Ketamine Relieves Depression by Restoring Brain Connections
- Thread starter Nic B
- Start date
Member- May 9, 2017
- 929
- Tinnitus Since
- 2013
- Cause of Tinnitus
- Noise-induced
Ketamine Nasal Sprays For Depression: Unpredictable Side Effects
"The efficacy and safety of intranasal ketamine for depression is under scrutiny, as a pilot trial is stopped early due to poor side effects in patients.
Nasal spray devices have been touted as a promising way to deliver ketamine to patients with treatment-resistant depression, with this application easier to use and less invasive than other clinical delivery methods such as injections.
But new research from the Black Dog Institute and UNSW Sydney reveals the unpredictable nature of intranasal ketamine tolerance from one person to the next. The pilot trial aimed to test the feasibility of repeated doses of ketamine through an intranasal device amongst 10 participants with severe depression, ahead of a larger randomised controlled trial.
[...]
However, the pilot study was eventually suspended after testing with five participants due to unexpected problems with tolerability. Side effects included high blood pressure, psychotic-like effects and motor incoordination which left some participants unable to continue to self-administer the spray."
__________________
Repeated intranasal ketamine for treatment-resistant depression – the way to go? Results from a pilot randomised controlled trial
First Published March 15, 2018
Background
Ketamine research in depression has mostly used intravenous, weight-based approaches, which are difficult to translate clinically. Intranasal (IN) ketamine is a promising alternative but no controlled data has been published on the feasibility, safety and potential efficacy of repeated IN ketamine treatments.
Methods
This randomised, double-blind, placebo-controlled pilot study compared a 4-week course of eight treatments of 100 mg ketamine or 4.5 mg midazolam. Each treatment was given as 10 separate IN sprays, self-administered 5 min apart. The study was stopped early due to poor tolerability after five treatment-resistant depressed participants were included. Feasibility, safety (acute and cumulative), cognitive and efficacy outcomes were assessed. Plasma ketamine and norketamine concentrations were assayed after the first treatment.
Results
Significant acute cardiovascular, psychotomimetic and neurological side effects occurred at doses < 100 mg ketamine. No participants were able to self-administer all 10 ketamine sprays due to incoordination; treatment time occasionally had to be extended (>45 min) due to acute side effects. No hepatic, cognitive or urinary changes were observed after the treatment course in either group. There was an approximately two-fold variation in ketamine and norketamine plasma concentrations between ketamine participants. At course end, one participant had remitted in each of the ketamine and midazolam groups.
Conclusions
IN ketamine, with the drug formulation and delivery device used, was not a useful treatment approach in this study. Absorption was variable between individuals and acute tolerability was poor, requiring prolonged treatment administration time in some individuals. The drug formulation, the delivery device, the insufflation technique and individual patient factors play an important role in tolerability and efficacy when using IN ketamine for TRD.
"The efficacy and safety of intranasal ketamine for depression is under scrutiny, as a pilot trial is stopped early due to poor side effects in patients.
Nasal spray devices have been touted as a promising way to deliver ketamine to patients with treatment-resistant depression, with this application easier to use and less invasive than other clinical delivery methods such as injections.
But new research from the Black Dog Institute and UNSW Sydney reveals the unpredictable nature of intranasal ketamine tolerance from one person to the next. The pilot trial aimed to test the feasibility of repeated doses of ketamine through an intranasal device amongst 10 participants with severe depression, ahead of a larger randomised controlled trial.
[...]
However, the pilot study was eventually suspended after testing with five participants due to unexpected problems with tolerability. Side effects included high blood pressure, psychotic-like effects and motor incoordination which left some participants unable to continue to self-administer the spray."
__________________
Repeated intranasal ketamine for treatment-resistant depression – the way to go? Results from a pilot randomised controlled trial
First Published March 15, 2018
Background
Ketamine research in depression has mostly used intravenous, weight-based approaches, which are difficult to translate clinically. Intranasal (IN) ketamine is a promising alternative but no controlled data has been published on the feasibility, safety and potential efficacy of repeated IN ketamine treatments.
Methods
This randomised, double-blind, placebo-controlled pilot study compared a 4-week course of eight treatments of 100 mg ketamine or 4.5 mg midazolam. Each treatment was given as 10 separate IN sprays, self-administered 5 min apart. The study was stopped early due to poor tolerability after five treatment-resistant depressed participants were included. Feasibility, safety (acute and cumulative), cognitive and efficacy outcomes were assessed. Plasma ketamine and norketamine concentrations were assayed after the first treatment.
Results
Significant acute cardiovascular, psychotomimetic and neurological side effects occurred at doses < 100 mg ketamine. No participants were able to self-administer all 10 ketamine sprays due to incoordination; treatment time occasionally had to be extended (>45 min) due to acute side effects. No hepatic, cognitive or urinary changes were observed after the treatment course in either group. There was an approximately two-fold variation in ketamine and norketamine plasma concentrations between ketamine participants. At course end, one participant had remitted in each of the ketamine and midazolam groups.
Conclusions
IN ketamine, with the drug formulation and delivery device used, was not a useful treatment approach in this study. Absorption was variable between individuals and acute tolerability was poor, requiring prolonged treatment administration time in some individuals. The drug formulation, the delivery device, the insufflation technique and individual patient factors play an important role in tolerability and efficacy when using IN ketamine for TRD.
This article is for recreational & chronic ketamine abuse, instead of medicinal/therapeutic use which would apply here. Good information though.
My experience: I thought this was a logical approach for trial so I made my own trial out of it since their method was pretty basic.
I decided to get infused at a local ketamine clinic. I was accepted to receive the infusion ($250). Because I might be sensitive due to prior experiences with medications (mainly an SSRI) I asked for a lower dose. In the study they use 0.5 mg/kg IV of ketamine hydrochloride in saline, this was also clinic's standard dose for depression. Instead, they did .3mg for me to start.
What it felt like: I pretty much knew what to expect... feeling a bit out of control of your body in a drugged sense. Generally, the thought of this makes me uncomfortable as I'm a little bit of a control freak and do not like being "drugged". I had also gotten panic attacks in the past from pot so I was prepared for the worst. But if it meant the possibility of improving my tinnitus I didn't give a crap. You literally feel it after about 1-2 minutes. The nice thing about an infusion vs an injection, is that it can be stopped at any time - so if you're feeling really horrible, once they stop it, the effects stop within a few minutes. I suddenly felt a weird dizziness and weakness come over me, really like I had been drugged (well, I had been), then you feel a little out of control of your senses. At that 3 min mark, I was ready to stop because it felt pretty weird but I stuck with it and realized, it actually didn't get much stronger/worse than that. It seemed to come in waves where you just feel zonked out but I was able to talk to the physician most of the time. For me, I think I did really well.
What the tinnitus felt like: Mine fluctuates constantly throughout the day so unless it literally "shut off" measuring it was going to be difficult. I have some pure tones which fluctuate an on my loud days, I have tea kettle tinnitus in additional to "brain" electrical tinnitus. I woke up having a pretty loud day before going to get the infusion. My loud days tend to get louder as the day progresses. During the middle of the infusion, it seemed to get a tiny bit lower but that could have just been a fluctuation for no reason (this also happens when I'm talking so that might have been the case). The infusion lasted 40 min. Afterwards, it was louder but I'm pretty sure it was not due to the infusion itself but to fact that it was later in the day around the time my tinnitus gets louder.
What changed: In the car on the way home (while wearing ear muffs because I also have hyperacusis) I heard a new beeping sound in my left ear. I got pretty scared but it only happened a couple times then stopped. Since then, I've been waking up with a beeping sound which is annoying but then it stops a few minutes after I get up. But here's the nice part. My left ear had recently gotten worse (months before the infusion) and I was having a stronger pure to that was worse when lying down and was getting more constant throughout the day as the months went by. What I realized is that the beeping was the pure tone BREAKING UP. I had the infusion almost 2 weeks ago and I have not have the loud left ear pure tone since. Just the beeping in the morning for a few minutes when waking - vs the stronger solid pure tone I used to have. I can't tell if the rest of the tinnitus has gotten softer due to the constant fluctuations but it feels slightly less violent at least for time being.
I'm pretty sure I will go for another infusion soon I wanted to wait a little first just to properly assess the changes that have happened so far to make sure I'm headed in the right direction.
Did it help with depression? I'm mostly depressed due to the tinnitus but I also have a thalamacortical dysrythmia - look it up and it's association to tinnitus (a possible treatment for this is said to be ketamine) which is another reason why I really wanted to try it. I think it might have helped with the depression a bit. I've been feeling a little more detached from the tinnitus and indifferent, nothing drastic, but I see how it can potentially help other people with "normal" depression.
Lots of talk on here about Ketamine and it wasn't really a big deal to just go try it.
Thanks. For the next infusion, I was going to move up the dose a little. I will keep everyone informed of any changes.@Cal18 maybe for you is more effective a low dosage. Please keep on with this dosage and make us know. Happy for you
1MW
Member
- Nov 25, 2014
- 614
- Tinnitus Since
- 2008 but cured and relapsed from benzos
- Cause of Tinnitus
- ssnhl/benzos/unknown
@Cal18 ketamine is ototoxic and I suggest you to avoid it.
The results are not permanent and it has side effects.
Check your diet and add vitamins, metals, minerals, certain aminoacids / protein & complex carbs, also good lipids to your diet.
Sun exposure & sex also very important.
That's the way to fix depression.
The results are not permanent and it has side effects.
Check your diet and add vitamins, metals, minerals, certain aminoacids / protein & complex carbs, also good lipids to your diet.
Sun exposure & sex also very important.
That's the way to fix depression.
Please! This is very exciting. Thanks so much for trying it and taking the time to report back.
3ri0w
Member
- Nov 25, 2015
- 398
- Tinnitus Since
- 2012, H 2016, 12/2018(?)
- Cause of Tinnitus
- loud noises, ringing came back 12/2018 after 1year of silent
I've had ketamine infusions many times and I have also had ketamine in hospital (for pain). It was not a tinnitus cure any time 
There are infusion clinics that even list "Tinnitus" as a thing that the infusions could cure. But it didn't cure mine, too bad. I was so excited for AM-101 ;__; I really thought that the NMDA related things would have been THE cure.
There are infusion clinics that even list "Tinnitus" as a thing that the infusions could cure. But it didn't cure mine, too bad. I was so excited for AM-101 ;__; I really thought that the NMDA related things would have been THE cure.
3ri0w
Member
- Nov 25, 2015
- 398
- Tinnitus Since
- 2012, H 2016, 12/2018(?)
- Cause of Tinnitus
- loud noises, ringing came back 12/2018 after 1year of silent
Helps like 70 % of people I read... I belong to the 30 %... Spent thousands of bucks and it did not cure me.. but it's worth a try if you are really down, because atleast it is not ototoxic like SSRI/SNRI and the other antidepressants, and like even if the other antidepressants are not ototoxic "per se", some of them do cause tinnitus for some people and the ringing does not stop (many cases of SSRI tinnituses on this forum).
What I don't get about ketamine is that like you have to get "booster shots" every once in a while. And how often, for every person it is different, someone is good for a month, someone for six months etc. But in the US of A you can get ketamine to take at home so you don't have to go to the clinic to take them expensive boosters.
Also another thing, why is it so darn expensive? I'm pretty sure ketamine is in every major ER/Hospital around as a backup anesthetic.
It almost seems like they've found a way to make a profit back for a stagnant anesthesia stock.
It almost seems like they've found a way to make a profit back for a stagnant anesthesia stock.
- May 7, 2015
- 1,050
- Tinnitus Since
- 29.09/2014
- Cause of Tinnitus
- Acoustic trauma using headphones
Gordon Groves
Member
- Sep 15, 2019
- 1
- Tinnitus Since
- 2/21/17
- Cause of Tinnitus
- put in closed MRI without headphones
I have tinnitus of 9000 Hz and 80 decibels, and have started ketamine nasal spray sessions twice weekly at a clinic for suicidal thoughts. Unfortunately the ketamine increases the volume of the noise and hyperacusis, so it may outweigh the benefits I receive for depression and anxiety. Any anaesthetic or painkiller, anti-inflammatory or strong drug like ketamine I have tried have all aggravated my tinnitus to no end. I have found the best anti-depressant in my case is a good psychotherapist.
https://www.riverdalepress.com/stor...he-noise-group-finds-support-knowledge,70757?
"Martinez recently visited the group to share details of a clinical trial that will use small doses of ketamine, a mild sedative, to treat tinnitus. The ketamine is expected to calm down the thalamus, the part of the brain that, simply, tells you what to pay attention to.
When someone is walking down the street, talking to a friend as an ambulance races with its sirens blaring, it's the thalamus that prompts you to pay attention to the ambulance and figure out what's going on. Martinez believes that small doses of ketamine — a drug used primarily in anesthesia — will convince the thalamus to stop telling the brain to pay attention to the ringing."
"Martinez recently visited the group to share details of a clinical trial that will use small doses of ketamine, a mild sedative, to treat tinnitus. The ketamine is expected to calm down the thalamus, the part of the brain that, simply, tells you what to pay attention to.
When someone is walking down the street, talking to a friend as an ambulance races with its sirens blaring, it's the thalamus that prompts you to pay attention to the ambulance and figure out what's going on. Martinez believes that small doses of ketamine — a drug used primarily in anesthesia — will convince the thalamus to stop telling the brain to pay attention to the ringing."
jacob256
Member
- Mar 30, 2020
- 16
- Tinnitus Since
- 02/2019
- Cause of Tinnitus
- Genuinely believe excessive sexual activity + stress
Hey guys, I'm curious about this and I'm going to give a background story as well.
So after nearly a year of chronic stress, I started having a bunch of odd health issues. Long story short I ended up in the hospital because of a few things, one including the worst headache I've ever had by a massive margin. My headaches are always in the exact same spot - on the right side of my head next to my ear.
They injected me with 5 or so drugs by IV; the first ones didn't have any effect on my pain but the last one, a Ketamine infusion, made the 9/10 level super headache go away within a minute. I also had some adverse effects from it though such as a rash and an increased heart rate (25 bpm or so).
A little less than a month after this, I developed my tinnitus after randomly waking up with it one day. After noticing that Klonopin (benzo drug) significantly reduced my tinnitus within 30 minutes (I tested this 3 times), I came to the conclusion that mine was caused by a Glutamate/GABA balance issue, which can be caused by long term stress (too much Glutamate and too little GABA). I can "feel" my tinnitus in the same spot that I had the headache.
I like to read scientific literature and it seems that ketamine has been described as potentially the most important breakthrough in treating depression in the 21'st century.
https://www.nature.com/articles/s41398-019-0500-z
The above article states the following:
"The rapid and robust antidepressant and anxiolytic effects of ketamine, which acts on the GLUTAMATE system, suggest that dysfunction of glutamate neurotransmission may be an early and primary pathology of stress-related disorders".
This leads me to believe that the insane headache I had might have been related to a glutamate overload. If you're one of the people who just randomly woke up with tinnitus one day and you think it may be stress related, I think maybe it would be worth looking into a Ketamine infusion! Just throwing something out there haha.
So after nearly a year of chronic stress, I started having a bunch of odd health issues. Long story short I ended up in the hospital because of a few things, one including the worst headache I've ever had by a massive margin. My headaches are always in the exact same spot - on the right side of my head next to my ear.
They injected me with 5 or so drugs by IV; the first ones didn't have any effect on my pain but the last one, a Ketamine infusion, made the 9/10 level super headache go away within a minute. I also had some adverse effects from it though such as a rash and an increased heart rate (25 bpm or so).
A little less than a month after this, I developed my tinnitus after randomly waking up with it one day. After noticing that Klonopin (benzo drug) significantly reduced my tinnitus within 30 minutes (I tested this 3 times), I came to the conclusion that mine was caused by a Glutamate/GABA balance issue, which can be caused by long term stress (too much Glutamate and too little GABA). I can "feel" my tinnitus in the same spot that I had the headache.
I like to read scientific literature and it seems that ketamine has been described as potentially the most important breakthrough in treating depression in the 21'st century.
https://www.nature.com/articles/s41398-019-0500-z
The above article states the following:
"The rapid and robust antidepressant and anxiolytic effects of ketamine, which acts on the GLUTAMATE system, suggest that dysfunction of glutamate neurotransmission may be an early and primary pathology of stress-related disorders".
This leads me to believe that the insane headache I had might have been related to a glutamate overload. If you're one of the people who just randomly woke up with tinnitus one day and you think it may be stress related, I think maybe it would be worth looking into a Ketamine infusion! Just throwing something out there haha.
- Jul 22, 2018
- 49
- Tinnitus Since
- 03/2015
- Cause of Tinnitus
- amitriptyline, hidden hearing loss, whiplash (?), stress (?)
Thanks for this post, interesting theory and helpful to compare experiences.
FWIW, my tinnitus was mostly likely caused by stress and chronic sleep deprivation leading to excess glutamate, and I participated in this ketamine trial at Columbia and it had no impact.
Of course the purpose of the study is not treatment but rather research, so I am still glad I participated, and I am just one subject out of many. Nevertheless, it does provide a counterpoint to this thesis and to other theories on ketamine's potential use as a tinnitus treatment.
Who knows though, perhaps recurring ketamine treatment and/or higher doses from a private lab might do something my tinnitus as well... but that is something I cannot afford.
I moved from lozenges to compounded spray. During the sessions at home my tinnitus can sound louder but I could care less. I am on ketamine at that point. My tinnitus has been louder during the day but I don't know if it is because of going up on my stupid OCD med which is a tricyclic with a high tinnitus rate. Shrooms doing microdose doesn't have an effect. Won't touch LSD or MDMA.
May I ask, did this continue to provide you benefit over time?My experience: I thought this was a logical approach for trial so I made my own trial out of it since their method was pretty basic.
I decided to get infused at a local ketamine clinic. I was accepted to receive the infusion ($250). Because I might be sensitive due to prior experiences with medications (mainly an SSRI) I asked for a lower dose. In the study they use 0.5 mg/kg IV of ketamine hydrochloride in saline, this was also clinic's standard dose for depression. Instead, they did .3mg for me to start.
What it felt like: I pretty much knew what to expect... feeling a bit out of control of your body in a drugged sense. Generally, the thought of this makes me uncomfortable as I'm a little bit of a control freak and do not like being "drugged". I had also gotten panic attacks in the past from pot so I was prepared for the worst. But if it meant the possibility of improving my tinnitus I didn't give a crap. You literally feel it after about 1-2 minutes. The nice thing about an infusion vs an injection, is that it can be stopped at any time - so if you're feeling really horrible, once they stop it, the effects stop within a few minutes. I suddenly felt a weird dizziness and weakness come over me, really like I had been drugged (well, I had been), then you feel a little out of control of your senses. At that 3 min mark, I was ready to stop because it felt pretty weird but I stuck with it and realized, it actually didn't get much stronger/worse than that. It seemed to come in waves where you just feel zonked out but I was able to talk to the physician most of the time. For me, I think I did really well.
What the tinnitus felt like: Mine fluctuates constantly throughout the day so unless it literally "shut off" measuring it was going to be difficult. I have some pure tones which fluctuate an on my loud days, I have tea kettle tinnitus in additional to "brain" electrical tinnitus. I woke up having a pretty loud day before going to get the infusion. My loud days tend to get louder as the day progresses. During the middle of the infusion, it seemed to get a tiny bit lower but that could have just been a fluctuation for no reason (this also happens when I'm talking so that might have been the case). The infusion lasted 40 min. Afterwards, it was louder but I'm pretty sure it was not due to the infusion itself but to fact that it was later in the day around the time my tinnitus gets louder.
What changed: In the car on the way home (while wearing ear muffs because I also have hyperacusis) I heard a new beeping sound in my left ear. I got pretty scared but it only happened a couple times then stopped. Since then, I've been waking up with a beeping sound which is annoying but then it stops a few minutes after I get up. But here's the nice part. My left ear had recently gotten worse (months before the infusion) and I was having a stronger pure to that was worse when lying down and was getting more constant throughout the day as the months went by. What I realized is that the beeping was the pure tone BREAKING UP. I had the infusion almost 2 weeks ago and I have not have the loud left ear pure tone since. Just the beeping in the morning for a few minutes when waking - vs the stronger solid pure tone I used to have. I can't tell if the rest of the tinnitus has gotten softer due to the constant fluctuations but it feels slightly less violent at least for time being.
I'm pretty sure I will go for another infusion soon I wanted to wait a little first just to properly assess the changes that have happened so far to make sure I'm headed in the right direction.
Did it help with depression? I'm mostly depressed due to the tinnitus but I also have a thalamacortical dysrythmia - look it up and it's association to tinnitus (a possible treatment for this is said to be ketamine) which is another reason why I really wanted to try it. I think it might have helped with the depression a bit. I've been feeling a little more detached from the tinnitus and indifferent, nothing drastic, but I see how it can potentially help other people with "normal" depression.
Lots of talk on here about Ketamine and it wasn't really a big deal to just go try it.
This study was introduced to me by a colleague of mine who has suffered with intrusive tinnitus since 2014. I searched around on the forum and have not come across any details or awareness of this particular study so I thought I'd share it. If this has been discussed before, my apologies and please have it merged with any ongoing thread.
That said, Columbia University Department of Psychiatry in New York City is currently performing Phase 2 trials investigating the effect of ketamine on tinnitus and it appears that it is on a rolling recruitment cycle. Considering I live in the area, I provided them with my contact information this afternoon and am currently awaiting for them to get in touch regarding trial info and requirements. If I get any feedback from them, I'll provide updates with any details I receive.
Link for the Columbia University Medial Martinez Lab:
https://www.columbiapsychiatry.org/research-labs/martinez-lab
Link for Clinical Trial Information:
https://clinicaltrials.gov/ct2/show/NCT03336398
Heads up for anyone interested: the trial does require two MRI scans. I know there is a lot of hesitation when it comes to MRI's on this forum, and for good reason, but I think it's a chance I would personally be willing to take as there have been anecdotal reports of ketamine potentially impacting the pitch and loudness of tinnitus in a positive way.
That said, Columbia University Department of Psychiatry in New York City is currently performing Phase 2 trials investigating the effect of ketamine on tinnitus and it appears that it is on a rolling recruitment cycle. Considering I live in the area, I provided them with my contact information this afternoon and am currently awaiting for them to get in touch regarding trial info and requirements. If I get any feedback from them, I'll provide updates with any details I receive.
Link for the Columbia University Medial Martinez Lab:
https://www.columbiapsychiatry.org/research-labs/martinez-lab
Link for Clinical Trial Information:
https://clinicaltrials.gov/ct2/show/NCT03336398
Heads up for anyone interested: the trial does require two MRI scans. I know there is a lot of hesitation when it comes to MRI's on this forum, and for good reason, but I think it's a chance I would personally be willing to take as there have been anecdotal reports of ketamine potentially impacting the pitch and loudness of tinnitus in a positive way.
What are the alternatives? I'm not about to run to the streets to get my hands on something I know nothing about. Plus, there's the upside of being part of a study which may have the potential to help others.
Why not? You could probably just buy Ketamine from one of those shady foreign pharmacies.
There is a place near me in Westchester that does Ketamine therapy intravenously, but they don't take insurance and I think it would be like $1,400 bucks for me. Still, I may try it if things don't get better via other means.
I was a bit rash in responding to my earlier post when I asked about alternatives... forgot about these Ketamine infusion therapies. There is a place out in Arizona that actually lists tinnitus as one of their treatments and each of their infusions is $375, and they have package deals for multiple infusions.
https://arizonaketamine.com/tinnitus-treatment-ketamine/
I don't know if there are any protocols or prerequisites before you're allowed to get the infusions, or do they accept you if you can pay? I'm getting to a point where I feel like I'd try anything.
Nice, I would imagine as long as you aren't on meds that are contraindicated with Ketamine, they would just let you walk in and give you some.
I hear you trying anything - I am at 4 months - my "good" days are when the tinnitus is just annoying, and my bad days are when it is utterly debilitating. I am also considering anything I can get my hands on that has some anecdotal efficacy.
Might give the clinic in Lower Manhattan and or Long Island a call next week and see what they have to say. I've also struggled with some severe anxiety earlier in the year, which did get much better, and depression that's been up and down all year long, so it might be a worthwhile shot.
I just hit eight months earlier this week. Seems like you and I share the definition of "good" days vs. bad/regular days.
Log in or register to get the full forum benefits!
Similar threads
