25 replies to this topic

[Default8]

So I'm on Sodium Valproate for bipolar and lately it has been causing huge problems with focus and attention (looking for solutions is what lead me to longcity). I have found that Sodium Valproate is know to cause cognitive impairment and I am seeing my doctor tomorrow and I'm thinking I'll ask to get put me on Lamotrigine which has shown to cause some of the least cognitive impairment for first line mood stabilisers. I am thinking of taking this with Memantine as it is apparently both neuroprotective and anti-inflamitory but have read some conflicting opinions about memantine here with some saying it's anti-nootropic.

• Firstly would anyone have any reason why Lamotrigine and Memantine should not be combined, any better alternatives?

• I would also like to try Piracetam, Lion's Mane and currently taking Bacopa. Would Memantine be bad with these? Any better Nootropic solutions?

• Another alternative mood stabiliser that has little cognitive impairment is Oxcarbazepine and it seems to have less side effects but little saying that it actually works, any opinions?

• One last question, I really wanted to try Riluzole until I realised that it's ridiculously expensive. It is now available as a generic medicine, do prices of medicines drastically go down after a while when this happens or will it be likely that Riluzole will not be affordable for a long time.

Sorry for all of the questions. I would be very grateful if anyone could answer just one of them at least.

[Default8]

So just realised that Lamotrigine inhibits glutamate release. Would this combined with Memantine acting as an unselective antagonist at NMDA-type glutamate receptors cause a combined effect at decreaseing glutamate activity? Oxcarbazepine seems to also inhibit NMDA but that is from one in vivo test and I can't find out anthing more on this :/

But then I find "Similar potency of carbamazepine, oxcarbazepine, and lamotrigine in inhibiting the release of glutamate and other neurotransmitters" which thinks it's doubtful... I don't know what to think.

Edited by Default8, 19 June 2013 - 01:04 PM.

[Tom_]

Standard second option after Valp acid is lithium. Not pleasnt side effects at higher doses but at very low doses people often use it for its nootropic effects.

Low does AAP (atypical anti-psychotic). Aripiprazole is actually a D2 parital agonist.

I wouldn't recommend Lamotrigine due to lack of evidence for efficacy.

[Default8]

I can't post links yet but there is a study done called "Comparative Neurocognitive Effects of 5 Psychotropic Anticonvulsants and Lithium" although it is only a meta-analysis and isn't a study with randomised drug allocation it shows lithium to give poor cognitive flexibility and attention. Maybe I should just go for really low dose of lithium and aripiprazole... I actually thought Aripiprazole lacked evidence and Lithium side effects worried me but just read a study showing Aripiprazole adjunctive to Lithium increased time to relapse.

Edited by Default8, 20 June 2013 - 01:53 AM.

[Tom_]

There is no point in trying low dose. Look for your sweet spot. If the dose is casuing unwanted side effects then swap drugs.

Do you have type 1 or 2 bi-polar? Fast switching? How fast? Primary mood state (depressed, manic, mixed, eythmic), any other problems (anxiety, personaluty disorder etc)?

I would trial at least two AAP's before going to lithium. Aripiprazole is appoved for Bi-polar and there is evdence behind it.

Maybe reducing the dose of acid and introducing the Aripiprazole. A dose of between 500-1000 and 10-15 mg respectively might be effective. If you are suffering with a lot of depression Agomelatine might be a very useful antidepressant.

While I would never recommend it even as an adjunct to a normal antimanic or antipsychotic Omega 3 at does of 1-3 grams have evidence for mood stabilzing effects. I would take that simply dueto lack of side effects and inability to hurt.

[Default8]

My doctor never told me if it is Bipolar I or II. I had one episode that I would classify as mania. And I would say I have more hypomanic episodes then depressed and ultra-rapid cycling, some weeks it may be day to day. No anxiety problems or personality disorders.

The side effects of Aripiprazole scare me a bit, are they not that bad and what's it's cognitive impact like?

Edited by Default8, 20 June 2013 - 02:33 AM.

[Default8]

There is a study called "Neurocognitive effects of aripiprazole in adolescents and young adults with bipolar disorder." which suggest it might help.

Thanks for the suggestion I'll see if my doctor agrees and I hope I can try it.

[Tom_]

Ultra rapid cycling is already setting alarm bells off in my head for it not being a 'pure' Bipolar variant - don't get me wrong, they do exist but they are rare. Changing at a speed like that ususally implies personality disorder or something else is in the mix.

What are your hypo/mania's like?
What about the depressive episodes?

I would compare the side effects of acid and Aripiprazole at about even. If you intend to use a lower dose of both you (500-1000 and 10-15) that should be fine.

I'm assuming you are well controlled and at the moment either having no episodes or very mild ones?

I recommend you continue with your normal dose of acid while you start the Aripiprazole and then slowly VERY slowly decrease the dose.

There is also evidence of efficacy for .3mg T3 in slowing down rapid cycling. (Some for T4 but I'm not as well versed in the research).

[Default8]

Before Valproate hypomanias were like I'm on ecstacy; feel awesome, body feels awesome, racing thoughts and coming up with lots great schemes and ideas. My biggest episode I had one day where I felt out of it and kind of like I had smoked marijuana which worried me. These normally peaked for a few days but the bigger ones would last about a week. I've had a few hypomanias on Valproate, both at times when I have reduced my dose and they lacked the ecstacy feeling and were more racing thoughts and over excitement.

I have only had a few severe depressions but quite a few minor periods or even just days of being depressed. The biggest thing I feel when depressed is lack of enjoyment in activities and lack of motivation. Also I physically just feel uncomfortable.

Honestly if there was something else I wouldn't be surprised with ADHD but I would be surprised if it's a personality disorder. I originally thought my lack of attention from the valproate could of been from a co-morbid ADHD but my doctor assumed it was the Valproate.

[Tom_]

I'd stick with my advice.

[penisbreath]

look into Keppra

[Default8]

I have a bit but have yet to find anything beyond theoretical reasoning as to it's effectiveness. It's a good one to keep in mind if other options don't work though.

[stablemind]

If you have issues with sleep as well look into Seroquel. It's helps me knock out every night and controls my mood very well.

[Tom_]

Quetiapine is known to kill cognitive functioning. If he is worried about the side effects of Aripiprazole then you will have a hard time selling him on Quetiapine.

[Default8]

I don't have problems with sleeping so I think Aripirazole suits me better than Seroquel not including the side effects.

My doctor was happy with the idea of Aripiprazole. I'm starting on 5mg and apart from having a pretty bad headache for the first night seems to be tolerable so far. I tried talking to him about neuroprotective supplements but he seemed to have the traditional view that you treat bipolar purely by trying to stabilise mood with antipsychotics, anticonvulsants and antidepressants and said cognitive impairment is only from mania episodes. There seems to be a huge amount of papers showing cognitive impairment in euthymic bipolar patients. Most interesting is this study http://www.ncbi.nlm....pubmed/23232419 which thinks that the link between episodes and cognitive impairment might be the impairment causing increased episodes. I haven't dealt with psychiatrists very much, will most be pretty closed minded to new research? Should I be looking for non-perscription things that will offer neuroprotection? NAC, Fish Oil, anything else???

[hani]

The results did not support the hypothesis that the experience of successive episodes is related to a progressive neurocognitive decline. On the contrary, cognitive impairment could be the cause more than the consequence of poorer clinical course.

So basically the cognitive impairment increases the frequency of episodes not the other way round?

Also, I have a question. Has their been a study that shows euthymic cognitive impairment in unmedicated individuals? The medications that bipolar patients take are quite strong, so surely they might have a strong effect on intelligence and cognitive functioning.

[hani]

Some studies:

A comparison of cognitive functioning in medicated and unmedicated subjects with bipolar depression

Deficits in affective processing were found in the medicated group, while unmedicated subjects appear to be unaffected. In particular, the MBD group made more errors during happy conditions, indicating a potential attentional bias in subjects with bipolar depression on mood-stabilizing medications. The present study also implicates impairment in sustained attention for medicated subjects with bipolar disorder, particularly those with the type II variety.

Distinct profiles of neurocognitive function in unmedicated unipolar depression and bipolar II depression.

These data indicate differing profiles of cognitive impairment in unmedicated depressed MDD versus BDII subjects. Moderately depressed BDII subjects displayed relatively intact cognitive function, whereas MDD subjects demonstrated a broader range of executive impairments. These cognitive deficits in depression were not attributable to current medication status.

Neurocognitive function in unmedicated manic and medicated euthymic pediatric bipolar patients.

The absence of differences in the deficits of neurocognitive profiles between acutely ill unmedicated patients and euthymic medicated patients suggests that these impairments are trait-like characteristics of pediatric bipolar disorder. The cognitive deficits found in individuals with pediatric bipolar disorder suggest significant involvement of frontal lobe systems supporting working memory and mesial temporal lobe systems supporting verbal memory, regardless of ADHD comorbidity.

The last one relates to pediatric patients, so maybe if bipolar hits early when the brain is still forming, cognitive impairment occurs.

[Tom_]

I'll make this as clear as possible. There is nothing else with any evidence (good and repeated) to support mood stabilzing effects apart from some anti-psychotics, Li+ and antiepeleptics.

Adding Omega 3 is harmless but I would wait two weeks after you have stopped titrating with Aririprazol so you can see if it has any positive effect.

[Default8]

I wasn't talking about mood stabilising effects, I'm talking about neuroprotective hence the Memantine at the start. I would rather be a bit unstable without cognitive impairment then stable but with loss of cognitive function.

[Tom_]

The evidence is pretty clear, cognitive impairment is a side effect of Bi-polar. It is admittedly also a side effect of some meds. Neuroprotective is entirely new, you were asking for improved cognitive function.

If you want to risk it you can add in modafinil but if its main action is dopamine, I don't want to be around there when you flip your shit.

[Default8]

I'll put up a bunch of my research that I have done which might explain some of my reasoning for Fish Oil and NAC... keep in mind I am kind of out of it especially since starting aripiprazole :P

Oxidative stress markers in bipolar disorder: A meta-analysis

Results

Thiobarbituric acidic reactive substances (TBARS) (p = 0.001) as well as NO activity (p = 0.02) were significantly increased in BD with a large effect size for TBARS and a moderate effect size for increase in NO. No significant effect sizes were observed for the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase (all p>0.05).
Conclusions

The present meta-analysis suggests that oxidative stress markers are increased in BD and that oxidative stress may play a role in the pathophysiology of BD.

Synergist effects of n-acetylcysteine and deferoxamine treatment on behavioral and oxidative parameters induced by chronic mild stress in rats.

Treatment with NAC and DFX decreased the oxidative damage, which include superoxide and TBARS production in submitochondrial particles, and also thiobarbituric acid reactive substances (TBARS) levels and carbonyl proteins in the prefrontal cortex, amygdala and hippocampus. Treatment with NAC and DFX also increased the activity of the antioxidant enzymes, superoxide dismutase and catalase in the same brain areas...

...In conclusion, these results suggests that treatment with NAC or DFX alone or in combination on oxidative stress parameters could have positive effects against neuronal damage caused by oxidative stress in major depressive disorders.

Increased oxidative stress as a mechanism for decreased BDNF levels in acute manic episodes.

RESULTS:

Serum thiobarbituric acid reactive substances and brain-derived neurotrophic factor levels were negatively correlated in bipolar disorder patients (r = -0.56; p = 0.001), whereas no significant correlation was observed in the control group..
CONCLUSION:

These results suggest that alterations in oxidative status may be mechanistically associated with abnormal low levels of brain-derived neurotrophic factor observed in individuals with bipolar disorder.

Elevated C-reactive protein and cognitive deficits in individuals with bipolar disorder

Conclusions

Inflammation may play a major role in the cognitive deficits associated with bipolar disorder.

Association between use of specialty dietary supplements and C-reactive protein concentrations.

These results suggest that glucosamine and chondroitin supplements are associated with reduced inflammation in humans and provide further evidence to support an inverse association between use of fish oil supplements and inflammation.

(All fish oil studies seem to be about serium levels and there are probably more well proven options but fish oil is cheap)

Selective DNA methylation of BDNF promoter in bipolar disorder: differences among patients with BDI and BDII.

Present findings suggest selective changes in DNA methylation of BDNF promoter in subjects with BD type II and highlight the importance of epigenetic factors in mediating the onset and/or susceptibility to BD, providing new insight into the mechanisms of gene expression. Moreover, they shed light on possible mechanisms of action of mood-stabilizing compounds vs antidepressants in the treatment of BD, pointing out that BDNF regulation might be a key target for their effects.

So my goal is try to both reduce oxidative stress, inflammation and increase/regulate BDNF levels. So NAC/Memantine for oxiditve stress, Fish Oil/Memantine for inflammation and nootropics for BDNF levels, plus a traditional bipolar treatment too.

Interestingly the last study found that Valproate (which I was on) increases BDNF although another study "Valproate Alters Dopamine Signaling in Association with Induction of Par-4 Protein Expression" (and another one as well) found it reduced cAMP levels which would likely reduce BDNF and TrkB binding so making BDNF less useful.

If you are really interested one of the more interesting things on Valproate that I found which had suspect credibility was this... https://helda.helsin...dle/10138/38112



I actually did try Modafinil in a desperate attempt to help me focus for exams but it didn't help with the memory problems in the short term and yeah I don't think I will ever chronically use Modafinil.

Edited by Default8, 23 June 2013 - 11:30 AM.

[Becoming1]

Hi there,
I suffer from big polar without a diagnosis of type.
I use seroquel/quetiapine right now but my day to day functioning suffers dramatically.
I don't have the knowledge or understandind that you guys have here and am desperate to relieve my depression and live a more fulfilling life.
I take 400mg at night of seroquel and it leaves me sluggish,dull and seems to take the colour out of my life.
I have been informed that a detox using zeolites would be a good place to start so that any toxins that may be exaserbating my condition can be taken out of the equation.
what have you settled on and what is working at the moment?

[BarbCat]

I have much experience with almost all of the bipolar meds and the atypicals.  I'll say this once and many times to come.  Stay away from the atypicals.  Run like hell.  They make you fat, real fat real quick, and no amount of dieting or exercise will do a thing until you try and try to get off them.  They are a very potent antihistamine.  This in large part is why they 'work', especially with sleep, but have the effect of actually raising histamine in a backlash manner, and trying to get off them is awful.  Excess histamine causes symptoms of bipolar, insomnia, racing heart, GERD and it's a vicious cycle.  I've been on most of the atypicals and they're all deadly.  After a spell with Risperdal, my husband had to feed me, dress me and speak for me for 6 months, and guys aren't the only ones who get moobs on this crap.  Guys may not think that huge boobs would be a problem for women, but try lugging around 40 pounds of moobs!  Atypicals are a dopamine antagonist, and dopamine is needed to make endorphins, so your life will definitely look less bright and devoid of soothing.

 

I haven't tried Latuda (very expensive) but heard it works better than the other APs.  If you have anxiety, trileptal (Oxcarbazepine) may increase it.  Lamictal IMO is probably the best of the usual bipolar meds but didn't really help that much.  Depakote is a stooopid drug and lithium at the therapeutic doses will cause tremors and hypothyroid, but probably the least harmful of them at lower doses but doesn't help much during the depressive stage.  I'm looking forward to sourcing some nitromementine and am currently and recently trying mementine.  My problem may not be bipolar after all but other things that look like bipolar.  A copper imbalance can also cause bipolar symptoms, but you need to get tested since messing around with copper, high or low, can cause big problems.  I'll look into zeolite because I have mold toxicity and want to get it out.  Mold toxicity causes neurological problems.

Edited by BarbCat, 18 April 2015 - 09:14 PM.

[ExtraCrispy]

I think some of you seem to totally ignore the fact that certain medications and substances have different effects on different people.  Just because something doesn't work for you doesn't mean it won't work for them.  Lamictal was incredibly effective for me for the time I was on it.

[twistednerve]

I think some of you seem to totally ignore the fact that certain medications and substances have different effects on different people.  Just because something doesn't work for you doesn't mean it won't work for them.  Lamictal was incredibly effective for me for the time I was on it.

 

Sadly, I agree. Seroquel is actually lowering my appetite and making me more energetic.

 

Very atypical for an atypical, though. 

[graatch]

Would this combined with Memantine acting as an unselective antagonist at NMDA-type glutamate receptors cause a combined effect at decreaseing glutamate activity?

 

Yes. It also prevents NMDA antagonist neurotoxicity, if you believe that takes place in humans; NMDA antagonist neurotoxicity seems to occur due to a secondary overexcitation of glutamate in specific areas, and in any case is aggravated in rats by coadministration with acetylcholinesterase inhibitors, such as donepezil. Which may be the reason that the donepezil-memantine combination seems to cause faster decline in dementia patients. We need more data on that.

 

I would be concerned about preserving long-term potentiation if lamotrigine was combined with memantine, but perhaps with the addition of certain things this could be helped: psychostimulants, things which increase glutamate binding such as piracetam or nicotine, etc.

 

(At the same time, NMDA antagonist neurotoxicity has also been thought to be due to a disruption of acute LTP processes needed for neuronal survival, but the fact that anticonvulsants, benzodiazepines, barbiturates, α2A agonists prevent it is a fairly strong vote against that theory in my opinion.)

Edited by graatch, 08 October 2019 - 07:11 AM.