10 replies to this topic

[BlueCloud]

Any one here been on Buspirone ?

I've been on and off it for a year now, and I'm giving it a try again because my options for finding a decent anxiolityc are shrinking to almost nothing after trying almost every supplement under the sun ( I'm not keen on trying research chemicals however) . The only thing that works better is benzos, wich I rather skip, not because of tolerance as I never had any problems with it , but because the hit on cognition and memory is always too strong. I just can't function with them during the day.

The problem with Buspirone is the severe nausea and dizziness it provokes, even from tiny doses. Nausea so strong that I have to lie down in bed for a couple of hours sometimes before it subsides. And those side-effects just won't diminish with time : I took it for three consecutive months last year, and the nausea/dizziness stayed as strong as ever. 1 every 3 times , I wouldn't get any nausea ( or very little ), and the anxiolityc effects are great, with no sedation or serious cognitive impairment. But the remaining 2 out of 3 times, the negative is so strong compared to the postive gain , I just gave up in the end.

Has anyone been able to counter the side-effects ? Or maybe something I could supplement to diminish the nausea/dizziness ? I tried ginger to no avail..

[Tom_]

Sadly they are the the two most common side effects from Buspirone. If they haven't disappeared within three months then they aren't going to.

Other options are:

Trazadone: partial 5HT1a agonist like Buspirone as well as an antagonist at other receptors and an SSRI, also increases noradrenaline activity. It may cause othostatic hypotension but nausea is rare (may be in the first few weeks). Weight gain and sexual side effects are rare. Causes sedation although tends to wear off and again, taken at night often isn't much or any problem.

Vortioxetine is also an SSRI with partial 5HT1a agonist effects, very mild NRI effects and serotonin antagonist effects at various receptors. Side effects are nausea and dizziness (but its MOA suggests this shouldn't happen so it may be an option) and on occasion sexual dysfunction (but seems to be reported more rarely than with SSRIs). For depression its clearly effective, anxiety has more mixed results.

Vilazodone is a potent SSRI and a 5HT1a partial agonist. Sexual dsyfunction isn't often reported. Rates of nausea where high but 90% were reported as mild to moderate. Dizziness was also reported quite commonly.

Any drug with effects on 5HT1a effects are likely going to cause nausea and possibly dizziness. However this is likely also causing your improvement in anxiety. The best bet to reduce these side effects is blocking 5HT3 receptors. Low dose mirtazapine (7.5-15mg) or low dose Quetiapine (an atypical antipsychotic) are the only realistic options.

Mirtazapine doesn't directly act as a parital agonist of 5HT1a but "does" and its clearly effective for anxiety, you could likely very successfully try this by itself starting at a dose at 15-45mg.

A novel combination might be Viloxazine and Mirtazapine. Viloxazine is new and may be approved in france (not sure). It has a novel mechanism of action (upregulates GABA-B receptors in frontal cortex via an unknown mechanism, mild SRI effects and potent NRI) and while it most commonly causes nausa and dizziness combined with Mirtazapine it may be both extremely effective and normalize apetite/sickness and stop dizziness due to...fuck it, some weird complicated shit to do with 5HT3, 5HT1a, alpha2 receptors and bla bla bla.

Pregabalin: potent, quick effect, reasonable side effects but dizziness is common, no chucking.

[BlueCloud]

Vilazodone is a potent SSRI and a 5HT1a partial agonist. Sexual dsyfunction isn't often reported. Rates of nausea where high but 90% were reported as mild to moderate. Dizziness was also reported quite commonly.

You know, I think pharma companies are masters at skewing the statistics in such a way as to downplay some of the reported side-effects without "technically" lying. If you look at the stats for Buspirone, dizziness and nausea are reported at only around 10% , when in reality it's probably closer to 80%.. In fact, not feeling nausea from it is the exception rather than the norm. Now when I see reported percentages for side-effects, i multiply them by at least 3 to get a more realistic number...

Any drug with effects on 5HT1a effects are likely going to cause nausea and possibly dizziness. However this is likely also causing your improvement in anxiety. The best bet to reduce these side effects is blocking 5HT3 receptors. Low dose mirtazapine (7.5-15mg) or low dose Quetiapine (an atypical antipsychotic) are the only realistic options.

Mirtazapine doesn't directly act as a parital agonist of 5HT1a but "does" and its clearly effective for anxiety, you could likely very successfully try this by itself starting at a dose at 15-45mg.

I've been on Mirtazapine 2 years ago. It's also a very potent antihistaminic, and in fact I think many of its "therapeutic" effects are in no small part due to that , rather than it blocking 5HT receptors. Antihistamines are powerful anti-emetic too. Unfortunately , even at very small doses it made me completely sleepy , day and night, almost numbed, and with strong side-effects of the antihistaminic variety ( dry mouth, dry eyes, etc..). I was in a constant fog.
It made for great sleeping ( all antihistaminics have been helpful for my insomnia, and I still take diphenhydramine/doxylamine/cyproheptadine on a regular basis ). But its half-life is huge, so I was sleepy 24 hours a day.. Dumped it after a month.

A novel combination might be Viloxazine and Mirtazapine. Viloxazine is new and may be approved in france (not sure). It has a novel mechanism of action (upregulates GABA-B receptors in frontal cortex via an unknown mechanism, mild SRI effects and potent NRI) and while it most commonly causes nausa and dizziness combined with Mirtazapine it may be both extremely effective and normalize apetite/sickness and stop dizziness due to...fuck it, some weird complicated shit to do with 5HT3, 5HT1a, alpha2 receptors and bla bla bla.

Aah Viloxazine... Brings back old memories .. It's actually an old drug, and I got it prescribed probably a decade ago. It's an extremely potent NRI , and made me like a raging bull, always angry and pissed off, constantly confrontational with people for no reason. It felt like drinking a baril of expresso coffee. Also lots of gastro-intestinal distress with occasional vomiting.. Very crappy drug. In fact it's been taken off the market in France five or six years ago.

Pregabalin: potent, quick effect, reasonable side effects but dizziness is common, no chucking.

Yeah, I've been thinking about that one, but lots of very negative reports about it.
Also considering Trazadone, and the sedation could help with my insomnia when taken at night, but only if it doesn't linger on during the day ( like Mirtazapine ).
Another thing I'm considering is propranolol, although I'm not sure if it can be taken on a daily basis.

Shame though about Buspirone, if it didn't cause such strong nausea and dizziness, it could be quite nice with its lack of cognitive impairment and very little sedation.

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

[Tom_]

Propranolol can be taken on a daily basis but it won't treat the underlying pathology and doesn't tend to improve symptoms related to psychic or cognitive anxiety (worrying, over thinking etc..) it is however great for physical manifestations such as palpitations, increased blood pressure (of course), nausea and panic attacks.

You are right it is an old drug...there are three with names beginning with V and I keep forgetting which two are just approved and which one isn't haha.

I was thinking Viloxazine and Mirtazapine would be the 'perfect' combination. One for the morning and one for the evening. However you have plenty of other mono-therapy options which is always better.

I haven't banged on about therapy (in particular CBT (for anxiety)) and I won't other than to ask have you tried psychotherapy? How long, how many times and what type/s?

Can I ask for a list of meds you have tried?

Trazadone lacks antihistamine effects (significant at least) and so typically people find it less sedating. It should be started at 150mg - some doctors prescribe it at 50 or 100 to start with but those doses are only indicated for insomnia. I'm not convinced that Trazadone won't cause most of the same side effects problems as Buspirone.

Pregabalin is the most different and I've heard some fairly unpleasant stories but I've heard a lot more good than bad.

[Tom_]

I can't believe I forgot to ask! What type of anxiety are we talking about? Panic, Generalized, Phobic, OCD, PTSD?

Do you have any other diagnoses; Neuropsychiatric (depression etc) or otherwise?

I assume you've had bloods drawn and other tests were appropriate?

[BlueCloud]

I can't believe I forgot to ask! What type of anxiety are we talking about? Panic, Generalized, Phobic, OCD, PTSD?

Do you have any other diagnoses; Neuropsychiatric (depression etc) or otherwise?

I assume you've had bloods drawn and other tests were appropriate?

Anxiety : Generalized + Social Phobia.
Occasional depression, wich I consider more of a secondary consequence of the other main issues ( Chronic fatigue, constant anxiety, brainfog, insomnia ) that I had for more than decade.

Yes, blood tests, EEGs, etc.. that was a long time ago. To make a long story short, everything began around 15 years ago with a 3 months long flu-like sickness, from wich I seem to have never recovered, and only went downhill. After lots of tests , and most doctors being clueless to what my problem could be, I was "classified" under Chronic Fatigue Syndrome ( I did have elevated Epstein-Barr virus , wich at the time was considered a strong indicator for CFS). From there on , I went through all sorts of treatments and medications with no results, and I myself considered all sorts of theories, like Adrenal Fatigue ( If such thing really exists..). With the years, some symptoms were alleviated a bit ( the fatigue), while others became worse ( the anxiety, the insomnia, "brain fog" )

I haven't banged on about therapy (in particular CBT (for anxiety)) and I won't other than to ask have you tried psychotherapy? How long, how many times and what type/s?
Can I ask for a list of meds you have tried?

- List of meds.. Too long to list Between the natural supplements and the pharmaceuticals, easily a hundred substances, if not more..( plus all the odd things, acupuncture, homeopathy, etc.. I was so desperate at that time was ready to try anything at all )

- CBT and therapy ? Yes, a long time ago too. That was actually funny, because it was a complete and utter failure... I have this very perverted mind where I'm able to take any argument by the therapist considering the "un-reality" of my anxious thoughts, twist them around and prove to them that those thoughts are very rational and have a provable strong foundation, I almost enjoyed proving them wrong and dismantling their arguments one by one.. They all gave up in the end and probably became depressed and needed therapy, hahaha ! Amazing how my brain can turn against itself.

Oddly , the best therapy I had was conducted by myself, when taking Piracetam. Pira often gave me this sort of big picture view over the ensemble of my thoughts and emotions, and I was able to untie some mental knots created by myself, and therefore lessening my anxiety on some levels. If one is well prepared, Piracetam can be a great tool for self-therapy, not miraculous, but truly useful.

Propranolol can be taken on a daily basis but it won't treat the underlying pathology and doesn't tend to improve symptoms related to psychic or cognitive anxiety (worrying, over thinking etc..) it is however great for physical manifestations such as palpitations, increased blood pressure (of course), nausea and panic attacks.

You're right, but I'm hoping for ,perhaps, breaking the feedback loop at some point, or at least weakening it. Anxiety often feeds of itself to become stronger, anxiety leading to more anxiety, more bad habits and avoidance, etc.. I was especially intrigued after reading this : http://scienceblogs....arful-memories/
Maybe this could break the loop when being exposed to some specific stressors. Perhaps it's not a complete solution, but could be a useful adjunct.

Edited by BlueCloud, 22 October 2013 - 09:21 PM.

[Tom_]

Briefly on the propanolol - the memory 'thing' is mostly related to stopping the development of PTSD. It could also be used (with extra success when combined with behavioral exposure) for Phobias or as a PRN for stressful social events and the like.

A list of pharmacological treatments would be of use. As many as you can remember, if its not complete its not complete.

I was an idiot for not taking a history. CSF/like symptoms change things, sorry about that.

Do you think chronic sub-clinical depression could be an element of your problems (what ever the cause?).

I'm not an 'expert' on CFS but I can give some advice on symptom management. I'm also not convinced it is CFS (at least now), CFS tends to have resolved by 10 years. Its possible that its now morphed into a depressive/anxiety disorder. On the other hand it could be CFS.

My concern is that Propanolol may cause more bouts/worse depression and that it will worsen your brain fog. While the Pregabalin will not likely worsen depression (might help) it could also worsen brain fog.

I'm just going to go ahead and give options in general that I think might be useful for all of your symptoms (including anxiety), if none of it is of any interest to you apart from anxiety then hey at least I might learn something! Not that there is anything wrong with the ideas you already have but these might or might not be interesting for you.

My first 'genius' idea is clonidine or guanfacine long release. These are approved for ADHD in a lot of countries and increase dopamine and noradenergic transmission in the pre-frontal cortex. They are also sedating (clonidine a lot more than guanfacine). The major side effects are othostatic hypotension and sleepiness. They seem to maintain effectiveness for at least up to two years. In healthy people clonidine although possibly not guanfacine tend to decrease some cognitive abilities rather than improve them (and since you don't have ADHD this is possible but the reverse also is).

They will definitely help with anxiety and insomnia and may help improve cognition. They could also be combined with a few other things to make them more effective.

Nortriptyline: It can be mildly sedating but more commonly is mildly activating. Its a potent NRI (so you might not be interested) but has much more sert inhibiton than the V drug. Its often used in chronic fatigue syndrome - mostly for pain but might also improve sleep - is on lience for anxiety and depression and may improve fatigue and brain fog. At lower doses (mostly used in CFS) side effects are normally fairly mild.

Malnacipran: an SNRI approved for depression and pain, research suggests is also effective for anxiety. It is the only SNRI with stronger NRI than SRI effects but both are very significant so you may well avoid the ranging bull effect. It could defintely be used with guanfacine and maybe clonidine. Malnacipran in the morning to activate you and as an antidepressant for anxiety (and brain fog), the clonidine or guanfacine for sleep and anxiety and brain fog. Sexual dsyfunction however is a big problem.

Amitriptyline/Trimipramine: used in low doses at bed time they will almost certainly have you asleep. The sedative effects are much stronger than Mirtazapine but may well ware off quicker. At a low dose or slightly higher being better they will also help with anxiety. Might be best to combine them with a stimulant in the morning IF you find they leave you fatigued. Trimipramine is the only hypnotic known not to interfere with sleep architecture.

Modafinil: its not as likely to cause anxiety (or as much in some cases) as most or all other stimulants and its a more a wakefulness promoting agent. It can improve brain fog a lot as well.

Agomelatine: is a novel antidepressant that acts as a melatonergic agonist and 5HT2b/c antagonist. It more of a 'natural' sedative and definetely seems to normalize sleep. It might not be as an effective anxiolytic but certainly seems useful for OCD. It increases dopamine and noradrenergic activity in the pre-frontal cortex so might help with the brain fog. Combing this with 100-400mg of modafinil might be useful.

Amantadine: I don't really know why I'm suggesting this. The evidence for its use in any disorder other than parkinons disease is almost non-existant. Its an anti-viral (may or may not be of some use), an MAO-A inhibitor and is an antagonist of NDMA and the nicotinc 7 receptor. Its might have stimulating, anxiolytic and antidepressive properties. It may have some use in brain fog.

I have some possible ideas for behavioural-psycho-social interventions that might make it easier for your brain to engage with, if you are interested. If not I won't write about them but I do think they could help.

[BlueCloud]

I'm not an 'expert' on CFS but I can give some advice on symptom management. I'm also not convinced it is CFS (at least now), CFS tends to have resolved by 10 years. Its possible that its now morphed into a depressive/anxiety disorder. On the other hand it could be CFS.

CFS is still an enigma and not very well understood anyway. I did share a lot of the common symptoms ( like constant low-grade inflammation, alelrgies, etc), and many biomarkers, but I think It did morph in recent years, with less fatigue but more anxiety and "brain fog", sleepiness during the day and insomnia at night.

- Not feeling too enthusiastic about clonidine and guafancine, I already have a bad case of orthostatic hypotension, even fell a couple of times and injured myself
- Amitryptiline : This was actually the first AD i've been prescribed, and I did really badly on it. Couldn't tolerate it at all
- I tried Modafinil ( or was it Adrafinil ? can't remember) on my own in the past and strangely enough it made me sleepy all the time...
- Amantadine : now it's interesting that you mention it. I took it almost ten years ago, at the suggestion of my doc, both because of its subtle dopaminergic and antiviral effect ( to see if it could impact whatever mysterious viruses I might have ). And I actually felt decently well on it for a short while ( it was one perhaps the first time anything really helped ), then it just completely stopped working. We re-tried it later again with no results.

Today I dropped the Buspirone again, for good this time. I just can't handle the nausea and drowsiness..

Bottom line , after many years of trials and errors, I'm getting this big picture :
- All my attempts at trying to directly lower my anxiety with supposed anxiolytic substances ( both natural and pharmaceutical ) have pretty much failed. On the pharma side , only benzos work, but with severe cognitive hit, and on the supplement side , Magnesium ( 400mg or more) and Kava Kava had a clear effect with little cognitive sfx, but very moderate or insufficient anxiolisys to make a real difference.

- All SSRIs made feel like shit. I hate them with a passion.

- Anything that increases Norepinephrine is a big NO-NO to me. SNRI and NRIs alike. I feel an increase in energy and lessening of fatigue at first, but very quickly my anxiety shoots sky high, my insomnia becomes absolute, my facial tics increase, start sweating like a pig ( and I already sweat a LOT) ,etc..

- Anything that increases Dopamine often makes feel the best I've ever felt , diminishes my fatigue, removes the brain fog, and paradoxally (?) diminishes my anxiety and lessens my facial tics. Only insomnia stays as bad as before ( only antihistaminics like Diphenhydramine &co still help me on that front ). Only problem is that after a few days , my anxiety slowly increase to become as bad or worse than before. I attribute that to the Dopamine converting to Norepinephrine.

So, the road is becoming clear to me, to find ways how to safely increase Dopamine while preventing too much conversion to Norepinephrine. I've had some succesful experiences recenty ( mainly with CDP-Choline +Tyrosine and Sulbutiamine) , see my posts on this page and on this thread

Maybe I should open a new thread to document my progress on following this route.

Edited by BlueCloud, 23 October 2013 - 06:02 PM.

[Tom_]

I've had another idea. Hardly any clinical evidence and but a bit of pre-clinical evidence alongside a good theoretical background.

The basic idea is to reduce proinflammatory cytokine induced damage to the CNS (caused by an infection - even if the infection is now over) without using anything stupidly side effect heavy like TNF inhibitors.

I almost never suggest really out of the book treatments but there is very small benefits for standard drug treatments in CFS - but you do get to use Pregabalin, so if it does nothing else it should help the anxiety.

I've been doing research today after I noticed of late a severe drop in my mood (some stress but not to much and nasty case of illness) after being reasonably stable on an MAOI and Modafinil. I have two infections (bacterial on my leg and chest infection). Desperate to prove to myself it wasn't tacyphaxsis (poop out) I tried to find another explanation. I've found one I find both acceptable and more likely than poop-out.

Pregabalins effects on the CNS are wide, its effects on substance P, calcium channels, CGRP and Glutamate modify immune system function in the brain and to a lesser extent peripherally. So actually it might improve cognitive functioning for you or me.

Memantine an NMDA antagonist may have antidepressant/antianxiety properties and modulates monoamines. It also reduces pro-inflammatory cytokines and increases anti-inflammatory cytokines.

Both hopefully will start to increase hippocampal volume but you may be left with residual symptoms requiring a serotonergic antidepressant course of 12-16 weeks minimum.

I would certainly start the Pregabalin first and titrate to a dose you feel happy with.

[Tom_]

If you are within the normal (and you should have it anyway if you are low) triiodothyronine might make an added improvement.

[BlueCloud]

Well, buspirone is a Fail overall, but I might have found a new use for it in my case.

Last week I bought some L-Tryptophan to try. I took around 2 grams in the evening, and didn't feel much, if anything at all. Maybe a very weak anxiolityc effect, but so weak it could have been my imagination.
Then yesterday, my anxiety was so high during the day, I gave up and tried another dose of buspirone in the evening, 5mg. It did take off the edges of my anxiety nicely, and I just suffered through the nausea because I really needed a relief.
Then an hour before bed, I gave the Tryptophan another try to see if it would help my insomnia as I've stopped taking antihitamines for this, with a 1600mg dose . This time the effect was huge , in less than an hour I felt really sleepy, quite relaxed. Went to bed easily and had a decent sleep . The morning after I felt in a much better mood, less anxiety overall, more optimistic, in fact I haven't felt this good in a while. The feeling was very close to some SSRIs i took long time ago , except much cleaner and less intrusive.

The fact that I had such a strong effect this time and not the first time leads to think buspirone probably augmented the effect. It is in fact often suggested as an adjunct to SSRIs. ( Highly unlikely to provoke serotonin syndrome with such tiny doses )
We'll see if I can repeat and sustain the effect for a few more days, this time with an even smaller dose of buspirone ( 2,5 mg )