Depression old-timer & possible BP2 newcomer needs meds advice

[sming]

Hi,

I'm a 43 yo guy who's been severely depressed since I was 19 and I'm amazed I'm still alive. Antidepressants (and there's very few I haven't tried, including the popular combos) either do nothing, make me more depressed or help partially for a few weeks and then poop-out. I've never had mania/hypomania (other than a period on Abilify).

After my stay at an inpatient psych ward in February, a young PDoc added Lithium to my Nardil (which, incidentally has been my most successful med to date but now does nothing) on the hunch that I might be BP2-ish. Whilst I can't say I went "WOO I'M FIXED", the Lithium certainly had a positive effect for a couple of months. Which has since just waned and stopped. So now I'm desperately depressed again. 

I'm seeing my PDoc soon to discuss alternative BP2 treatments. Top of my list of suggestions (since he is malleable in his dispensing) is Lamictal. But should it be? I read a lot of positive feedback on it's effect on depression but the data says it's poor. Should I perhaps be aiming towards an alternative? There are so many it's quite bewildering and I'm relatively new to the BP2 scenario.

Any tips are most appreciated.

Pete

 

[BipolarSpinster]

Actually, Lamictal works really well for both depression and a mood stabilizer in BP. 

Many people here are on it and swear by it. I’m on it, but seems to have lost its umph over the 20 years I’ve been on it. 

I’d say worth a try!

[sming]

12 hours ago, BipolarSpinster said:

Actually, Lamictal works really well for both depression and a mood stabilizer in BP. 

Many people here are on it and swear by it. I’m on it, but seems to have lost its umph over the 20 years I’ve been on it. 

I’d say worth a try!

Thanks BipolarSpinster. He called it in earlier and so I start it tonight. I'm just praying that it'll lift my mood.

Pete

[BipolarSpinster]

Good luck. 

[argh]

13 hours ago, sming said:

Hi,

I'm a 43 yo guy who's been severely depressed since I was 19 and I'm amazed I'm still alive. Antidepressants (and there's very few I haven't tried, including the popular combos) either do nothing, make me more depressed or help partially for a few weeks and then poop-out. I've never had mania/hypomania (other than a period on Abilify).

After my stay at an inpatient psych ward in February, a young PDoc added Lithium to my Nardil (which, incidentally has been my most successful med to date but now does nothing) on the hunch that I might be BP2-ish. Whilst I can't say I went "WOO I'M FIXED", the Lithium certainly had a positive effect for a couple of months. Which has since just waned and stopped. So now I'm desperately depressed again. 

I'm seeing my PDoc soon to discuss alternative BP2 treatments. Top of my list of suggestions (since he is malleable in his dispensing) is Lamictal. But should it be? I read a lot of positive feedback on it's effect on depression but the data says it's poor. Should I perhaps be aiming towards an alternative? There are so many it's quite bewildering and I'm relatively new to the BP2 scenario.

Any tips are most appreciated.

Pete

 

Out of curiosity, when the lithium started pooping out, were your blood levels still within the therapeutic range?

Recent-ish paper does indicate that of all mood stabilizers, Lamictal has some of the best efficacy for the depression part of BP. Other types of mood stabilizers like valproic acid tend to act to quash mania more than depression.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615936/

As far as a DX goes, there is a prevailing theory that it isn't as much as MDD vs BP1/BP2, but a BP spectrum. Treatment resistance, meds making things worse, pooping out, recurrence, family history, early onset, etc in theory, suggests traditional treatment for MDD might not be effective, where as, BP like treatment may work.

Also curious, do you have other BP like symptoms, despite the absence of any form of mania?

Off the top of my head, we have a number of members with an MDD DX, not hit mania/hypomania, but have benefited from anticonvulsant mood stabilizers.

@HydroCat has had luck with lamictal

@jt07 has had luck with carbamazapine

@Juniper29 and myself have had luck with low doses of gabapentin

@looking for answers while on lithium, not an AC, doesn't have mania, but might be BP2

I'm sure there are many more in this board with almost the same story, I just haven't been around for that long in this board.

[looking for answers]

I love lithium

[argh]

also of note,

http://www.dbsalliance.org/pdfs/medication_charts/BPmedication_chart.pdf (PDF warning)

The first two pages and the last page may be of interest to you.

[Iceberg]

I wouldn't say that lithium helping means BP2. I've heard of it being used at lower doses as an MDD add-on especially for suicidal ideation. The reason I say that is slapping a definite label on it can lead to getting pidgeonholed as far as med options. Ex (and I don't know what uve taken, just an example) stimulants can help treatment resistant depresson but if your BP II many pdocs would have more reservation about using them despite the fact that they can be helpful. As mentioned above the spectrum idea can be useful. When I was walking the MDD/BP line my doc gave me a DX of MOOD DISORDER NOS because he said it would give me the most flexibility for treatment until things got nailed down 

[sming]

1 hour ago, argh said:

Out of curiosity, when the lithium started pooping out, were your blood levels still within the therapeutic range?

I think so yes. I was at 900mg. I tried 1200mg but it was just too much, I felt poisoned somehow - very difficult to put into words.

1 hour ago, argh said:

Recent-ish paper does indicate that of all mood stabilizers, Lamictal has some of the best efficacy for the depression part of BP. Other types of mood stabilizers like valproic acid tend to act to quash mania more than depression.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615936/

Thank you. I'll try and read up on that paper when I've the energy.

1 hour ago, argh said:

As far as a DX goes, there is a prevailing theory that it isn't as much as MDD vs BP1/BP2, but a BP spectrum. Treatment resistance, meds making things worse, pooping out, recurrence, family history, early onset, etc in theory, suggests traditional treatment for MDD might not be effective, where as, BP like treatment may work.

Yes, I'm aware of the spectrum and totally buy into it. At the end of the day though I still think the distinct labels are useful, even if to describe the majority of one's DX.

1 hour ago, argh said:

Also curious, do you have other BP like symptoms, despite the absence of any form of mania?

Well I tick all the boxes on wikipedia's definition of the symptoms:

• Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, or hopeless) or observation made by others (e.g., appears tearful). (Note: In children and adolescents, can be irritable mood.)

• Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation).

• Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. (Note: In children, consider failure to make expected weight gain.)

• Insomnia or hypersomnia nearly every day.

• Psychomotor agitation or retardation nearly every day (observable by others; not merely subjective feelings of restlessness or being slowed down).

• Fatigue or loss of energy nearly every day.

• Feelings of worthlessness or excessive or inappropriate guilt nearly every day (not merely self-reproach or guilt about being sick).

• Diminished ability to think or concentrate, possible irritability or indecisiveness, nearly every day (either by subjective account or as observed by others).

• Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, a suicide attempt, or a specific plan for committing suicide.

1 hour ago, argh said:

Off the top of my head, we have a number of members with an MDD DX, not hit mania/hypomania, but have benefited from anticonvulsant mood stabilizers.

@HydroCat has had luck with lamictal

@jt07 has had luck with carbamazapine

@Juniper29 and myself have had luck with low doses of gabapentin

@looking for answers while on lithium, not an AC, doesn't have mania, but might be BP2

I'm sure there are many more in this board with almost the same story, I just haven't been around for that long in this board.

Thanks man, I really appreciate the reply.

Pete

1 hour ago, argh said:

also of note,

http://www.dbsalliance.org/pdfs/medication_charts/BPmedication_chart.pdf (PDF warning)

The first two pages and the last page may be of interest to you.

brilliant - cheers.

[sming]

1 hour ago, Iceberg said:

I wouldn't say that lithium helping means BP2. I've heard of it being used at lower doses as an MDD add-on especially for suicidal ideation.

-- Yep. I met someone on the psych ward who was on low dose for that. And it was giving them crazy SI. Go figure.

The reason I say that is slapping a definite label on it can lead to getting pidgeonholed as far as med options. Ex (and I don't know what uve taken, just an example) stimulants can help treatment resistant depresson

-- Yep, I find all stimulants very helpful with my depression. That's why being stuck on Nardil is such a ******. However they do tend to lose effectiveness quite quickly.

but if your BP II many pdocs would have more reservation about using them despite the fact that they can be helpful. As mentioned above the spectrum idea can be useful. When I was walking the MDD/BP line my doc gave me a DX of MOOD DISORDER NOS because he said it would give me the most flexibility for treatment until things got nailed down 

-- Good idea.

 

[Juniper29]

29 minutes ago, sming said:

I

Well I tick all the boxes on wikipedia's definition of the symptoms:

• Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, or hopeless) or observation made by others (e.g., appears tearful). (Note: In children and adolescents, can be irritable mood.)

• Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation).

• Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. (Note: In children, consider failure to make expected weight gain.)

• Insomnia or hypersomnia nearly every day.

• Psychomotor agitation or retardation nearly every day (observable by others; not merely subjective feelings of restlessness or being slowed down).

• Fatigue or loss of energy nearly every day.

• Feelings of worthlessness or excessive or inappropriate guilt nearly every day (not merely self-reproach or guilt about being sick).

• Diminished ability to think or concentrate, possible irritability or indecisiveness, nearly every day (either by subjective account or as observed by others).

• Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, a suicide attempt, or a specific plan for committing suicide.

 

 

Is this different from criteria for a major depressive episode? I think it's the same, no?

[argh]

1 hour ago, Juniper29 said:

Is this different from criteria for a major depressive episode? I think it's the same, no?

Yeah, that sort of sounds like MDD.

This is what I see on the NIH gov site for BP

• Feel very “up,” “high,” or elated
• Have a lot of energy
• Have increased activity levels
• Feel “jumpy” or “wired”
• Have trouble sleeping
• Become more active than usual
• Talk really fast about a lot of different things
• Be agitated, irritable, or “touchy”
• Feel like their thoughts are going very fast
• Think they can do a lot of things at once
• Do risky things, like spend a lot of money or have reckless sex

 

@sming There are also two other members in particular that i'll tag here. @mikl_pls and @browri who are practically walking encyclopedias when it comes to pharmacology. They might be able to give you a recommendation for either mono-therapy or a synergizing cocktail

[sming]

9 hours ago, argh said:

Yeah, that sort of sounds like MDD.

This is what I see on the NIH gov site for BP

• Feel very “up,” “high,” or elated
• Have a lot of energy
• Have increased activity levels
• Feel “jumpy” or “wired”
• Have trouble sleeping
• Become more active than usual
• Talk really fast about a lot of different things
• Be agitated, irritable, or “touchy”
• Feel like their thoughts are going very fast
• Think they can do a lot of things at once
• Do risky things, like spend a lot of money or have reckless sex

 

@sming There are also two other members in particular that i'll tag here. @mikl_pls and @browri who are practically walking encyclopedias when it comes to pharmacology. They might be able to give you a recommendation for either mono-therapy or a synergizing cocktail

Hey, yes, I only listed the symptoms that apply to me since I get none of the [hypo]mania symptoms that you've listed, apart from being touchy/agitated/irritable which frankly is also applicable to depression symptoms.

This is what is confusing/terrifying/worrying me:

• I don't respond to MDD treatments - tens and tens of AD's and many AD combo's (including ketamine, ECT and dTMS),
• I respond well to stimulants (Vyvanse, concerta), Nuvigil/Provigil, Abilify, Lithium and Nardil but they all seem to poop-out
• But I have zero [hypo]mania symptoms. Like zero. None.
• SO WHAT THE HELL IS GOING ON?

I buy the spectrum view of things but ultimately psych health care needs you in a category e.g. insurance. Plus I deeply just want to ****** know what's caused 20+ years of intense suffering  

[argh]

31 minutes ago, sming said:

Hey, yes, I only listed the symptoms that apply to me since I get none of the [hypo]mania symptoms that you've listed, apart from being touchy/agitated/irritable which frankly is also applicable to depression symptoms.

This is what is confusing/terrifying/worrying me:

• I don't respond to MDD treatments - tens and tens of AD's and many AD combo's (including ketamine, ECT and dTMS),
• I respond well to stimulants (Vyvanse, concerta), Nuvigil/Provigil, Abilify, Lithium and Nardil but they all seem to poop-out
• But I have zero [hypo]mania symptoms. Like zero. None.
• SO WHAT THE HELL IS GOING ON?

I buy the spectrum view of things but ultimately psych health care needs you in a category e.g. insurance. Plus I deeply just want to ****** know what's caused 20+ years of intense suffering  

Wow. Ok. Thought there was at least a bit more overlap than virtually none.

hope the lamictal works out for you.

[mikl_pls]

I have misplaced my DSM-V and absolutely cannot find it (my room is a complete mess...) but, to me, it sounds like this could be depression with atypical features.

@sming, with your depression, do you have "mood reactivity?" That is, does your mood brighten in response to positive stimuli, and then return back to depression?

Also, do you have two or more of the following?

1. Significant weight gain/increase in appetite (as opposed to weight loss/anorexia)
2. Hypersomnia (sleeping too much, as opposed to the insomnia present in melancholic depression)
3. "Leaden paralysis" (i.e., heavy, leaden feelings in arms or legs)
4. Long-standing pattern of interpersonal rejection sensitivity (not limited to episodes of mood disturbance) that results in significant social or occupational impairment

Also, psychomotor retardation tends to be prevalent rather than psychomotor agitation (i.e., movement tends to be slower and you may tend to become more of a "couch potato" so much more so that others may notice, rather than the opposite, wherein you can't stay still long enough...)

37 minutes ago, sming said:

This is what is confusing/terrifying/worrying me:

• I don't respond to MDD treatments - tens and tens of AD's and many AD combo's (including ketamine, ECT and dTMS),
• I respond well to stimulants (Vyvanse, concerta), Nuvigil/Provigil, Abilify, Lithium and Nardil but they all seem to poop-out
• But I have zero [hypo]mania symptoms. Like zero. None.
• SO WHAT THE HELL IS GOING ON?

It is possible to be bipolar type 2 without experiencing much hypomania at all. Sometimes hypomania disguises itself very cleverly. I really wish I had my DSM-V because I don't have the criteria memorized off-hand, but hypomania can manifest either euphorically or dysphorically (i.e., mixed episodes). I tend to have mixed episodes almost exclusively when I have hypomania.

I also almost exclusively tend to respond to stimulants. Lithium was a disaster for me. MAOIs sorta worked for me, but the side effects were worse than the benefits (if any) I received. Emsam was okay, Parnate was great with Adderall, but it pooped out. Never tried Nardil. Marplan was... meh... I had anger issues with Marplan. Very emotionally labile.

Out of almost all the atypical antipsychotics I've tried, Abilify has worked the best for me. I've had to discontinue it very recently, however, because of a possible compulsive spending habit, though. Not sure yet, though, if switching has fixed it though. Time will tell.

37 minutes ago, sming said:

I buy the spectrum view of things but ultimately psych health care needs you in a category e.g. insurance. Plus I deeply just want to ****** know what's caused 20+ years of intense suffering

I definitely empathize with you for wanting to get to the bottom of all this suffering. I wish we could tell you, but we can't diagnose. I think either atypical deppresion or bipolar 2, of which the depressive episodes most often feature atypical features anyway.

I believe that it is possible there are some genetic make up issues that has prevented you from achieving remission from all the therapies you have tried like ECT and dTMS, even ketamine. I forget which genes are involved, but it would probably be looking into. A standard Genesite test wouldn't be able to check for this. I've done 23andme and analyzed my own raw data with Selfdecode.com and other 3rd party sites to help me analyze it and have found various genes that explain why it has been so difficult to achieve remission from standard therapies, and some genes that show that it would be probably futile to try ECT and other therapies like that.

I think Lamictal + Nardil would be a good option to try as for a medicine combination.

Have you ever tried a combination of an MAOI (Nardil) + a tricyclic antidepressant or an MAOI (Nardil) + a stimulant? They're classically contraindicated, but they can safely be used together.

The secondary amine tricyclics (TCAs) like nortriptyline, desipramine, and protriptyline can be combined with MAOIs, both in low doses. They both have to be started at the same time, otherwise you run the risk of hypertensive crisis. I think the TCA can already be started before the MAOI too, and the MAOI added on top of it, but otherwise, the MAOI has to be washed out before starting this combination.

https://books.google.com/books?id=wwP1iOanWAAC&pg=PA168&lpg=PA168&dq=maoi+tca+combination+25+mg+amitriptyline&source=bl&ots=gM2kCSJrp5&sig=OcaTvRI1Kt7ZZCZi3Xi4b9jjChE&hl=en&sa=X&ved=0ahUKEwiJo5OgtdTKAhVE2D4KHXh7C6QQ6AEIHDAA#v=onepage&q=maoi tca combination 25 mg amitriptyline&f=false

Quote

The consensus of experienced clinicians is that combination treatment is safest if the following protocol is adhered to. The patient should be free from either medication for 2 weeks. Both medications are then started simultaneously, at a low dose. For example, the TCAwould be started at an equivalent of 25 mg amitriptyline [replace with nortriptyline or desipramine] h.s. and the MAOI started the next morning at 15 mg for phenelzine (10 mg for tranylcypromine or isocarboxazid). Every week the dose of each would be raised by an additional tablet [or capsule for nortriptyline]; thus on day eight, 50 mg TCA would be given at h.s. and on day nine, 15 mg phenelzine at a.m. and noon. The  total dose of TCA can be given h.s.; the dose of MAOI should be split during the mornin (to avoid insomnia). Dosage can be raised weekly in this fashion to three pills MAOI, three pills TCA at which time 2 weeks should be permitted to elapse, to observe the patient for beneficial response. (Frequently, lower dosages are effective in combination treatment.)

If the patient has still not responded, the TCA could be increased by one additional tablet [capsule] per week. Currently, dose equivalents of 45 mg phenelzine and 75 to 150 mg TCA (amitriptyline) have been recommended as therapeutic doses. If the patient still has not responded, consideration should be given to further increases. In particular, one might seek to attain 85% platelet MAO inhibition while avoiding severe suppression of the enzyme (greater than 95%) and the use of the laboratory would be particularly helpful in this case.

There are some reports that, in combination treatment, amitriptyline and triimipramine have relatively greater safety among TCA, and imipramine less; phenelzine and isocarboxazid are thought to be safer than tranylcypromine. However, it must be stressed that the schedule and route of drug administration is infinitely more important than the specific agent used. Further, it should be reiterated that the evidence for the above folk wisdom comes from drug interactions observed when they were not prescribed in the recommended manner, and from megadose animal experiments. Their relevance for recommended usage is limited.

The indications for use of combined treatment at this time are basically for patients refractory to a single drug. It has been more difficult to define a group of patients where combined treatment might be indicated as less than treatment of last resort or better than ECT. We would recommend TCA-MAOI combination for endogenous depressives after trials of two different classes of TCA, TCA + T₃, TCA + Ritalin, a subsequent trial of MAOI alone, MAOI + lithium or MAOI + tryptophan, and who refused ECT or in whom ECT failed.

Stimulants like methylphenidate and dextroamphetamine can be used in combination with MAOIs as well. Methylphenidate is supposedly safer to use in combination with MAOIs because it doesn't increase serotonin levels, but it is a 5-HT_1A agonist (but then again, serotonin syndrome arises from excessive 5-HT_2A stimulation, if I'm not mistaken...). But methylphenidate can be used in doses of up to 60 mg and dextroamphetamine in doses up to 30 mg in combinations of an MAOI when titrated very sloooowly and very carefully.

https://books.google.com/books?id=_I7LBQAAQBAJ&pg=PA71&lpg=PA71&dq=maoi+tca+stimulant+combination+treatment&source=bl&ots=vGbJPCI7si&sig=Wt6aQCwM9RGhYQ6JSqvqIuOwero&hl=en&sa=X&ved=0ahUKEwiT7u7Bh5rKAhXKPiYKHesvBBIQ6AEITDAI#v=onepage&q=maoi tca stimulant combination treatment&f=false

https://www.ncbi.nlm.nih.gov/pubmed/3997787

I personally was on a combination of an MAOI + TCA + stimulant a few years ago, which is a mega-nono according to classical contraindications! I was on Emsam 9 mg/24 hr, nortriptyline 50 mg, and dextroamphetamine ER 30 mg. It actually didn't do that much for me. Emsam, to me, is a very weak MAOI. I needed the 12 mg patch, but my pdoc wouldn't prescribe it. The second time I took Emsam, I experimented and used a 6 mg + 9 mg patch for 15 mg (greater than the max dose!) and only then did I start to feel something... but again, my pdoc wouldn't hear of it. That was when I switched to Parnate (tranylcypromine), which cause immense weight gain, + Adderall 30 mg. 

On top of all this, Lamictal should have no problem being added to this combination.

So one of the articles mentioned the combination of thyroid hormine (T₃). That would also be a possible combination therapy, if you haven't already tried it. I would recommend trying the lowest dose possible, like 2.5-5 mcg of liothyronine (Cytomel). You don't want to mess up your thyroid hormone balance. I would also recommend taking it for the shortest amount of time possible, and if you need it long term, you need to take liothyronine with levothyroxine (Synthroid) in a ratio of 4:1 of T₄:T₃ (e.g., 12.5 mcg + 2.5 mcg of levothyroxine and liothyronine, respectively).

Also, the newer eugeroics/stimulants, Nuvigl/Provigil, which you mentioned that you respond to well would be good options to augment with as well, but good luck getting your insurance to cover them without a diagnosis of a sleep disorder like narcolepsy or OSA (unless you have them, in which case go ahead and try them with your MAOI! They'd be a safer option than the classic stimulants... perhaps less effective though).

If you responded well to Abilify, it might be worth considering adding it to your cocktail. Might I ask why you stopped it? If you don't tolerate Abilify well, you might consider Rexulti. It's not "Abilify 2.0" as people keep calling it around here. It's a separate entity to its own with different pharmacodynamics all to itself. It may feel somewhat similar at higher doses as low doses of Abilify, but at low doses, it feels like a completely different medicine--very calming, sedating even for some. I actually can't tolerate it at low doses, I need higher doses. Vraylar is another med that is somewhat related and is even a phenylpiperazine like Abilify and Rexulti, but works a little differently than Rexulti and Abilify. It is more selective for the D₃ receptor than the D₂ receptor, but is also a partial agonist for the two receptors like Abilify and Rexulti. So if Rexulti doesn't appeal to you, there's always that option.

So if I were you in your position, I would consider the following cocktail:

• Phenelzine (Nardil)
• Either TCA (nortriptyline (Pamelor), desipramine (Norpamin), possibly protriptyline (Vivactil)) or stimulant (methylphenidate (Ritalin/Ritalin LA/Metadate CD/Concerta/etc...), dextroamphetamine (Dexedrine/Dexedrine Spansule), amphetamine/dextroamphetamine (Adderall), modafinil (Provigil), armodafinil (Nuvigil)), or both at once
• Atypical antipsychotic with dopamine partial agonism (aripiprazole (Abilify), Rexulti (brexpiprazole), or Vraylar (cariprazine))
• Lamotragine (lamotrigine)
• Liothyronine (Cytomel) (low dose, 2.5-5 mcg) (and if successful and needs to be taken long term, add levothyroxine (Synthroid, Levothroid, Unithroid) in a ratio of 4:1 of T₄:T₃, so liothyronine 2.5-5 mcg + levothyroxine 12.5-25 mcg)

I think that might put quite a dent in your depression, and if not, I would definitely reconsider ECT while on this combo, making sure to try bilateral ECT (while it may have more adverse effects, it may have better effects on depression). If you ask your pdoc about trying donepezil (Aricept), it may prevent adverse effects on memory while doing ECT. There are ways to potentiate the seizures induced by ECT that may help the outcome of ECT, but I forget. Like, I think taking something like Thorazine (chlorpromazine) before the ECT treatments helps relax you and also helps potentiate the seizures. Also, using ketamine as the anesthetic also helps potentiate the effects of ECT.

Hope this helps!

[browri]

14 hours ago, Juniper29 said:

Is this different from criteria for a major depressive episode? I think it's the same, no?

Believe it or not, in the DSM V, even for Bipolar 1 and 2, depressive episodes are still referred to as major depressive episodes not bipolar depressive episodes. And so in that regard, the depressive episodes specifically experienced by people with bipolar disorder wouldn't necessarily have different symptoms than someone with MDD, unless of course we were talking about a mixed episode, which would have a different symptom set.

@sming you are right that there are certainly differing opinions on whether Lamictal actually works or not. In my experience it does. I've taken Lamictal before alone and in combination with one AAP at a time. I found that it certainly delayed episodes from occurring both hypomanic and depressive. If something depressed me, I was just kinda able to "get over it" quicker. Things rolled off my shoulders more easily. But I still experienced the feeling of something making me upset which is still important to leading a normal life. If you squash your moods out completely, then you'll just feel like a zombie.

Lamictal is nice because after you adjust to it, for many people it can have almost no side effects. I'm starting it back up now because the new insurance company in July may not cover my Trintellix. But I've been feeling "up" the past several weeks and been out of any major depressive episodes for several months. I do think Rexulti has been a big help as well, but I wanted to replace the Trintellix with Lamictal because while Lamictal isn't great at treating things ACUTELY, in the long term it's quite tolerable and for me at least, quite effective.

However, I can say that starting back up on it this time has been a bit rough. Noticing some GI discomfort, some headaches that come and go. Kind of an anxious antsy feeling. You may notice with Lamictal that things get worse before they get better. Trust me when I say that if you don't get the rash, you should try your hardest to get to 100mg. You may find it to be a game changer.

Like others have indicated, it is becoming more commonplace to use Lamictal alone or in combination with an antidepressant for depression in people that don't appear to have experienced hypomanic episodes. However, like @mikl_pls pointed out, hypomania is subtle and can be difficult to diagnose because it may not be outwardly apparent to the clinician. But it's usually a red flag when you've tried and failed several antidepressants. That was my pdocs red flag for me when he started seeing me ~4 years ago. We immediately started titrating down the Cymbalta and used Prozac to come off of it while I was starting Lamictal. Let me tell you that it was a rough couple of weeks, but when I came out of it, I finally started to feel normal again. As you can see from my signature, we've come a long way from Lamictal monotherapy, but I do believe I have finally found a combo that works for me (Depakote+Trintellix+Rexulti+Vyvanse). Now the goal is to see if I can make it through a winter without an antidepressant and without experiencing one of my typical seasonal depressions. As an FYI, the DSM-V does now acknowledge depressive episodes "with seasonal pattern" for those with bipolar disorder, essentially calling out that there could in fact be some crossover between bipolar disorder and seasonal affective disorder (SAD). May also be why Wellbutrin, which is the one medication that has the most evidence for this indication also happens to be the one antidepressant that seems to have a much lower rate of manic switch.

If you're curious about what hypomania might feel like, I actually wrote a post recently in another thread where @Matt G was also wondering if he may be bipolar. I linked it below. It may provide some insight of how simple things that many people do can be associated with bipolar behaviors. Things like DUIs or sleeping around, impulsive shopping. These are things that would likely happen to you between depressive episodes when you're feeling "good" (i.e. if you're really bipolar, "I feel SO much better after starting this medication" is something that could also be a red flag).

I can also say that I responded the same way to lithium as you did. I felt ill. Everything about it just made me feel like I was poisoning myself. I was waking up drenched in sweat and I just felt so sick and "off". I only lasted maybe 10 days. Depakote by contrast has been an absolute DREAM. I feel so much more calm on it.

Following on what @mikl_pls said, genetics can play a big role in it. For example, I have several SNPs for the MAO-A (monoamine oxidase A) gene that cause me to be under-produce this enzyme, which is important to breaking down monoamines in the brain like serotonin, norepinephrine, and dopamine. In this case, I would have higher levels of those neurotransmitters than most. And as we know in the brain, there is both a too much and a too little. I also have an under-functioning COMT (catechol-O-methyltransferase) gene. See the below article. I'm the "Worrier":

https://www.selfhacked.com/blog/worrier-warrior-explaining-rs4680comt-v158m-gene/

The beauty in my med combination is I've actually worked with my pdoc to introduce medications that correct underlying genetic dysfunctions. If I focus specifically on MAO-A and COMT, then I can tell you that Depakote is a fairly strong MAO inducer (the exact OPPOSITE of Nardil). It increases the metabolism of serotonin in the brain and reduces its levels. Additionally, it also reduces the synthesis of catecholamines like dopamine and norepinephrine. Rexulti and Vyvanse both also increase COMT. Additionally, Depakote increases the conversion of glutamate (an excitatory neurotransmitter in the brain) to GABA (a "depressing" neurotransmitter, target of many drugs from Ativan to Rohypnol) and then inhibits the breakdown of GABA to allow more available in the brain, leading to a calming state. This also of course leads to side effects like sedation, but in the long run, your sleep improves and subsequently your mood as well.

The recommendations above all seem like good starting points to talk with your pdoc. It would be wise to have your thyroid levels checked to make sure that some of your depression isn't due to hypo- or hyperthyroidism. Additionally, checking B vitamin and folate levels should be a good way of telling if you have a mutation on the MTHFR gene that would negatively impact your body's ability to properly absorb folate which is a necessary precursor to the synthesis of neurotransmitters in the brain. There are various different steps in these neurochemical processes and some of the best pharmacotherapies address the problem at multiple levels, hence the drug cocktails we take.

If this reinforces your thinking further that you may be bipolar. I just completed a closed study through 23andMe of people with either depression or bipolar disorder. I was one of <10,000 people selected for the bipolar set. At the end of the 9-month study we received a report of some of the preliminary statistics that came out of their investigation. One of the ones that struck me the most is that of all the people in the study with bipolar disorder almost 50% of were previously misdiagnosed as MDD. It's actually quite common for BP2 particularly to be discovered after someone reporting depression fails multiple medications or they repeatedly poop out within months.

Edited June 19, 2018 by browri
Lamictal stupids

[Iceberg]

@mikl_pls.i did the Thorazine thing with the ECT...idk how much it helped but they said it's not uncommon to try. I would add that rexulti (if you haven't tried it) was basically the only med that helped my bipolar depression directly, I always recommend it for BP2 (ish) where depression is the major problem...I also found it not as over-activating as other meds I've gotten for BP depresson. Cytomel is a good idea too. It didn't do a ton for me but if your not responding to all the normal stuff I think it never hurts to come at it from a different angle. Also, have you ever tried a dopamine agonist (mirapex)? It's a pretty last line thing and a lot of docs won't use it but there is evidence for its use in treatment resistant depression. The drug interaction checker I use said it didn't interact with Nardil but obviously your doc would know better about that I don't know all the MAOI guidelines, but it might be worth looking in to

[Juniper29]

1 hour ago, sming said:

Hey, yes, I only listed the symptoms that apply to me since I get none of the [hypo]mania symptoms that you've listed, apart from being touchy/agitated/irritable which frankly is also applicable to depression symptoms.

This is what is confusing/terrifying/worrying me:

• I don't respond to MDD treatments - tens and tens of AD's and many AD combo's (including ketamine, ECT and dTMS),
• I respond well to stimulants (Vyvanse, concerta), Nuvigil/Provigil, Abilify, Lithium and Nardil but they all seem to poop-out
• But I have zero [hypo]mania symptoms. Like zero. None.
• SO WHAT THE HELL IS GOING ON?

I buy the spectrum view of things but ultimately psych health care needs you in a category e.g. insurance. Plus I deeply just want to ****** know what's caused 20+ years of intense suffering  

I understand the desire to have a clear category. I have a MDD diagnosis but many features suggestive of bipolarity according to the spectrum theory (strong family history, early onset, atypical depression, recurrence, psychotic features). I also experience irritability and rage. No hypomania as far as I can tell, no risky behaviors or anything. It's totally possible that my dx will eventually change to BPII, but for now, since unlike you I respond to antidepressants, I guess it makes sense to keep it as MDD ... although Lamictal has been suggested as a good option if my current meds stop working.

Theres not really much point to this post except that you're not alone in inhabiting the gray area.

Let us know how the Lamictal turns out.

[mikl_pls]

3 hours ago, Iceberg said:

@mikl_pls.i did the Thorazine thing with the ECT...idk how much it helped but they said it's not uncommon to try. I would add that rexulti (if you haven't tried it) was basically the only med that helped my bipolar depression directly, I always recommend it for BP2 (ish) where depression is the major problem...I also found it not as over-activating as other meds I've gotten for BP depresson. Cytomel is a good idea too. It didn't do a ton for me but if your not responding to all the normal stuff I think it never hurts to come at it from a different angle. Also, have you ever tried a dopamine agonist (mirapex)? It's a pretty last line thing and a lot of docs won't use it but there is evidence for its use in treatment resistant depression. The drug interaction checker I use said it didn't interact with Nardil but obviously your doc would know better about that I don't know all the MAOI guidelines, but it might be worth looking in to

Yes, I'm on Rexulti right now for like, the 4th (?) time lol. I agree that it can be very helpful. I would definitely recommend a trial if dopamine partial agonists help. I did mention that if OP responded well to Abilify, then most likely dopamine partial agonists like Rexulti and Vraylar would also be good options.

I also forgot to mention dopamine agonists, like you mentioned, Mirapex (pramipexole), which was something else I also tried... (my friends who know about my medical conditions and my medicine history tell me I'm a walking pharmacy T__T). I've also tried Requip (ropinirole) and Neupro patch (rotigotine transdermal), as well as Sinemet and Rytary (both carbidopa/levodopa) for tremor, but both are the same drug, just the latter is a combination of IR and ER beads in a capsule that is a dopamine precursor with a drug that inhibits premature levodopa conversion in the periphery, which theoretically should act the same as a dopamine agonist. I didn't really get much results from any of them, though, except maybe Mirapex.

Cytomel did the most for me, but at a dose of 50 mcg which put me into severe hyperthyroidism! I had to stop taking it. Be super careful with this, as I mentioned in my previous post, and start at the lowest dose possible! (2.5-5 mcg, and if you need to take it long term, take it with levothyroxine in a ratio of 4:1 with levothyroxine to liothyronine).

[argh]

I think what @Iceberg's doc did might work out the best for you while they sort out your meds..assuming your insurance plays nice with it.

I get the need/desire to have an official Dx. Something definitive after decades of sort of working our way through this is rough. Hit year 22 for me, this year.

But who knows what the guidelines may look like in the future. My MDD seems somewhat atypical, haven't had good luck with ADs (though I haven't been through the wringer to the extent that you have), early onset,  anger/rage, sleep issues, fast/rapid thoughts, pressured speech etc. Many of us may get re-Dxed into BP2 or maybe even future classifications of BP3, BP4, BP5, etc. Address symptoms first, whatever they end up calling it is secondary.

[sming]

On 19/06/2018 at 12:11 PM, mikl_pls said:

I have misplaced my DSM-V and absolutely cannot find it (my room is a complete mess...) but, to me, it sounds like this could be depression with atypical features.

@sming, with your depression, do you have "mood reactivity?" That is, does your mood brighten in response to positive stimuli, and then return back to depression?

Apologies for late response, I'm not getting notifications from the site.

Wow, that's a lot of info - thanks man!  I would say I don't have mood reactivity. I discount and undermine positive events as per classic depression. My mood doesn't brighten.

On 19/06/2018 at 12:11 PM, mikl_pls said:

Also, do you have two or more of the following?

1. Significant weight gain/increase in appetite (as opposed to weight loss/anorexia)
2. Hypersomnia (sleeping too much, as opposed to the insomnia present in melancholic depression)
3. "Leaden paralysis" (i.e., heavy, leaden feelings in arms or legs)
4. Long-standing pattern of interpersonal rejection sensitivity (not limited to episodes of mood disturbance) that results in significant social or occupational impairment

3 & 4 definitely. Lots of rejection OCD as well.

On 19/06/2018 at 12:11 PM, mikl_pls said:

Also, psychomotor retardation tends to be prevalent rather than psychomotor agitation (i.e., movement tends to be slower and you may tend to become more of a "couch potato" so much more so that others may notice, rather than the opposite, wherein you can't stay still long enough...)

Yep, when down I move & do very little. I just want to be unconscious/dead/asleep.

On 19/06/2018 at 12:11 PM, mikl_pls said:

It is possible to be bipolar type 2 without experiencing much hypomania at all. Sometimes hypomania disguises itself very cleverly. I really wish I had my DSM-V because I don't have the criteria memorized off-hand, but hypomania can manifest either euphorically or dysphorically (i.e., mixed episodes). I tend to have mixed episodes almost exclusively when I have hypomania.

the one thing that springs to my mind was it expressing as irritability, which I definitely have almost constantly.

On 19/06/2018 at 12:11 PM, mikl_pls said:

I also almost exclusively tend to respond to stimulants. Lithium was a disaster for me. MAOIs sorta worked for me, but the side effects were worse than the benefits (if any) I received. Emsam was okay, Parnate was great with Adderall, but it pooped out. Never tried Nardil. Marplan was... meh... I had anger issues with Marplan. Very emotionally labile.

That's the bummer - you can't take Adderall with MAOI's. I took too much by accident and ended up in hospital. It was worth the prior reduction in depression, though. Ritalin also helped me a lot.

On 19/06/2018 at 12:11 PM, mikl_pls said:

Out of almost all the atypical antipsychotics I've tried, Abilify has worked the best for me. I've had to discontinue it very recently, however, because of a possible compulsive spending habit, though. Not sure yet, though, if switching has fixed it though. Time will tell.

Yes, Abilify initially worked wonders for me and made me hypomanic (the only time other than early days on Nardil). I was jogging before work and all sorts. It was fantastic. But it pooped out. Saphris might be worth a look?

On 19/06/2018 at 12:11 PM, mikl_pls said:

I definitely empathize with you for wanting to get to the bottom of all this suffering. I wish we could tell you, but we can't diagnose. I think either atypical deppresion or bipolar 2, of which the depressive episodes most often feature atypical features anyway.

Thanks and I know. It's still worth getting a 2nd, 3rd or 4th opinion though when every PDoc you've had essentially gives up on you. 

On 19/06/2018 at 12:11 PM, mikl_pls said:

I believe that it is possible there are some genetic make up issues that has prevented you from achieving remission from all the therapies you have tried like ECT and dTMS, even ketamine. I forget which genes are involved, but it would probably be looking into. A standard Genesite test wouldn't be able to check for this. I've done 23andme and analyzed my own raw data with Selfdecode.com and other 3rd party sites to help me analyze it and have found various genes that explain why it has been so difficult to achieve remission from standard therapies, and some genes that show that it would be probably futile to try ECT and other therapies like that.

That's fascinating. I was thinking about trying 23andme the other day after some privacy headline I read. I wish it would have saved me from ECT and dTMS. What a giant amount of effort I put into them for zero benefit. Other than confirming they don't work for me.

On 19/06/2018 at 12:11 PM, mikl_pls said:

I think Lamictal + Nardil would be a good option to try as for a medicine combination.

Have you ever tried a combination of an MAOI (Nardil) + a tricyclic antidepressant or an MAOI (Nardil) + a stimulant? They're classically contraindicated, but they can safely be used together.

My PDoc absolutely refuses Nardil+Stimulant which pisses me off no end. He's the type to take the first google result as to whether a combo is safe or not. Yeah exactly. Haven't tried a TCA+MAOI but TCA's are all horrible for me.

On 19/06/2018 at 12:11 PM, mikl_pls said:

The secondary amine tricyclics (TCAs) like nortriptyline, desipramine, and protriptyline can be combined with MAOIs, both in low doses. They both have to be started at the same time, otherwise you run the risk of hypertensive crisis. I think the TCA can already be started before the MAOI too, and the MAOI added on top of it, but otherwise, the MAOI has to be washed out before starting this combination.

https://books.google.com/books?id=wwP1iOanWAAC&pg=PA168&lpg=PA168&dq=maoi+tca+combination+25+mg+amitriptyline&source=bl&ots=gM2kCSJrp5&sig=OcaTvRI1Kt7ZZCZi3Xi4b9jjChE&hl=en&sa=X&ved=0ahUKEwiJo5OgtdTKAhVE2D4KHXh7C6QQ6AEIHDAA#v=onepage&q=maoi tca combination 25 mg amitriptyline&f=false

Ken Gillman (MAOI guru) says you don't need to order the TCA and MAOI BTW: https://psychotropical.info/ (not sure where on that site).

On 19/06/2018 at 12:11 PM, mikl_pls said:

Stimulants like methylphenidate and dextroamphetamine can be used in combination with MAOIs as well. Methylphenidate is supposedly safer to use in combination with MAOIs because it doesn't increase serotonin levels, but it is a 5-HT_1A agonist (but then again, serotonin syndrome arises from excessive 5-HT_2A stimulation, if I'm not mistaken...). But methylphenidate can be used in doses of up to 60 mg and dextroamphetamine in doses up to 30 mg in combinations of an MAOI when titrated very sloooowly and very carefully.

https://books.google.com/books?id=_I7LBQAAQBAJ&pg=PA71&lpg=PA71&dq=maoi+tca+stimulant+combination+treatment&source=bl&ots=vGbJPCI7si&sig=Wt6aQCwM9RGhYQ6JSqvqIuOwero&hl=en&sa=X&ved=0ahUKEwiT7u7Bh5rKAhXKPiYKHesvBBIQ6AEITDAI#v=onepage&q=maoi tca stimulant combination treatment&f=false

https://www.ncbi.nlm.nih.gov/pubmed/3997787

Yeah I messed up with Vyvanse as I mentioned earlier. My BP hit 230+ or something. I went semi-delirious, rocking back and forth, gibbering and screaming from the vice-like pain in my head. Not the most fun morning.

On 19/06/2018 at 12:11 PM, mikl_pls said:

I personally was on a combination of an MAOI + TCA + stimulant a few years ago, which is a mega-nono according to classical contraindications! I was on Emsam 9 mg/24 hr, nortriptyline 50 mg, and dextroamphetamine ER 30 mg. It actually didn't do that much for me. Emsam, to me, is a very weak MAOI. I needed the 12 mg patch, but my pdoc wouldn't prescribe it. The second time I took Emsam, I experimented and used a 6 mg + 9 mg patch for 15 mg (greater than the max dose!) and only then did I start to feel something... but again, my pdoc wouldn't hear of it. That was when I switched to Parnate (tranylcypromine), which cause immense weight gain, + Adderall 30 mg. 

I tried Parnate, thinking it would be more energising than Nardil but after a mild temporary improvement with severe insomnia, it did nothing. I felt super-depressed on it. Really gutting.

On 19/06/2018 at 12:11 PM, mikl_pls said:

On top of all this, Lamictal should have no problem being added to this combination.

So one of the articles mentioned the combination of thyroid hormine (T₃). That would also be a possible combination therapy, if you haven't already tried it. I would recommend trying the lowest dose possible, like 2.5-5 mcg of liothyronine (Cytomel). You don't want to mess up your thyroid hormone balance. I would also recommend taking it for the shortest amount of time possible, and if you need it long term, you need to take liothyronine with levothyroxine (Synthroid) in a ratio of 4:1 of T₄:T₃ (e.g., 12.5 mcg + 2.5 mcg of levothyroxine and liothyronine, respectively).

No, haven't tried thyroid stuff. Mainly because I've had tons of regular blood panels and my T levels always come back fine. I've prayed for them to be off but they're always fine.

On 19/06/2018 at 12:11 PM, mikl_pls said:

Also, the newer eugeroics/stimulants, Nuvigl/Provigil, which you mentioned that you respond to well would be good options to augment with as well, but good luck getting your insurance to cover them without a diagnosis of a sleep disorder like narcolepsy or OSA (unless you have them, in which case go ahead and try them with your MAOI! They'd be a safer option than the classic stimulants... perhaps less effective though).

yeah I've tried them on many occasions with AD's including the MAOI's. As usual they can be spectacular for a few weeks and then... nothing. It's absolutely confounding, never mind utterly depressing. I actually get mine from a pharma in India via mail.

On 19/06/2018 at 12:11 PM, mikl_pls said:

If you responded well to Abilify, it might be worth considering adding it to your cocktail. Might I ask why you stopped it? If you don't tolerate Abilify well, you might consider Rexulti. It's not "Abilify 2.0" as people keep calling it around here. It's a separate entity to its own with different pharmacodynamics all to itself. It may feel somewhat similar at higher doses as low doses of Abilify, but at low doses, it feels like a completely different medicine--very calming, sedating even for some. I actually can't tolerate it at low doses, I need higher doses. Vraylar is another med that is somewhat related and is even a phenylpiperazine like Abilify and Rexulti, but works a little differently than Rexulti and Abilify. It is more selective for the D₃ receptor than the D₂ receptor, but is also a partial agonist for the two receptors like Abilify and Rexulti. So if Rexulti doesn't appeal to you, there's always that option.

I stopped Abilify since I wasn't sure what it was doing for me as part of a 3-med cocktail. I got a sample of Rexulti but never really got a feel for it, what with other changes going on at the time. I've not heard of Vraylar though, that might be worth a shot. Nice one.

On 19/06/2018 at 12:11 PM, mikl_pls said:

So if I were you in your position, I would consider the following cocktail:

• Phenelzine (Nardil)
• Either TCA (nortriptyline (Pamelor), desipramine (Norpamin), possibly protriptyline (Vivactil)) or stimulant (methylphenidate (Ritalin/Ritalin LA/Metadate CD/Concerta/etc...), dextroamphetamine (Dexedrine/Dexedrine Spansule), amphetamine/dextroamphetamine (Adderall), modafinil (Provigil), armodafinil (Nuvigil)), or both at once
• Atypical antipsychotic with dopamine partial agonism (aripiprazole (Abilify), Rexulti (brexpiprazole), or Vraylar (cariprazine))
• Lamotragine (lamotrigine)
• Liothyronine (Cytomel) (low dose, 2.5-5 mcg) (and if successful and needs to be taken long term, add levothyroxine (Synthroid, Levothroid, Unithroid) in a ratio of 4:1 of T₄:T₃, so liothyronine 2.5-5 mcg + levothyroxine 12.5-25 mcg)

Yikes, that's quite the cocktail. I'd definitely go the stimulant variant (over TCA). I don't think many PDoc's would prescribe this all together though TBH. And it would be very hard to tweak - how would you know which med needs lowering/raising dose? Thanks for the idea though.

On 19/06/2018 at 12:11 PM, mikl_pls said:

I think that might put quite a dent in your depression, and if not, I would definitely reconsider ECT while on this combo, making sure to try bilateral ECT (while it may have more adverse effects, it may have better effects on depression). If you ask your pdoc about trying donepezil (Aricept), it may prevent adverse effects on memory while doing ECT. There are ways to potentiate the seizures induced by ECT that may help the outcome of ECT, but I forget. Like, I think taking something like Thorazine (chlorpromazine) before the ECT treatments helps relax you and also helps potentiate the seizures. Also, using ketamine as the anesthetic also helps potentiate the effects of ECT.

Hope this helps!

Thank you tons for all this info. Certainly food for thought. I've had enough of ECT for the time being (had it done in March) though and it literally did nothing for my mood. It just made me clumsy, of all things.

Thanks again,

Pete

[mikl_pls]

19 hours ago, sming said:

Yep, when down I move & do very little. I just want to be unconscious/dead/asleep.

I know that feel all to well, very sorry to hear that...

19 hours ago, sming said:

That's the bummer - you can't take Adderall with MAOI's. I took too much by accident and ended up in hospital. It was worth the prior reduction in depression, though. Ritalin also helped me a lot.

You can take it with an MAOI, just not too much... Very sorry to hear you had a bad experience... That's got to be rough!!

19 hours ago, sming said:

Yes, Abilify initially worked wonders for me and made me hypomanic (the only time other than early days on Nardil). I was jogging before work and all sorts. It was fantastic. But it pooped out. Saphris might be worth a look?

I loved Saphris! At first... I took it with Abilify, 5 mg at bedtime, for sleep. It worked wonders for anxiety, and then depression, but then after about a month or so, I started to feel very dysphoric. I wonder what the 2.5 mg dose would've done? It might not have helped me as well for sleep, but it might have helped me a little with anxiety and depression a little better possibly without the dysphoria. It also tastes very nasty! They're sublingual tablets that are supposed to taste like black cherry, and they taste like a "very disappointing cherry liquor" to quote a friend who also took it. It also has something that numbs your mouth in it which just adds to the whole experience of taking it. But all in all, it's a pretty great medicine! The pharmacodynamics of it are really great. The 5-HT_2A/2C and α_2A/2C antagonism are greater than that of the D₂ antagonism, which should increase serotonin, dopamine, and norepinephrine quite nicely.

19 hours ago, sming said:

That's fascinating. I was thinking about trying 23andme the other day after some privacy headline I read. I wish it would have saved me from ECT and dTMS. What a giant amount of effort I put into them for zero benefit. Other than confirming they don't work for me.

You could also get some nice psychiatric assays from them just for the fun of it. Also, a nice methylation and drug detox profile.

19 hours ago, sming said:

My PDoc absolutely refuses Nardil+Stimulant which pisses me off no end. He's the type to take the first google result as to whether a combo is safe or not. Yeah exactly. Haven't tried a TCA+MAOI but TCA's are all horrible for me.

That's a bummer! I loved the Parnate + Adderall combo, well, while it lasted... Parnate 20 mg + Adderall 30 mg was great, then when I asked to increase the Parnate because it quit working, my pdoc took away the Adderall, and everything went to hell. I had already gained 50 lb anyway, so to hell with it...  

Which TCAs have you tried?

I'm on desipramine at just 50 mg and really love it. I do wonder what 75-100 mg would feel like, but at this point, I kinda don't want to rock the boat.

19 hours ago, sming said:

Ken Gillman (MAOI guru) says you don't need to order the TCA and MAOI BTW: https://psychotropical.info/ (not sure where on that site).

Really? Interesting... I'll have to see if I can find that...

19 hours ago, sming said:

Yeah I messed up with Vyvanse as I mentioned earlier. My BP hit 230+ or something. I went semi-delirious, rocking back and forth, gibbering and screaming from the vice-like pain in my head. Not the most fun morning.

Man, that's brutal... I wonder if it's because you were on Vyvanse, an ER stimulant? Then again, I was on the Dexedrine Spansules with Emsam (different ER mechanism though...), but Emsam is kinda a weak MAOI compared to Nardil and Parnate... Do you remember what dose of Vyvanse you were on?

19 hours ago, sming said:

I tried Parnate, thinking it would be more energising than Nardil but after a mild temporary improvement with severe insomnia, it did nothing. I felt super-depressed on it. Really gutting.

See, that's how Emsam was for me. That's why I quit it the first time. I tried it a second time, and just to see, I pushed the dose up to 15 mg (beyond the max dose) on my own and only then did I feel anything, but my pdoc refused to even prescribe the max dose, even if we ditched the stimulant. Don't know why... It's like, why bother make the 12 mg patch if no one would prescribe it? Plus, many pdocs prescribe two patches for their patients because it's apparently so weak. Like 9 mg + 6 mg for 15 mg, 2x9 mg for 18 mg, even up to 2x12 mg for 24 mg...

19 hours ago, sming said:

No, haven't tried thyroid stuff. Mainly because I've had tons of regular blood panels and my T levels always come back fine. I've prayed for them to be off but they're always fine.

See, even euthyroid patients can be prescribed thyroid hormone supplements. That's why I was mentioning taking super low doses. Cytomel (T₃) works better than Synthroid (T₄) generally, even though Synthroid is converted into T₃ peripherally... (but some people have issues with peripheral conversion of T₄ to T₃). So just 2.5 to 5 mcg shouldn't be a problem. I started on 25 mcg, which really is too high of a dose for a euthyroid patient, and even that didn't really help much, but I was super depressed at the time.

19 hours ago, sming said:

yeah I've tried them on many occasions with AD's including the MAOI's. As usual they can be spectacular for a few weeks and then... nothing. It's absolutely confounding, never mind utterly depressing. I actually get mine from a pharma in India via mail.

Did you try just modafinil or armodafinil or both? Personally, armodafinil (250 mg) worked way better than modafinil (400 mg), but both meds' effects were extremely subtle. Like you, even armodafinil's effects worked great at first for me and then vanished, though. It was an idea, though.

19 hours ago, sming said:

Yikes, that's quite the cocktail. I'd definitely go the stimulant variant (over TCA). I don't think many PDoc's would prescribe this all together though TBH. And it would be very hard to tweak - how would you know which med needs lowering/raising dose? Thanks for the idea though.

Yeah, that was a bit overly aggressive, I admit, though I was just thinking back to when I was in my most depressed state, and what I was taking for it. Tweaking it would be an art that would be up for an expert pdoc to do. My pdoc was very good at managing my MAOI+TCA+stim cocktail (plus AAP and mood stabilizers).

19 hours ago, sming said:

Thank you tons for all this info. Certainly food for thought. I've had enough of ECT for the time being (had it done in March) though and it literally did nothing for my mood. It just made me clumsy, of all things.

You're quite welcome! I just hope it helps!

Michael

[sming]

On 19/06/2018 at 12:38 PM, browri said:

 

@sming you are right that there are certainly differing opinions on whether Lamictal actually works or not. In my experience it does. I've taken Lamictal before alone and in combination with one AAP at a time. I found that it certainly delayed episodes from occurring both hypomanic and depressive. If something depressed me, I was just kinda able to "get over it" quicker. Things rolled off my shoulders more easily. But I still experienced the feeling of something making me upset which is still important to leading a normal life. If you squash your moods out completely, then you'll just feel like a zombie.

That's good to hear. I took it in conjunction with Nardil years ago and could never ascertain its effectiveness/benefits. It certainly coincided with periods of good health but that could have also been the Nardil.

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Lamictal is nice because after you adjust to it, for many people it can have almost no side effects. I'm starting it back up now because the new insurance company in July may not cover my Trintellix. But I've been feeling "up" the past several weeks and been out of any major depressive episodes for several months. I do think Rexulti has been a big help as well, but I wanted to replace the Trintellix with Lamictal because while Lamictal isn't great at treating things ACUTELY, in the long term it's quite tolerable and for me at least, quite effective.

However, I can say that starting back up on it this time has been a bit rough. Noticing some GI discomfort, some headaches that come and go. Kind of an anxious antsy feeling. You may notice with Lamictal that things get worse before they get better. Trust me when I say that if you don't get the rash, you should try your hardest to get to 100mg. You may find it to be a game changer.

I have the GI discomfort (on top of IBS-C - great) and the antsy/nervous/anxious feelings. I prefer this a lot to the unbearable feelings of depression I've been enduring. I hadn't heard about 100mg specifically. I'm already at 50mg and am pushing hard for higher doses.

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Like others have indicated, it is becoming more commonplace to use Lamictal alone or in combination with an antidepressant for depression in people that don't appear to have experienced hypomanic episodes. However, like @mikl_pls pointed out, hypomania is subtle and can be difficult to diagnose because it may not be outwardly apparent to the clinician. But it's usually a red flag when you've tried and failed several antidepressants. That was my pdocs red flag for me when he started seeing me ~4 years ago. We immediately started titrating down the Cymbalta and used Prozac to come off of it while I was starting Lamictal. Let me tell you that it was a rough couple of weeks, but when I came out of it, I finally started to feel normal again. As you can see from my signature, we've come a long way from Lamictal monotherapy, but I do believe I have finally found a combo that works for me (Depakote+Trintellix+Rexulti+Vyvanse).

>> (Depakote+Trintellix+Rexulti+Vyvanse) sounds interesting to me. I know I like Abilify and Vyvanse so there's a fair chance I might like the others.

Now the goal is to see if I can make it through a winter without an antidepressant and without experiencing one of my typical seasonal depressions. As an FYI, the DSM-V does now acknowledge depressive episodes "with seasonal pattern" for those with bipolar disorder, essentially calling out that there could in fact be some crossover between bipolar disorder and seasonal affective disorder (SAD). May also be why Wellbutrin, which is the one medication that has the most evidence for this indication also happens to be the one antidepressant that seems to have a much lower rate of manic switch.

If you're curious about what hypomania might feel like, I actually wrote a post recently in another thread where @Matt G was also wondering if he may be bipolar. I linked it below. It may provide some insight of how simple things that many people do can be associated with bipolar behaviors. Things like DUIs or sleeping around, impulsive shopping. These are things that would likely happen to you between depressive episodes when you're feeling "good" (i.e. if you're really bipolar, "I feel SO much better after starting this medication" is something that could also be a red flag).

Yeah unfortunately (DX discovery-wise) I've never exhibited any of those behaviours. I have felt very good after starting some meds but I'm confident that was just the brief relief from depression I sometimes get.

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I can also say that I responded the same way to lithium as you did. I felt ill. Everything about it just made me feel like I was poisoning myself. I was waking up drenched in sweat and I just felt so sick and "off". I only lasted maybe 10 days. Depakote by contrast has been an absolute DREAM. I feel so much more calm on it.

Interesting. Never tried it. The taste / dry mouth is another unpleasant one. Everything tastes of metallic waste water or something.

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Following on what @mikl_pls said, genetics can play a big role in it. For example, I have several SNPs for the MAO-A (monoamine oxidase A) gene that cause me to be under-produce this enzyme, which is important to breaking down monoamines in the brain like serotonin, norepinephrine, and dopamine. In this case, I would have higher levels of those neurotransmitters than most. And as we know in the brain, there is both a too much and a too little. I also have an under-functioning COMT (catechol-O-methyltransferase) gene. See the below article. I'm the "Worrier":

https://www.selfhacked.com/blog/worrier-warrior-explaining-rs4680comt-v158m-gene/

The beauty in my med combination is I've actually worked with my pdoc to introduce medications that correct underlying genetic dysfunctions. If I focus specifically on MAO-A and COMT, then I can tell you that Depakote is a fairly strong MAO inducer (the exact OPPOSITE of Nardil). It increases the metabolism of serotonin in the brain and reduces its levels. Additionally, it also reduces the synthesis of catecholamines like dopamine and norepinephrine. Rexulti and Vyvanse both also increase COMT. Additionally, Depakote increases the conversion of glutamate (an excitatory neurotransmitter in the brain) to GABA (a "depressing" neurotransmitter, target of many drugs from Ativan to Rohypnol) and then inhibits the breakdown of GABA to allow more available in the brain, leading to a calming state. This also of course leads to side effects like sedation, but in the long run, your sleep improves and subsequently your mood as well.

The recommendations above all seem like good starting points to talk with your pdoc.

I think this is all waaaay out of his comfort zone. He wouldn't know or want to know any of this. I need to find a new PDoc big time.

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It would be wise to have your thyroid levels checked to make sure that some of your depression isn't due to hypo- or hyperthyrodism. Additionally, checking B vitamin and folate levels should be a good way of telling if you have a mutation on the MTHFR gene that would negatively impact your body's ability to properly absorb folate which is a necessary precursor to the synthesis of neurotransmitters in the brain. There are various different steps in these neurochemical processes and some of the best pharmacotherapies address the problem at multiple levels, hence the drug cocktails we take.

every full blood panel I've had - and I've had A LOT - has come back totally clean. Everything's in range every time. How I've prayed for a simple reason for all this suffering.

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If this reinforces your thinking further that you may be bipolar. I just completed a closed study through 23andMe of people with either depression or bipolar disorder. I was one of <10,000 people selected for the bipolar set. At the end of the 9-month study we received a report of some of the preliminary statistics that came out of their investigation. One of the ones that struck me the most is that of all the people in the study with bipolar disorder almost 50% of were previously misdiagnosed as MDD. It's actually quite common for BP2 particularly to be discovered after someone reporting depression fails multiple medications or they repeatedly poop out within months.

Yes I was just reading about this. Can't recall the paper/source. But basically they found that BP2 was massively misdiagnosed and typically for long periods of time.

Edited June 23, 2018 by sming