Depression Cocktail *Updated*

[Cetkat]

Alright, so right now I'm on what's in my sig line. I have depression that simply will not go away, and has actually gotten worse. Prior to this, Cymbalta helped and I could still think straight. Now Cymbalta doesn't do what it once did, and I'm on the stimulant for augmentation and concentration - which I now really need.

The norepinephrine inhibitor in the Effexor exacerbated my anxiety, but its serotonin effect makes it work a little bit like the Cymbalta did. The stimulant doesn't really make me anxious.

So I desperately need something else and would love any suggestions/comments on what else to try.

1. I haven't been on any TCA's. Pdoc says there would be no point in trying them since they work alot like Effexor... but Cymbalta was my best med. Is he right, or should I try them anyway just in case?

2. Other than Cymbalta; Lithium and Lamictal made the most impact. Lithium is now ineffective without a working Cymbalta, and Lamictal's side effects made my depression worse.. but the med part of it worked at first. This makes me think a mood stabilizer would be good. So I plan on mentioning the GABA meds like Neurontin, and even trying Lamictal again with an emphasis on mitigating the side effects. Any thoughts on this? Also.. would Depakote or Topamax be worth trying? I want to raise the floor on my mood, but I don't have any mania to speak of to even out.

3. The pdoc mentioned adding a Thyroid med. I have no problems with that.

4. The only other things I can think of on this front are Mirapex (dopamine), Buprenex (opiate), Ultram (opiate/nor/ser), and BuSpar (augmenter).

5. If nothing else works, I'm going to try Ensam => other MAOI's => ECT

So.. am I missing anything? Any other treatments to consider; and also, what should I try first? I'm not going to get any more benefit from what I'm on, and I need to come up with a treatment plan for my next appt.

Edit: Title

[null0trooper]

1. I haven't been on any TCA's. Pdoc says there would be no point in trying them since they work alot like Effexor... but Cymbalta was my best med. Is he right, or should I try them anyway just in case?

For the most part he's wrong.

The TCAs that hit both NA and 5HT affect both at the same time - very much unlike Effexor's dose dependency. Nortriptyline may be more like Cymbalta.

Some TCAs are very sedating because they can be strong antihistamines as well as SRIs. Effexor isn't a strong antihistamine.

Some, like amitriptyline, shotgun nearly every major receptor to some extent.

Others - desipramine and protriptyline, are primarily NARIs, and can very activating.

Keep in mind that this is a "class" of medications that includes Doxepin and Vivactil. And when dealing with a medication that may not be selective about it's targets, it will generally have more side effect potential and less predictability from patient to patient. You and your doctor will have to research the individual medication more closely than you would an SSRI or stimulant.

Watch out for cut-and-paste "information" collated by folks who think that since all SSRIs are alike, all TCAs must be alike. But also watch out for legit information about serious side effects and contraindications.

4. The only other things I can think of on this front are Mirapex (dopamine), Buprenex (opiate), Ultram (opiate/nor/ser), and BuSpar (augmenter).

People tend to forget that PD meds like Mirapex are researched to *avoid* mood changes from elevated dopamine and to target levels in the motor function pathways (where it's really, really needed).

When considering MAOIs, remember that you may have to discontinue a number of other medications first. That can be a rough period for some.

[Velvet Elvis]

Well. Make sure you have the diagnosis right. If you've got insurance, find a decent internist and get a physical and blood workup.

How high did you get with the Effexor? Is there any reason why you were not able to add a benzo or somthing to control the anxiety and keep punching the dose?

Any medication that works on the principle of reuptake inhibition will have no effect if the targeted neurotransmitters are depleated to begin with. Have you tried buspar in combination with any kind fo SRI? Stahl has a theorized that it could kickstart 5HT replenishment. He suggests that pindolol, a beta blocker, might have a similar effect.

Some other options for treatment resistant depression, again according to Stahl:

1. Combos where there is a synergistic effect between a SRI and a 5HT-2A agonist

• SSRI + trazadone
  
• some SSRIs/ low dose venelfexine + low dose nefazadone (if you can still get it. i'm working with an older version of his textbook)
  
• low dose SNRI + trazadone/nefazadone
  
• SSRI/venelfexine + Atypical AP
  
• SSRI + mirtazapine
  

2. Combos with NA synergy

• NDRI + NRI (Wellbutrin + Reboxitine, desipramine, maprotilene, nortryptiline or protryptiline)
  
• NDRI/NRI + stimulant (Wellbutrin + methyphenidate or d-amphetimine)
  
• NDRI/NRI + DA agonist / pramepexole
  
• NRI + d,l amphetamine
  

3. "Heroic combos" in which synergistic action boosts both NA and 5HT

• High dose venelfexine + mirtazapine (he calls this "California rocket fuel")
  
• High dose venelfexine + NDRI
  
• High dose venelfexine + NRI
  
• High dose venelfexine + stimulant
  
• High dose venelfexine + nefazodone (if you can find it)
  
• mirtazapine + SSRI
  
• mirtazapine + NRI (he recomends reboxitine, but it's not available in the US. the copy of the textbook I'm working with is old enough to not have Strattera)
  
• mirtazapine + NDRI
  
• mirtazapine + stimulant (the stimulants he recomends are d-amphetimine, methylphenidate, phentimine (yeah right!) and diethypropion. A direct DA agonist such as pramipexole may also be used)
  
• SSRI + NRI (snri preferable but norepinephic TCAs (desipramine, nortryptiline, maprotiline, protryptiline) may be used with serum level monitoring)
  
• SSRI + NDRI
  
• SSRI + stimulant
  
• NDRI + nefazodone / trazodone
  

I've been intending to a make a sticky topic about this for ages. The above is pretty much what I have so far.

I've got a buttload of supplements which function as mild cognitive enhancers listed in the supplements section of the crazystore. Take a look at what's there but check with wikipedia and preferably your doc before you take any of 'em. A couple can mess with hormone levels in ways that may not be desirable if they are not wonky to begin with.

One thing you should try is a second opinion from a new psychiatrist. Definitely do that before you give up cheese for MAO-Is or get ECT.

[Cetkat]

For the most part he's wrong.

The TCAs that hit both NA and 5HT affect both at the same time - very much unlike Effexor's dose dependency. Nortriptyline may be more like Cymbalta.

Some TCAs are very sedating because they can be strong antihistamines as well as SRIs. Effexor isn't a strong antihistamine.

Some, like amitriptyline, shotgun nearly every major receptor to some extent.

Others - desipramine and protriptyline, are primarily NARIs, and can very activating.

So overall this would mean that the NA/5HT TCA's would behave closer to Cymbalta (which worked for me), with the closest being Nortriptyline. Which other TCA's fall into this catagory?

Does Amitriptyline fall more into the activating or sedating group?

As far as NARI's go, do you know if there are any correlations between the kind of activation they achieve and their results on depression? Cymbalta's NA wasn't activating nor anxiety producing, Effexor activated and produced anxiety, and my stimulant activates without causing anxiety. So, basically, would it be worth dropping the stimulant and going the TCA NARI route.. or is it best to stick with the NA that has the best result so far?

Keep in mind that this is a "class" of medications that includes Doxepin and Vivactil. And when dealing with a medication that may not be selective about it's targets, it will generally have more side effect potential and less predictability from patient to patient. You and your doctor will have to research the individual medication more closely than you would an SSRI or stimulant.

Watch out for cut-and-paste "information" collated by folks who think that since all SSRIs are alike, all TCAs must be alike. But also watch out for legit information about serious side effects and contraindications.

Point taken. I suspect my pdoc is mainly comming from the pov that these are older meds with more side effects.. so why take them if something else can do the same thing. I reason that if it was worth trying Effexor when the Cymbalta stopped working.. it's worth trying the TCA's. They just interact differently.

People tend to forget that PD meds like Mirapex are researched to *avoid* mood changes from elevated dopamine and to target levels in the motor function pathways (where it's really, really needed).

Does this mean that it would have an effect opposite of raising my mood, or none at all?

Unfortunately, I do know that MAOI's don't play well with others. Hence I'd rather try other alternatives first.

[Cetkat]

Well. Make sure you have the diagnosis right. If you've got insurance, find a decent internist and get a physical and blood workup.

How high did you get with the Effexor? Is there any reason why you were not able to add a benzo or somthing to control the anxiety and keep punching the dose?

No insurance right now. I suppose it is time to get another blood workup however. I will have to schedule that once I get some coverage.

I went up to 300mg on Effexor. I was also on Xanax, Nadolol, and Lithium at the same time. The anxiety (with paranoia) was impacted, but didn't go away. I spent alot of time on 225mg + Wellbutrin. Ended up dropping the Lithium once the full NA effects of Effexor kicked in (too much tremor/shakiness for the beta-blocker and benzo to handle without problems). Ultimately it's the impact of the raised Effexor blood pressure; trying to control it with the beta-blocker; severe constipation; and paranoia that got to me.

I've dropped to 150mg now + stimulant, and the benifit hasn't decreased. So, ultimately, I didn't go higher becuase there's no possitive difference between 150 & 300. (Just like I had no positive difference on Cymbalta between 60 & 120).

Any medication that works on the principle of reuptake inhibition will have no effect if the targeted neurotransmitters are depleated to begin with. Have you tried buspar in combination with any kind fo SRI? Stahl has a theorized that it could kickstart 5HT replenishment. He suggests that pindolol, a beta blocker, might have a similar effect.

Good point. I have not tried the buspar yet. Do you think that, with perhaps the thyroid med, would be a good next step as opposed to a mood stabilizer? Does Stal think that only pindolol would have that effect, or any beta-blocker?

I've got a buttload of supplements which function as mild cognitive enhancers listed in the supplements section of the crazystore. Take a look at what's there but check with wikipedia and preferably your doc before you take any of 'em. A couple can mess with hormone levels in ways that may not be desirable if they are not wonky to begin with.

One thing you should try is a second opinion from a new psychiatrist. Definitely do that before you give up cheese for MAO-Is or get ECT.

I will take a look at that. I've taken L-Tryosine before for pain & I'm putting more Omega-3 in my diet now. Right now I'm on my third pdoc, so I think I'll stick with him for the time being. However, once we both get to the point where the options have been exausted, I think I'll take you up on that second opinion. Best to make sure nothing's been forgotten I suppose. Ultimately I'm more worried about getting to them and them not working than actually using them.

{I'll reply to that list later.. have to go to a GP appt..}

[r.mcmurphy]

"4. The only other things I can think of on this front are Mirapex (dopamine), Buprenex (opiate), Ultram (opiate/nor/ser), and BuSpar (augmenter). "

cetcat

, DO NOT ADD ULTRAM to SSRIs! that combination landed me in the ER for the first time in 40 years. You would be setting your self up for seratonin syndrome. YOU DO NOT want to go there.

if you think that i am talking through me hat then go to AIDSMEDS.COM and hit tools. there you will find the best drug interaction info that i have found. if i knew how to post a link to it, i would.

seratonin sydrome will make you delerious, unable to walk unasisted, nor sleep for days on end. No antidote that i know of. you gotta tough it out until the stuff clears your system.

i ain't bullshooting you. dumb fucking VA pdoc added ssri to my existing drug regimen and he hadn't a clue. 102 fever, 67 consecutive hours in ER with no sleep. the ambien that i take regularly as well as a heavy dose of zanax did diddly.

an entire week at home w/o sleep and just now am i getting back on my pins.

go to that site and enter all the drugs that you take and what you may want to try and a screen will appear with possible interactions, probable interactions, and slight interaction possibilitys.

hope that you read this!

[null0trooper]

So overall this would mean that the NA/5HT TCA's would behave closer to Cymbalta (which worked for me), with the closest being Nortriptyline. Which other TCA's fall into this catagory?

Imipramine (which is metabolized to desipramine), possibly nortriptyline, and amitripyline.

Does Amitriptyline fall more into the activating or sedating group?

It might depend on what else you take with it. Some of the side effects cautions may place it on the activating side.

As far as NARI's go, do you know if there are any correlations between the kind of activation they achieve and their results on depression? Cymbalta's NA wasn't activating nor anxiety producing, Effexor activated and produced anxiety, and my stimulant activates without causing anxiety. So, basically, would it be worth dropping the stimulant and going the TCA NARI route.. or is it best to stick with the NA that has the best result so far?

I think this is one of the areas where psych medicine veers into "art" (or "voodoo", take your pick!) From your description, Cymbalta + stimulant would be a reasonable option.

People tend to forget that PD meds like Mirapex are researched to *avoid* mood changes from elevated dopamine and to target levels in the motor function pathways (where it's really, really needed).

Does this mean that it would have an effect opposite of raising my mood, or none at all?

Um. Maybe. Dopamine elevated in the wrong parts of the brain has been implicated in psychosis, bipolar mood swings, changes in prolactin levels ... all sorts of fun stuff. With ADD, there might be a chunk of frontal lobes praying for just such an event, so YMWV.

For my own part, I prefer selegiline as an augmenting medication, at levels where it stays a MAO-B inhibitor. That helps more with cognition and alertness than mood, but that's not a bad thing. However, I think there's little or no research to support that use.

Unfortunately, I do know that MAOI's don't play well with others. Hence I'd rather try other alternatives first.

Yeah. Combinations can be used, but the synergy is most likely multiplicative, rather than additive.

To confuse the issue more, T3 hormone has been shown to augment imipramine in rat brains. Now if only I had a use for happy rat brains...

[null0trooper]

, DO NOT ADD ULTRAM to SSRIs! that combination landed me in the ER for the first time in 40 years. You would be setting your self up for seratonin syndrome. YOU DO NOT want to go there.

if you think that i am talking through me hat then go to AIDSMEDS.COM and hit tools. there you will find the best drug interaction info that i have found. if i knew how to post a link to it, i would.

Sometimes the interaction is based on one medication inhibiting the clearance/metabolism of another. For example, Ultram/Tramadol is metabolized by the P450 2D6 isoenzyme. While you could probably get away with taking it with Lexapro (a very weak 2D6 inhibitor), adding Ultram to Paxil, Prozac, Fluvox, Wellbutrin, or Cymbalta (medium to damned strong inhibitors) could make you wish you had never been born and that you could do something about the prescribing physician ever having been born.

r.mcmurphy is sooooo NOT kidding about the insomnia, and myoclonic twitching isn't relaxing either.

[Cetkat]

Sometimes the interaction is based on one medication inhibiting the clearance/metabolism of another. For example, Ultram/Tramadol is metabolized by the P450 2D6 isoenzyme. While you could probably get away with taking it with Lexapro (a very weak 2D6 inhibitor), adding Ultram to Paxil, Prozac, Fluvox, Wellbutrin, or Cymbalta (medium to damned strong inhibitors) could make you wish you had never been born and that you could do something about the prescribing physician ever having been born.

r.mcmurphy is sooooo NOT kidding about the insomnia, and myoclonic twitching isn't relaxing either.

Thanks for that information. I didn't know Ultram/Tramadol had that much of a serotonin kick. I've been on Cymbalta, Prozac, and Wellbutrin all together without incident. Would an Ultram + Cymbalta/Effexor/TCA really top that?

[null0trooper]

Thanks for that information. I didn't know Ultram/Tramadol had that much of a serotonin kick.

It doesn't, as long as the liver is able to metabolize it. But once the 2D6-inhibiting SSRI (how much you want to bet it was Paxil? It also requires 2D6 for it to be metabolized) and the Ultram started building up in the bloodstream because they couldn't be cleared... ick.

I've been on Cymbalta, Prozac, and Wellbutrin all together without incident.

My usual reference table indicates that Prozac can also be metabolized by isoenzyme 2C9; Wellbutrin by 2B6. Even so, if you were a "slow metabolizer" (usually refers to clearing medications via 2D6) you almost certainly would have had an incident on that combination. A few people may be overly fast metabolizers, so some enzyme inhibition may not always be a bad thing ... until an OTC medication starts interacting as well.

Would an Ultram + Cymbalta/Effexor/TCA really top that?

You'd have tramadol, duloxetine, and venlafaxine all competing for your liver's pool of 2D6 isoenzyme, with duloxetine inhibiting some of it. If the TCA in question were amitriptyline, desipramine, imipramine, or clomipramine the competition would be even tougher. Only then, you could also have levels of a potentially cardiotoxic antihistamine building up on top of increasing SRI activity. And that could become very bad.

If you're going to add a TCA to a cocktail, you really only want to go one med at a time, and very slowly and carefully at that. Possibly imipramine or amitriptyline, as both are metabolized using multiple isoenzymes. And of those two, imipramine could become very "activating" because of desipramine blood levels building up.

If it all sounds like a risky business, it should - because it is.

[Cetkat]

So overall this would mean that the NA/5HT TCA's would behave closer to Cymbalta (which worked for me), with the closest being Nortriptyline. Which other TCA's fall into this catagory?

Imipramine (which is metabolized to desipramine), possibly nortriptyline, and amitripyline.

To confuse the issue more, T3 hormone has been shown to augment imipramine in rat brains. Now if only I had a use for happy rat brains...

I'm actually going to get a follow-up Thyroid test today. I did some blood-work and my TSH was too high, with a normal T4. If I actually do have a thyroid issue I will be very relieved. However, it would only have just occurred a couple of months ago. I saw the study you linked to on another thread. This, "In a recent meta-analysis including eight studies with a total of 292 euthyroid patients refractory to TCA therapy, it has been reported that approximately 50% of patients treated with T3 augmentation strategy became responsive to antidepressant treatment" is particularly interesting. Just how closely related are Imipramine/Effexor/Cymbalta? Would they be interchangeable for the purpose of that study?

As far as NARI's go, do you know if there are any correlations between the kind of activation they achieve and their results on depression? Cymbalta's NA wasn't activating nor anxiety producing, Effexor activated and produced anxiety, and my stimulant activates without causing anxiety. So, basically, would it be worth dropping the stimulant and going the TCA NARI route.. or is it best to stick with the NA that has the best result so far?

I think this is one of the areas where psych medicine veers into "art" (or "voodoo", take your pick!) From your description, Cymbalta + stimulant would be a reasonable option.

(LOL) That combo make sense to me to.. best of both worlds. Right now, that's exactly what I'm doing; 60mg Cymbalta + 150mg Effexor + 10-20mg Metadate.

Dopamine elevated in the wrong parts of the brain has been implicated in psychosis, bipolar mood swings, changes in prolactin levels ... all sorts of fun stuff. With ADD, there might be a chunk of frontal lobes praying for just such an event, so YMWV.

So Mirapex would inhibit mania and mess with prolactin levels (up or down, btw?); but if the common mood stabilizers lift you up, could Mirapex do the same?

For my own part, I prefer selegiline as an augmenting medication, at levels where it stays a MAO-B inhibitor. That helps more with cognition and alertness than mood, but that's not a bad thing. However, I think there's little or no research to support that use.

That makes sense to me. What can you suggest pairing it with, med wise? I could only drop what I have to and keep the rest if/when I start Ensam.

----

I've been on Cymbalta, Prozac, and Wellbutrin all together without incident. Would an Ultram + Cymbalta/Effexor/TCA really top that?

My usual reference table indicates that Prozac can also be metabolized by isoenzyme 2C9; Wellbutrin by 2B6. Even so, if you were a "slow metabolizer" (usually refers to clearing medications via 2D6) you almost certainly would have had an incident on that combination. A few people may be overly fast metabolizers, so some enzyme inhibition may not always be a bad thing ... until an OTC medication starts interacting as well.

You'd have tramadol, duloxetine, and venlafaxine all competing for your liver's pool of 2D6 isoenzyme, with duloxetine inhibiting some of it. If the TCA in question were amitriptyline, desipramine, imipramine, or clomipramine the competition would be even tougher. Only then, you could also have levels of a potentially cardiotoxic antihistamine building up on top of increasing SRI activity. And that could become very bad.

If you're going to add a TCA to a cocktail, you really only want to go one med at a time, and very slowly and carefully at that. Possibly imipramine or amitriptyline, as both are metabolized using multiple isoenzymes. And of those two, imipramine could become very "activating" because of desipramine blood levels building up.

Ok, I think I understand now. Where do you find the chart you mention?

I meant for the '/' to indicate 'this or that'.. didn't mean to confuse. However, that information is helpful. So, untimately, I could try adding Ultram to my cocktail.. but since it needs 2D6 - just like Effexor and Cymbalta.. I'd be better off waiting to try it with imipramine. With the "cardiotoxic antihistamine" are you referring to the bulidup of the TCA in the system from the 2D6 overload or a TCA+other antihistamine interaction? Also, what is the difference between the antihistamine in that and pseuodoephedrine?

[Cetkat]

As promised.. a reply to Stahl's list.

My meds in order of occurance:

Wellbutrin (Middle School)

- - (Break)

College - 1st Pdoc:

Zoloft/Seroquel

Zoloft/Cymbalta/Seroquel

- - (Break)

2nd Pdoc:

Cymbalta/Prozac/Lithium

Cymbalta/Prozac/Lithium/Wellbutrin

Cymbalta/Lamicatal/Wellbutrin/Remeron

Cymbalta/Lexapro/Lithium/Remeron/Wellbutrin

Cymablta/Abilify/Lithium/Remeron/Wellbutrin

Cymbalta/Zyprexa/Lithium/Remeron

Cymbalta/Geodon

Cymbalta/Lithium (This is when Cymbalta & Lithium stopped working)

Paxil/Cymbalta/Risperdal

Effexor/Cymbalta/Risperdal

Effexor/Risperdal/Lithium

Effexor/Cymbalta/Risperdal/Wellbutrin/Remeron

Effexor/Cymbalta/Risperdal/Remeron/Lamictal/Metadate CD/BuSpar

Some other options for treatment resistant depression, again according to Stahl:

What I haven't tried in bold; with the particular part underlined. I am wondering if the NRI part is interchangeable with Cymbalta/Metadate CD... as seems to basically be the more stimulating TCA's.. or is it better to see it as Strattera? I also see venelfexine as interchangeable with Cymbalta (when it was actually working).

1. Combos where there is a synergistic effect between a SRI and a 5HT-2A agonist

• SSRI + trazadone
  
• some SSRIs/ low dose venelfexine + low dose nefazadone (if you can still get it. i'm working with an older version of his textbook) [Can't get Nefazadone..]
  
• low dose SNRI + trazadone/nefazadone
  
• SSRI/venelfexine + Atypical AP
  
• SSRI + mirtazapine
  

2. Combos with NA synergy

• NDRI + NRI [TCA](Wellbutrin + Reboxitine, desipramine, maprotilene, nortryptiline or protryptiline)
  
• NDRI/NRI [TCA]+ stimulant (Wellbutrin + methyphenidate or d-amphetimine)
  
• NDRI/NRI + DA agonist / pramepexole (mirapex)
  
• NRI + d,l amphetamine
  

3. "Heroic combos" in which synergistic action boosts both NA and 5HT

• High dose venelfexine + mirtazapine (he calls this "California rocket fuel")
  
• High dose venelfexine + NDRI
  
• High dose venelfexine + NRI
  
• High dose venelfexine + stimulant
  
• High dose venelfexine + nefazodone (if you can find it)
  
• mirtazapine + SSRI
  
• mirtazapine + NRI (he recomends reboxitine, but it's not available in the US. the copy of the textbook I'm working with is old enough to not have Strattera)
  
• mirtazapine + NDRI
  
• mirtazapine + stimulant (the stimulants he recomends are d-amphetimine, methylphenidate, phentimine (yeah right!) and diethypropion. A direct DA agonist such as pramipexole may also be used)
  
• SSRI + NRI (snri preferable but norepinephic TCAs (desipramine, nortryptiline, maprotiline, protryptiline) may be used with serum level monitoring)
  
• SSRI + NDRI
  
• SSRI + stimulant
  
• NDRI + nefazodone / trazodone
  

So it seems like all that's really left are the TCA's, Strattera, Mirapex, and Trazodone.

Right now I'm on Effexor/Cymbalta/Risperdal/Remeron/Lamictal/Metadate CD/BuSpar.. I may be adding Strattera; and I've thought about dropping the BuSpar, adding a T3 to my thyroid medication, and introducing Mirapex & Trazodone (and maybe L-Tyrosine / Mucuna pruriens).

Other than that, I don't know what to try but switching to a TCA, then an MAOI..

Am I missing anything? Does the L-Tyrosine/Mucuna pruriens/Mirapex sound like a good idea? I don't know what I'm going to do if this doesn't work.

[AnneMarie]

Lamictal usually has AD effects up to 200mg. You could also pair it with Lithium, Geodon, Abilify, etc. Lithium could also be paired with the AAPs, or heh, do a three way. (The Lamictal-Lithium-Zyprexa combo worked on depression for me, I just keep cycling so Zyprexa is being weened out for Depakote.)

The reason I'm bringing up the stabilizer combo's is twofold: 1) I don't know much about ADs, 2) as you probably know, refractory depression is increasingly thought to be tied in with bipolar. Since you were on either an AP or Lithium for a number of cocktails, it'd be hard to know if otherwise the ADs would have created a bipolar response. If your depression can be highly agitated, that's another sign. I assume you are familiar with this stuff. Anyway, you have a bunch of options in stabilizerland before MAOIs or ECT.

If you're T3 is below normal range average, go with supplementing. STAR-D results when paired with an AD were promising, more so than Lithium.

As for Omega-3s, 1-2 grams of the EPA ingredient are recommended. I do get a lift out of this, but only when the EPA is over a gram.

[mel1]

My pdoc told me lamictal and abilify work really well together. How does she know that? I have no idea. But the combo works really good for me for depression. Just have to watch out for anxiety.

[Cetkat]

Lamictal usually has AD effects up to 200mg. You could also pair it with Lithium, Geodon, Abilify, etc. Lithium could also be paired with the AAPs, or heh, do a three way. (The Lamictal-Lithium-Zyprexa combo worked on depression for me, I just keep cycling so Zyprexa is being weened out for Depakote.)

The reason I'm bringing up the stabilizer combo's is twofold: 1) I don't know much about ADs, 2) as you probably know, refractory depression is increasingly thought to be tied in with bipolar. Since you were on either an AP or Lithium for a number of cocktails, it'd be hard to know if otherwise the ADs would have created a bipolar response. If your depression can be highly agitated, that's another sign. I assume you are familiar with this stuff. Anyway, you have a bunch of options in stabilizerland before MAOIs or ECT.

If you're T3 is below normal range average, go with supplementing. STAR-D results when paired with an AD were promising, more so than Lithium.

As for Omega-3s, 1-2 grams of the EPA ingredient are recommended. I do get a lift out of this, but only when the EPA is over a gram.

Yeah, I had thought about adding Lithium back in to get a Lithium/Lamictal combo. My Risperdal works well.. so that would be my AAP. Abilify caused extreme akathisia but did help my mood. Zyprexa did absolutely nothing, and Seroquel only helps my sleep. I've been generally unresponsive to everything except: Effexor, Cymbalta, Risperdal, Ablilify, Lithium, Zoloft (only for anxiety), Wellbutrin (made me more alert), Geodon (slight help, but had really bad effects).

More Info Here

You make a good point about always being on a mood stabilizer. I have been on a Zoloft/Cymbalta/Seroquel (prn) combo, and Cymbalta/Prozac for about 2 weeks before adding Lithium (forgot that in the list). But that by no means is exhaustive in regards to BP (which I really do think I have in a very NOS way). The AD's just seem to either do nothing at all or (in the case of Cymbalta/Effexor) raise my mood - which could be seen as being hypo if my mood swing got that high. Instead, my cycle goes: Severe Depression -> Dysthymic -> (Rarely) Feeling OK. I can still be suicidal at all three. The best I've gotten was the Feeling OK on Cymbalta/Lithium - and also Abilify.

One thing I worry about with the Lithium is the effect it could have on my Thyroid. I believe I've been mildly hypo for most of my life (based upon symptoms and the fact that the normal range was updated in 2003.. so I could have tested 'normal' and not have been); but, the fact that I've taken Lithium quite a bit over the past two years makes me wonder if it may be the reason my TSH level jumped higher about 6 months ago. If the hypo amount would stay the same.. I wouldn't worry about it. But at 9.5 TSH; it's nowhere near as bad as it could get 30-300ish. So, my thyroid is underactive, yet still functioning; but it might not be if I continue Lithium... but if Lithium would start to really work well again (it hasn't without a working med to support it) it may be worth it. Last time, when it worked; it worked well. Brought me out of being suicidal.

Either way, my Free T3 is lower-mid on the scale (133 out of 87-178).. so it could definitely be boosted. I plan to do that soon. (Probably with Armour Thyroid since it costs less than Sythroid+Cytomel).

I also wonder if I might be able to add Abilify back in if I take Cogentin. It does say that Cogentin binds to the dopamine transporter and inhibits dopamine reuptake. So that may be helpful in trying to produce a Dopamine Agonist + Dopamine Reuptake Inhibitor combo. I'm still trying to find out if Trazodone is a Dopamine agonist. I'm getting conflicting information.. Do you happen to know? Any thoughts on a Cogentin (+Abilify?) +Trazodone+Mucuna pruriens+Mirapex combo?

I think that I'm already going to add the L-Tyrosine back in. I don't think I'd hurt anything.. and it might make my aches & pains go away again.. even without taking it with Wellbutrin.

So, anyway.. what mood stabilizer(s) should I try, and at what point in my cocktail? I'm not yet at 200mg with Lamictal, so I would probably be adding one on to that rather than switching.

My pdoc told me lamictal and abilify work really well together. How does she know that? I have no idea. But the combo works really good for me for depression. Just have to watch out for anxiety.

Thanks mel! Have you had anxiety problems with the Abilify; and if so, how did you manage them? Also - did your pdoc mean that Ablilify was just a good med to try.. or is there actually a boosting effect when using both together?

[null0trooper]

Ok, I think I understand now. Where do you find the chart you mention?

http://medicine.iupui.edu/flockhart/table.htm

I meant for the '/' to indicate 'this or that'.. didn't mean to confuse. However, that information is helpful. So, untimately, I could try adding Ultram to my cocktail.. but since it needs 2D6 - just like Effexor and Cymbalta.. I'd be better off waiting to try it with imipramine. With the "cardiotoxic antihistamine" are you referring to the bulidup of the TCA in the system from the 2D6 overload or a TCA+other antihistamine interaction? Also, what is the difference between the antihistamine in that and pseuodoephedrine?

Pseudoephedrine is a alpha-adrenergic decongestant - it yields all the body effects of speed (physical effects that may include higher heart rate and blood pressure, increased sweating, etc. which are too often confused with the mental states of "anxiety", "panic", and "agitation" ) and few if any of the actual mental effects. It can be used alone or as an adjunct to antihistamines to control rhinitis.

Antihistamines are used to target/block histamine receptors. Used correctly they are quite helpful, but in excess the effects can be dire (e-medicine article.) The antihistamine TCAs are generally also anticholinergic ... Acetylcholine is important for minor functions such as cognition and firing the neurons that cause muscles to contract.

[null0trooper]

I saw [link=http://www.nature.com/npp/journal/v24/n6/full/1395642a.html" target="_blank]the study[/link] you linked to on another thread. This, "In a recent meta-analysis including eight studies with a total of 292 euthyroid patients refractory to TCA therapy, it has been reported that approximately 50% of patients treated with T3 augmentation strategy became responsive to antidepressant treatment" is particularly interesting. Just how closely related are Imipramine/Effexor/Cymbalta? Would they be interchangeable for the purpose of that study?

Probably not, although T3/SSNRI combinations sound like an obvious choice for a study or two, and duloxetine is not completely dissimilar from the threeheaded monster molecules. It comes back to "TCA" being a structural category and not an effect category.

[null0trooper]

Right now I'm on Effexor/Cymbalta/Risperdal/Remeron/Lamictal/Metadate CD/BuSpar.. I may be adding Strattera; and I've thought about dropping the BuSpar, adding a T3 to my thyroid medication, and introducing Mirapex & Trazodone (and maybe L-Tyrosine / Mucuna pruriens).

Effexor would be the first thing I'd think about dropping, probably using a Prozac taper-down schedule.

Risperdal is likely playing games with dopamine that you're now trying to counteract with Metadate and dopamine precursors. That would be another med to strongly consider dropping.

Lamictal, Remeron, BuSpar - those should all be working in their own way to reduce anxiety.

Am I missing anything? Does the L-Tyrosine/Mucuna pruriens/Mirapex sound like a good idea? I don't know what I'm going to do if this doesn't work.

Not entirely a good idea at this point. The point of that combination would be to elevate your mood and activity and/or reduce akathisia. However, you're on sedating anxiolytics and an antipsychotic. The best you can expect from speedballing like that is a sucky mood and tons of side effects.

Hm.

Your med changes do look a little bipolar: too activated and an AD is added; too zonked and a noradrenergic added. And it's all spiralled out of control with Risperdal.

If you could survive for a while on Armour/Cymbalta/Lamictal/Medate or Armour/Cymbalta/Lamictal/Remeron/Metadate just to get things simplified a little it might help. ('cause stimulants can always be dropped when you're too jacked up or just don't need them)

[null0trooper]

Me very talky today.

Any votes for combining the above into one massive post (My boss' boss says I shouldn't oughta though, cause I do that too much already)

[AnneMarie]

So, anyway.. what mood stabilizer(s) should I try, and at what point in my cocktail? I'm not yet at 200mg with Lamictal, so I would probably be adding one on to that rather than switching.

Gee, so many options. I'm in no way an expert, but can share some of my limited knowledge. The thing about polypharm is that what works or doesn't work in one combination does not necessarily predict how it will work in another combo. I personally favor mini-poly, but am now learning to accept a little more poly than the mini.

One possible route could be weening off of other psych meds except the AP to see if Lamictal (LGT) ~200mg +Risperdal (that you are already on) works. Then maybe try swapping APs, especially if LGT is sedating, to a more activating one. As w/Lamictal, dose can mean a lot. Seroquel, for example, is mostly a sedative under 100mg (avg) but has AD effects of varying degrees at varying doses over that (or it's just feels like a lethargic sedative no matter what dose). Geodon can be agitating at lower doses and smoother at higher ones for many. It works the opposite way for others. Abilify... gave me akathisia, too, so no comment except that it can behave sort of like Geodon. Zyprexa gives me some AD effect, but to be honest, I'd need to be well into psychotic dosing territory to really get anti-d effects I need from it.

If your mood is bouncing or agitated (BPIII style) on LGT and AP, then adding Lithium or Trileptal/Depakote/Tegretol might make some sense. These could also be sub'd for the AP. If you are only Depressed, then this route might not make so much sense w/the exception of considering Lithium augmentation.

Although Phelp's isn't a definitive source, his description of soft bipolar is pretty useful. If you haven't read it yet, give it a look over. "Soft Signs" of Bipolar Disorder

The other thing that strikes me in looking at your sig is, whooah, so very many meds. Have you taken each to a high therapeutic level alone or paired with only one or two other meds?

Oh, right, light therapy might help. Have you tried it?

[Catnapper]

I had to speed read through some of the heavy science, too much on my mind today to concentrate very well. However, I do have some anecdotal experience of treating recurrent depression:

The last episode I was in was finally fixed by adding in Vivactil (protryptiline) and Adderall, sorry, don't know the generic name. The side effects from the Vivactil sucked. When I first started augmenting the Wellbutrin, the pdoc had me do a simple daily mood chart on a 1 - 10 scale, one being suicidal and ten equivilent to falling in love and hitting the lottery.

After about six weeks, I asked to quit the Vivactil because of extreme dry mouth and constipation. Unfortunately, it was clear with the help of the mood chart that it actually was beneficial, so I resumed taking it. After a few more months, Adderall was added and that seemed to kick me into gear.

Since I've been better, I'm just on the Wellbutrin and so far, so good. I don't have anxiety, though, and have the three-toed sloth variety of depression. Hope you find something that works, or at least pass the chemistry exam!

[Greenyflower]

Actually nefazodone is still available in the US, but not brand name Serzone by Bristol Myers Squib. It was pulled off the market when it caused bad, really bad, liver reactions in some users. However, it still available as a generic, though you should get your liver checked reasonably often. Most pdocs just shy away from it, but it has been an effective AD for many and for some, the only one that works.

[Cetkat]

Pseudoephedrine is a alpha-adrenergic decongestant.

Antihistamines are used to target/block histamine receptors. Used correctly they are quite helpful, but in excess the effects can be [link=http://www.emedicine.com/emerg/topic38.htm" target="_blank]dire (e-medicine article.)[/link] The antihistamine TCAs are generally also anticholinergic ... Acetylcholine is important for minor functions such as cognition and firing the neurons that cause muscles to contract.

My bad. You're right pseudoephedrine is the decongestant part. I see what you mean about the anticholinergic properties causing issues. Basically, what I meant to ask was whether or not OTC allergy meds have a common enough method of action with the antihistamine part of MI meds that a built up tolerance to one would translate to the other. It takes alot of overdosing of multiple OTC meds to have any real negative effect - so I pretty much don't ever have to worry about it.

------------------------------------------------------------------------

Just how closely related are Imipramine/Effexor/Cymbalta? Would they be interchangeable for the purpose of that study?

Probably not, although T3/SSNRI combinations sound like an obvious choice for a study or two, and duloxetine is not completely dissimilar from the threeheaded monster molecules. It comes back to "TCA" being a structural category and not an effect category.

The last episode I was in was finally fixed by adding in Vivactil (protryptiline) and Adderall, sorry, don't know the generic name. The side effects from the Vivactil sucked. When I first started augmenting the Wellbutrin, the pdoc had me do a simple daily mood chart on a 1 - 10 scale, one being suicidal and ten equivilent to falling in love and hitting the lottery.

After a few more months, Adderall was added and that seemed to kick me into gear.

Thanks Catnapper.

I guess it seems that after trying Amitriptyline & Nortriptyline it may be a good idea to give Imipramine and Protryptiline a shot.. That's basically just going down the list for TCA's.

[null0trooper]

I see what you mean about the anticholinergic properties causing issues. Basically, what I meant to ask was whether or not OTC allergy meds have a common enough method of action with the antihistamine part of MI meds that a built up tolerance to one would translate to the other. It takes alot of overdosing of multiple OTC meds to have any real negative effect - so I pretty much don't ever have to worry about it.

It's really going to depend on the medications. diphenhydramine is fairly anticholinergic, so if you're "used" to that desipramine wouldn't even register on that

front (good for avoiding side effects mostly) Amitriptyline or doxepin would probably still knock you out, and belladonna could still kill you in overdose.

[Cetkat]

Amitriptyline or doxepin would probably still knock you out, and belladonna could still kill you in overdose.

Well, I guess that means I'll be trying Amitriptyline before Nortriptyline. I can't sleep worth a damn.

Oh- and I added to the entry above this one.. / And, feel free to combine your other posts if you want. Doesn't bother me either way.

[Cetkat]

Right now I'm on Effexor/Cymbalta/Risperdal/Remeron/Lamictal/Metadate CD/BuSpar.. I may be adding Strattera; and I've thought about dropping the BuSpar, adding a T3 to my thyroid medication, and introducing Mirapex & Trazodone (and maybe L-Tyrosine / Mucuna pruriens).

Effexor would be the first thing I'd think about dropping, probably using a Prozac taper-down schedule.

Why Effexor instead of Cymbalta? Because Cymbalta used to work? My concern is losing the little bit of anti-depressant I have working. (Although it's starting to feel like dropping down to 75mg dropped the effectiveness as well.) Ultimately, Effexor isn't a good med due to the side effects. Even at 150mg it started giving me hot flashes... and it raises my blood pressure.

Risperdal is likely playing games with dopamine that you're now trying to counteract with Metadate and dopamine precursors. That would be another med to strongly consider dropping.

Actually, the real tiredness didn't kick in until about a month on Risperdal. Doesn't help depression, does help anxiety (ruminations), and a little bit on sleep. Then, my thyroid got all out of whack.. and I became super exhausted, unable to think straight, and gained weight. Metadate cut through the fog, and my T4 medication has helped (but I need to go up on the latter). I really don't know if all that set aside I would need the Metadate or not. But it's the mental fog that I'm fighting. And Risperdal didn't contribute to that to my knowledge. I could go off of Risperdal, but my one worry is that I need it to get through the Lamictal titration. Last time I had to stop Lamictal at 100mg due to the tired-insomnia-anxiety. The Risperdal/Ambien combo is forcing me to get some sleep and pushing the rumination away - though not keeping me from being anxious. Lamictal is making me a mess right now..

Lamictal, Remeron, BuSpar - those should all be working in their own way to reduce anxiety.

Lamictal is actually causing anxiety by wearing me out; Remeron is only good for getting me a little more Stage 4 sleep & helping me not have a headache upon waking up after far too much REM; and BuSpar... hard to tell, but if I had to guess - I'd say it's doing absolutely nothing. Risperdal and Xanax are the only anti-anxiety meds I have, and they still don't get over my anxiety from Lamictal.

Am I missing anything? Does the L-Tyrosine/Mucuna pruriens/Mirapex sound like a good idea? I don't know what I'm going to do if this doesn't work.

Not entirely a good idea at this point. The point of that combination would be to elevate your mood and activity and/or reduce akathisia. However, you're on sedating anxiolytics and an antipsychotic. The best you can expect from speedballing like that is a sucky mood and tons of side effects.

Can you explain this more? Right now the Xanax is prn; I thought norepinephrine was the main cause for anxiety; and doesn't the Risperdal just act as a reuptake inhibitor on various S/N/D receptors? Why would further inhibitions and (as a result) focusing of dopamine be counter-productive? I could see L-Tyrosine causing anxiety - even though it didn't last time... so therefore could just agree with me like the Metadate does. Dopamine could cause "speedballing"?

Your med changes do look a little bipolar: too activated and an AD is added; too zonked and a noradrenergic added. And it's all spiralled out of control with Risperdal.

And my baseline without meds is panic/anxiety/severe depression/constant exhaustion. Oh, and Risperdal isn't as effective as it should be. I felt nothing at lower doses - and I should have. So the zonking is a combo of horrible sleep and thyroid malfunction. Ironically, the med that has the most effect now is Lamictal.. and it's a negative one. Risperdal and Metadate as least do what they were meant to.

If you could survive for a while on Armour/Cymbalta/Lamictal/Medate or Armour/Cymbalta/Lamictal/Remeron/Metadate just to get things simplified a little it might help. ('cause stimulants can always be dropped when you're too jacked up or just don't need them)

I could do that if and when Lamictal stops being activating. Otherwise, without something to sedate me it's a recipe for disaster. Even then, more than likely, it would feel like Cymbalta wasn't even there.

[Cetkat]

One possible route could be weening off of other psych meds except the AP to see if Lamictal (LGT) ~200mg +Risperdal (that you are already on) works. Then maybe try swapping APs, especially if LGT is sedating, to a more activating one. As w/Lamictal, dose can mean a lot. Seroquel, for example, is mostly a sedative under 100mg (avg) but has AD effects of varying degrees at varying doses over that (or it's just feels like a lethargic sedative no matter what dose). Geodon can be agitating at lower doses and smoother at higher ones for many. It works the opposite way for others. Abilify... gave me akathisia, too, so no comment except that it can behave sort of like Geodon. Zyprexa gives me some AD effect, but to be honest, I'd need to be well into psychotic dosing territory to really get anti-d effects I need from it.

Lamictal could be a good AD if I can get past the activating effects. Risperdal is basically just for anxiety and a (slight) sleep helper. Right now, I do need the Metadate to function.. but that may change as I raise my thyroid levels. An activating med like Abilify would be good. Abilify also works as an D2 agonist. So my line of reasoning is use a dopamine agonist coupled with Mirapex to keep it from hitting things it shouldn't... Metadate to work on NE.. and basically engineer a different Abilify that works without driving me crazy. Geodon was horrible and did nothing & Zyprexa made me gain weight and did nothing.

If your mood is bouncing or agitated (BPIII style) on LGT and AP, then adding Lithium or Trileptal/Depakote/Tegretol might make some sense. These could also be sub'd for the AP. If you are only Depressed, then this route might not make so much sense w/the exception of considering Lithium augmentation.

I would be agitated on LGT & Risperdal (since, if I take away the negative from the Lamictal I'd still be left with anxiety). Doubly so on LGT & Abilify. But I'd also still be depressed. Lithium only works when I'm already half-way there. So if Lithium *really* works, it may be worth a shot. But taking Lithium now does pose a risk to my thyroid. And if the other mood stabilizers don't work on depression.. it's still only a partial improvement (on the anxiety side -- hopefully).

The other thing that strikes me in looking at your sig is, whooah, so very many meds. Have you taken each to a high therapeutic level alone or paired with only one or two other meds?

Tell me about it. I've been on all those for 1-3 months depending on the med.. Effexor up to 300mg and Cymbalta up to 120mg. I've reached the therapeutic level on everything on my long list of meds in my previous post except Paxil (which was switched after a month to Cymbalta). I've always been on some sort of combo. Mostly taking the Cymbalta and going through all the meds trying to find something that worked in addition. Now that Cymbalta doesn't work.. the idea is to take what you can get from whatever I can, and hopefully hit something that keeps my head above water.

Oh, right, light therapy might help. Have you tried it?

No. I would, but I can't afford it.

[AnneMarie]

If I was you, I'd find the closest university with a reputable mood disorder clinic and go in for an evaluation. (Most likely, if you don't have much resources, they'll work with you.) Here's why. You may be treating the wrong symptom. ADs make you agitated so you've been using add on APs. Sounds like you have sleep issues, too. I may very well be projecting, but those two together sound like they may add up to something moving beyond agitated depression.

This is sort of a real time thing going on with me. My pdoc has the theory that the depression I've been dealing with lately is a mixed state. Well, when Klonopin didn't work for the anxiety and I started needing less sleep, even I could figure it out. We are now in the process of adding Depakote, weening off Zyprexa, then moving towards lowering Lithium and perhaps d/c'ing. We'll see. I hope she is right because ADs are not my friends. Anyway, the same theory may hold for you. Treat the upside and mixed stuff (if applicable to you) and the depression may alleviate or dissipate.

Even if you are 100% MDD, you've been thru enough meds to seek out a current eval from somewhere highly respected.

[Velvet Elvis]

Can you explain this more? Right now the Xanax is prn; I thought norepinephrine was the main cause for anxiety; and doesn't the Risperdal just act as a reuptake inhibitor on various S/N/D receptors? Why would further inhibitions and (as a result) focusing of dopamine be counter-productive? I could see L-Tyrosine causing anxiety - even though it didn't last time... so therefore could just agree with me like the Metadate does. Dopamine could cause "speedballing"?

Lots of stuff can cause anxiety and that cause is not always relevant to what will work to make it better.

The term "speedball" originally refered to a combination of cocaine and heroin but more loosely is used to refer to any combination of contradictory agents.

A lot of people have found L-tyrosine to be mania in a bottle so if there is any chance you lean that way it would be a good idea to stay away from it.

Have you ruled out non-psychiatric causes like endocrine disorders, allergies and environmental toxins? Common sense says that when multiple medications targeted at a specific indication fail to make you feel better, it's because the wrong indication is being targeted.

[Velvet Elvis]

If I was you, I'd find the closest university with a reputable mood disorder clinic and go in for an evaluation. (Most likely, if you don't have much resources, they'll work with you.) Here's why. You may be treating the wrong symptom. ADs make you agitated so you've been using add on APs. Sounds like you have sleep issues, too. I may very well be projecting, but those two together sound like they may add up to something moving beyond agitated depression.

This is sort of a real time thing going on with me. My pdoc has the theory that the depression I've been dealing with lately is a mixed state. Well, when Klonopin didn't work for the anxiety and I started needing less sleep, even I could figure it out. We are now in the process of adding Depakote, weening off Zyprexa, then moving towards lowering Lithium and perhaps d/c'ing. We'll see. I hope she is right because ADs are not my friends. Anyway, the same theory may hold for you. Treat the upside and mixed stuff (if applicable to you) and the depression may alleviate or dissipate.

Even if you are 100% MDD, you've been thru enough meds to seek out a current eval from somewhere highly respected.

We've been coming to a similar conclusion with me, that I have some kind of cyclic unipolar that isn't in the DSM. No mania, just regular three week patches of pitch blackness. I guess that would really be rapid cycling unipolar if you were to try and use the existing terms as they relate to episode frequency. If I've had probably over 50 episodes by now and I'm in my early 30s, that's pointing in a direction other than recurrent depression.

[null0trooper]

Effexor would be the first thing I'd think about dropping, probably using a Prozac taper-down schedule.

Why Effexor instead of Cymbalta? Because Cymbalta used to work?

1. Because the Cymbalta seems to have been working throughout most of this. However, that could be part of the many problems.

2. At 75 mg, Effexor can be replaced by just about any SSRI - the Prozac taper basically allows the Effexor to be replaced without as many side effects, and then the Prozac is tapered down as needed.

Keep in mind that while the serotonin boosters usually reduce GAD/MDD anxiety, they often do it at the cost of feeling more tired, less motivated, and getting less quality sleep.

Risperdal is likely playing games with dopamine that you're now trying to counteract with Metadate and dopamine precursors. That would be another med to strongly consider dropping.

Actually, the real tiredness didn't kick in until about a month on Risperdal. Doesn't help depression, does help anxiety (ruminations), and a little bit on sleep.

"ruminations" aren't anxiety, and most ADs will not help that. Depending on the underlying cause, APs, Topomax, even Wellbutrin or a stimulant will do far more towards shutting that down.

Lamictal, Remeron, BuSpar - those should all be working in their own way to reduce anxiety.

Lamictal is actually causing anxiety by wearing me out; Remeron is only good for getting me a little more Stage 4 sleep & helping me not have a headache upon waking up after far too much REM; and BuSpar... hard to tell, but if I had to guess - I'd say it's doing absolutely nothing. Risperdal and Xanax are the only anti-anxiety meds I have, and they still don't get over my anxiety from Lamictal.

So you are not actually taking the Buspar - which IS prescribed as an anti-anxiety medication.

Remeron should be helping with the anxiety as you've described it, by getting you some sleep.

Am I missing anything? Does the L-Tyrosine/Mucuna pruriens/Mirapex sound like a good idea? I don't know what I'm going to do if this doesn't work.

Not entirely a good idea at this point. The point of that combination would be to elevate your mood and activity and/or reduce akathisia. However, you're on sedating anxiolytics and an antipsychotic. The best you can expect from speedballing like that is a sucky mood and tons of side effects.

Can you explain this more?

Risperdal has a number of different functions; reuptake inhibition isn't one of them. "Risperidone is a strong dopamine blocker (antagonist); i.e., it inhibits functioning of postsynaptic dopamine receptors." Some of those receptors are needed for cognition, among other things.

You are on:

Remeron - a sedating AD

Buspar - an anxiolytic

Effexor - SSRI-style AD at your dose, anxiolytic

Xanax - benzo anxiolytic

Risperdal - an antipsychotic

Multiple "downers"

And you want to take precursors for dopamine and noradrenaline, the key neurotransmitters released by speed, along with Metadate which is a stimulant.

i.e., "uppers" and that's without counting the effects from Lamictal and Cymbalta

All in all, that's basically speedballing, the main difference is that you aren't using heroin for the downer component.

I agree with Stacia, it's past time to get a thorough psychiatric and sleep evaluation by someone else.

But you also need some quality time with a therapist or counsellor to nail down the medically correct terms for what you are actually feeling. At this point I'm fairly convinced that you are using the wrong words to describe that, and it's running you into trouble.

I would not be surprised if they end up wanting you off everything except the thyroid med for a couple of months so they can start treating the original problems and not the medications for the problems from other medications. And I would fully expect it to be rough.

[Cetkat]

If I was you, I'd find the closest university with a reputable mood disorder clinic and go in for an evaluation. (Most likely, if you don't have much resources, they'll work with you.) Here's why. You may be treating the wrong symptom. ADs make you agitated so you've been using add on APs. Sounds like you have sleep issues, too. I may very well be projecting, but those two together sound like they may add up to something moving beyond agitated depression.

This is sort of a real time thing going on with me. My pdoc has the theory that the depression I've been dealing with lately is a mixed state. Well, when Klonopin didn't work for the anxiety and I started needing less sleep, even I could figure it out. We are now in the process of adding Depakote, weening off Zyprexa, then moving towards lowering Lithium and perhaps d/c'ing. We'll see. I hope she is right because ADs are not my friends. Anyway, the same theory may hold for you. Treat the upside and mixed stuff (if applicable to you) and the depression may alleviate or dissipate.

Even if you are 100% MDD, you've been thru enough meds to seek out a current eval from somewhere highly respected.

I have wondered if there may be some underlying BP-like agitation involved with the anxiety. I'm often stressed out, and without meds I do get some energy with a circular anxiety=>ruminations=>exhaustion or panic then exhaustion. But I never really swing towards less sleep and always loose that energy fairly quickly. I suppose it could be a type of mixed state. You're right about having sleep issues. I've thought about doing a study, but since the problem is consistent I've had time to figure out the underlying problems of stress/not being able to turn my mind off causing insomnia; lack of stage 4 sleep and too much REM from stress causing exhaustion and headaches; and sleeping more due to the depression and exhaustion.

Also the only AD that has increased my agitation is Effexor. Cymbalta worked well, and SSRI's did nothing at all.. save Zoloft helping anxiety a bit. The ruminations that have gone away with Risperdal have always been there, and aren't the result of other meds. The other AP's have been used to try and increase the effectiveness of Cymbalta, without success. Risperdal was rx'd before Effexor's negative effects to help my anxiety by stopping my ruminations.

I will look into the universities..

We've been coming to a similar conclusion with me, that I have some kind of cyclic unipolar that isn't in the DSM. No mania, just regular three week patches of pitch blackness. I guess that would really be rapid cycling unipolar if you were to try and use the existing terms as they relate to episode frequency. If I've had probably over 50 episodes by now and I'm in my early 30s, that's pointing in a direction other than recurrent depression.

Right.. it will get worse periodically and I'll be incapacitated for a little over a week. Then I'll go back to the 'normal' functioning depression. Have you come up with any ideas for the best way to treat it?

Lots of stuff can cause anxiety and that cause is not always relevant to what will work to make it better.

The term "speedball" originally refered to a combination of cocaine and heroin but more loosely is used to refer to any combination of contradictory agents.

A lot of people have found L-tyrosine to be mania in a bottle so if there is any chance you lean that way it would be a good idea to stay away from it.

Have you ruled out non-psychiatric causes like endocrine disorders, allergies and environmental toxins? Common sense says that when multiple medications targeted at a specific indication fail to make you feel better, it's because the wrong indication is being targeted.

Ok. I had asked if L-tyrosine + Metadate would increase nor. too much.. I'm not looking to do anything that would be bad for me. I've only experienced it with Cymbalta and Wellbutrin. It didn't cause any mania-like activity then (the only thing that has come close-ish is Abilify), but Metadate is stronger than Wellbutrin.

I do have an issue with my thyroid. I'm hoping that treating that will help. All my other levels are normal. I'm allergic to dust and wheat, and the only environmental problem was a paper plant that aggravated my allergies. I've since moved and can now go without my Zyrtec. I've never had any allergic reactions to medications or anything.

I'm honestly not confident that any psych meds will help me. Serotonin isn't the answer, nor. at least actually does help with energy and focus even though it doesn't alleviate depression, increasing dopamine specifically is something that I haven't tried. I don't know what else to target besides working with the stabilizers.

The idea isn't to reverse the stimulant, but to only use things that increase energy without causing anxiety.. and then use something else to help anxiety. And hopefully help the depression in the process.

1. Because the Cymbalta seems to have been working throughout most of this. However, that could be part of the many problems.

A problem, even though it helped with depression? How so?

2. At 75 mg, Effexor can be replaced by just about any SSRI - the Prozac taper basically allows the Effexor to be replaced without as many side effects, and then the Prozac is tapered down as needed.

Keep in mind that while the serotonin boosters usually reduce GAD/MDD anxiety, they often do it at the cost of feeling more tired, less motivated, and getting less quality sleep.

Discontinuing Effexor shouldn't be a problem. I accidentally went out of town without it once & had to go without. I got a little unsteady - but it actually cleared up before I got home. Nothing particularly bothersome.

Thanks for pointing that out about the boosters. That's a good point.

"ruminations" aren't anxiety, and most ADs will not help that. Depending on the underlying cause, APs, Topomax, even Wellbutrin or a stimulant will do far more towards shutting that down.

They're not.. but they are a strong perpetuator for me. Take away the ruminations and some of my anxiety goes with it. Hence, I often relate the two - and Risperdal indirectly helps my anxiety.

Lamictal is actually causing anxiety by wearing me out; Remeron is only good for getting me a little more Stage 4 sleep & helping me not have a headache upon waking up after far too much REM; and BuSpar... hard to tell, but if I had to guess - I'd say it's doing absolutely nothing. Risperdal and Xanax are the only [edit: working] anti-anxiety meds I have, and they still don't get over my anxiety from Lamictal.

So you are not actually taking the Buspar - which IS prescribed as an anti-anxiety medication.

Remeron should be helping with the anxiety as you've described it, by getting you some sleep.

I am taking the Buspar. 15mg morning & 15mg night.. I just haven't noticed an effect.

You're right about the Remeron. I wasn't thinking about that connection. I stand corrected.

Risperdal has a number of different functions; reuptake inhibition isn't one of them. "Risperidone is a strong dopamine blocker (antagonist); i.e., it inhibits functioning of postsynaptic dopamine receptors." Some of those receptors are needed for cognition, among other things.

You are on:

Remeron - a sedating AD

Buspar - an anxiolytic

Effexor - SSRI-style AD at your dose, anxiolytic

Xanax - benzo anxiolytic

Risperdal - an antipsychotic

Multiple "downers"

And you want to take precursors for dopamine and noradrenaline, the key neurotransmitters released by speed, along with Metadate which is a stimulant.

i.e., "uppers" and that's without counting the effects from Lamictal and Cymbalta

All in all, that's basically speedballing, the main difference is that you aren't using heroin for the downer component.

Alright, thanks for the explanation. I've never heard of speedballing. I'm used to mixing Cymbalta with various "downers", so it didn't seem contradictory. I want an upward boost, but only enough to raise my mood.

But you also need some quality time with a therapist or counsellor to nail down the medically correct terms for what you are actually feeling. At this point I'm fairly convinced that you are using the wrong words to describe that, and it's running you into trouble.

I would not be surprised if they end up wanting you off everything except the thyroid med for a couple of months so they can start treating the original problems and not the medications for the problems from other medications. And I would fully expect it to be rough.

So what words should I be using & what trouble am I getting into?

What I'm trying to say is that besides using meds to counteract the Lamictal (temporarily) - meds I was already taking anyway, I'm not treating the medications. They're for different base symptoms and only work minimally. Remeron and Risperdal aren't sedating, Metadate increases my concentration (which wasn't impaired by Risperdal) but I can still fall asleep on it, Cymbalta and Buspar are neutral, and Effexor is apparently too activating at any effective dose (in a very different way than Metadate).