Visual Snow, Visual Blur, Visual Weird

Last week’s post on Antidepressants and Retinal Detachment has generated a lot of very interesting comments.  There will be another post on vision issues after this one – probably called Vision Weird.

Serotonin reuptake inhibiting antidepressants can cause a range of problems on starting that continue or sometimes only appear on stopping. These include visual, sexual, balance, and other protracted withdrawal problems – see Visual Snow Epidemic, Balancing Bodies and Selves and very many posts on PSSD.

Reports of treatment related visual problems to RxISK have enabled us to link SSRIs to visual problems with one article already published, another submitted to a journal and one more being written.

The headline problem is called Visual Snow or Visual Snow Syndrome (VSS) but we have as large a number of reports from people reporting Visual Blurring and other problems without using the word Snow. We also have Snow and Blur reports on drugs like mirtazapine that are not SSRIs.

There are other things SSRIs do to Vision, at the moment best termed Visual Weird because no-one has much idea what is going on.  There will be a follow up post on Visual Weird next week.  Everything in these vision posts is completely pertinent to Sexual function also so folk with PSSD or PGAD might find this worth thinking about.

Lithium and Vision

Among other actions, SSRIs act on p63 regulatory proteins, which stimulate stem cell production and activity. Based on University of Milan research, SSRIs appear to turn these proteins off and linked to that possibly inhibit stem cell production. This action may be linked to the capacity of SSRIs, and thalidomide which also acts on p63 proteins, to cause birth defects.

Lithium may act in the opposite way on p63 proteins enhancing stem cell activity. This is consistent with one of its well-known effects – it increases white blood cell counts. It is routinely given to cancer chemotherapy patients to counteract the white cell lowering effect of these drugs.

Recent work in the Department of Ophthalmology in Oslo suggests lithium’s action to stimulate ‘stemness’ may also benefit corneal transplants.  See Oslo Abstract. We have emailed several of these authors, explaining we hope lithium might help people with SSRI triggered visual problems, but if they know of any reason it should not be tried, could they let us know.

We have had no responses.  The emails may have not gotten through. Or, ophthalmologists, like specialists in general, may be reluctant to comment on the effects of drugs (SSRIs) they know nothing about.  If any readers can find someone in the Oslo or any other group working in this area, or if you know an ophthalmologist, who might respond let us know.

There are other problems that lithium may be able to help with. There are reports from people with sexual problems that low dose lithium has been of help to them but more in terms of improving emotional connection than with their sexual problems.

While this email is about visual problems, if any reader tries lithium and notes anything else that seems to happen for good or bad – please let us know.

If lithium helps with visual problems, it is likely to do so in the 50 to 100 mg range.  The usual clinical dose treating bipolar disorder is 800-1200 mg. Doses from 800 mg up risk toxicity and people are advised to have 3 monthly blood tests to check their blood levels are not too high – see below. This should not apply at the 50-100 mg range.

Lithium in History

Lithium was used in the 50 mg dose range as a health-water for a century from roughly 1850 to 1950.  It even found its way into 7-UP.  See note below.

Efforts in the US to use lithium as a replacement for salt in diet led to people over-using it on food and in 1947 it was banned for this purpose.

It re-appeared in 1954 when Mogens Schou in Denmark established its benefits for manic-depressive illness.  See Mania – a history of manic-depressive illness and its treatment from Greek times to the current day.

Lithium and its side effects, as used clinically, feature in Psychiatric Drugs Explained. It has serious problems in high doses but despite this, many doctors prefer it for bipolar disorder to anticonvulsants also marketed for this purpose – partly because the information we have about lithium is more honest and reliable.  See Lithium and Mood-Stabilizers.

Lithium has 3 clinical forms – lithium citrate, lithium carbonate and lithium orotate.  People trying lithium for PSSD and reporting on Reddit prefer lithium carbonate to lithium orotate.  Mogens Schou preferred lithium citrate to lithium carbonate.

Lithium and Vision

When ophthalmologists look into the eyes of people with SSRI triggered problems, who complain about a lot of floaters, speckled or blurred vision or other problems, they can usually see nothing – whereas they can see the normal floaters we all get and complain about.  As a result they think people with SSRI linked visual problems have a ‘mental’ or ‘brain’ problem and not an eye problem. The word functional neurological disorder (FND) is commonly used. It’s the modern term for hysteria.

Prescription medicine induced problems, like Visual Snow or Blur, are not mental and likely not brain-based either. This leaves the cornea and retina as possible sites of key changes.  The cornea, it turns out, has one of the densest nerve supplies in the body but amazingly we can see through it without these nerves disturbing our vision. We are researching corneal nerves in people with sexual problems and peripheral neuropathy after SSRIs but at present nothing on people with Visual problems.  See Window to the Body.

Getting research set-up and done takes years. Initially no-one knows what to look for. Once we have hints what to look for it, getting the work done can take ages.

Someone with Visual Snow or related problems, who is taking no other meds, and who finds a difference taking low dose lithium can do an end-run around this. If there is a benefit (or no benefit) with no other way to explain it – this could dramatically advance our efforts to understand SSRI linked visual problems.

Lithium Dose

Lithium preparations vary from country to country so you may find 150 and 300 mg pills or 200 and 400 mg along with higher doses. We suggest no more than 100 mg.  Depending on the way the pill is made, the availability of a pill-chopper or ability to dissolve it, may allow you make up a 50 mg dose in powder or liquid form.

A compounding pharmacist may be able to help you and advise further.

Like coffee, lithium in any dose is a diuretic – it might make you more likely to pass water – and so it is better taken in the morning.

Given we are aiming at tickling stem cells into an activity that might correct subtle abnormalities, through some corneal cell regrowth or repair of damage, it may need several months at this low dose before anything useful becomes apparent.

If in the ,process of trying lithium in doses as low as this, anything gets worse, you should stop immediately.

There are a number of ways readers might be able to help.  The post in a week’s time on Visual Weird may help with some ideas about things that might be noticeable.

We need a few people with clear visual effects they link to their SSRI use, ideally who are on no other medicines for any other reason, and who have no other conditions, to persuade their doctor to prescribe them the lowest possible dose of lithium.

You are welcome to and ideally should show this post to your doctor and pharmacist.

If you know of any friends or relatives on regular lithium in the usual clinical dose – 800 mg – ask about any visual effects they notice.  Many people on lithium will be on lots of other meds – we ideally need people who are not on antidepressants or have not been on them for months to let us know if there are any grounds to think lithium has caused or helped any visual problems.

If lithium has any effects these are best filed on a RxISK Report or emailed to me at david.healy@RxISK.org.  I am also happy to try to answer any questions.

If you have links to a forum set up by folk with VS or any visual problems, it would help if you can draw this post to the attention of folk in the forum.

Lithium in 7-UP

What was the lithium concentration in 1940’s 7-Up? 

Question

I just came across this article in the New York Times, where lithium (or more correctly, lithium salts), a known anti-depressant had been added to beverages in the 1940’s. They also mention that a study found negative correlation between the suicide rate of a county and the amount of lithium in its tap water, despite the fact that the concentration is relatively low (0.170 mgL−1<0.170 mgL), especially compared to the doses administered in therapy.

I was wondering what the lithium content in those beverages was but couldn’t find anything?

The article mentions that you can still buy lithia water (0.50 mgL−10.50 mgL), but I’m more interested in the 1940’s 7-Up mentioned, as those probably had different food standards at the time they were made.

Answer

Given that the formula was a trade secret and lithium was removed from the product ~70 years ago, the likelihood of this question being answered by providing a detailed formula seems remote. Note in addition that the formula might have evolved to reduce cost or improve market reception. You might therefore want to settle for an estimate of the upper limit on the lithium citrate concentration, which is relatively easy to provide.

A basic estimate can be made based on (1) the historical limits of sodium concentration in sodas; (2) the current composition of 7-up; and (3) the relative saltiness (taste) of lithium citrate versus sodium.

First one can attempt to determine what range of sodium concentration makes for a flavorful soda. Here is a quote:

The amount of sodium in soda varies depending on the type. A well-known brand of cola has 46 milligrams of sodium in a 12-ounce can. The same sized can of root beer has 71 milligrams; a can of lemon-lime soda has 64 milligrams; a 12-ounce can of all-natural soda contains 36 milligrams. These are just examples, and the amounts in particular brands of soda may differ. It’s best to check the label of your favorite soda to make sure.

This leads to a range of ~150-200 mg/L sodium concentration.

Next, consider the current formula for 7-up (in the USA) in 12 fl oz (355 mL): 40-50 mg sodium, 60 mg potassium.  This means 110-140 mg/L sodium and ~170 mg/L potassium.

Finally, consider the saltiness of lithium citrate versus sodium. Lithium citrate was the salt form of lithium in the 7-up recipe according to a number of sources including the Wikipedia:

The soft drink 7Up was originally named “Bib-Label Lithiated Lemon-Lime Soda” when it was formulated in 1929 because it contained lithium citrate. The beverage was a patent medicine marketed as a cure for hangover. Lithium citrate was removed from 7Up in 1948.[Ref 4] and this one (which cites Ref 1):

As to why “7Up,” C.L. Grigg never explained how he came up with the cryptic name. Several theories exist about its origin: “7Up was the product of seven ingredients. (Which, in a way, was at least true with regard to the classes of ingredients in that original formulation: sugar, carbonated water, essences of lemon and lime oils, citric acid, sodium citrate, and lithium citrate.)”

Lithium and potassium are among few cations with a salty flavor similar to that of sodium, albeit weaker. Citrate reduces the saltiness further. According to Ref 2, the saltiness of lithium and potassium can be estimated to be ~0.4 and 0.6 that of sodium, repectively, while Ref 3 explains that citrate has an inhibitory effect.

Consider now the potassium concentration (~170 mg/L) in the current formula of 7-up. Potassium is added as the citrate salt, and could be replaced with the lithium salt with little change in taste perception, according to what is reported on the relative saltiness of the cations and citrate salts. This suggests that if the taste of the beverage has remained reasonably constant since inception, it is not unreasonable to estimate an upper bound of ~200 mg/L in the concentration of lithium citrate (replacing the potassium salt) in the original recipe.

Note this is based entirely on the taste perception and not on any medical implications of consuming lithium at such concentrations. Lithia water (a brand of spring water sold in the USA) contains only ~0.5 mg/L of lithium. For reference, an online medical advice site suggests that a dose for treatment of depression is ~60 mg of lithium daily. So a dose of ~60 mg lithium citrate per serving certainly seems high relative to lithium-rich spring water but is just about a typical clinical dose.

References

1. Rodengen, Jeffrey. The Legend of Dr. Pepper/7Up. Fort Lauderdale: Write Stuff Syndicate, 1995. ISBN 0-945903-49-9.
2. McLaughlin, S., Margolskee, R.F.. The Sense of Taste. American Scientist, 82, 538-545 (1994).
3. M.D. Man. Technological functions of salt in food products. in Reducing Salt in Foods, Woodhead Publishing, 2007. ISBN 978-1-84569-018-2.
4. Gielen, Marcel; Edward R. T. Tiekink (2005). Metallotherapeutic drugs and metal-based diagnostic agents: The use of metals in medicine. John Wiley and Sons. p. 3. ISBN 0-470-86403-6.

To be continued with Vision Weird, Vision Blurred and Visual Snow