of l-methylfolate with certain genes and biomarkers, it says:
"Pooled mean change from baseline on the HDRS-28 with l-methylfolate versus placebo was ...not significantly greater for the MTHFR 677 CT/TT or MTHFR 1298 AC/CC genotypes compared to the respective homozygous dominant genotypes."

Here are the results from the Papakostas paper. Response rate looks better in individuals with identified MTHFR susceptibility alleles. Results for those without MTHFR susceptibility alleles ("normal") look disappointing. Why would individuals with normal folate metabolism require L-methylfolate? All it does is bypass the step that people with MTHFR variants can't do for themselves.

 

[clozareal]

Interestingly, I just did an intake recently on a teen who is on an SSRI + lamotrigine combination and is in remission from GAD, MDD, and panic disorder. Didn't get into remission from depression until starting lamotrigine as augmentation agent.

 

[hamstergang]

Here are the results from the Papakostas paper. Response rate looks better in individuals with identified MTHFR susceptibility alleles. Results for those without MTHFR susceptibility alleles ("normal") look disappointing.

Well the graph does look nice, but the statistics suggest we shouldn't read so much into that. I suspect that this is the paper I've seen referenced before which led to my conclusion that the alleles don't predict response (whereas obesity does, for some reason). That being said, your other 2 papers do support your position in a convincing way.

With the question of whether it works aside, I want to address the question of why it works:

Why would individuals with normal folate metabolism require L-methylfolate? All it does is bypass the step that people with MTHFR variants can't do for themselves.

Why would individual with normal serotonin activity require SSRIs? It could have been the case that l-methylfolate was doing something more, or that a reduction in even normal homocysteine levels was beneficial. It's not clear that the mild elevations in homocysteine associated with the MTHFR polymorphisms are clinically significant in many cases, so we can't just assume that l-methylfolate supplementation for those patients is working through correcting that problem.

 

[tr]

Well the graph does look nice, but the statistics suggest we shouldn't read so much into that. I suspect that this is the paper I've seen referenced before which led to my conclusion that the alleles don't predict response (whereas obesity does, for some reason). That being said, your other 2 papers do support your position in a convincing way.

Look, there are like 100+ known allele variants in the folate metabolism pathway. Some of them have functional consequences, some of them don't. The paper suggests that the MTHFR 677 SNP isn't as consequential as some of the other ones. That doesn't mean that the whole concept of targeted L-methylfolate supplementation for people who actually do have consequential mutations is bunk. Actually most of the variants they studied look pretty darn consequential to me.

Before they added the MTHFR screens to the Genomind panel I used to check homocysteine as a more functional overall readout for errors in folate metabolism, vs trying to cover every individual MTHFR SNP that might or might not be functionally consequential. I do still try to get homocysteine levels before I start people on Deplin, but often people are just bad about going to the lab again so it's convenient that there's some info included in the Genomind panel together with the other information that comes out of that.

With the question of whether it works aside, I want to address the question of why it works:

Why would individual with normal serotonin activity require SSRIs?

Uh, because the concept of 'normal serotonin activity' is neurobiologically meaningless and the mechanism by which SSRIs work isn't specific to their serotonergic function???

Certainly there is no logical parallel with micronutrient repletion.

It could have been the case that l-methylfolate was doing something more, or that a reduction in even normal homocysteine levels was beneficial. It's not clear that the mild elevations in homocysteine associated with the MTHFR polymorphisms are clinically significant in many cases, so we can't just assume that l-methylfolate supplementation for those patients is working through correcting that problem.

What do you mean 'the mild elevations in homocysteine aren't clinically significant'? Homocysteine isn't the cause of the problem, it's the pileup that you get that can't go back to methionine when MTHFR isn't working. It's just a signal of malfunctioning folate metabolism.

 

[hamstergang]

What do you mean 'the mild elevations in homocysteine aren't clinically significant'? Homocysteine isn't the cause of the problem, it's the pileup that you get that can't go back to methionine when MTHFR isn't working. It's just a signal of malfunctioning folate metabolism.

But if homocysteine isn't elevated, then do you really have a problem with methionine? Isn't that why you were checking homocysteine levels? By the way, I do think that's a more reasonable test since it matters more than the genes themselves, though I understand your point about getting people to follow through with lab work.

 

[aim-agm]

OK but where do you draw the line? How far over the FDA max are you comfortable going if someone is tolerating the medication but seeing no benefit?

My understanding is that for most medications uptitration is most appropriate when there is partial benefit at lower doses, but unlikely to be effective if there is no response at reasonable therapuetic dose. So if there is no benefit I might stop the trial well before getting to FDA max.

If there is benefit, how high I'd go mostly comes down to risk. Medications with significant AE not related to therapeutic MOA (e.g. bupropion, venfalaxine, citalopram, etc.) I'd stick strictly to FDA max. Similar for medications with potential for tolerance/dependence (e.g. amphetamines). However, for some medications (e.g. sertraline, buspirone) if they are well tolerated then the line might be very high indeed so long as each uptitration is associated with increased efficacy.

 

[aim-agm]

But if homocysteine isn't elevated, then do you really have a problem with methionine? Isn't that why you were checking homocysteine levels? By the way, I do think that's a more reasonable test since it matters more than the genes themselves, though I understand your point about getting people to follow through with lab work.

Before they added the MTHFR screens to the Genomind panel I used to check homocysteine as a more functional overall readout for errors in folate metabolism, vs trying to cover every individual MTHFR SNP that might or might not be functionally consequential. I do still try to get homocysteine levels before I start people on Deplin, but often people are just bad about going to the lab again so it's convenient that there's some info included in the Genomind panel together with the other information that comes out of that.

Has there been a study of homocysteine levels pre and post treatment in patients with depression who respond to L-methylfolate?

Also, what comes to mind is that some patients with RLS with normal iron studies, CBCs, etc. still respond to iron supplementation because the iron deficiency is isolated to CNS. So it's certainly not unheard of for laboratory workup to not reflect underlying pathophysiology well because the human body is complicated.

 

[tr]

Has there been a study of homocysteine levels pre and post treatment in patients with depression who respond to L-methylfolate?

Also, what comes to mind is that some patients with RLS with normal iron studies, CBCs, etc. still respond to iron supplementation because the iron deficiency is isolated to CNS. So it's certainly not unheard of for laboratory workup to not reflect underlying pathophysiology well because the human body is complicated.

here ya go

Correlation of Clinical Response With Homocysteine Reduction During Therapy With Reduced B Vitamins in Patients With MDD Who Are Positive for MTHFR C677T or A1298C Polymorphism: A Randomized, Double-Blind, Placebo-Controlled Study

Article AbstractObjective: This study was designed to evaluate the efficacy and safety of reduced B vitamins as monotherapy in adults with major depressive disorder (MDD) who were also positive for at least 1 methylenetetrahydrofolate reductase (MTHFR) polymorphism associated with depression and...

www.psychiatrist.com

n

 

[clozareal]

Look, there are like 100+ known allele variants in the folate metabolism pathway. Some of them have functional consequences, some of them don't. The paper suggests that the MTHFR 677 SNP isn't as consequential as some of the other ones. That doesn't mean that the whole concept of targeted L-methylfolate supplementation for people who actually do have consequential mutations is bunk. Actually most of the variants they studied look pretty darn consequential to me.

Before they added the MTHFR screens to the Genomind panel I used to check homocysteine as a more functional overall readout for errors in folate metabolism, vs trying to cover every individual MTHFR SNP that might or might not be functionally consequential. I do still try to get homocysteine levels before I start people on Deplin, but often people are just bad about going to the lab again so it's convenient that there's some info included in the Genomind panel together with the other information that comes out of that.



Uh, because the concept of 'normal serotonin activity' is neurobiologically meaningless and the mechanism by which SSRIs work isn't specific to their serotonergic function???

Certainly there is no logical parallel with micronutrient repletion.


What do you mean 'the mild elevations in homocysteine aren't clinically significant'? Homocysteine isn't the cause of the problem, it's the pileup that you get that can't go back to methionine when MTHFR isn't working. It's just a signal of malfunctioning folate metabolism.

View attachment 365725

This is an interesting chart since SAMe is one of the augmentation agents that is used for depression.

 

[tr]

This is an interesting chart since SAMe is one of the augmentation agents that is used for depression.

Yeah and I think we have a ways to go in figuring out which patients are likely to be helped by SAM-e. There's probably some subset of people with variations in their methionine cycle pathways that specifically benefits, just like for L-methylfolate.

 

[Merovinge]

Interestingly, I just did an intake recently on a teen who is on an SSRI + lamotrigine combination and is in remission from GAD, MDD, and panic disorder. Didn't get into remission from depression until starting lamotrigine as augmentation agent.

Or whatever else was happening in their life when Lamictal was added, which frankly is more likely to be responsible than low efficacy adjunctive agents like this. Now if that change was finding a new doc who they liked and felt was prescribing a medication that was helping them, you could do a whole lot worse than carefully titrated Lamictal.

I actually liked it in OP practice when I got these cases because if Lamictal was helping, it was a slam dunk to keep going and if it wasn't helping, people were usually pretty happy to try something else, particularly if it had more efficacy.

 

[clozareal]

Or whatever else was happening in their life when Lamictal was added, which frankly is more likely to be responsible than low efficacy adjunctive agents like this. Now if that change was finding a new doc who they liked and felt was prescribing a medication that was helping them, you could do a whole lot worse than carefully titrated Lamictal.

I actually liked it in OP practice when I got these cases because if Lamictal was helping, it was a slam dunk to keep going and if it wasn't helping, people were usually pretty happy to try something else, particularly if it had more efficacy.

It could be but they were with the same psychiatrist for several years. When they tried to titrate off lamictal after 6 months of remission, they became more depressed so went back up and now scared to go back down for fear of relapse.

 

[ObsequiousAplomb]

What the heck? What kind of literature are you guys reading?

The first result on a Google Scholar search for 'ECT vs TMS acceptability tolerability" is the following meta-analysis:

Comparative efficacy and acceptability of electroconvulsive therapy versus repetitive transcranial magnetic stimulation for major depression: A systematic review and multiple-treatments meta-analysis

The effects of electroconvulsive therapy (ECT) and bilateral, left prefrontal, and right prefrontal repetitive transcranial magnetic stimulation (rTMS…

www.sciencedirect.com

"ECT was the most efficacious, but least tolerated, treatment, while R-rTMS was the best tolerated treatment for MDD. B-rTMS appears to have the most favorable balance between efficacy and acceptability."

Also, have you ever seen anyone with near-global memory loss from TMS?? The worst they ever get is like a minor headache.

Quoting that exact study's abstract (because it is in fact the one I was referencing with my comment):

"ECT was the most efficacious treatment with the cumulative probabilities of being the most efficacious treatment being: ECT (65%), B-rTMS (25%), R-rTMS (8%), and L-rTMS (2%). R-rTMS was the best-tolerated treatment with the cumulative probabilities of being the best-tolerated treatment being: R-rTMS (52%), B-rTMS (17%), L-rTMS (16%), and ECT (14%). Coherence analysis detected no statistically significant incoherence in any comparisons of direct with indirect evidence for the response rate and drop-out rate."

17%, 16%, and 14% are almost exactly the same number. The R-rTMS 52% is what's bringing the TMS average up so much. Considering R-rTMS was only 8% likely to be the most efficacious, I'd say that you really ought to be comparing the B-rTMS and ECT. Ineffective treatments with minimal adverse effect profiles are not what I refer patients for.

Permanent near-global memory loss from ECT is incredibly rare. I've never seen near-global memory loss from ECT that wasn't clearly malingered.

 

[tr]

Permanent memory loss from ECT is incredibly rare. I've never seen near-global memory loss from ECT that wasn't clearly malingered.

OK well reasonable individuals may differ in opinion. The amount of memory loss and cognitive impairment I observed from ECT has led me to consider it a treatment of last resort. (Keep in mind that the full extent of those side effects may not be apparent until near the completion of the course of therapy, so they would not necessarily be reflected in the dropout rates.)

 

[splik]

Permanent memory loss from ECT is incredibly rare. I've never seen near-global memory loss from ECT that wasn't clearly malingered.

Permanent autobiographical memory loss around the time of treatment is extremely common. Persistent Global memory loss from ECT isn't a thing however.

 

[tr]

Permanent autobiographical memory loss around the time of treatment is extremely common. Persistent Global memory loss from ECT isn't a thing however.

Fine, I admit that statement was a rhetorical excess. Nonetheless, were I in the patient's shoes, I wouldn't personally want to have ECT unless I had absolutely exhausted all of the other available options. TMS I would have no qualms about other than the time investment.

 

[tr]

Ineffective treatments with minimal adverse effect profiles are not what I refer patients for.

Also I have to say that I am surprised the general perception of TMS efficacy is so poor. That is not my clinical experience at all. However, TMS technology is rapidly evolving and the efficacy is highly dependent on the protocol. Most of my experience with referring patients for TMS was at an AMC with an expert TMS group. (Outing myself somewhat, it was these guys

Psychiatry Online

ajp.psychiatryonline.org

- but I'm not there anymore and the TMS group at my current institution is not as well developed.)

They were on top of more efficacious approaches including accelerated protocols, theta-burst stimulation and, more recently and apparently very effectively, functional targeting. Generally I would say the patients I referred for TMS had excellent results. But that may not reflect the modal TMS available in the community.

 

[clozareal]

Also I have to say that I am surprised the general perception of TMS efficacy is so poor. That is not my clinical experience at all. However, TMS technology is rapidly evolving and the efficacy is highly dependent on the protocol. Most of my experience with referring patients for TMS was at an AMC with an expert TMS group. (Outing myself somewhat, it was these guys

Psychiatry Online

ajp.psychiatryonline.org

- but I'm not there anymore and the TMS group at my current institution is not as well developed.)

They were on top of more efficacious approaches including accelerated protocols, theta-burst stimulation and, more recently and apparently very effectively, functional targeting. Generally I would say the patients I referred for TMS had excellent results. But that may not reflect the modal TMS available in the community.

I wonder if it's because they read the academic papers rather than having actual clinical experience with patients getting it from someone who knows what they are doing (there's also poor TMS treatments out there). The TMS experts including the ones in the paper you cited say that if you're not getting response to current TMS treatment, the patient probably just needs a higher dose of it and they get to almost everyone responding in that case.

 

[tr]

I wonder if it's because they read the academic papers rather than having actual clinical experience with patients getting it from someone who knows what they are doing (there's also poor TMS treatments out there). The TMS experts including the ones in the paper you cited say that if you're not getting response to current TMS treatment, the patient probably just needs a higher dose of it and they get to almost everyone responding in that case.

Sounds about right. Although I suspect continuing dose increases may be low yield past a certain point.

The targeting, however, seems extremely promising. Seems obvious that you would get better results when you hit the correctly identified circuit, versus using external anatomical landmarks and hoping you get close to the right spot. I don't know how they are going to translate fMRI-based targeting to widespread clinical use but maybe once they figure it out they will be able to find a way to do it using a more accessible modality, like fNIRS or something.

 

[Stagg737]

Fine, I admit that statement was a rhetorical excess. Nonetheless, were I in the patient's shoes, I wouldn't personally want to have ECT unless I had absolutely exhausted all of the other available options. TMS I would have no qualms about other than the time investment.

It’s interesting because I have the complete opposite view. If I developed truly severe depression I would hope someone would initiate ECT fairly quickly and screw the med trials.