A recent Mad in America Webinar on Antidepressant Dysregulation Syndromes introduced the idea that tapering might not be the only way to solve some of the problems SSRI antidepressants can cause. Tapering supporters give the impression tapering is the only legitimate way to go, leaving little or no room for the possibility that antidotes might help.
Quite aside from tapering supporters, others are cautious about looking for a quick fix to a problem that an SSRI quick fix has caused.
And I get nervous when people start drawing boxes about what SSRIs have caused at various receptors. These boxologists then claim to have worked out logically something that is almost certain to help. It rarely does and boxology of this sort has led to the deaths of people with PSSD.
The antidotes outlined below are not based on biobabble or boxology. They arise from the experience of people given a medicine for other reasons who then noticed there was an unexpected benefit happening in real life as opposed to an on-paper solution.
Acetazolamide
Psychiatric Drugs Explained has listed Acetazolamide since its first publication in 1993. Acetazolamide is what you might call an atypical anticonvulsant. Most anticonvulsants inhibit sodium currents or act on the GABA system, some do both. Acetazolamide does neither.
It is a Carbonic Anhydrase Inhibitor. Two other anticonvulsants share a carbonic anhydrase inhibiting action with it – Topiramate and Zonisamide.
While listing it in PDE, I had never seen Acetazolamide used. There was mention that people took it to prevent altitude sickness. This very recently led to my finding that there is evidence SSRIs can make altitude sickness worse, or at altitude they seem to stop working well.
This fits with another well known use for Acetazolamide. It is a treatment for acute glaucoma – the kind that SSRIs can cause. SSRIs it seems can increase the pressure in an eyeball, which is what glaucoma means. They do this by increasing fluid production in the eye. Glaucoma can cause blindness so it is something of an ocular emergency.
Increased fluid production is not in itself an emergency. The most common cause of glaucoma is a blockage to the drainage system of the eye and this can lead to an acute emergency. The SSRI problem is more insidious. Raised pressure over time can affect vision, cause blurred vision and perhaps lead to retinal tears without causing an acute crisis.
SSRIs and many antipsychotics are carbonic anhydrase activators. Activating Carbonic Anhydrase can lead to a build up of fluid in confined spaces – like eyeballs . A build up of fluid in the cerebrospinal canal is linked to what is called Benign Intracranial Hypertension. BIH is not always completely benign.
SSRI-triggered fluid build up is not like the fluid build up in Heart Failure or Edema, where diuretics like Furosemide can help tremendously. Furosemide is not a treatment for the local fluid build up that happens in eyes and that Acetazolamide can treat. Acetazolamide meanwhile has weak general diuretic properties and is not used to treat Heart Failure the way Furosemide is.
RxISK’s interest in Acetazolamide as an antidote stems from two reporters telling us that it had improved their SSRI induced visual problems and reporting that it seemed helpful for what is called Visual Vertigo and Vestibular Migraine
Acetazolamide and Akathisia
RxISK’s interest in Acetazolamide is two-fold. The fact that it appears for some people to offer some benefits in a number of SSRI triggered problems, and as medicines go it is generally viewed as having a benign side effect profile, is one interest.
An additional interest stems from the fact Acetazolamide seems to help some conditions that seem linked to akathisia. Raised eyeball pressure gives rise to an uncomfortable gritty feeling, which could be viewed as an eyeball akathisia.
Another akathisia like state is Pre-Menstrual Tension, which is linked to fluid retention. SSRI companies have tried to convert this into a new illness Pre-Menstrual Dysphoric Disorder – PMDD – and claim their drugs can treat this nightmarish condition. The emotional muting that SSRIs cause can be of some help but as regards the irritability, or akathisic element of this condition, which is traditionally linked to aggression, the clinical trial data suggest SSRIs significantly increase aggressive episodes.
In contrast, Acetazolamide appears a good treatment for PMDD, especially in women who do not show a good response to SSRIs.
Finally, there is also a possible benefit for Acetazolamide in Persistent Genital Arousal Disorder (PGAD). This is essentially a state of genital akathisia, leading to repeated distressing and unwanted orgasms. SSRI withdrawal, especially during the peri-menopausal period, is its most common trigger.
The distress PGAD causes leads women to contemplate clitoridectomies and other drastic procedures to alleviate the problem, which perhaps gives some indication as to the severity of the condition and why it seems reasonable to view it as an akathisia related state. Akathisia is such an uncomfortable state that it is the leading cause of death by suicide and a common trigger to homicides and aggression.
Recently a woman with confirmed PGAD has reported significant benefit from Mounjaro – tirzepatide – Eli Lilly’s version of Ozempic/Wegovy. Mounjaro injections last several weeks and while they last she is symptom free but as the injection wears off the symptoms return.
A fascinating feature to this is that Mounjaro – Tirzepatide – and Ozempic – Semaglutide – are Carbonic Anhydrase Inhibitors like Acetazolamide.
Can anyone on Mounjaro/Zepbound or Ozempic/Wegovy who has PGAD get in touch and let us know more.
Can anyone who has been put on any of these drugs who has had akathisia also get in touch and let us know – did these drugs make any difference to your akathisia?
Another fascinating aspect to all this is that the original drug that caused and brought akathisia to everyone’s attention as the akathisia was so intense it led to suicides, was a drug working on the serotonin system called reserpine which was derived from the roots of this Rauwolfia Serpentina plant.
Reserpine is a carbonic anhydrase activator and it blocks the anticonvulsant action of Acetazolamide.
Alcohol is a carbonic anhydrase inhibitor and in the form of red wine appears to relieve akathisia
Rather than use alcohol in their clinical trials to mask the akathisia caused by SSRIs, companies have used Benzodiazepines. Benzodiazepines are carbonic anhydrase inhibitors.
RxISK has run many posts on Akathisia – trying to bring it to the attention of the wider world. Here are some of them.
- Akathisia Challenge
- Akathisia Anthem
- Akathisia Depression and Suicide
- 500 Drugs that Cause Akathisia
We have liaised closely with groups like The Medication Induced Suicide Prevention and Education Foundation in Memory of Stuart Dolin – MISSD – set up by Wendy Dolin and run by an impressive group of people whose lives have all been touched by the catastrophes akathisia can visit on families.
At the risk of sounding like I’m indulging in the Boxology and Biobabble I condemned above, it does look like there might be a chink of light here to establish what underpins akathisia. It was described first 70 years ago and we are no nearer working out what happens in us when we get akathisic. Perhaps because everyone is looking in the brain and this is the wrong place. See Madness, Normality and Dysregulation.
When Bruce Springsteen called it ‘an endless, irritating angst embedded in his bones’ he may have been more accurate than he thought. There is a thin skin that covers bones – the periosteum – and fluid collecting in the confined space underneath this, somewhere where it should not be, may be exactly the kind of thing that gives rise to akathisia.
Finding out what is going on might enable us to ease if not cure the problem for those affected. Of course it might also make it possible for Lilly and other companies to run trials on their drugs and hide the problem even more effectively than they have done in the past. .
Lithium Gluconate
Several weeks ago RxISK wrote to large number of people, who have reported visual problems, including visual snow and a range of other problems suggesting that Lithium in a very low dose might be a helpful treatment for SSRI linked visual problems – See Visual Snow, Visual Blur and Visual Weird.
We did so on the basis of research brought to our attention that Lithium might have effects to stimulate the production of new cells linked to the cornea of the eye which might conceivably repair some SSRI induced corneal and perhaps other eye damage.
Reports from Norway suggested that Lithium can stimulate stem cells into activity. This is consistent with Lithium’s ability to increase white cell counts – something it is often prescribed for in people being treated for cancer where their chemotherapy risks wiping out their white cells.
But another action of Lithium has now come into the frame. It has long been known to be a diuretic and is usually given in the morning for this reason. Lithium can also treat glaucoma but while it reduces fluid pressure in the eye at present the researchers are not talking about carbonic anhydrase.
When we put the idea of using lithium to RxISK reporters several asked what dose and others asked would lithium orotate, which is available over the counter work?
At Mad in America’s Antidepressant Dysregulations Webinar, C – an attendee, said that Lithium Gluconate had stopped her akathisia stone dead. She had benzodiazepine withdrawal linked akathisia and had discovered Lithium Gluconate from French articles on its use for benzodiazepine withdrawal – See Stopping Benzodiazepines. She tried it and it worked.
There is in fact a French industry of giving Lithium Gluconate or Lithium Oligosol for irritability. This comes very close to the original use of Lithium in spa waters in the nineteenth century aimed at promoting a sense of wellbeing. The original 7 UP was a carbonated lithium water. The dose of these compounds is of the order of 10 mg per day – very very very low compared to the doses used in mental health for bipolar disorder, which range up to 1000 mg per day or more.
SSRIs and Brain Damage
The focus of the Dysregulation Webinar was on the difficulties people can have getting off SSRIs. One of the questions asked was whether these difficulties point to a withdrawal syndrome or brain damage? I was leaning toward saying that even with grim conditions like PSSD, which can look like damage, there are recoveries and windows of recovery.
Another of our RxISK reporters got in touch to say we had badly downplayed the damage these drugs can do. He had a diagnosed encephalopathy with Brain Scans and EEGs to show the damage.
We have a post about this – Could your Stimulant or Antidepressant cause Dementia? Which said they could.
Among the earliest problems noted with SSRIs was that they could cause low sodium. Most cases were mildly low but even so these could lead to confusion. Some were extremely low and this risked cardiac arrest and other problems.
A story emerged that attempting to correct these very low sodium levels too quickly could lead to Osmotic Demyelination. The low sodium led to increased fluid in cells and replacing sodium dragged fluid out of cells. This made sense but in fact is wrong. We do not know what causes osmotic demyelination.
The Demyelination affects the midbrain mostly – the area around the Pons – but it can happen elsewhere and gives rise to what are called white-matter intensities. The white area in the middle of the brain just above the dark area shows what can happen. The link to the Pons area has led to this condition also being called Central Pontine Myelinolysis.
This is unquestionably damage and badly affects and can kill some people. The original story was that it only happened to older people – which perhaps reduced the importance of the problem. But some years ago a mother of a relatively young girl was in touch describing how it had killed her daughter. We hoped she would write up the story but she never did. There have been other cases involving young women that have come our way since and they are heart breaking.
While restoring sodium too quickly with all the changes in fluid balance that go with that is not the cause of the damage, Osmotic Demyelination brings home the story that these drugs act on the water in us and the salts like sodium that are in our bodily fluids.
For the researchers among our readers and contributors, on whom we depend for everything that RxISK finds out, between the Acetazolamide issues above and the Osmotic Demyelination below, this post contains a lot of detail, all of which deserves further chasing.
There are for instance 10 different isoforms of carbonic anhydrase – and likely only some of these are important for people on SSRIs or antipsychotics – which ones? It feels like there is a door slightly ajar here that with a good push might open onto a room with some interesting secrets.
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