Lamictal augmentation for unipolar depression

[FlowRate]

Beg pardon, Lamictal rashes are not uncommon, and while statistically I understand most are benign, how do you know a priori which ones are 'serious'? If you stop the drug quickly the rash usually resolves. That doesn't mean it wouldn't have progressed to 'serious' without prompt discontinuation.

I've had several patients with very concerning skin manifestations from Lamictal (oral ulcers etc) and I'm mid-career. Doesn't stop me from using it but I wouldn't characterize ltg rash as rare.

(That said, the only patient of mine that ever ended up hospitalized for a drug rash had gotten a nasty case of DRESS from Wellbutrin, of all things. Go figure)

The data doesn't back you up here although you are implying that you think guidance to DC with any signs of a rash is causing reduced identification of potentially serious reactions. Risk of SJS/TEN with LTG in a recent high quality study is 2.82/10,000 and older data was 4.4/10,000. Seems to be trending down over time with increased adherence to modern slow-titration guidance.

Benign drug rashes? Much higher incidence. Anecdotally, I've also had more patients with serious rashes from bupropion than from LTG (and prescribe both often.)

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[annoyedpsychiatrist]

1. Ive seen reported incidences of the benign form of the rash from lamictal to be roughly 10 percent. Even though its benign, people who get the benign version are at higher risk for SJS, from what ive seen. Lamictal also takes a while to even titrate to a high dose. You can easily add abilify 2-5mg without issue. Sometimes i use lamictal for bipolar depression. I would prefer things that work faster

2. I pretty much never have patients have any significant side effects with abilify 2-5mg or rexulti 1-2mg. Higher doses of abilify, like >10mg i see increasing rates of akethesia, and sometimes even weight gain

3. From what ive seen SGAs have way more evidence for depression unipolar augmentation than lamictal

4. I use buspirone for anxiety, ive never seen consistent evidence it helps with depression unless perhaps depression 2/2 to anxiety

5. I probably would use low dose lithium over lamictal and would probably prefer SGAs>lithium>>>>lamictal. Most people with TRD also have significant stressors, personality disorders, drug use, etc that is contributing to it regardless

6. Id also rather use adjunct TMS or even perhaps ECT for severe MDD episode

edit: this is not counting stuff like wellbutrin, remeron, etc

 

[whopper]

The evidence-based data for Lamotrigine is laid out to a degree where there should be no debate it's a solid option to treat depression as an augmentation agent. The question shouldn't be does it work or not. It's already proven to do so but nuances with using it.

I haven't seen much Lamictal augmentation for mood for unipolar depression through training, but when I took a second to think about it, I don't really see why it couldn't work, given that lithium is used for mood augmentation.

The reasoning is off. The mechanisms by how they work are very different. Some mood stabilizers do some things such as extinguish mania, others like Lamotrigine don't but can prevent mania. They are very different medications despite that they are both "mood stabilizers" which is also a crude manner to label medication classes. What could happen in the near future is psych medications could be reclassified by their binding profiles.

I'm assuming its not typically done or I haven't heard much about it as there does not seem to be many studies or data backing up it's use, with Star*D using lithium and other agents, and not Lamictal.

I'm making an assumption that could be wrong and feel free to correct me. You may be in a training situation where none of your attendings or few of them are prescribing this medication. I've seen residency programs where the graduates all prescribe in a very similar manner that was biased by who was training them. Lamotrigine is a solid treatment option for Bipolar Disorder, depression, and antidepressant augmentation. It's cheap, doesn't cause weight gain, doesn't require labwork, and while it could cause SJS the risk is low.

 

[ObsequiousAplomb]

1. Ive seen reported incidences of the benign form of the rash from lamictal to be roughly 10 percent. Even though its benign, people who get the benign version are at higher risk for SJS, from what ive seen. Lamictal also takes a while to even titrate to a high dose. You can easily add abilify 2-5mg without issue. Sometimes i use lamictal for bipolar depression. I would prefer things that work faster

2. I pretty much never have patients have any significant side effects with abilify 2-5mg or rexulti 1-2mg. Higher doses of abilify, like >10mg i see increasing rates of akethesia, and sometimes even weight gain

3. From what ive seen SGAs have way more evidence for depression unipolar augmentation than lamictal

4. I use buspirone for anxiety, ive never seen consistent evidence it helps with depression unless perhaps depression 2/2 to anxiety

5. I probably would use low dose lithium over lamictal and would probably prefer SGAs>lithium>>>>lamictal. Most people with TRD also have significant stressors, personality disorders, drug use, etc that is contributing to it regardless

6. Id also rather use adjunct TMS or even perhaps ECT for severe MDD episode

edit: this is not counting stuff like wellbutrin, remeron, etc

I'm glad that your patients don't gain weight with the Abilify 2-5 mg. The literature is very clear that people are more likely to gain 5% body weight than reach remission for TRD when Abilify is added to their regimen.

 

[TheRightMedication]

The evidence-based data for Lamotrigine is laid out to a degree where there should be no debate it's a solid option to treat depression as an augmentation agent. The question shouldn't be does it work or not. It's already proven to do so but nuances with using it.



The reasoning is off. The mechanisms by how they work are very different. Some mood stabilizers do some things such as extinguish mania, others like Lamotrigine don't but can prevent mania. They are very different medications despite that they are both "mood stabilizers" which is also a crude manner to label medication classes. What could happen in the near future is psych medications could be reclassified by their binding profiles.



I'm making an assumption that could be wrong and feel free to correct me. You may be in a training situation where none of your attendings or few of them are prescribing this medication. I've seen residency programs where the graduates all prescribe in a very similar manner that was biased by who was training them. Lamotrigine is a solid treatment option for Bipolar Disorder, depression, and antidepressant augmentation. It's cheap, doesn't cause weight gain, doesn't require labwork, and while it could cause SJS the risk is low.

A solid choice in that it can help, sure. But to consistently make it the go-to augmentation choice, as was initially proposed, is not in keeping with the evidence or clinical practice as I know it.

 

[whopper]

It's an option. Should be considered a first line option among others such as Buspirone. A problem with Lamotrigine is because of the slow titration schedule it can take several weeks before patients feel a significant difference with it.

 

[Merovinge]

I'm glad that your patients don't gain weight with the Abilify 2-5 mg. The literature is very clear that people are more likely to gain 5% body weight than reach remission for TRD when Abilify is added to their regimen.

Did something else change with this? I thought a big metanalysis came out roughly a year ago showing Abilify to be weight neutral in adults. Certainly in the adolescent population it is associated with significantly more weight gain than people initially thought (although was clearly obvious to anyone who did significant ASD work). I like to have all you adult psychiatrists keep me up to date on things I don't see anymore doing pure peds.

 

[Celexa]

Did something else change with this? I thought a big metanalysis came out roughly a year ago showing Abilify to be weight neutral in adults. Certainly in the adolescent population it is associated with significantly more weight gain than people initially thought (although was clearly obvious to anyone who did significant ASD work). I like to have all you adult psychiatrists keep me up to date on things I don't see anymore doing pure peds.

I just cannot believe abilify is weight neutral. I've seen plenty of people gain weight on it (usually not at the low end of the dose range, but still)

 

[calvnandhobbs68]

The evidence-based data for Lamotrigine is laid out to a degree where there should be no debate it's a solid option to treat depression as an augmentation agent. The question shouldn't be does it work or not. It's already proven to do so but nuances with using it.

I'm not sure I've seen good studies showing lamictal is a good augmentation agent vs placebo for non-bipolar depressive disorders?

 

[calvnandhobbs68]

I'm glad that your patients don't gain weight with the Abilify 2-5 mg. The literature is very clear that people are more likely to gain 5% body weight than reach remission for TRD when Abilify is added to their regimen.

I mean here I can just pull out one of the Abilify RCTs that doesn't actually show that. Again, I don't hand out atypical antipsychotics willy nilly but if you're going to make statements like "the literature is very clear" I'd hope to see the literature backing this up.

Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants - PubMed

For some patients with MDD who do not obtain adequate symptom relief with antidepressant monotherapy, adjunctive therapies can significantly improve depressive symptoms. As reported, adjunctive aripiprazole was associated with a two-fold higher remission rate than adjunctive placebo. This, and...

pubmed.ncbi.nlm.nih.gov

8 week lead in with basically any SSRI
Abilify mean dose 10mg (but a decent amount up to 15-20mg)

At the end of another 6 weeks:
Remission Abilify- 36.8%
Remission placebo- 18.9%
Response Abilify- 46.6%
Response placebo- 26.6%
No significant difference in weight gain (+1.2kg vs 0.8kg) vs placebo
Difference in patients gaining >7% of weight 4.5% abilify vs 1.2% placebo

A lot of the issues (as always with longitudinal studies) looking at longer term use of Abilify/Rexulti and subsequent weight gain is that they then drop the control group. So there is very little information as to other factors that could be contributing to weight gain besides the adjunctive agent.

 

[ObsequiousAplomb]

I mean here I can just pull out one of the Abilify RCTs that doesn't actually show that. Again, I don't hand out atypical antipsychotics willy nilly but if you're going to make statements like "the literature is very clear" I'd hope to see the literature backing this up.

Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants - PubMed

For some patients with MDD who do not obtain adequate symptom relief with antidepressant monotherapy, adjunctive therapies can significantly improve depressive symptoms. As reported, adjunctive aripiprazole was associated with a two-fold higher remission rate than adjunctive placebo. This, and...

pubmed.ncbi.nlm.nih.gov

8 week lead in with basically any SSRI
Abilify mean dose 10mg (but a decent amount up to 15-20mg)

At the end of another 6 weeks:
Remission Abilify- 36.8%
Remission placebo- 18.9%
Response Abilify- 46.6%
Response placebo- 26.6%
No significant difference in weight gain (+1.2kg vs 0.8kg) vs placebo
Difference in patients gaining >7% of weight 4.5% abilify vs 1.2% placebo

A lot of the issues (as always with longitudinal studies) looking at longer term use of Abilify/Rexulti and subsequent weight gain is that they then drop the control group. So there is very little information as to other factors that could be contributing to weight gain besides the adjunctive agent.

Yeah you are quoting 6 weeks. Very few things cause that much weight gain within 6 weeks. It's when you look at 6 months and a year that the weight gain for TRD is higher than the remission rate.

And to respond to an above comment, Abilify is more likely to cause weight gain in TRD than schizophrenia. There's also the major flaw in the studies claiming weight neutrality in schizophrenia were from patients who weren't antipsychotic naive. Antipsychotic naive patients will gain weight by 6 months with Abilify.

 

[calvnandhobbs68]

Yeah you are quoting 6 weeks. Very few things cause that much weight gain within 6 weeks. It's when you look at 6 months and a year that the weight gain for TRD is higher than the remission rate.

And to respond to an above comment, Abilify is more likely to cause weight gain in TRD than schizophrenia. There's also the major flaw in the studies claiming weight neutrality in schizophrenia were from patients who weren't antipsychotic naive. Antipsychotic naive patients will gain weight by 6 months with Abilify.

Sure, RCTs generally end up limited by the length of time of the RCT in assessing adverse effects. Again though the problem with long term observational studies is that you drop any kind of control group, they generally can't account for dropouts or people who discontinue the medication during the observational period or other characteristics of the population in the observation period. Discontinuation/loss to followup can be a big factor here as a good proportion of people may feel well enough over a longer time period that they decide to self discontinue or stop the medication or just stop showing up...which means the treatment worked. It can certainly go the other way too, where people decide they don't want to take the medication or any medication anymore because of lack of efficacy.

There's also of course the variable observations that SSRIs themselves may be associated with weight gain in some people and so are you also capturing some proportion of people that may have gained weight due anyway with SSRI/SNRI treatment over that time period (not necessarily saying the SSRI was causative).

There also isn't clear overlap between these groups of people. So the people who remit aren't also necessarily the people who had weight gain in the longer term followups.

I mean I've obviously seen people gain weight with Abilify as well and this isn't really a discussion about are there better tolerated augmentation or switch agents. You have to balance possible benefit vs side effects. But we're primarily talking about this in the context of utilizing agents with well established efficacy as augmentation agents for MDD vs unclear or negative trials.

 

[clozareal]

I think the most frustrating part of this management is no medicine is at max dose despite being on a second med.

I don't think this is frustrating. There's evidence that augmentation with two low doses of a med is more tolerable and effective than maxing out a dose of one medication for MDD that was posted in the other thread.

My approach would be to keep increasing the dose but if it plateaus at a certain dose and increasing it didn't increase benefit, I would go back to that lower dose where it plateaued and then augment.

 

[forchinet121]

Lol this is the reason why the standard of care is so low, you have academic psychiatrists that can’t even agree on the basics of depression augmentation so anything can fly in the community because at the end of the day everyone has a different opinion

 

[Desired Member]

Did something else change with this? I thought a big metanalysis came out roughly a year ago showing Abilify to be weight neutral in adults. Certainly in the adolescent population it is associated with significantly more weight gain than people initially thought (although was clearly obvious to anyone who did significant ASD work). I like to have all you adult psychiatrists keep me up to date on things I don't see anymore doing pure peds.

Studies show that Abilify helps with MDD, schizophrenia, mania, and mixed episodes, but I've never seen a patient stable on Abilify. I realize there are a lot of confounding factors when judging medication efficacy based on one's own clinical experience, and I know that Abilify should be a first line or second line medication for aforementioned conditions, but I find myself not wanting to use it because I've just never seen it help with anything. And supposedly it doesn't cause significant weight gain, but I have seen it cause noticeable weight gain in adults

 

[tr]

I mean here I can just pull out one of the Abilify RCTs that doesn't actually show that. Again, I don't hand out atypical antipsychotics willy nilly but if you're going to make statements like "the literature is very clear" I'd hope to see the literature backing this up.

Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants - PubMed

For some patients with MDD who do not obtain adequate symptom relief with antidepressant monotherapy, adjunctive therapies can significantly improve depressive symptoms. As reported, adjunctive aripiprazole was associated with a two-fold higher remission rate than adjunctive placebo. This, and...

pubmed.ncbi.nlm.nih.gov

8 week lead in with basically any SSRI

No significant difference in weight gain (+1.2kg vs 0.8kg) vs placebo
Difference in patients gaining >7% of weight 4.5% abilify vs 1.2% placebo

Ok so the Abilify group gained 50% more weight total and was was nearly 4x as likely to gain >7% of weight in a 6 week period (!).

This didn't hit the arbitrary threshold of statistical significance but certainly isn't a demonstration that Abilify is weight neutral. I'd guess if you followed them for longer you would see that weight gain hit significance.

 

[annoyedpsychiatrist]

Ok so the Abilify group gained 50% more weight total and was was nearly 4x as likely to gain >7% of weight in a 6 week period (!).

This didn't hit the arbitrary threshold of statistical significance but certainly isn't a demonstration that Abilify is weight neutral. I'd guess if you followed them for longer you would see that weight gain hit significance.

yea but correct me if im wrong, that study is using doses of anywhere from 2-20mg. Im talking about doses 2-5mg. I agree that people can weight from abilify but I would argue that significant weight gain from 2-5mg is not common at all from what ive seen.

Also the reality is that in people you're using abilify for, their diet is typically absolute garbage to begin with. A lot of these people who were reportedly having weight gain from abilify 2-5mg, even though 5% is statistically significant, its also very easy to gain 5% in America because all our patients eat terribly, lets be real, lol. 5% in someone who is 200 lbs, is 10 pounds, and from a logical perspective, if they're at 200 pounds, going to 210 is far from a stretch. Especially when many of the people with TRD have comorbid psychosocial issues such as low income, physical disability, etc and I would wager are likely to have poor dietary habits. Quite often people with TRD have other issues going on.

 

[calvnandhobbs68]

Ok so the Abilify group gained 50% more weight total and was was nearly 4x as likely to gain >7% of weight in a 6 week period (!).

This didn't hit the arbitrary threshold of statistical significance but certainly isn't a demonstration that Abilify is weight neutral. I'd guess if you followed them for longer you would see that weight gain hit significance.

Sure but the argument I was replying to was that more patients (as a percentage of the total population treated) gain a significant amount of weight on Abilify than have remission.

Even in the long term studies though, Abilify is actually weight neutral for the majority of people followed. The information is that a significant minority (20-30% range it seems) gain a significant portion (generally defined as >7% change) of weight over the course of a year depending on the study you look at although there's only a couple studies that looked at this in the US. One in Japan only had single digits percentage but may be a quite different population than the US population.

 

[FlowRate]

Studies show that Abilify helps with MDD, schizophrenia, mania, and mixed episodes, but I've never seen a patient stable on Abilify. I realize there are a lot of confounding factors when judging medication efficacy based on one's own clinical experience, and I know that Abilify should be a first line or second line medication for aforementioned conditions, but I find myself not wanting to use it because I've just never seen it help with anything. And supposedly it doesn't cause significant weight gain, but I have seen it cause noticeable weight gain in adults

I'm curious, do you still prescribe it or do you avoid it because of early experience with it not being helpful? I've certainly had patients see benefit from the med for a host of different issues. Like any other augmentation strategy, you're by definition treating people who are somewhat treatment resistant so it's not like getting new-to-mh-treatment first-time MDD/GAD SSRI responders.

 

[mistafab]

I don't think this is frustrating. There's evidence that augmentation with two low doses of a med is more tolerable and effective than maxing out a dose of one medication for MDD that was posted in the other thread.

My approach would be to keep increasing the dose but if it plateaus at a certain dose and increasing it didn't increase benefit, I would go back to that lower dose where it plateaued and then augment.

Your approach would be optimal. The likelihood that this occurred is almost nil. It is a fundamental pharmacologic principal that you minimize exposure to multiple classes of medications. The more (independent) drug classes are present the higher risk of adverse effects. This is seen across studies and across samples; child, adult, and geriatric psychiatric patients.

Especially patient 3 highlights this. Most likely scenario is overprescribing and polypharmacy. Plus the growing problem of failure to deprescribe.

 

[whopper]

When Abilify first came out it was advertised as metabolically neutral cause the initial studies had smaller groups and missed the weight gain. Yes it does cause weight gain although it's rare.

The group, however, that gains weight, when it happens it can be significantly bad.

Even in the long term studies though, Abilify is actually weight neutral for the majority of people followed.

Yes for the majority, the majority doesn't gain weight but it's not an over 90% majority. It's a majority where you still have to be concerned about weight gain at first. Just like the majority of people on SSRIs doesn't get sexual side effects but the amount that do is a significant minority.

 

[Merovinge]

Studies show that Abilify helps with MDD, schizophrenia, mania, and mixed episodes, but I've never seen a patient stable on Abilify. I realize there are a lot of confounding factors when judging medication efficacy based on one's own clinical experience, and I know that Abilify should be a first line or second line medication for aforementioned conditions, but I find myself not wanting to use it because I've just never seen it help with anything. And supposedly it doesn't cause significant weight gain, but I have seen it cause noticeable weight gain in adults

I use a lot of Abilify (particularly following it going generic and being covered by every insurance) and did as well in the adult population. I have seen a lot of patients stable on Abilify ranging from first episode psychosis to bipolar I disorder to ASD w/ marked aggression. I do rarely see Abilify knock it out of the park for TRD but have seen cases clearly improve with it (and essentially nothing knocks it out of the park with TRD, lets see more about this SAINT TMS).

 

[Merovinge]

Your approach would be optimal. The likelihood that this occurred is almost nil. It is a fundamental pharmacologic principal that you minimize exposure to multiple classes of medications. The more (independent) drug classes are present the higher risk of adverse effects. This is seen across studies and across samples; child, adult, and geriatric psychiatric patients.

Especially patient 3 highlights this. Most likely scenario is overprescribing and polypharmacy. Plus the growing problem of failure to deprescribe.

I agree with this typically but there are some notable exceptions. The one with the overwhelming science behind it is the concurrent use of psychostimulants with alpha-2-agonsits for ADHD in youth. Not only do the SE tend to help cancel each other out but the combination actually works better than either alone.

There are other corner cases that come up not infrequently:
1) SRI intolerance, promoting use of say Wellbutrin + Buspar for mood/anxiety that would have otherwise been best served with a SSRI/SNRI
2) Patient comes on middle to low dose of SSRI, remains anxious/depressed but also struggles with appetite/insomnia and is better served with adjunctive Remeron than raising SSRI

I am sure there are a lot more, certainly first principal is consider monotherapy when possible but there are definitely good reasons to go beyond this a number of cases.

 

[mistafab]

I agree with this typically but there are some notable exceptions. The one with the overwhelming science behind it is the concurrent use of psychostimulants with alpha-2-agonsits for ADHD in youth. Not only do the SE tend to help cancel each other out but the combination actually works better than either alone.

There are other corner cases that come up not infrequently:
1) SRI intolerance, promoting use of say Wellbutrin + Buspar for mood/anxiety that would have otherwise been best served with a SSRI/SNRI
2) Patient comes on middle to low dose of SSRI, remains anxious/depressed but also struggles with appetite/insomnia and is better served with adjunctive Remeron than raising SSRI

I am sure there are a lot more, certainly first principal is consider monotherapy when possible but there are definitely good reasons to go beyond this a number of cases.

Completely agree. You don't always know if someone's regimen was through a process of careful titration and thoughtful intervention, or if it was smattered together haphazardly. Best to give benefit of the doubt - but on SDN we swing hammers and see only nails.

 

[clozareal]

I agree with this typically but there are some notable exceptions. The one with the overwhelming science behind it is the concurrent use of psychostimulants with alpha-2-agonsits for ADHD in youth. Not only do the SE tend to help cancel each other out but the combination actually works better than either alone.

There are other corner cases that come up not infrequently:
1) SRI intolerance, promoting use of say Wellbutrin + Buspar for mood/anxiety that would have otherwise been best served with a SSRI/SNRI
2) Patient comes on middle to low dose of SSRI, remains anxious/depressed but also struggles with appetite/insomnia and is better served with adjunctive Remeron than raising SSRI

I am sure there are a lot more, certainly first principal is consider monotherapy when possible but there are definitely good reasons to go beyond this a number of cases.

For people who have ADHD + anxiety/depression, I often do a stimulant + mirtazapine combo too although I don't believe there are trials out there looking at this, especially in children. It works out well for stimulant side effects of appetite suppression and insomnia (stimulants can also worsen mood/anxiety for some despite the meta analysis showing a reduction of anxiety symptoms).

I don't think starting with two medications is best and I don't recommend that approach because you are assuming they will have side effects from that first medication that you're using a second medication to treat or that the first medication wouldn't be effective or tolerated at higher doses.

 

[annoyedpsychiatrist]

its extremely interesting seeing how polarized we are in our view of abilify with two distinct camps people tend to fall in on this thread, lol. This is the last thing i would have thought to cause a disagreement.

 

[annoyedpsychiatrist]

I use a lot of Abilify (particularly following it going generic and being covered by every insurance) and did as well in the adult population. I have seen a lot of patients stable on Abilify ranging from first episode psychosis to bipolar I disorder to ASD w/ marked aggression. I do rarely see Abilify knock it out of the park for TRD but have seen cases clearly improve with it (and essentially nothing knocks it out of the park with TRD, lets see more about this SAINT TMS).

i tend to agree with 99.9% of your posts

 

[forchinet121]

its extremely interesting seeing how polarized we are in our view of abilify with two distinct camps people tend to fall in on this thread, lol. This is the last thing i would have thought to cause a disagreement.

There’s disagreement on abilify, lamictal, and buspar

 

[Stagg737]

Exactly. This is how I was trained for unipolar MDD hence the post.

SSRI/SNRI
+
Lithium
Remeron
Wellbutrin
Buspar
T3
Antipsychotics preferably partial agonists

Never lamictal as depression augmentation. Off label for borderline, yeah sure. Even though medications generally suck.

There's obviously nuances when you'd pick one over the other, but after single SSRI/SNRI for straight MDD my adjunct order is generally wellbutrin/mirtazapine, partial D2 agonists, Lithium/SGAs. After that the evidence gets a lot weaker and dependent on more variables, but I will generally pick more benign options like lamotrigine or buspar before higher risk options.

Let's also not forget that there are also plenty of patients who would be best served by TCA or MOAI monotherapy over an SSRI/SNRI + half the pharmacy, so plenty of other options out there as well.

Okay this is why I’m always telling people to actually read the studies. Look at the actual first meta analysis paper. All the studies that showed benefit are published in Chinese journals and are literally in Chinese (like not even mainstream enough to be translated) so you can’t even look up the papers themselves on pubmed (as far as I can tell, someone feel free to prove me wrong) to see the actual info in them. I honestly rarely have faith in rando foreign articles published in rando foreign journals, many of which you can literally pay to just publish your paper. Some of these could be legit but there’s no good way to verify.

Additionally, all the studies that showed benefit seem to NOT be placebo controlled if you look at the actual table for characteristics of the studies. They conveniently skirt around this by saying “Characteristics of eight double-blinded randomized controlled trials” not PLACEBO controlled trials. The only two placebo controlled trials didn’t show benefit. Which makes sense, are patients more likely to believe the drug they’ve already been on which hasn’t been working is going to magically start working in the next 6-12 weeks?

Those aren't the only studies there are, but those were the first to come up with a quick google. I agree that the data isn't good, but there is still some data suggestive that it can be beneficial. Non-Chinese studies from a 5 minute Pub-med review (to prove you wrong, lol) below:

A double-blind placebo-controlled trial of lamotrigine as an antidepressant augmentation agent in treatment-refractory unipolar depression - PubMed

clinicaltrials.gov Identifier: NCT00901407.

pubmed.ncbi.nlm.nih.gov

Lithium versus lamotrigine augmentation in treatment resistant unipolar depression: a randomized, open-label study - PubMed

Treatment-resistant depression affects up to 70% of patients. In our 8-week, randomized, open-label, prospective study of 34 treatment-resistant depression patients lamotrigine-add-on was compared with lithium-augmentation. Both treatments resulted in clinically significant reduction in Hamilton...

pubmed.ncbi.nlm.nih.gov

Lamotrigine compared to placebo and other agents with antidepressant activity in patients with unipolar and bipolar depression: a comprehensive meta-analysis of efficacy and safety outcomes in short-term trials - PubMed

Lamotrigine was superior to placebo in improving unipolar and bipolar depressive symptoms, without causing more frequent adverse effects/discontinuations. Lamotrigine did not differ from lithium, olanzapine+fluoxetine, citalopram, or inositol.

pubmed.ncbi.nlm.nih.gov

The data for lamotrigine for unipolar depression augmentation is there. No, it's not as strong as other options, but it is an option worth considering for the right patients, and I wouldn't exclude "unipolar depression" from that group.

Yes because I’m concerned about side effects, lithium causes renal disease and a ton of side effects..why would I use an agent that will likely cause renal disease and can easily kill you if you take too much versus a benign agent, I’ve used lamictal a lot and it was heavily emphasized in my program I guess that’s the bias, I don’t have any experience with thyroid, I also don’t treat very high acuity depressed patients regularly so I’m more concerned about side effects than effect in my mind when a lot of general outpatient is less biological depression and more personality and social/psychological issues

The bolded is actually not as clear cut as a lot of people think and the evidence that lithium causes irreversible renal disease without episodes of acute injury isn't much better than the data for lamictal for depression augmentation. Yes, there's a much higher risk AKI and resulting kidney problems, but there's fairly good data that most renal stress is reversible. Ironically, I'm actually a lot more concerned about patients developing thyroid problems from long-term lithium use than the renal side effects as the data for thyroid dysfunction 2/2 chronic lithium use is stronger. May be somewhat doxxing myself, but I say this as someone who trained at a program where the academic hospital has historically been responsible for a large portion of research on certain renal disorders internationally and the psych program specifically has a significant background in research on lithium.

(That said, the only patient of mine that ever ended up hospitalized for a drug rash had gotten a nasty case of DRESS from Wellbutrin, of all things. Go figure)

Benign drug rashes? Much higher incidence. Anecdotally, I've also had more patients with serious rashes from bupropion than from LTG (and prescribe both often.)

This is really interesting to me, I'm aware of the associated risk but I've never seen major dermatologic problems with using Wellbutrin.

 

[calvnandhobbs68]

Those aren't the only studies there are, but those were the first to come up with a quick google. I agree that the data isn't good, but there is still some data suggestive that it can be beneficial. Non-Chinese studies from a 5 minute Pub-med review (to prove you wrong, lol) below:

A double-blind placebo-controlled trial of lamotrigine as an antidepressant augmentation agent in treatment-refractory unipolar depression - PubMed

clinicaltrials.gov Identifier: NCT00901407.

pubmed.ncbi.nlm.nih.gov

Lithium versus lamotrigine augmentation in treatment resistant unipolar depression: a randomized, open-label study - PubMed

Treatment-resistant depression affects up to 70% of patients. In our 8-week, randomized, open-label, prospective study of 34 treatment-resistant depression patients lamotrigine-add-on was compared with lithium-augmentation. Both treatments resulted in clinically significant reduction in Hamilton...

pubmed.ncbi.nlm.nih.gov

Lamotrigine compared to placebo and other agents with antidepressant activity in patients with unipolar and bipolar depression: a comprehensive meta-analysis of efficacy and safety outcomes in short-term trials - PubMed

Lamotrigine was superior to placebo in improving unipolar and bipolar depressive symptoms, without causing more frequent adverse effects/discontinuations. Lamotrigine did not differ from lithium, olanzapine+fluoxetine, citalopram, or inositol.

pubmed.ncbi.nlm.nih.gov

The data for lamotrigine for unipolar depression augmentation is there. No, it's not as strong as other options, but it is an option worth considering for the right patients, and I wouldn't exclude "unipolar depression" from that group.

Soooo yeah I actually stand by my first statement of actually even skimming the studies instead of googling and pulling whatever you get on pubmed.

That first one is literally one of the studies that was on the meta-analysis in the first place (Barbee 2011). It's also one of the ones that didn't show a difference between lamictal and placebo haha.

The second one is just comparing lamictal to lithium for augmentation and was totally open, no blinding of anyone to any part of it. So quite weak. There's also all kinds of confounding stuff with that study. Only 34 people total, they were all recruited from inpatient units, 20 of them had been on combinations of antidepressants before, 27 of them had been on atypical antipsychotics before, 4 of them had been on MAO-i, 5 of them had ECT and 2 had gotten T3 before. Also "The majority (LTG n = 13; Li n = 14) of the patients remained in inpatient status throughout the study period". Those patients who remitted (LTG n = 4; Li n = 3) were discharged and seen by our outpatient service every week
So without a placebo group, how many of these patients just benefitted from being in an inpatient psych unit or seen weekly for 2 months?

The third one is a meta-analysis that just includes the same studies for augmentation for unipolar depression (Santos 2008 and Barbee 2011). Everyone else is bipolar disorder.

 

[Stagg737]

As for Abilify, I've generally found that for most patients it's weight neutral or pretty close to it at depression augmentation doses (<10mg) but have also noticed certain subsets of patients who seem to experience significant weight gain. I've found those with notable ASD (especially kids), other genetic disorders with ID associated, and those with TBIs to be particularly prone to weight gain.

I will typically choose low-dose abilify as an augmenting agent for unipolar depression over lamotrigine both from a theoretical (adding a dopamine partial agonist) as well as EBM (efficacy data is stronger for abililfy) standpoint.

 

[Stagg737]

Soooo yeah I actually stand by my first statement of actually even skimming the studies instead of googling and pulling whatever you get on pubmed.

That first one is literally one of the studies that was on the meta-analysis in the first place (Barbee 2011). It's also one of the ones that didn't show a difference between lamictal and placebo haha.

The second one is just comparing lamictal to lithium for augmentation and was totally open, no blinding of anyone to any part of it. So quite weak. There's also all kinds of confounding stuff with that study. Only 34 people total, they were all recruited from inpatient units, 20 of them had been on combinations of antidepressants before, 27 of them had been on atypical antipsychotics before, 4 of them had been on MAO-i, 5 of them had ECT and 2 had gotten T3 before. Also "The majority (LTG n = 13; Li n = 14) of the patients remained in inpatient status throughout the study period". Those patients who remitted (LTG n = 4; Li n = 3) were discharged and seen by our outpatient service every week
So without a placebo group, how many of these patients just benefitted from being in an inpatient psych unit or seen weekly for 2 months?

The third one is a meta-analysis that just includes the same studies for augmentation for unipolar depression (Santos 2008 and Barbee 2011). Everyone else is bipolar disorder.

I'm aware, but you're ignoring the final conclusion of the first study: "However, post hoc analyses suggest that future studies of lamotrigine's efficacy might focus on specific subgroups with depression." That's pretty much the basis of how I'd use lamotrigine as an augmenting agent in that it can be beneficial for the right sub-types, including some non-bipolar depression patients, but that it's not a great option for most individuals.

 

[calvnandhobbs68]

I'm aware, but you're ignoring the final conclusion of the first study: "However, post hoc analyses suggest that future studies of lamotrigine's efficacy might focus on specific subgroups with depression." That's pretty much the basis of how I'd use lamotrigine as an augmenting agent in that it can be beneficial for the right sub-types, including some non-bipolar depression patients, but that it's not a great option for most individuals.

Yeah that's a very very weak statement. I mean it's the typical "maybe we should study this more" statement. They also reference one scale subgroup on their secondary outcome measure when saying "post hoc analyses suggest" (HDRS-17). You're ignoring the actual primary outcome of the study.

So none of this would lead me to state there is any actual evidence for lamictal augmentation in MDD. Which is fine, I'd just be aware of this when using it.

 

[Stagg737]

Yeah that's a very very weak statement. I mean it's the typical "maybe we should study this more" statement. They also reference one scale subgroup on their secondary outcome measure when saying "post hoc analyses suggest" (HDRS-17). You're ignoring the actual primary outcome of the study.

So none of this would lead me to state there is any actual evidence for lamictal augmentation in MDD. Which is fine, I'd just be aware of this when using it.

If you really want the data I can spend some time to digging it up. It's there. Not strong, but it is there.

 

[MedMan80]

Good to see everyone putting their admin time to good use

 

[clozareal]

As for Abilify, I've generally found that for most patients it's weight neutral or pretty close to it at depression augmentation doses (<10mg) but have also noticed certain subsets of patients who seem to experience significant weight gain. I've found those with notable ASD (especially kids), other genetic disorders with ID associated, and those with TBIs to be particularly prone to weight gain.

I agree with this. In addition, children and teens are more prone to weight gain than adults with Abilify.

The largest meta-analysis to date for TRD shows that four augmentation agents worked for it: lithium augmentation, thyroid augmentation, or augmentation with aripiprazole or quetiapine.

Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: systematic review and network meta-analysis - PubMed

Quetiapine and aripiprazole appear to be the most robust evidence-based options for augmentation therapy in patients with treatment-resistant depression, but clinicians should interpret these findings cautiously in light of the evidence of potential treatment-related side effects.

pubmed.ncbi.nlm.nih.gov

 

[calvnandhobbs68]

If you really want the data I can spend some time to digging it up. It's there. Not strong, but it is there.

I think they would have been able to nab any better data in the 2 meta-analyses you've already presented, both of which just kind of recycled the same studies.

Good to see everyone putting their admin time to good use

Hey at least we're debating something real impacting patient care and not "how much money can I make in the least amount of hours in psychiatry???"

 

[clausewitz2]

I agree with this. In addition, children and teens are more prone to weight gain than adults with Abilify.

The largest meta-analysis to date for TRD shows that four augmentation agents worked for it: lithium augmentation, thyroid augmentation, or augmentation with aripiprazole or quetiapine.

Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: systematic review and network meta-analysis - PubMed

Quetiapine and aripiprazole appear to be the most robust evidence-based options for augmentation therapy in patients with treatment-resistant depression, but clinicians should interpret these findings cautiously in light of the evidence of potential treatment-related side effects.

pubmed.ncbi.nlm.nih.gov

. . . and of course in terms of tolerability that study says that the only one of those that did not separate from placebo (in a bad way) was thyroid augmentation.

I have only sporadically had success with thyroid augmentation. The literature seems to suggest it is more likely to be effective in women than in men for depression. Mostly I end up using it to correct mild hypothyroidism in people I have given mild hypothyroidism to with lithium.

I am familiar with the literature on supraphysiological dosing. Michael Bauer (one of the co-authors of that meta-analysis, it looks like) has argued that we should really be dosing people with more like 250-600 mcg of thyroid hormone if we are following evidence of actual efficacy. Apparently much better tolerated than you might expect. I have a book on my shelf that someone in private practice self-published on the topic, but have never quite had the guts to pull the trigger. Has anyone actually done this?

EDIT: and apparently the clinical anecdata about people who respond well to it for depression tolerating huge doses without much difficulty has been supported by actual experimental evidence:

Redirecting

 

[Stagg737]

I think they would have been able to nab any better data in the 2 meta-analyses you've already presented, both of which just kind of recycled the same studies.



Hey at least we're debating something real impacting patient care and not "how much money can I make in the least amount of hours in psychiatry???"

I mean, everyone knows we should just augment with high doses of lithium and get labs Q3months so we can optimize billing by using 99215....

 

[clausewitz2]

I mean, everyone knows we should just augment with high doses of lithium and get labs Q3months so we can optimize billing by using 99215....

Just throw on 50 mg of clozapine as augmentation for everyone, it's good for what ails ya

 

[pyrrion89]

Lamictal is great. I tend to use it when I suspect someone has borderline traits on top of their depression. Or if we are in a BPAD vs BPD conundrum diagnostically.

 

[clozareal]

. . . and of course in terms of tolerability that study says that the only one of those that did not separate from placebo (in a bad way) was thyroid augmentation.

I have only sporadically had success with thyroid augmentation. The literature seems to suggest it is more likely to be effective in women than in men for depression. Mostly I end up using it to correct mild hypothyroidism in people I have given mild hypothyroidism to with lithium.

I am familiar with the literature on supraphysiological dosing. Michael Bauer (one of the co-authors of that meta-analysis, it looks like) has argued that we should really be dosing people with more like 250-600 mcg of thyroid hormone if we are following evidence of actual efficacy. Apparently much better tolerated than you might expect. I have a book on my shelf that someone in private practice self-published on the topic, but have never quite had the guts to pull the trigger. Has anyone actually done this?

EDIT: and apparently the clinical anecdata about people who respond well to it for depression tolerating huge doses without much difficulty has been supported by actual experimental evidence:

Redirecting

They've done it in unipolar and bipolar depression patients without risk of switching to mania, did improved rapid cycling, and doesn't have heightened risk of osteoporosis, heart disease (cardiac arrhythmias), or mortality. Interestingly, those without uni/bipolar depression who took supraphysiological doses of thyroid had side effects to it.

 

[Stagg737]

Risk is higher in kids, I don’t treat kids, the risk of serious rash is very very tiny meaning you’ll see it once a career as an adult psych

It is tiny, but not that tiny. Meant to address this point but I actually saw legit SJS twice in training before becoming an attending. Fortunately it was identified relatively early and both patients were fine, but given the potential clinical outcomes of the rash it's not an eff around and find out kind of situation.

 

[forchinet121]

It is tiny, but not that tiny. Meant to address this point but I actually saw legit SJS twice in training before becoming an attending. Fortunately it was identified relatively early and both patients were fine, but given the potential clinical outcomes of the rash it's not an eff around and find out kind of situation.

The risk is like 1/3000

 

[clozareal]

I was fortunate to rotate on an inpatient dermatology hospital unit while in medical school and saw several cases of SJS and two cases of TEN. I was horrified. These were people covered up in bandages like a mummy, lost all facial features like lips, nose structure, eyebrows, basically just a few holes on their face for their eyes, nostril, and mouth but otherwise smooth. These were not children where the risk of mortality is lower but it was still horrible. I don't remember which medication caused it but I told myself that day that I would always take it seriously.

 

[forchinet121]

I was fortunate to rotate on an inpatient dermatology hospital unit while in medical school and saw several cases of SJS and two cases of TEN. I was horrified. These were people covered up in bandages like a mummy, lost all facial features like lips, nose structure, eyebrows, basically just a few holes on their face for their eyes, nostril, and mouth but otherwise smooth. These were not children where the risk of mortality is lower but it was still horrible. I don't remember which medication caused it but I told myself that day that I would always take it seriously.

You should take all side effect seriously, but the risk is 1/3000 versus much higher risk of diabetes and heart disease for antipsychotics, furthermore you can see this developing and stop it while it’s much harder to do with diabetes

 

[Stagg737]

You should take all side effect seriously, but the risk is 1/3000 versus much higher risk of diabetes and heart disease for antipsychotics, furthermore you can see this developing and stop it while it’s much harder to do with diabetes

Yes, but there's also a difference between a med with solid evidence as treatment that causes a side effect like CV disease which is arguably dose dependent that develops over the course of years and can be easily avoided with monitoring and discontinuation vs a med with weak evidence for treatment that can cause an adverse effect which can kill your patients in less than a week or at the very least leave them permanently maimed if not addressed within days of onset. Like always, it's a risk benefit conversation and the benefits of lamictal for unipolar depression are just not worth it being a regular consideration for most patients. This is coming from someone who does consider it for depression augmentation.

I'm assuming you also generally avoid prescribing TCAs and SNRIs to depressed patients if you're this concerned about CV/DM side effects in your patients.

 

[clausewitz2]

I'm assuming you also generally avoid prescribing TCAs and SNRIs to depressed patients if you're this concerned about CV/DM side effects in your patients.

I'm with you on lamictal not being a common thing I reach for in depression augmentation but the risk of metabolic and CV side effects from neuroleptics is much higher than TCAs at prescribed doses. Not sure this is a fair comparison.

 

[Merovinge]

I was fortunate to rotate on an inpatient dermatology hospital unit while in medical school and saw several cases of SJS and two cases of TEN. I was horrified. These were people covered up in bandages like a mummy, lost all facial features like lips, nose structure, eyebrows, basically just a few holes on their face for their eyes, nostril, and mouth but otherwise smooth. These were not children where the risk of mortality is lower but it was still horrible. I don't remember which medication caused it but I told myself that day that I would always take it seriously.

Saw one case as an M3 and that never leaves you. I do prescribe Lamictal a decent bit, but certainly not without the standard slow titration schedule and I am quick to point out the concerns in patient's who medication adherence has been less than ideal.

 

[forchinet121]

Yes, but there's also a difference between a med with solid evidence as treatment that causes a side effect like CV disease which is arguably dose dependent that develops over the course of years and can be easily avoided with monitoring and discontinuation vs a med with weak evidence for treatment that can cause an adverse effect which can kill your patients in less than a week or at the very least leave them permanently maimed if not addressed within days of onset. Like always, it's a risk benefit conversation and the benefits of lamictal for unipolar depression are just not worth it being a regular consideration for most patients. This is coming from someone who does consider it for depression augmentation.

I'm assuming you also generally avoid prescribing TCAs and SNRIs to depressed patients if you're this concerned about CV/DM side effects in your patients.

What are your top 7 ssri augmentation agents