12 replies to this topic

[penisbreath]

I'm trying Mirtazapine for my horrendous insomnia. Weirdly, I thought lower doses were more sedating, but I took 7.5mg an hour before bed last night and felt mildly sedated at best. I then took the remaining 7.5mg and was out in 5 minutes. Crazy, awesome, cinematic dreams, but sleep wasn't terribly refreshing and today I'm feeling restless, my legs are crampy/ache and I'm edgy/irritable.

I don't know why the lower dose didn't work.. I was trying to avoid the NEergic side-effects; I've been using Doxylamine (25-50mg) on and off for the past year, so is it just extreme antihistamine tolerance?

I'll do anything to sleep at this point .. does anyone know if the 'activating' side-effects pass at 15mg?

[nowayout]

Go back to the lower dose. The half life is long so it builds up over a few days.

The restlessness should hopefully go away after a few days.

The quality of my sleep was horrendous on this drug though. Bad dreams all night that left me exhausted upon waking instead of rested. And like smy antihistamine, I got tolerant very quick.

[Tom_]

Your sleep likely was pretty refreshing - its a good chance of being a hang over. I doubt what you are experiencing now is actually NEergic side effects (alpha antagonists combined with 5ht2c receptor antagonism is sedating), more likely serotonergic hyperactivity while the receptors down regulate. If it is NAergic, combining it with low dose clonidine might do the trick.

Pregabalin reduces NA effects and is an anxiolytic by itself. Seeminly without tolerance you could combine it to further improve sleep.

I'm sure I've mentioned it before: Trimipramine is the most sedating antidepressant and doesn't seem to fuck with sleep architecture (which isn't always a good thing).

Mianserin is even more sedating and might be an option.

I don't know what meds you are trialing at the moment but I've just had a quick attack of an idea. Although it does involve lots of Mirtazapine/Mianserin (more preferable).

You could combine Mirtazapine/Mianserin alongside Vortioxetine and Viloxazine alongside Pregabalin (something at the back of my head tells me you haven't tried this yet) as an adjunct at treatment partial success. The V drugs are both very new and seem to be about as effective as anything else.

You get the benefit of NRI and SRI effects combined with Mirtazapine/Mianserin (Californian rocket fuel) alongside up-regulation of GABA-B receptors in the pre-frontal cortex.

You could swap the NaSSA for Trimipramine but the side effects could be hell and you would also be putting enough stress on the cardie-respitory system.

[Tom_]

Do you think you could give a full list of the stuff you have tried again? And the official diagnoses given and ones you suspect? I'm in the middle of class with nothing to do and would rather do something useful for someone, even if you decide my suggestions (quite likely) are a bunch of shit.

Edited by Tom_, 22 October 2013 - 09:51 AM.

[penisbreath]

Thanks for the helpful response, Tom.

Your sleep likely was pretty refreshing - its a good chance of being a hang over. I doubt what you are experiencing now is actually NEergic side effects (alpha antagonists combined with 5ht2c receptor antagonism is sedating), more likely serotonergic hyperactivity while the receptors down regulate. If it is NAergic, combining it with low dose clonidine might do the trick.

Maybe you're right.. I'm still incredibly fatigued, despite all the sleep, so maybe it isn't NEergic. I do feel mentally (over)stimulated and am clenching my jaws etc. though, which might be the 5ht2c antagonism.

Pregabalin reduces NA effects and is an anxiolytic by itself. Seeminly without tolerance you could combine it to further improve sleep.

You mean tolerance doesn't develop to the sleep-inducing effects? I'm seeing a new psychiatrist in a couple of weeks, so will keep it in mind .. I walked into a random GP's office yesterday to get Mirtazapine and didn't wanna start getting too off-label (Lyrica is scheduled here).

I'm sure I've mentioned it before: Trimipramine is the most sedating antidepressant and doesn't seem to fuck with sleep architecture (which isn't always a good thing).

Hmm, interesting .. I wrote off tricyclics, since even 20mg of amitriptyline doesn't do anything anymore (tolerance?) but I'll also keep that in mind.

Mianserin is even more sedating and might be an option.

I didn't like Mianserin; tolerance developed to the sedation very quickly, and I felt similarly wired the next day.

I don't know what meds you are trialing at the moment but I've just had a quick attack of an idea. Although it does involve lots of Mirtazapine/Mianserin (more preferable).

You could combine Mirtazapine/Mianserin alongside Vortioxetine and Viloxazine alongside Pregabalin (something at the back of my head tells me you haven't tried this yet) as an adjunct at treatment partial success. The V drugs are both very new and seem to be about as effective as anything else.

You get the benefit of NRI and SRI effects combined with Mirtazapine/Mianserin (Californian rocket fuel) alongside up-regulation of GABA-B receptors in the pre-frontal cortex.

You could swap the NaSSA for Trimipramine but the side effects could be hell and you would also be putting enough stress on the cardie-respitory system.

I'm not trialing anything at the moment .. just trying to get some rest, while I wait to see a new psychiatrist in a few weeks. I do have some supplements I want to explore (particularly high-dose Inositol), but was just trying to ensure my sleep was under control first.

I don't think Vortioxetine is out yet in Australia, and I would be slightly worried about using Mirtazapine in conjunction with an S(N)RI, since the restlessness I'm getting at the moment is bordering on akathisia. Sometimes it's hard to distinguish between akathisia and simply being overstimulated, however. Would you link the restlessness to serotonergic hyperactivity (to quote you)? Would it likely pass with time in that case?

I may keep up with 15mg of Mirtazapine for now, if there's a chance the side-effects pass .. otherwise I'll lower the dose.

The trimipramine tip sounds good, however, and so does Lyrica, pending tolerance doesn't develop, so I'll definitely keep those in mind the next chance I get to see a psychiatrist.

[penisbreath]

Do you think you could give a full list of the stuff you have tried again? And the official diagnoses given and ones you suspect? I'm in the middle of class with nothing to do and would rather do something useful for someone, even if you decide my suggestions (quite likely) are a bunch of shit.

Sure thing.

I have OCD, ADHD (predominantly inattentive) and atypical depression.

Since my anxiety is so extreme, most practitioners write off the ADHD (even though I believe sincerely, with all my being, that I've had it since childhood; I don't even give a rats ass about stimulants anymore .. it's just about making sense of my life and academic shortcomings, and I have 3 page's worth of general difficulties it's caused me) .. so if you have any tips about getting a comorbidity recognized, that would be fantastic.

I have a lot of irritability, agitation and am prone to overstimulation. My old psychiatrist (the best I've seen to date) believed it was a medication sensitivity .. I have no idea, but otherwise wonder if I am on the Bipolar spectrum, or could benefit from a mood stabilizer regardless. I have been experimenting with caffeine and Lithium Orotate lately, and there's a nice synergy where it gets rid of the jitters, irritability etc.; I have the same reaction to conventional stimulants, which mess up my mood.

I've never had anything resembling classic hypomania/mania .. just the other, shitty stuff like irritability, dysphoria and so on.

SSRIs (other than Prozac and Zoloft, which caused too much anxiety) destroy my executive function .. it's hard to explain but I lose any sense of will, and can otherwise lie in bed all day. I wonder if this is related to ADHD. They also don't help my hypervigilance.

I've also tried: APs like Zyprexa, Risperal, Seroquel .. I know they're meant to augment SSRIs, but I get akathisia on SSRIs these days, as well as APs independently, so the combo caused a lot of nasty movement side-effects and I was more anxious for some reason.

tried benzos, which paradoxically agitate me

tried stimulants .. when they work, I feel a lot more stable and in control of my thoughts, actions etc., which is fantastic, but my mood craps out quickly .. I wish I could find some reliable way to harness the effects.

tried Neurontin .. great for anxiety and sleep in high doses, but I felt lobotomized; lower doses just stimulated me.

random stuff: buspar (made me anxious and agitated for some reason), Memantine (paradoxical reaction to NMDA antagonists), Riluzole (see Memantine)

Parnate .. best AD to date, and even helped ADD, but again I grew overstimulated on it (either my sensitivity, or the fact that I was taking clonazepam at the time and didn't know I couldn't take benzos).

FWIW, I've been using Doxylamine on-and-off to sleep the past year and have been told it can cause irritability, so am not sure how much that is contributing to my current feelings of overstimulation, irritability and the like. I also took it with Parnate, so it may have contributed to the side-effects.

Things I'm interested in at the moment are mood-stabilizers like Lithium, Lamictal (might help anxiety/agitation and let me tolerate a stimulant), mirapex (might help anhedonia, sleep, anxiety and allow me to tolerate an anti-depressant) .. someone here said I should just go back to Parnate, and while I worry a lot about the restrictions, they might be right, since nothing else (aside from stimulants) have helped my awful leaden paralysis etc. to the same degree (currently have trouble leaving bed due to fatigue).

[Tom_]

Good! Maybe this Psychiatrist will actually get hold of some quality psychotherapy for you.

You may find tolerance develops, although bar poop out tolerance to anxiolytic/antidepressive effects aren't going to happen. I'll lead with the ones that are least likely to be prescribed due to risk, lack of evidence or just random theory.

I'm sure you know you should be trialing stuff for 14 weeks. Providing you haven't tried the drug I'd suggest you be willing to start with something as simple as an SSRI providing the Psychiatrist assures you he/she is willing use complex polypharmacy as treatment resistance does or doesn't crop up (although I suspect they won't bother). I have recently met a few people who went back to SSRI's (very unhappily) under a new psych having tried a few and a fuck load of other meds with surprising success - what I'm trying to say is that meds can be weird.

Amantadine - NDMA antagonist, MAO-A-I (not sure if reversible or not) and seems to increase release or re-uptake inhibition and a nicotinic alpha-7 antagonist (possible antidepressive effects). There are one or two (I mean 1 or 2) case studies hanging about for OCD and maybe 1 tiny open label for MDD. Side effects unsurprisingly are mainly anxiety/agitation but then again, some people with OCD improve on amfetamine so who knows?

Tramadol - seems to be effective in resistant OCD but addictive, activating and unpleasant for some.

Phenelzine - think you already tried it and you said there was a little response but nothing magical. Know you tried Tranyclpromine. Phenelzine is likely the better bet due to GABA effects. Can combine safely with a mood stabilizer or fairly safely with AAP (I'll be going on about these in a min).

Meclobremide and Clomipramine - risk of serotonin toxidrome(but not severe by any means - reasonably standard) and mild risk of hypertensive crisis. Take it slow and steady and use benzos for any activation at the start.

The serotonergic combo buster: Clomipramine (I think you couldn't tolerate it? if not swap for SNRI if tolerable otherwise SSRI), Lithium, Trazadone (medium to high dose).

The obscene Serotonergic combo buster: Clomipramine, Lithium, Trazadone & Tramadol - Without doubt a risk of Serotonin toxidrome.

Standard treatment resistance combos:

Calafornian rocket fuel (Mirtazapine or Mianserin plus an SNRI) +/- PRN/Buspirone/Pregabalin
SS/NRI/Chlomipramine plus Quetiapine/Aripriazole/Amisulpride/Respidone/Olazepine
SS/NRI/Chlomipramine + Quetiapine/Aripriazole/Amisulpride/Respidone/Olazepine + Pregabalin

You read about antipsychotics side effects and you never want to go on one. You try the wrong one first and you swear never to go on one again.

I think you have tried one or two but If I remeber correctly its one of a few areas that hasn't been well explored for you.

Quetiapine is well evidenced, isn't eactly reknown for having a great (but not awful) side effect profile and can be tried both at low (dopaminergicish) and high doses (antidopinergic) for OCD/anxiety.
Olanzepine will make you gain more weight than you knew possible if you happen to get weight gain as a side effect. Again, it has good evidence and a similar MOA to Quetapine.

Aripiprazole is the only AAP that works as a Dopamine parital agonist at 2 and 3 while being a D4 antagonist. It also is a 5HT1a partial agonist (always good). Think you might have tried this as well and developed terrible akinesia (fairly rare although increase in anxiety is possible). Well I have it on good authority a combo being tried in teriary psychosis clinics and occationally for TRD is a combination of Aripiprazole and another AAP with more sedative qualities with some promising results. This could be a possibility. You could try high/low dose of Aripiprazole and the other AAP both to see what happens.

Low dose Amisulpride is very selective for autoreceptors and a potent antidepressant (plus mild GHB binding effects) (with equal effiacy to amitriptyline). However both low dose and high dose seem to be highly effective (between 200-600 seems ideal with an average of around 350mg). Weight gain is pretty likely as is slight sedation. One study found patients already on an SSRI had a negative response to 400mg (akenthsia) but this may be related to need for down/up-regulation first.

Amisulpride and Aripiprazole is possibly a good choice, if nothing else both would seem to reduce each others side effects. Starting both off at low doses and then increasing one or the other and then both if neither work at lower doses. This is probs the best option I can think of.

Asenapine is an option but I wouldn't be keen until you've tried a few.

Clozepine - this should be the thing you try pretty much just before you decide on major invasive surgey. Of course in combo with a potent serotonergic drug.

Mood stabilizers/antiepeleptics seem to be ones you haven't tried much if at all.
Lamotragine & Carbamazepine seem ineffective but only a few very small trials show this.
Valporate again doesn't seem to do much but may be useful as an agumentation agent or a pre-treatment.
High dose Gabapentin 2400-3600mg may be effective
Pregabalin doesn't have much actual evidence for OCD but clearly reduces anxiety.
Tiagabine at 15mg worked pretty well in one patient on a fuck load of an SSRI
Levetiracetam has a the odd case study supporting its use but thats about it.
Topiramate bar pregabalin may be the most effective (works a little like ruliziole so alone might make you anty).

You could try a combination of up to three seperate antiepeleptics (Topiramate, Tiagabine & Pregabalin or Gabapentin, Topiramate & Pregabalin). Obviously its not something I'd recommend.

An antipsychotic, antidepressant and a mood stabilizer might be worth a go. Or Amisulpride, Aripiprazole and an Topiramate/Pregabalin/Gabapentin (but thats lacking an AD which isn't ideal). You could go for four meds and add in an AD but...talk about fun side effects.

Either way there are still plenty of entirely new combinations. I'd def look into Pregabalin, high dose Gabapentin, Topiramate, Amisulpride, Aripiprazole and a re-trial of Clomipramine.

Antidepressant + antipsychotic + antiepileptic or Antidepressant + antipsychotic x 2 or Antidepressant + antiepileptic x2 can be tried after both AD + antipsychotic and AD + Antiepileptic.

Dear god, I think my brain melted writing that.

Edited by Tom_, 22 October 2013 - 11:50 AM.

[Tom_]

More coming. That was written before i read your second reply. Much of it still applies.

[penisbreath]

Thanks, Tom. I didn't downvote your post, by the way.

I realize you hadn't seen my first post, but no, I've adequately trialed the atypical antipsychotics (Zyprexa, Seroquel and Risperdal) and was not satisfied. I had relentless akathisia on 6.25mg of Seroquel multiple times; it wasn't as bad on Zyprexa, but still distracting. I just don't think the risk is worth it and the past couple of psychiatrists I've worked with just don't want to prescribe them.

Clomipramine was also awful and caused agitation and akathisia, far worse than anything I experience on SSRIs.

I've always wanted to try low-dose amisulpride, but aren't it's pro-dopaminergic effects probably contradicted in OCD?

What do you think about Provigil and OCD?

Keppra is another drug that sounds interesting, and which I forgot about it; a friend with bipolar and severe OCD finds it extremely helpful for anxiety.

[Tom_]

First off and feel free to disagree, I don't think in your case managing the ADHD is most important. After the anxiety and MDD have been resolved or treated to satisfaction a clearer picture of the ADHD will appear. I don't know if you have it or not and I certainly am not in a place online to suggest you do or don't while you have severe co-morbidity.

I think there are symptoms of personality disorder (although I don't think its completely differentiated cluster C traits are most obvious with some cluster B traits being possible) and this is supported by your really weird reaction to every serotonergic drug under the sun. Without any doubt what so ever you have OCD and Major Depressive Disorder, Panic and agoraphobia. Idiopathic hypersomnia is possible but I suspect its a mix environmental, psychophysiological, sleep hygiene and depression.

I definitely can see the benefits of re-starting an MAOI. I think Phenelzine is a better choice than transdermal selegiline or Tranyclpromine being more sedating and roughly equal in efficacy in managing ADHD.

I don't think Modafinil or Pramipexole are good ideas due to there dopaminergic effects. Pramipexole in particular.

Trimipramine might be useful as an antidepressant being devoid of any significant monoamine re-uptake inhibition and so could be 'the antidepressant'.

Lamotrigine doesn't seem to improve OCD (although most of the few studies used low doses) and most people find it activating. Its not all that effective for depression.

Lithium is great for depression and may be useful for refractory OCD, although its going to have to be used with an AD. There is also about as much evidence for addition of T3 for OCD and it also is an excellent adjunct for MDD (on par with Lithium).

Amisulpride's effects on dopamine are a bit two way even at lower doses. I certainly don't think its contraindicated even more so because its novel mechanism on GHB receptors. Starting at a dose 200mg and holding out two weeks if there is severe agitation would be ideal but increasing the dose to 300 after 7 days is reasonable. It may because of its novel MOA not cause the problems. I certainly think this is worth a go - before Lithium or T3. Starting it alongside Trimipramine (which is a moderate strength D2 antagonist and like I said a very powerful sedative) might mean if Amisulpride causes agitation at first this is blunted. However you are going to need an ECG before you start both and have reasonably careful monitioring of your heart. Starting Trimipramine, Amisulpride, Aripiprazole or Pregabalin would be my first choice in your shoes. Although Aripiprazole is known to be more activating than other AAP's it might be the drug that normalizes dopamine<>serotonin neurotransmission (because of the parital agonism) meaning for you agitiation is may be less likely. You could start Trimipramine alongside any one of the three but if you do I'd recommend you keep the Trimipramine at as low a dose as possible at least at first and if you find theraputic effiacy I'd start to VERY slowly cross titrate to a more typical AD - maybe start with something simple like an SSRI then if those are tolerable SNRI or low dose Clomipramine.

Topiramate, Tiagabine or Levetiracetam could be considered but I'd try the above first.

[Tom_]

You could combine Moclobemide with Trimipramine or another one of them.

You could (although of course this has inherent dangers bla bla bla) combine an MAOI plus Trimipramine.

[penisbreath]

I don't really think treating half my symptom cluster is a valuable approach .. I mean, I understand OCD is the most acute problem, but ADHD prevents me from concentrating on stuff, which gives me some vague reason to remain alive. Since most anti-anxiety, anti-depressive approaches destroy what remains of my executive function, the trade-off isn't really worth it.

I don't really understand what you mean about serotonergics and a personality disorder?

[Tom_]

Half of the cognitive dsyfunction is caused by the anxiety/depression (anybody with chronic mental health problems along the affective spectrum is going to be effected). Furthermore while suffering from from the depression/anxiety are unable to use what ever benefit you might gain from the ADHD treatment (If I recall correctly you struggle to leave the house fairly often). However the biggest reason I say there isn't much point in ADHD therapy is that you can't tolerate it - no fault of your own but I suspect as your other problems begin to drastically improve so will you're ability to tolerate stims (I can't see how nearly/every drug you try can lead to a bad reaction without some of them being behaviorally learned/psychosomatic - everybody has bad reactions after trying a few but there is no reason to struggle with all of them that can easily be pin pointed to a physiological cause - again I could be wrong, its more It's more I just can't THINK of another reason, doesn't mean there isn't one).

Additionally some of the drugs I've suggested are likely to bring about some (or a lot of improvement with ADHD). Obviously MAOIs and RIMA's have clear and similar efficacy to amfetamine based stimulants. Certain TCAs have some efficacy that while not the same is significant. Certain atypical antipsychotics appear to have an effect (Aripiprazole, Amisulpride) above that of just acting as major tranquilizers (like quetiapine or halopradol) and while there is a poverty of research its what I have read is positive - both in pure ADHD and highly co-morbid ADHD.

PD's have shown again and again a risk for more adverse reactions from drugs for any reason. I was lucky, bar a one or two drugs I barely got adverse reactions worth writing home about other than ED (although no use from them until now either).

You may still disagree - the above of course is just my view.