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Treatment-resistant anxiety

treatment-resistance generalized anxiety disorder panic attacks emetophobia hypochondria agoraphobia serotonin syndrome

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#1 piglet

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Posted 21 June 2018 - 11:07 PM

Hey guys,


I just discovered this place, and would like some help clearing up some confusion regarding my rather difficult to treat anxiety.


Anxiety/Medical history:



Developed claustrophobia as a child, avoided playing (american) football in the playground or being trapped in tight environments. They would cause me to feel trapped and at a loss for breath.

Palpitations while playing football/soccer would freak me out, physical examinations and EKG were normal.

Perennial allergies to various aeroallergens, progressively got worse throughout the years. 



Went on a summer vacation to India, became terribly ill and was hospitalized for fainting and falling down the stairs from vomiting and diarrhea.

Returned home, gastric symptoms lingered. Became fearful and hypersensitive to the smallest inclinations of physical ailments.

When nausea would hit during class, would become fearful of vomiting and being humiliated and escape to the washroom, if the feeling didn't dissipate would go home. 



Anxiety dissipated early-on after high school, good balance of school, work and social life.

Entering university was unable to study or pay attention in class, completely disinterested, would skip entire semesters and only showed up for finals. I guess agoraphobic behavior started to kick in around here.

Occasional minor panic attacks, when nausea would kick in at bars, restaurants, etc.

Despite never studying or attending class got my bachelor's of engineering.



Here is where severe symptoms commence

Immediately after graduating start noticing whenever, I am out in public I would get hit with nausea and suffer from a panic attack. In under a few weeks I was house-bound. Even at home I would suffer these attacks.

Went to the hospital to get my blood checked, took me days to gather the necessary courage to do so.

After the nurse took my blood, I almost fainted and was sent to the ER, where the doctor ordered abdominal x-rays, abdominal ultrasound more blood works and urine work. After being cleared, she suspected I might have an ulcer and prescribed me Pantoprazole (a proton-pump inhibitor) as well as Fluconazole (an antifungal) for yeast overgrowth.

Despite completing the course of medications, I did not feel any better and would still suffer from panic attacks.

After a month, went back to the ER, where I met with a gastroenterologist who did a gastroscopy and biopsy on me and everything came back normal.

I was seen by a psychiatrist for a psychiatric evaluation. He diagnosed me with Generalized Anxiety Disorder and Hypochondria/Illness Anxiety.


First SSRI trial

Escitalopram 20 mg for 5 weeks. No improvement. Side-effects: complete loss of libido and headaches.


First SNRI trial

Venlafaxine XR, up titration bi-weekly until 150 mg. Medication stopped, due to increased anxiety, terrible night sweats and nightmares.


Therapy 1

While tapering off Venlafaxine XR, started weekly sessions of therapy. Despite being very friendly therapist was very incompetent, spent half of the session talking about herself and the other half quoting self-help books. She recommended I distance myself from my friends, and since then I haven't had any friends. Went through 12 sessions. Was introduced to the concept of exposure therapy, not much cognitive work done here. The exposure allowed me to get used to having panic attacks in public, but was exhausting. By the end, I was scared of having panic attacks at the gym, library, shopping mall, etc.


Second SSRI trial

Once successfully tapered off Venlafaxine XR, met with another psychiatrist who put me on Sertraline. Up-tapered until 100 mg. Thinks were looking good, but found out my dad might have cancer and suffered a relapse back into agoraphobia.

Had basically given up, until my father was cleared of cancer. Then went to see another psychiatrist, who I would stay with until this very day.

The psychiatrist couldn't diagnose me anything, told me I definitely have anxiety, but I could have other cormorbidities including Bipolar II, Major Depression Disorder.

He increased my Sertraline dosage to 150 mg. At this point, I started experiencing insomnia. Only sleeping 5 hours a night. So he added Seroquel 25 mg to aid sleep, which caused nasty hangovers. No improvement was seen in terms of the anxiety.

Sertraline was increased to 175 mg, I suffered very high anxiety and complete insomnia. Sertraline was tapered down to 100 mg. I was given Lorazepam 1 mg to take as needed, only took these a few times as all they did was make me sleep. From this point I developed ringing in my ears, tinnitus, which seems to be aggravated by high anxiety levels.


Augmentation with Seroquel XR

Psychiatrist added Seroquel XR to Sertraline 100 mg, seeing if there could be a hidden Bipolar under the anxiety. Up-titrated until 300 mg. This essentially turned me into a zombie. I was drowsy and stoned from wake to sleep. Panic attacks certainly decreased, but functionality was non-existent. 


Augmentation with Olanzapine

Was taken off Seroquel XR and put on Olanzapine 7.5 mg combined with Sertraline 100 mg. The same effect as the Seroquel XR had.


Cognitive Behavioral Therapy 2

This therapist was more competent than a last one and had a lot more experience. She introduced me to Mindfulness, which I was skeptical of at first, but it did seem to alleviate some of the anxiety caused by overwhelming thoughts. Only saw her a few times, as she was very expensive $160/h.


Augmentation with Pregabalin and Trazadone

Pregabalin was introduced and up-titrated along side Sertraline until a dose of Pregabalin 150 mg, three times a day, and Sertraline 200 mg was reached. Since insomnia seems to kick in with high doses of Sertraline he added Trazadone 50 mg, which I hated as it accentuated my already crippling nausea.


Augmentation with Pregabalin and Clonazepam

Psychiatrist convinced me to try a long-acting benzodiazepine at this point, reluctantly accepted. At this point, was on; Sertraline 200 mg, Pregablin 150 mg x3, Clonazepam 0.5 mg AM and 1 mg PM. Largest reduction of anxiety by psychopharmacology occurred here, panic attacks were almost non-existent. But once again energy levels were non-existent, would require a lot of day-time napping and thus be impractical. Not Seroquel/Olanzapine zombie-mode, just tired.


First TCA trial

Sertraline was replaced with Imipramine. Up-titrated until reaching Imipramine 200 mg combined with Pregabalin 150 x2 (reduced due to drowsiness) and Clonazepam 0.5 mg AM and 1 mg PM. This medication caused severe constipation, even laxatives didn't work. It also caused severe drowsiness, required even more day-time napping then the previous combination. This medication did not impact any of my anxiety, the panic attacks had come back.


Augmentation with Clonidine

Clonidine 0.025 mg x3 was added to Imipramine 200 mg, Pregabalin 150 mg x2 and Clonazepam 0.5 mg AM and 1 mg PM. No change in anxiety.


Withdrawal from Imipramine, Pregabalin, Clonidine and Clonazepam

Brutal withdrawal, should've done one at a time and slower. But didn't want to waste time.


First stimulant trial

Saw therapist number 2 again, she recommended we try to see if there would be any ADHD causing some anxiety. Psychiatrist was skeptical, but took her advice and put me on Methylphenidate, up-titrated until reaching 15 mg x2. Anxiety was multiplied and the medication was stopped. For some reason the increased anxiety didn't come back to normal after stopping the medication.


Sertraline and Mirtazipine

Psychiatrist met with a pharmacologist who recommended to try this combination. Sertraline was up-titrated 50 mg/week, when 100 mg was reached Mirtazapine was added and up-titrated 15 mg/week. After reaching Sertraline 100 mg and Mirtazapine 15 mg, I had started to develop an exaggerated startle response/hyperarousal. Didn't make much of it and kept with the program. When the final dose of Sertraline 200 mg and Mirtazapine 30 mg was reached, I had started to show some serious adverse effects; hyperarousal, tongue/jaw spasms, restlessness and the highest anxiety I've ever experienced. Feared Serotonin Syndrome and went to the ER. All blood, urine work came back normal. Didn't have a fever. The psychiatrist was unfortunately a resident?, very young, he said maybe it was a mild form of Serotonin Syndrome and told me to stop Mirtazapine cold turkey and continue with Sertraline 200 mg. Reluctant to take his word, I contacted my psychiatrist, who agreed that it would be best to withdraw Sertraline by going down to 100 mg for a few days then stopping it, as Serotonin Syndrome is extremely hard to diagnose at its early stages.


Here is where I stand today. Surprisingly feel better now than I felt since the Sertraline, Pregabalin and Clonazepam combination. But I feel utterly confused at the moment. Even my psychiatrist and therapist are unsure with what to do. My psychiatrist has referred me to an Anxiety clinic in my city, where there is a specialist in anxiety disorders. But the appointment with the specialist might take months.


Regarding my current health/habits, they're relatively poor. I've always been incredibly underweight, BMI 16-18, with a very poor appetite, usually 2-3 meals a day. Not many veggies or much water. I don't exercise anymore either. Sleep is good, always more than 8 hours, seems to have solved itself somehow. Panic attacks are more easier to control as well, don't come out of the blue anymore. Allergies are really bad, urticaria lasts all year, while rhinoconjugivitis only happens in the spring/fall. I'm also reluctant to take Cetirizine or other second-generation anti-histamines, psychiatrist told me it's fine while the ER doctor told me it affects psychiatric conditions..


I'm sorry for writing this long history, but I would appreciate it if anyone had any recommendations (with sources if possible) to make.


Thank you for your time.

#2 Mind_Paralysis

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Posted 22 June 2018 - 08:15 AM

A very good intro-post - although perhaps a bit long - it does give a lot of useful information though.


All right, so, allergies first - there's 2.5 generation antihistamines as well - they are generally even more selective towards the peripheral nervous system, and H1-receptors, so the effects on psychiatric symptoms should be negligible with these.


LEVOcetirizine, is what I recommend - it's half the stereo-molecule of Cetirizine, since studies found that it's actually this part of Cetirizine that has the greatest effect on allergic symptoms, it also has lower Blood-Brain-Barrier permeability, which will lower its impact on the brain.





Since you've tried so many traditional drugs with such bad results I'm going to suggest something more unorthodox:


Memantine - an NMDA-antagonist, has effects on anxiety for some people.


You can read a bit more about animal-results here, as well as the basis for the idea:











A word of caution though, this study apparently found evidence that it could make anxiety WORSE, in rats:



This isn't anything I've ever heard reported from human use though - most people seem to react either neutrally or positively to it. (going from online reports)



Anyways, there's also evidence that Propranolol - a beta-blocker also has highly dose-dependent effects on the brain - if you take it in the right dose, it DECREASES activity out of the amygdala - the part of the brain that control the fight or flight mechanism. You've probably heard about this already, but, it's always worth a shot...

(I'd post the studies, but I'm too tired...)


I also suggest you have a look at these two experimental drugs:


AM-404: Selective Cannabinoid Reuptake Inhibitor - the active metabolite of Paracetamol/Acetaminophen.






(my thread above describes the basis of effect, but the other thread shows how there's even clearer, deeper theories about how modulation of the cannabinoid systems could decrease anxiety - the beauty of AM-404 is that it's selective though, none of that stupidity that comes with cannabis.)



BNC-210: Nicotinic Acetylcholine alpha-7 receptor-antagonist. The alpha-7 receptor controls a lot of the activity out of the amygdala, and this drug suppresses the receptor, lowering activity dramatically.





Both of those drugs are experimental, but are either well-tested on humans already anyway (am404 - you've already used paracetamol... like everyone else), or have come rather far in human trials (bnc-210, stage 2 human testing) - as such, they're reasonably safe to start experimenting with, for someone like you, whom have tried so many things.


They are of course out of reach at the moment - but YOU could start a group buy for these drugs! : D I know several people on these boards whom have organized such buys, and I'm sure if you are interested in it, they would be willing to teach you how its done. = )

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#3 piglet

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Posted 22 June 2018 - 03:54 PM

Thank you for your response.

That's interesting. I'll look into those. But on propranolol, I don't think it's recommended for anxiety. Here's a systematic review and meta-analysis of RCTs, https://www.ncbi.nlm...les/PMC4724794/.

On a side note, why is it that past a certain threshold of antidepressant dosage and any addition of stimulant there seems to be a multiplication of anxiety. I've read about activation, but don't understand it too well. How could something like that be treated or avoided? Did I up-titrate too fast? I think 50 mg/week is within the guidelines, and in the first Sertraline trial we went even slower maybe 25 mg/week, and there was still a significant increase in anxiety.

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#4 jack black

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Posted 22 June 2018 - 09:31 PM

Thank you for your response.

That's interesting. I'll look into those. But on propranolol, I don't think it's recommended for anxiety. Here's a systematic review and meta-analysis of RCTs, https://www.ncbi.nlm...les/PMC4724794/.





did you read the paper?



This systematic review and meta-analysis shows a lack of well-designed clinical studies. This limits the scientific evidence and allows neither firm conclusions in favour or against the use of propranolol in the treatment of anxiety disorders, nor recommendations for informed decision-making in clinical practice. More specifically, our meta-analyses found no statistical difference between the effects of propranolol and benzodiazepines on anxiety and panic attack frequency


that means we really don't have perfect studies, but what we have show it WORKS AS GOOD AS BENZOS.

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#5 piglet

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Posted 22 June 2018 - 10:49 PM

My apologies, went through it quickly and missed that.
But I still have reservations regarding it. Will the lowering of blood pressure allow me to function, or will I be really tired all the time? The lowering of blood pressure scares me, my blood pressure is usually around 120/80 pulse around 80 off all medications.

#6 piglet

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Posted 22 June 2018 - 10:56 PM

What do you guys think of MAOI's or Lithium (low dose) for my anxiety? Would they make the symptoms better or worse?

#7 Mind_Paralysis

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Posted 23 June 2018 - 09:10 AM

What do you guys think of MAOI's or Lithium (low dose) for my anxiety? Would they make the symptoms better or worse?


Lithium could definitively help, but the side-effects-profile of the available formulations aren't the best - sure, Lithium Orotate has a better profile, but it's not as studied. A small dosage of that probably won't hurt though, so sure, give it a try.


As for MAOI's, well, it depends on the MAOI - I hear Nardil (phenelzine) is one of the better ones when it comes to anxiety.



I'd try the things I suggested earlier first though, these two have far more problematic side-effects.

Perhaps a combo of Propranolol and Duloxetine? SNRI's actually have been proven in one meta-study to be MORE effective against anxiety in the long-run, than SSRI's. Propranolol will decrease the negative effects of the Noradrenaline, making it less speedy, and allow potential NE-mechanisms to down-regulate (after a few weeks) allowing Duloxetine to actually treat your anxiety.


Give it a try, mate! = )



You could of course also make this combo, since I'd say it's reasonably safe:




Low-dose Lithium


Edited by Mind_Paralysis, 23 June 2018 - 09:12 AM.

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#8 Junipersun

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Posted 25 June 2018 - 05:59 PM

What do you guys think of MAOI's or Lithium (low dose) for my anxiety? Would they make the symptoms better or worse?


Tranylcypromine or Phenelzine are great for treatment resistant anxiety, although you have to struggle through the initial side effects. The best resource for maois and their effect on anxiety is the social anxiety board. 

Also tagged with one or more of these keywords: treatment-resistance, generalized anxiety disorder, panic attacks, emetophobia, hypochondria, agoraphobia, serotonin syndrome

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