Lamotrigine Accelerates Brain Aging

[DaveFoster]

Lamotrigine, an anticonvulsant used to treat bipolar II disorder (cyclical depression without mania) has been shown to extend lifespan but induce motor retardation as a proxy for brain aging. Other anticonvulsants, including lithium and valproic acid (Depakote) have beneficial effects on both longevity and healthspan. Lithium and valproic acid both induce hypothyroidism, so it's not surprising that lamotrigine has similar metabolic effects, although lamotrigine has not been linked to an elevated TSH unlike lithium and valproic acid.

"The discovery of life extension in Caenorhabditis elegans treated with anticonvulsant medications has raised the question whether these drugs are prospective anti-aging candidate compounds. The impact of these compounds on neural modulation suggests that they might influence the chronic diseases of aging as well. Lamotrigine is a commonly used anticonvulsant with a relatively good adverse-effects profile. In this study, we evaluated the interaction between the impacts of lamotrigine on mortality rate, lifespan, metabolic rate and locomotion. It has been proposed in a wide range of animal models that there is an inverse relationship between longevity, metabolic rate, and locomotion. We hypothesized that the survival benefits displayed by this compound would be associated with deleterious effects on health span, such as depression of locomotion. Using Drosophila as our model system, we found that lamotrigine decreased mortality and increased lifespan in parallel with a reduction in locomotor activity and a trend towards metabolic rate depression. Our findings underscore the view that assessing health span is critical in the pursuit of useful anti-aging compounds."

Reference: Lamotrigine extends lifespan but compromises health span in Drosophila melanogaster. - PubMed - NCBI
​

Originally posted on the Foster Your Health blog: Lamotrigine Accelerates Brain Aging

 

[Ulysses]

It's amazing how so many of these drugs are complete garbage. Is there a single common neuropsychiatric medication that actually improves health?

 

[DaveFoster]

It's amazing how so many of these drugs are complete garbage. Is there a single common neuropsychiatric medication that actually improves health?

Tianeptine (Stablon,) but it's not prescribed very often in the U.S., and it's hard on the liver.

 

[Dhair]

Tianeptine (Stablon,) but it's not prescribed very often in the U.S., and it's hard on the liver.

It also has massive potential for abuse/addiction with difficult withdrawal symptoms.

 

[DaveFoster]

It also has massive potential for abuse/addiction with difficult withdrawal symptoms.

True, but most of those stories involve high dosages used chronically; they pursue the tolerance-building opioid qualities rather than the selective-serotonin reuptake enhancing (SSRE) and NMDA modulating properties of the drug.

Cyproheptadine has a far superior safety profile, but it's prescribed for neuropsychiatric conditions very seldom if at all.

Ceasing consumption of these substances without implementing other anti-stress measures in their place just invites degenerative changes and their respective symptoms.

 

[alywest]

Lamotrigine, an anticonvulsant used to treat bipolar II disorder (cyclical depression without mania) has been shown to extend lifespan but induce motor retardation as a proxy for brain aging. Other anticonvulsants, including lithium and valproic acid (Depakote) have beneficial effects on both longevity and healthspan. Lithium and valproic acid both induce hypothyroidism, so it's not surprising that lamotrigine has similar metabolic effects, although lamotrigine has not been linked to an elevated TSH unlike lithium and valproic acid.

"The discovery of life extension in Caenorhabditis elegans treated with anticonvulsant medications has raised the question whether these drugs are prospective anti-aging candidate compounds. The impact of these compounds on neural modulation suggests that they might influence the chronic diseases of aging as well. Lamotrigine is a commonly used anticonvulsant with a relatively good adverse-effects profile. In this study, we evaluated the interaction between the impacts of lamotrigine on mortality rate, lifespan, metabolic rate and locomotion. It has been proposed in a wide range of animal models that there is an inverse relationship between longevity, metabolic rate, and locomotion. We hypothesized that the survival benefits displayed by this compound would be associated with deleterious effects on health span, such as depression of locomotion. Using Drosophila as our model system, we found that lamotrigine decreased mortality and increased lifespan in parallel with a reduction in locomotor activity and a trend towards metabolic rate depression. Our findings underscore the view that assessing health span is critical in the pursuit of useful anti-aging compounds."

Reference: Lamotrigine extends lifespan but compromises health span in Drosophila melanogaster. - PubMed - NCBI
​

Originally posted on the Foster Your Health blog: Lamotrigine Accelerates Brain Aging

Do you think that using t3/t4 and progesterone in increasing amounts throughout might offset some of the metabolic issues caused by long term lamotrigine use?

 

[CoconutEffect]

It's amazing how so many of these drugs are complete garbage. Is there a single common neuropsychiatric medication that actually improves health?

Selegiline?

 

[DaveFoster]

Do you think that using t3/t4 and progesterone in increasing amounts throughout might offset some of the metabolic issues caused by long term lamotrigine use?

Yes, but a more biologically coherent substance could theoretically substitute for lamotrigine. What are you taking it for? I posted a study showing that T3 improves symptoms of bipolar II disorder.

Abruptly ceasing a psychiatric medication can exacerbate withdrawal symptoms.

Selegiline?

Rasagiline's probably safer, as selegiline has effects resembling amphetamine.

 

[alywest]

Yes, but a more biologically coherent substance could theoretically substitute for lamotrigine. What are you taking it for? I posted a study showing that T3 improves symptoms of bipolar II disorder.

Abruptly ceasing a psychiatric medication can exacerbate withdrawal symptoms.
Rasagiline's probably safer, as selegiline has effects resembling amphetamine.

I was given it for PTSD and pretty bad depression. I have also been taking higher and more consistent doses of Progesterone (250 mg), so I'm not really sure what is making me feel better. I've only been on the L for 3 weeks so I'm only at 50 mg. I've been taking thyroid for a few years and I'm pretty good at gauging what works and what doesn't even without labs now. Like I can barely lift my arms if I don't get enough. I'm about to start taking tyromax with cynomel and I'm really looking forward to that combo. I've been on Tyromix and it has definitely worked better than most things, but I have a good feeling about the combo I am waiting for in the mail from Mexico and Idealabs. So definitely thyroid plays a role, but I've accepted I'll be taking it for the rest of my life and have no problem taking more as needed.

 

[DaveFoster]

I was given it for PTSD and pretty bad depression. I have also been taking higher and more consistent doses of Progesterone (250 mg), so I'm not really sure what is making me feel better. I've only been on the L for 3 weeks so I'm only at 50 mg. I've been taking thyroid for a few years and I'm pretty good at gauging what works and what doesn't even without labs now. Like I can barely lift my arms if I don't get enough. I'm about to start taking tyromax with cynomel and I'm really looking forward to that combo. I've been on Tyromix and it has definitely worked better than most things, but I have a good feeling about the combo I am waiting for in the mail from Mexico and Idealabs. So definitely thyroid plays a role, but I've accepted I'll be taking it for the rest of my life and have no problem taking more as needed.

It's important to gauge the physiological response of any substance. Dr. Peat often recommends diet and other nutrients, hormones, and after that adaptogens or drug-like compounds like quinones, caffeine, aspirin, lidocaine and so on.

He recommends pharmaceuticals for use in the short-term and often emphasizes the ones with the best side-effect profile, such as cyproheptadine, ketotifen, lisuride and so on: mostly anti-histamine and anti-serotonin drugs, but thyroid lowers histamine and serotonin levels, which requires adequate carbohydrate and protein.

Out of curosity, what symptoms do you get from taking too much thyroid?

 

[CoconutEffect]

Yes, but a more biologically coherent substance could theoretically substitute for lamotrigine. What are you taking it for? I posted a study showing that T3 improves symptoms of bipolar II disorder.

Abruptly ceasing a psychiatric medication can exacerbate withdrawal symptoms.
Rasagiline's probably safer, as selegiline has effects resembling amphetamine.

Have you tried it?
Does that make it a better drug in your opinion?

 

[DaveFoster]

Have you tried it?
Does that make it a better drug in your opinion?

I use T3, but I haven't raised the dosage of T4 to an optimal level yet. It helps with anxiety and depression, but it's difficult to take T3 when your pulse is 100+ from T4's ensuing sensitization to adrenaline.

 

[alywest]

It's important to gauge the physiological response of any substance. Dr. Peat often recommends diet and other nutrients, hormones, and after that adaptogens or drug-like compounds like quinones, caffeine, aspirin, lidocaine and so on.

He recommends pharmaceuticals for use in the short-term and often emphasizes the ones with the best side-effect profile, such as cyproheptadine, ketotifen, lisuride and so on: mostly anti-histamine and anti-serotonin drugs, but thyroid lowers histamine and serotonin levels, which requires adequate carbohydrate and protein.

Out of curosity, what symptoms do you get from taking too much thyroid?

I used to be able to gauge my thyroid pretty accurately from my pulse but since I started the lamotrigine, my pulse has been really high so I'm not sure how to tell if I'm taking too much at this point! I'm not planning on upping my dose much, just changing the actual medication. I do know if I'm not taking enough I get heart palps which seems like that's backwards, however I listened to an interview on the herb doctors where Peat discusses that thyroid and progesterone allow the heart to fully pump all the blood out instead of "waterlogging." I wish I could remember the actual interview. So if I'm getting palps I actually take a bit of thyroid right away and it will go away. I have noticed with NDT I sometimes have to take more than what I take with synthetics, that is why I'm hoping the combo of cynomel with tyromax will be ideal.

 

[alywest]

I was wondering what you make of this excerpt from an old NY Times article discussing PMDD:

"my new psychiatrist concluded that I did not suffer from bipolar disorder complicated by PME, but rather only from PMDD. Mood stabilizers don’t work on PMDD. Instead, low doses of hormones, including birth controlpills, are often prescribed, as are S.S.R.I.’s. Research has also shown a positive effect from calcium supplements, light therapy and cognitive therapy.

Because evidence of the link between hormone replacement therapy and breast cancer made me skittish, I opted for S.S.R.I.’s taken the week immediately preceding my period. Though antidepressants normally take four to six weeks to become effective, in premenstrual women, as soon as S.S.R.I.’s are absorbed, they inhibit the enzyme 3-ß-HSD from metabolizing progesterone, and it’s the drop in progesterone that’s the culprit in premenstrual blues. The change is immediate and profound. Upon taking a pill, my mood lifts within 20 minutes. Incidentally, alcohol acts on the same receptors, so a glass of wine potentially has the same effect." https://nyti.ms/2jP5goS

 

[DaveFoster]

I used to be able to gauge my thyroid pretty accurately from my pulse but since I started the lamotrigine, my pulse has been really high so I'm not sure how to tell if I'm taking too much at this point! I'm not planning on upping my dose much, just changing the actual medication. I do know if I'm not taking enough I get heart palps which seems like that's backwards, however I listened to an interview on the herb doctors where Peat discusses that thyroid and progesterone allow the heart to fully pump all the blood out instead of "waterlogging." I wish I could remember the actual interview. So if I'm getting palps I actually take a bit of thyroid right away and it will go away. I have noticed with NDT I sometimes have to take more than what I take with synthetics, that is why I'm hoping the combo of cynomel with tyromax will be ideal.

Thank you. That's all very good info, and very unfortunate for the lamotrigine. I started taking more because I figured it would allow me to increase my thyroid dosage more rapidly, as I'd be able to tolerate the ensuing anxiety, but I suppose not.

I was wondering what you make of this excerpt from an old NY Times article discussing PMDD:

"my new psychiatrist concluded that I did not suffer from bipolar disorder complicated by PME, but rather only from PMDD. Mood stabilizers don’t work on PMDD. Instead, low doses of hormones, including birth controlpills, are often prescribed, as are S.S.R.I.’s. Research has also shown a positive effect from calcium supplements, light therapy and cognitive therapy.

Because evidence of the link between hormone replacement therapy and breast cancer made me skittish, I opted for S.S.R.I.’s taken the week immediately preceding my period. Though antidepressants normally take four to six weeks to become effective, in premenstrual women, as soon as S.S.R.I.’s are absorbed, they inhibit the enzyme 3-ß-HSD from metabolizing progesterone, and it’s the drop in progesterone that’s the culprit in premenstrual blues. The change is immediate and profound. Upon taking a pill, my mood lifts within 20 minutes. Incidentally, alcohol acts on the same receptors, so a glass of wine potentially has the same effect." All the Rage

Unfortunately the "selective" properties of many serotonergic antidepressants tend to increase circulating cortisol while opposing cortisol's effects in the brain.