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I'm a newbie so I'm likely making a mistake posting my question here so apologizing ahead of time. I've been a fan of crazymeds web site for years and love all the useful information. My question is with all the new SNRIs ava and the implications of trying to titrate off them why aren't prescribers not trying a std SSRI with Wellbutrin. This would make it easier to modulate the effect on norepinephrine and dopamine vs one pill that has a fixed impact. I know it's been prescribed by some but what's the point of the SNRIs if you can accomplish the same with two pills and adjust the doses to get the best effect?

Thanks
Matt

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Wellbutrin + Abilify is popular and Abilify acts on serotonin.

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Different meds have different metabolism speed with different users and we are not yet talking about cross-effects and interactions. If one drug (one active substance) can take care of one's symptoms it will probably be selected over mixing several drugs.

That aside, many times people, including me and many on this board, need to take more than one med eventually.

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Hey HydroCat,

Thanks for the feedback. That makes sense to me.

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Well, @Matt G, it's kind of a loaded question. We have to actually look at why doctors use Wellbutrin augmentation in the first place and some situations where it isn't so suitable.

Arguably one of the most common combinations is Lexapro + Wellbutrin. Lexapro is not the most potent SSRI for serotonin, but it is the most selective. In light of their experiences with tricyclic antidepressants and understanding that the extra activities could contribute to side effects, Lexapro + Wellbutrin was arguably a "clean" SNDRI (serotonin-norepinephrine-dopamine reuptake inhibitor) alternative to something like a tricyclic which was more multi-faceted, so to speak.

One of the things that most patients don't realize is that Wellbutrin has inhibiting effects on the liver enzymes that metabolize most SSRIs and tricyclic antidepressant, specifically CYP2D6. This means that taking Wellbutrin with Lexapro actually increases the blood levels of Lexapro and would then theoretically increase its effectiveness not counting for the new noradrenergic and dopaminergic activity from Wellbutrin.

Therefore, knowing that Wellbutrin can impact metabolism of other medications, there are a few SSRIs that are immediately off the table except in situations were the doctor is experienced with the combination or most other options have been tried:

Prozac (fluoxetine)

Paxil (paroxetine)

Luvox (fluvoxamine)

All of these SSRIs inhibit liver enzymes like Wellbutrin does, and this creates a "feedback loop" where Paxil will inhibit itself and Wellbutrin, and then Wellbutrin will further inhibit Prozac and so on and so forth. This doesn't go to toxic infinity or anything. It does level out. But as you can imagine, you have to use very low doses for several weeks to make sure you don't develop serotonin syndrome from the increased blood levels of the SSRI.

However, doctors have been taking advantage of these metabolic interactions for years as they've become part of the synergistic effect of monoamine reuptake inhibition.

To your question of why a doctor wouldn't use an SSRI + Wellbutrin instead of an SNRI is a matter of case-by-case basis. It depends on the balance of serotonergic to noradrenergic activity of the SNRI as opposed to what can be accomplished with SSRI + Wellbutrin. For example, Effexor at 37.5mg-75mg is just an SSRI, when you get to 150mg, it becomes an SNRI with much higher affinity for serotonin. Getting to 225mg-300mg, the noradrenergic activity is stronger but still less than serotonergic activity. Once you get above 300mg, you actually start to experience dopamine reuptake inhibition as well. Pristiq (the child metabolite drug - desvenlafaxine/O-desmethylvenlafaxine) on the other hand is almost strictly an SNRI and doesn't seem to touch dopamine in higher doses like its parent drug. Cymbalta also doesn't seem to touch the dopamine transporter but has an almost perfectly balanced affinity for serotonin and norepinephrine compared to Effexor and Pristiq and is much more potent of an SNRI than Effexor or Pristiq. Then of course there's Fetzima, which is actually stronger for norepinephrine than serotonin.

Wellbutrin is mostly a norepinephrine reuptake inhibitor. While it is classified as an NDRI, its affinity for the dopamine transporter is still negligible and most likely more of the elevated dopaminergic activity in the brain during Wellbutrin treatment is downstream to the increases in norepinephrine.

Some people just can't tolerate Wellbutrin. It works fairly well for me as an antidepressant but it can make me irritable and can really antagonize my anxiety. I found Aplenzin to be a better formulation of bupropion than Wellbutrin. Smoother, less jitters. However, many people who can't tolerate Wellbutrin can't tolerate SNRIs like Cymbalta for the same reasons....too stimulating. Cymbalta actually caused me to rapidly cycle. Granted I wasn't taking a mood stabilizer at that point, but hey....

So because doctors now know that Wellbutrin doesn't actually have as much direct effect on dopamine levels in the brain as they originally thought and because there are now more SNRIs available, it's still seen as preferrable to manage with as few medications as possible. However, Wellbutrin is still primo when it comes to addressing SSRI-induced side effects like weight gain, sexual dysfunction, apathy, anhedonia, energy/motivation, etc. Additionally, doctors have found more effective ways to increase dopamine levels through the serotonergic system with receptor blockage. For example, Trintellix is a potent SSRI and 5HT3 receptor antagonist. Blockade of 5HT3 inhibits GABA firing and increases glutamate release. It also increases the release of norepinephrine, dopamine, histamine, and acetylcholine, all contributing to increased alertness and cognition. 5HT1A agonism by Trintellix, Viibryd, and even Buspar also increases downstream dopamine release. The newer atypical antipsychotics are also often 5HT1A partial agonists which is why coupling them with an antidepressant like an SSRI can improve treatment response. SSRIs indiscriminately increase serotonin levels and activation of serotonin receptors can actually decrease dopamine signaling in certain situations.

Essentially, we've found more effective and efficient ways to modulate norepinephrine and dopamine along with glutamate and acetylcholine without the need for Wellbutrin.

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Thanks. Clearly you have a Chem E or Pharma background. I appreciate the technical information. I love to read about these meds, interactions etc. I'm currently on paxil 15mg for 12 yrs and wellbuutrin 50mg for 4 yrs. I was on .25mg of Klonopin for 11 yrs but titrated off it for a year and now been off for 10 months. I find myself very med sensitive. Small doses seem to have big impacts. My paxil finally pooped out on me about 6 months ago. I got the liquid form and am titrating very slowly down to a point where I can switch over to something like Effexor. I'm working with a young knowledgeable doctor and he recommend that one. I did ok on Paxil and the Wellbutrin helped with the brain fog. I know I'm probably on sub-thearuputic doses but instead of increased dose I'd prefer to try a different med. I suffer from mild depression and anxiety.

Thanks

Matt

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9 minutes ago, Matt G said:

Thanks. Clearly you have a Chem E or Pharma background. I appreciate the technical information. I love to read about these meds, interactions etc. I'm currently on paxil 15mg for 12 yrs and wellbuutrin 50mg for 4 yrs. I was on .25mg of Klonopin for 11 yrs but titrated off it for a year and now been off for 10 months. I find myself very med sensitive. Small doses seem to have big impacts. My paxil finally pooped out on me about 6 months ago. I got the liquid form and am titrating very slowly down to a point where I can switch over to something like Effexor. I'm working with a young knowledgeable doctor and he recommend that one. I did ok on Paxil and the Wellbutrin helped with the brain fog. I know I'm probably on sub-thearuputic doses but instead of increased dose I'd prefer to try a different med. I suffer from mild depression and anxiety.

Thanks

Matt

Lol actually I'm in Information Technology. I just find this stuff fascinating so I read more than is probably good for me :P

Interesting that you're already on the Paxil and Wellbutrin combination. I have to say it can be a very good thing to have a young doctor because they're taught with the latest and greatest that we know and they're usually more adventurous or "heroic" in their attempts.

In most cases though if you reach poop-out with an antidepressant, it's good to try a new one than push the dose and potentially introduce more side effects without improving efficacy.

Effexor is definitely a good choice. It pooped out on me and I switched to Cymbalta. I never went higher than 150mg though. I also wasn't taking a mood stabilizer at the time. So it's quite possible that it wasn't pooping out on me at all and I was actually experiencing a bipolar depressive episode that an antidepressant wouldn't have been able to effectively help. Switching to Cymbalta only kicked my cycling into overdrive until I finally switched to Lamictal. Definitely would recommend Lamictal as an augment to the Effexor if it doesn't work on its own or poops out on you.

You won't be continuing the Wellbutrin when you switch to Effexor will you?

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LOL.. Your like me.. I'm an engineer and read more than I probable should as well. I agree 100% on the whole dosing thing. I think they should make all these meds in a liquid formulation. I understand that most doctors want to just go with the std dose but I wonder how many people would be able to get by with less and have min size effects. I think a lot of people give up on a drug because of side effects but likely could get the effect they need at a smaller dose. Plus,, you can go slow up and down and this would seem like a logical way to go. For example for me.. It's possible I could get another few years out of Paxil at 17 mg instead of 15 mg.. Not sure.. I often wonder if i'm bipolar 2. I have several friends that are bipolar 1 and 2. I've looked at the criteria many times and just can't quite get there. I even got a script from another progressive doc that moved and had me try a small dose of lithium. I read a ton on lithium also. They are now saying that lithium in low doses can be very good for people that are depressed. You just rarely hear about it because big phara isn't making any money on it. If I go with Effexor I will stop the Wellbutrin for sure. Doc already mentioned that.

How did you know you were bipolar 2 and how long for you to figure it out? The other thing is I read that approx... Only 1% of the population has Bipolor 2.. I know I'm not 1.. No way. 

I read the criteria and say to myself .. yea maybe but it's so subjective I'm just now sure.

Thanks for helping.
matt

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15 minutes ago, Matt G said:

LOL.. Your like me.. I'm an engineer and read more than I probable should as well. I agree 100% on the whole dosing thing. I think they should make all these meds in a liquid formulation. I understand that most doctors want to just go with the std dose but I wonder how many people would be able to get by with less and have min size effects. I think a lot of people give up on a drug because of side effects but likely could get the effect they need at a smaller dose. Plus,, you can go slow up and down and this would seem like a logical way to go. For example for me.. It's possible I could get another few years out of Paxil at 17 mg instead of 15 mg.. Not sure.. I often wonder if i'm bipolar 2. I have several friends that are bipolar 1 and 2. I've looked at the criteria many times and just can't quite get there. I even got a script from another progressive doc that moved and had me try a small dose of lithium. I read a ton on lithium also. They are now saying that lithium in low doses can be very good for people that are depressed. You just rarely hear about it because big phara isn't making any money on it. If I go with Effexor I will stop the Wellbutrin for sure. Doc already mentioned that.

How did you know you were bipolar 2 and how long for you to figure it out? The other thing is I read that approx... Only 1% of the population has Bipolor 2.. I know I'm not 1.. No way. 

I read the criteria and say to myself .. yea maybe but it's so subjective I'm just now sure.

Thanks for helping.
matt

Actually statistically speaking they're finding that bipolar 2 is actually more common than major depressive disorder in some regards, it's just so often misdagnosed. A patient's diagnosis is changed as the pdoc and tdoc get wise to what's happening....and the patient for that matter. I recently participated in a 9-month study that 23andMe did on patients with major depressive disorder and bipolar disorder who took their DNA test. I think I was one of maybe 5,000-10,000 people with bipolar disorder in the study. The results of the study showed that about 45% of the people in the study with bipolar disorder (both types) previously had a diagnosis of major depressive disorder. That's high, like REALLY high. I mean it's almost HALF.

Keep in mind that bipolar 2 disorder is so often misdiagnosed because more time is spent in the depressed phase of the mood cycle, and the hypomanic episodes that are experienced in between are subtle to the objective eye. A patient may simply appear to be cheery and chipper. Easily excitable. And the patient is usually not delusional or psychotic as is more common in full manic episodes, but they may have a persistent "nothing's gonna get me down" kinda mood, a subjective experience of invincibility.

When there are no other medications involved and you introduce an antidepressant, one of two things can happen. The person can simply enter hypomania and stay there for a few days, to a few weeks, to a couple months and then "crash". It seems like the antidepressant is pooping out. In some cases it is, but in others it could just be the normal bipolar depression that comes after hypomania. It's part of the cycle. The alternative to this is the antidepressant causes rapid-cycling where your mood may switch a few times a week to a few times per day. I do believe from a statistics perspective, the younger the age of the person, the more mood switches will occur in a given period.

People with Bipolar 2 are effectively high-functioning individuals that get by just fairly well in society. They often go a very long time without diagnosis. For me, I've been experiencing depression pretty much ever since I hit puberty, which was a tad early actually, about 5th grade when it began if I recall correctly. By 7th grade I had to be put on antidepressants. Took 50mg of sertraline from maybe 2003 to 2005. Went off meds through high school. Not sure how I made it through. Then my freshman year of college (fall/winter 2009) the depression hit in full force. Started on citalopram, progressively increasing it as it "pooped out" until I hit the 40mg max. From there we added bupropion, which made me super amped and agitated. But my pdoc didn't catch it for what it was. So I was switched to Viibryd (vilazodone), that definitely made me hypomanic and made me rapidly cycle, but at some point I felt like I was losing motivation or something so we switched to Pristiq (desvenlafaxine), which I actually really liked. Only reason I switched from that one was because new insurance wouldn't cover it. Next to Effexor XR (venlafaxine) which pooped out. Then switched to Cymbalta (duloxetine) which made me rapidly cycle and really kind of hyper. Became a workaholic. Things. Finally started seeing a new psychiatrist in 2013 who immediately spotted it for what it was, cut my Cymbalta in half and started me on Lamictal (lamotrigine). Boy was that a rough couple of weeks. However, when I was finally titrated all the way to 200mg of Lamictal and was off the Cymbalta, I was still mildly depressed but I was more stable than I had ever been. Most importantly, when I would start to get worked up I could always come down from it more easily. Things like depressed days or hypomanic days really became a thing of the past because all of it was really muted.

Ultimately here I am today on Depakote, Trintellix, Rexulti, and Vyvanse. I've been on this combination of meds since September of last year, which I believe is the longest I've gone on the same meds without switching something. Ultimately the quality of my life has improved significantly. Most importantly, I'm not getting in trouble anymore the way that I used to. I got my DUI when I was taking Effexor XR without mood stabilizers. And most of my abuse of drugs over the years has been while I wasn't on a mood stabilizer. I'm far less impulsive than I was before 2013. I've also become much more responsible when it comes to my career, simple things like getting to work on time. But to the average on-looker, it would just appear as if I didn't have my shit together before and now I've figured it out. But in my head I have learned over the years that there's so much more to it than that.

All-in-all, asking yourself if you're bipolar is kind of a silly question. Unless MAYBE if you're Bipolar 1 in which case it may be much more obvious. What you're truly looking for are the behaviors that have defined you. Things like recklessness and risk-taking are common red flags. Promiscuous/unsafe sex could be another one. It could seem like ADHD too. Bipolar Disorder and ADHD have a lot of crossover. Another good thing to look at is if you've been through several antidepressants and feel like nothing works. That's usually not a good sign either.

You are right that there is some decent evidence to support low-dose augmentation with lithium to an antidepressant for unipolar depression. Same with Buspar (buspirone) as well as thyroid hormones like Synthroid (levothyroxine) or Cytomel (liothyronine). There seems to be some evidence for Lamictal (lamotrigine) augmentation to an antidepressant as well as Ritalin (methylphenidate). The Ritalin augmentation success can probably be explained by the same reason bupropion augmentation is so popular.

For me, with the 23andMe and AncestryDNA tests, I've taken the time to identify some of my genes that could potentially be dysfunctional. Went over the data with my pdoc, who isn't as knowledgeable about personalized therapeutics but went along for the ride and reviewed some of the studies I was able to pull based on the various polymorphisms. Ultimately the combination that I'm on now addresses several of my issues at various different levels. I'm a low MAOA producer, which is what Depakote is for. I'm also a low COMT producer, which is what Rexulti and Vyvanse are for. Low COMT and MAOA would be associated with elevated levels of neurotransmitters in the brain that could prove problematic and contribute to my mood swings. Tagging on what @notloki said earlier, the combo of amphetamines + Abilify or Wellbutrin + Abilify is actually really popular. All 3 of those medications increase the expression of COMT which would encourage the breakdown of dopamine, epinephrine, and norepinephrine. 

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Dam, You should change careers. You likely have much more knowledge on these meds than most doctors. My buddy was on depacoat before lithium. One question for you is how hard was the change on the meds you listed? It can be hard for some people to transition between them so just curious.

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Well it was like starting the medication merry-go-round all over again. Except instead of trying to find the right antidepressant, we were now looking for the right mood stabilizer. Some were awful. Some worked well. And don't get me wrong there was plenty of misery throughout the process as I tried things that didn't work. We started with just lamotrigine. It actually stabilized my moods really well, but I was left with a persistent, dull depression. We then toyed with adding an antipsychotic. So I started on lurasidone with the lamotrigine. This improved the depression some, but I still wasn't right. We cycled through several antipsychotics (asenapine, iloperidone, loxapine, aripiprazole, olanzapine) before we finally decided to try a combination of an anticonvulsant+antidepressant+antispychotic. This time I could definitely tell we were getting closer because I did much better on the combo of those 3 types of meds than on an anticonvulsant and antipsychotic and no antidepressant.

Ultimately while on mood stabilizers I went through fluoxetine, escitalopram, and bupropion. Of those three, fluoxetine was arguably the best for my depression. Escitalopram did really well too but it demotivated me and reminded me a lot of citalopram. Bupropion was probably better in that it didn't cause any mood switches for me. However, it did make my anxiety and irritability worse. And irritability is a tough symptom for me.

Finally, I switched to Trintellix and it was a game changer. Mind you during this time as well I also swapped out the lamotrigine for oxcarbazepine, which was a major improvement over the lamotrigine but didn't have as much anti-manic effect as I needed. Finally we switched the oxcarbazepine to valproate and I haven't looked back since.

In short, I started on this adventure in late 2013 but I didn't actually get to the right combo of meds until probably September of last year. It took quite a while, but it was so worth it now that I've finally found the right ones. It makes a huge difference in my day and overall quality of life. As I got to the right medications, my sleep came in check as well as my anxiety. Things just started falling into place with the help of a little therapy.

However, the genetics involved really encouraged me to take the bull by the horns and get more specific with the medication hunt. Another fear that I shed along the way was a fear of multiple medications. Being on too much stuff. I had to get past that in order to get here. And most likely I could have arrived at this point sooner if I wasn't so resistant. I was pretty resistant to valproate (Depakote) especially because of all the horror stories I heard. Except I've been on it now since maybe October of last year and haven't had any real side effects that I can put my finger on except my male-pattern baldness has accelerated a bit and I MIGHT have put on a bit of weight, but Trintellix and Rexulti can both cause weight gain as well. So I never read into it.

I was also very resistant to olanzapine because of the effects on weight, glucose and lipids, but ultimately I did try it and found that it was the one and only antipsychotic that helped both my depression and my hypomania at the same time. I didn't stay on it because I did end up gaining quite a bit of weight as I feared, but if I hadn't at least tried it I never would have known that I could go back to olanzapine in a crisis.

If someone is about to hop on the bipolar med merry-go-round for the first time, my advice is to keep an open mind and be willing to try new things.

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Your story is amazing. honestly I think what people struggle with is what is "feeling normal"? What is 'feeling happy" it depends alot on your reference point don't you think? I'm happy compared to a WW2 survivor but not sure compared to my next door neighbor. How did you know what feeling/mood you were looking for if you hadn't even experienced it? That's what I find most difficult. Plus, with kids, job, stress etc how can' one be sure what is influencing our moods vs genetics/ chemistry? Then add in the mix of not eating right, not enough excercise and drinking to much and it gets complicated real quick. I did take the genetic testing for the pysc meds.. It's interesting and shows how you metabolize which meds etc. I wish there was a blood test to indicate if you have Bipolar etc. I'm leaning toward not having Bipolar 2. What are your thoughts on the below info?

I must admit I can say that drinking to much contributes to bad behaviors.

 

One last question. Most of the meds you listed generally require 4-8 weeks to determine if they are working correct? It must have been pretty hard to cycle on and off them. Plus, you generally get all the side effects early on so right as you determine it doesn't work, you have to jump to the next one right?

I'm kinda scared of that.

 

Specific Symptoms of a Manic Episode

In order for a manic episode to be diagnosed, three (3) or more of the following symptoms must be present:

  • Inflated self-esteem or grandiosity
  • Decreased need for sleep (e.g., one feels rested after only 3 hours of sleep)
  • More talkative than usual or pressure to keep talking
  • Flight of ideas or subjective experience that thoughts are racing
  • Attention is easily drawn to unimportant or irrelevant items
  • Increase in goal-directed activity (either socially, at work or school; or sexually) or psychomotor agitation
  • Excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)

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19 hours ago, Matt G said:

Your story is amazing. honestly I think what people struggle with is what is "feeling normal"? What is 'feeling happy" it depends alot on your reference point don't you think?

Precisely. I didn't know what feeling "normal" was. In the beginning when the meds started stabilizing me, I didn't feel the hypomania's anymore. It FELT like my mood was JUST below the line. A dull depression. But as time went on, I came to realize that it probably wasn't a dull depression at all but rather that I just felt the way everyone else did. I had never felt that way before. It was indeed confusing. And that's what makes a bipolar diagnosis more of a long-term discovery process. When my pdoc told me that he thought I was bipolar I didn't believe him for a second but I looked back and realized I had just been going through one antidepressant after another and they all kinda stopped working. So I basically told myself I still didn't believe it, but I was going to go along with it because hey if things improved on bipolar meds instead of MDD meds, then maybe he was right.

19 hours ago, Matt G said:

I'm happy compared to a WW2 survivor but not sure compared to my next door neighbor. How did you know what feeling/mood you were looking for if you hadn't even experienced it? That's what I find most difficult. Plus, with kids, job, stress etc how can' one be sure what is influencing our moods vs genetics/ chemistry? Then add in the mix of not eating right, not enough excercise and drinking to much and it gets complicated real quick. I did take the genetic testing for the pysc meds.. It's interesting and shows how you metabolize which meds etc. I wish there was a blood test to indicate if you have Bipolar etc. I'm leaning toward not having Bipolar 2. What are your thoughts on the below info?

You are right. It's not all genetics. Food, exercise, and other things contribute. For example, the glutamate system has been implicated in bipolar disorder. Most people don't realize that gluten doesn't just sound similar to glutamate. Your body works with gluten as a precursor to glutamate, which is an excitatory chemical in the brain. This is why they sometimes encourage people with bipolar disorder to avoid simple carbs.

Genetics do pre-dispose you. For example, my sister also has mood issues, but she works out, eats well, specifically focusing on foods with nutrients that are good for the brain and overall mood. She still has difficulty from time to time, but she manages almost as well as I do, but I'm not as religious about physical activity and eating well as she is. However, there are certain things that can't be avoided. For example, as I said in a previous post, my sister and I both have a mutation on our MAOA gene which causes us to under-produce this enzyme. This leads to higher levels of serotonin, norepinephrine, and dopamine. I have underactive COMT as well (higher norepinephrine, epinephrine, and dopamine) but she is my half-sister so she didn't get that one. Adding insult to injury hormones impact the expression of both of these genes. So when my sister gets to that time of the month, she's likely to be much more moody than usual. Estrogen and progesterone both increase the expression of MAOA, reversing the mutation effectively and causes neurotransmitter levels to plunge. Decreased serotonin could lead to increased dopamine firing throughout the brain. Testosterone on the other hand DECREASES MAOA expression even further. I'm actually currently looking at my own hormone levels now because of these implications. You can see that the three major sex hormones have a profound effect on neurotransmitters, and the underlying problem could in fact be hormonal/endocrine in nature. In my case I have low COMT, but I also have low testosterone for someone my age, and testosterone is responsible for INCREASING COMT to reduce those neurotransmitters.

19 hours ago, Matt G said:

I must admit I can say that drinking to much contributes to bad behaviors.

Yeah alcohol causes increases in GABA and dopamine signaling, both of which would impact the reward system and lead to addiction.

19 hours ago, Matt G said:

One last question. Most of the meds you listed generally require 4-8 weeks to determine if they are working correct? It must have been pretty hard to cycle on and off them. Plus, you generally get all the side effects early on so right as you determine it doesn't work, you have to jump to the next one right?

I'm kinda scared of that.

Not necessarily. Trintellix starts working much faster than older antidepressants. It starts working faster than Prozac and takes about as long as Lexapro to start working. I do have to say that Rexulti did take a while to adjust to but when I did it was absolutely wonderful and a big deal for me to find an antipsychotic that had both mood stabilizing and antidepressant effects without TOO major side effects. I've had a bit of weight gain from Rexulti but the only other AP that was this effective OVERALL for me was olanzapine and that caused WAY more weight gain as well as changes in metabolic parameters on bloodwork (i.e. glucose, lipids)

Depakote works very quickly though. So does Vyvanse. However, with Vyvanse you almost have to wait until the initial burst of motivation wears off before you can tell how much it's doing for your focus/concentration.

Pay attention to the half-life of medications. The longer it is, the longer it will take for it to reach steady state in your system as well as clear your system. For example, Trintellix has a half-life of about 66 hours, and because it doesn't inhibit its own metabolism like Prozac or Paxil, the pharmacokinetics are linear and not a bell curve. A good rule of thumb for meds that don't inhibit their own metabolism is to take the half-life and multiply it by 5.5. This will tell you how many hours to reach steady state and how many hours to clear your system. So at 66 hours, that would be 363 hours or about 15 days. So basically you need to find a dose and stay at that dose for about 2 weeks before you decide if it is or isn't right for you or if you need to increase or decrease. Rexulti is longer with a half-life of 91 hours so it takes almost 3 weeks to truly reach steady state. For that reason, I was on 0.25mg of Rexulti for a month to 1.5 months before I finally adjusted and could start increasing the dose.

19 hours ago, Matt G said:
  • Inflated self-esteem or grandiosity

This is a tough one. Because when you read it, it doesn't give the right impression of what you're supposed to be looking for. Imagine feeling like you are capable of doing something one day, and then a few days later when you're depressed, that grandiose goal you set for yourself suddenly seems unattainable even though the circumstances haven't changed. For example, one day when I was a bit "elevated", I got it in my head that I wanted to change careers from IT to become a psych CRNP. Not a perfect example because I do think that one day if I do change careers, that's the direction I would go. But then again that would be a good example of how someone with bipolar disorder can channel their manic tendencies into useful productive activities.

19 hours ago, Matt G said:
  • Decreased need for sleep (e.g., one feels rested after only 3 hours of sleep)

This one on the other hand is easy and is DEFINITELY a red flag for me personally. Circadian rhythm is CRITICAL for maintaining a normal mood, whether it be unipolar or bipolar depression. If I'm trending towards hypomanic, I may not experience any other symptoms at first except I might have trouble falling asleep. It's normal to get a full night's sleep and feel well rested when you wake up, but when I'm headed towards hypomania, I need less sleep, AND when I wake up I'm wide awake from the second my eyes open. Not in a go go go kind of sense but rather it just is much easier to wake up in the morning than usual.

19 hours ago, Matt G said:
  • More talkative than usual or pressure to keep talking

I get really chatty as hypomania escalates. Sometimes I can be cheery and irritable/snappy at the same time. I talk faster, and my volume increases too.

19 hours ago, Matt G said:
  • Flight of ideas or subjective experience that thoughts are racing

Racing thoughts usually comes later for me. Or I don't notice it until the last second (i.e. when it's "too late"). However, you might be in a really good mood and feel like you have tons to get done and all at the same time you actually FEEL like you can accomplish it all.

19 hours ago, Matt G said:
  • Attention is easily drawn to unimportant or irrelevant items

This is what I was talking about with ADHD and Bipolar having a lot of overlap. People with bipolar disorder do have attention problems. We can look at this chemically to get an idea of what is really happening. People with ADHD have lower levels of dopamine in the prefrontal cortex. Stimulants like Adderall or Ritalin work to increase these levels in the PFC. With bipolar disorder, the underlying neurobiology isn't as clear, but we have an idea that there is a ramp-up in serotonin which suppresses dopamine signaling. With lower levels of dopamine being released into the synapse, dopamine receptors become quite sensitive. This over-sensitivity of dopamine receptors is believed to be part of the biology behind bipolar manias. Unfortunately, the brain has feedback mechanisms in place to compensate for this change. It's just that in bipolar disorder, these feedback loops are amplified to an unhealthy degree. After the increase in serotonin and decrease in dopamine, two things happen. Pre-synaptic serotonin receptors receive the serotonin that has flooded the synapse, and activation of those pre-synaptic receptors actually slows down the serotonin pump. So pressing the gas will cause the brain to automatically put on the breaks. Same with the dopamine system, because of the higher serotonin levels leading to lower dopamine, there is less dopamine binding to pre-synaptic receptors and the dopamine pump increases. With these two feedback loops working in OPPOSITE directions at a rapid pace, you then proceed to crash into depression.

One would think that with higher dopamine during the depressive phase, attention should improve but dopamine in the PFC works on a bell-curve where there is both too much and too little.

19 hours ago, Matt G said:
  • Increase in goal-directed activity (either socially, at work or school; or sexually) or psychomotor agitation

When I'm going hypo, I become a workaholic. I love working. I may get up from my desk more and move around. I also might start reaching out to friends I haven't talked to in a while for no good reason except I genuinely want to talk to them for some reason. I may be in a shopping kinda mood. I just feel like I want to go out and do SOMETHING.

19 hours ago, Matt G said:
  • Excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)

My DUI would be a good example here. Drug abuse is another good example. Sleeping around is another one. I've experienced all of these, not at the same time. For the most part though, the one that stands out is I make more impulsive purchases and I typically feel more buyer's remorse.

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Dude, You would be a great NP with the meds. The biggest trick is getting the diagnosis correct early on. I'd say that's hard to do. They say the avg person goes 10 or more years incorrectly diagnosed with BP. I'm 12 years on meds and am just  starting to consider it a possibility. I think i might be a soft BP 2. When you read the definitions it's not always easy to figure out.. I don't think most people stop and reflect on all their behaviors from 6 months ago or 3 etc. Unless you really analyze it you can easily miss it. I started keeping a journal years ago and that was helping me try to figure out why I felt good with lots of energy then I would crash. I use to think I was going through tollerence or withdrawl from klonopin or paxil or both. When I titrated off klonopin I felt like I was on speed for 6 months. I was running 8 miles 3 times a week. Now as i'm reflecting back and analyzing things I am really wondering if I have BP2.

When you were trying all the meds how did you know what "normal" feeling was? You clearly knew in your mind what you needed to feel like. Sometimes I am not sure what my reference point should be. It's like if I have BP2 then I want to be in that slight mania all the time because it feels good until it crashes.

 

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36 minutes ago, Matt G said:

Dude, You would be a great NP with the meds.

Haha thanks. I appreciate that :D

36 minutes ago, Matt G said:

Thebiggest trick is getting the diagnosis correct early on. I'd say that's hard to do. They say the avg person goes 10 or more years incorrectly diagnosed with BP. I'm 12 years on meds and am just  starting to consider it a possibility.

This is true. And it's generally statistically true that the longer a patient goes without the appropriate diagnosis, the worse their prognosis. Glutamate is important to activation of the brain, cognition, memory formation, among other things. But it can also be toxic in high and sustained levels. Mania is typically the product of glutamate excitotoxicity. This can have long term negative impact on the brain.

36 minutes ago, Matt G said:

i think i might be a soft BP 2. When you read the definitions it's not always easy to figure out..

From a genetics standpoint they're finding that disorders like bipolar disorder and autism actually have a myriad of different biomarkers that can be different from one bipolar person to the next. Amy combination of bad versions of those handfuls of genes could create a version of bipolar disorder that is similar enough to other versions to be diagnosable but different enough to make it VERY tricky. Additionally, severity could be different for each person as well. This is why in the new DSM-V they've moved to referring to autism as Autism Spectrum Disorder. They've eliminated Asperger's as a unique disorder and just decided that there are so many different types of autism with varying severities that it was easier to lump it under one huge overarching diagnosis.

36 minutes ago, Matt G said:

Idon't think most people stop and reflect on all their behaviors from 6 months ago or 3 etc. Unless you really analyze it you can easily miss it. I started keeping a journal years ago and that was helping me try to figure out why I felt good with lots of energy then I would crash.

No you're right. No one really does it until someone begs the question. And yes journaling really does help. I've started using the eMoods App which is catered towards bipolar disorder. I used it for a few days as the free version and ultimately spent the few bucks to get the lifetime paid version. Then I can add custom symptoms among a few other features. I can take journaling notes that are time-stamped or write an overview note for the day. It also helps you keep track of when you took your meds (or missed them), and then it can generate a PDF report that you can email to your pdoc if their EMR accepts them. The reports are actually pretty neat and very clinically oriented. They're interesting to look at after a few weeks.

36 minutes ago, Matt G said:

Iuse to think I was going through tollerence or withdrawl from klonopin or paxil or both. When I titrated off klonopin I felt like I was on speed for 6 months. I was running 8 miles 3 times a week. Now as i'm reflecting back and analyzing things I am really wondering if I have BP2.

When you were trying all the meds how did you know what "normal" feeling was? You clearly knew in your mind what you needed to feel like. Sometimes I am not sure what my reference point should be. It's like if I have BP2 then I want to be in that slight mania all the time because it feels good until it crashes.

 

What I found was most important was ensuring that I still maintained a somewhat normal emotional range. I hated the feeling of "flat soda". Not up and not really down. Robotic. It wasn't good. I was so unhappy with life because I couldn't actually truly feel excited about anything and no matter how frustrated that made me, I couldn't cry about it either. What I've now found is that things can make me happy but my reaction to that stimulus isn't inflated. Previously, even something as simple as finding out good news could trigger a few day joy ride. Now, I have days where I smile and I'm active, but I feel in control. And I still have days where life feels oppressingly monotonous and dull. But I hear other people who don't have mood disorders complain about the same things and I realize, oh so that dull depression I felt for one day is really just how anyone else might feel given the circumstances.

11 minutes ago, Matt G said:

This is fascinating and I would love to get it done as well. Very interesting about the concept of functional circuits and that would go along with the serotonin-dopamime reaction that I described earlier.

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Hi, I told me NP today I think I might be soft bipolar 2. He wanted me to tapper off paxil and cross taper up on effexor. I'm really thinking I can identify the cycling now after looking back. Still not 100% sure but going to evaluate it and watch it closely. Not going to make a switch on the meds yet. I have not had any real low depression in some time. Bad days and weeks sometimes but I am considering the amount of booze I have been drinking the last year and how it might impact things. I'm in good shape and eat well but i go through what might be soft mania where I just want to drink every night. More than I should. Sometimes I think it's because I get so much energy that the booze relaxes me. That could be mania in my book. I hit a wall about a month ago and now all that extra energy is gone and the mind racing and agitation is not as strong.  Your understanding of the meds far exceeds what most people would know. Where do you think you would be w out that knowledge? Honestly, I've seen several good, educated docs and what strikes me as most interesting is they each came up with a different med to try me on. Celexa by one, Viibrandt, and the guy I see now is saying Effexor.

I exercise almost every day pretty hard. I will say that helps me depression. If I go a few days without doing it I get really down.

What is first line defense for BP2? Depakote w an antidpressant right?

 

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@Matt G I don't know that Depakote with ad is the definitive BP 2 treatment. Many doc's like to start lamictal along with a quicker acting med to cover until the lamictal kicks in. I think it really depends on the nature of the symptoms and it's hard to generalize all of BP II. Personally I wouldn't touch Depakote for that but I think it depends on the person and the doc. Also the aaps that help depression (abilify, latuda, seroquel) can help as well 

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12 hours ago, Matt G said:

Hi, I told me NP today I think I might be soft bipolar 2. He wanted me to tapper off paxil and cross taper up on effexor. I'm really thinking I can identify the cycling now after looking back. Still not 100% sure but going to evaluate it and watch it closely. Not going to make a switch on the meds yet. I have not had any real low depression in some time. Bad days and weeks sometimes but I am considering the amount of booze I have been drinking the last year and how it might impact things. I'm in good shape and eat well but i go through what might be soft mania where I just want to drink every night. More than I should. Sometimes I think it's because I get so much energy that the booze relaxes me. That could be mania in my book. I hit a wall about a month ago and now all that extra energy is gone and the mind racing and agitation is not as strong.  Your understanding of the meds far exceeds what most people would know. Where do you think you would be w out that knowledge? Honestly, I've seen several good, educated docs and what strikes me as most interesting is they each came up with a different med to try me on. Celexa by one, Viibrandt, and the guy I see now is saying Effexor.

I exercise almost every day pretty hard. I will say that helps me depression. If I go a few days without doing it I get really down.

What is first line defense for BP2? Depakote w an antidpressant right?

 

Antidepressants are never first line defense in any kind of bipolar disorder. The only exception to this is the combination of Prozac and Zyprexa which was approved to treat bipolar depression. However there are no treatments available that are actually approved specifically for bipolar type II. All of them are indicated to treat either acute manic or mixed episodes associated with bipolar I disorder or bipolar depression (not specific to any type I don't think) like Latuda or Seroquel.

You should really try lamotrigine first because in comparison to all of the other available agents, it's far more mild assuming you aren't one of the select few who get the rash. It works really well for most people for both preventing mood swings (although not as good for an acute episode) and improving the symptoms of bipolar depression. Sometimes it will be used in combination with lithium. Unfortunately I couldn't tolerate lithium. So we tried AAPs. Went through Latuda, Saphris, Zyprexa, loxapine, Fanapt, Abilify, and now Rexulti (not in that order), and I was constantly searching specifically for a smaller combo of meds. I didn't want to be taking handfuls of pills every day so I was resistant to multiple medications. However my pdoc was very resistant to putting me on an antidepressant or a stimulant for the first 2-3 years because they general make the treatment more risky.

If you're male, Depakote is less problematic. They avoid it moreso in women because of it's pro-androgenic effects. Still, lamotrigine would be a better place to start from a tolerability perspective. Fewer side effects. And if you're still having trouble try a low dose AAP or lithium add-on to it. Talk to your pdoc about it and see what he has to say. Keep an eye on the Effexor though if you do start it. Statistically it has a higher rate of manic switch than most other SSRIs and SNRIs.

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23 minutes ago, Matt G said:

That's solid advice. I'm not starting the Effexor. What are your thoughts on this?

https://www.ncbi.nlm.nih.gov/pubmed/18271912

Yes this is very much the case for lamotrigine. The problem is that you can't titrate up on it fast enough safely due to the rash risk. Weeks 1-2 are 25mg. Then Weeks 3-4 are 50mg. Then Weeks 5-6 are 100mg. Then from there you can increase by 50mg every 1-2 weeks. Any faster than that and you can develop a very serious rash. Some people develop the rash no matter how slowly they titrate, and for those people, lamotrigine just isn't an option.

Additionally, lamotrigine has proven effective at specifically delaying the onset to mood episodes both manic and depressive. This is why it's the only drug to be considered as complete a mood stabilizer as lithium. However, lamotrigine is principally used for maintenance treatment once you've already been stabilized on something else. It's not all that effective at stopping something that's already in motion. AAPs are better for that.

If you aren't in dire straits right now, I would say lamotrigine is definitely a good thing to try if you're even considering you might be bipolar, because it's one of those medications that can be good for both bipolar and unipolar depression by simply smoothing out the waves a little bit. Lamotrigine augmentation to antidepressants for treatment-resistant depression is becoming more common. And it's even becoming popular as a mood stabilizer augmented with low doses of antidepressants that have a low switch risk in mild cases of bipolar II like you were suggesting earlier. However, that is still not considered front-line treatment.

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How hard would it be to tapper from paxil and wellbutrin onto this med? I'm down to 13mg of paxil from 15mg and I can feel it already.. I was going to try to go slow 10% reduction per month and make it to the end or transition to something new.

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1 minute ago, Matt G said:

what is aap?

Sorry, atypical antipsychotic. If you see AP, that means antipsychotic which would include all the older typicals like Haldol and Thorazine vs AAP which is just the atypicals all the new ones like Risperdal, Seroquel, Abilify, etc.

1 minute ago, Matt G said:

How hard would it be to tapper from paxil and wellbutrin onto this med? I'm down to 13mg of paxil from 15mg and I can feel it already.. I was going to try to go slow 10% reduction per month and make it to the end or transition to something new.

Taper onto which med? Lamotrigine? It would be a slow process. Lamotrigine titration is sometimes rocky for some people. It can give you mild mood swings for a few days after dose changes. It's fairly safe to say though that you could probably peel back the Paxil and Wellbutrin more easily once you've hit 100mg of lamotrigine. Recommended dose for bipolar disorder in any indication is 200mg.

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I'm going to give it a try. I'm prone to getting almost every side effect possible on meds. I'm going to try it and go really really slow. I'm feeling ok lately. I can see that as I think about things, I think I have set my reference point in life to be hypomanic. In many ways I like it alot. I hit that wall about a month ago and now I can focus, I'm not wired out, all that extra energy is gone, less agitated, etc.

 

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