The Neuroshrink

By Soman via Wikimedia

It sounds like the setup for an off-color joke, but it’s true: Viagra and the other phosphodiesterase inhibitors (definitely Cialis, and probably Levitra too) can trigger an episode of transient global amnesia (TGA), one of the more mysterious and freaky cognitive syndromes one can encounter. TGA isn’t like amnesia in the soap operas, where people awake after a coma or head injury and can’t remember their name or recognize their family. TGA is a brief episode of primarily anterograde amnesia, which is the inability to form new memories. The soap opera amnesia is retrograde amnesia, where past events are not recalled but the character can learn (or relearn) and rebuild an identity. Transient global amnesia can also involve retrograde amnesia but past events prior to the onset of amnesia are generally recalled without much difficulty. TGA resolves on its own, typically over the course of a few hours to a day, and usually doesn’t recur.

One of the most interesting things about TGA is that, although it has been well-described for decades, there is no real agreement about how it happens. There are well-described triggers: vigorous exercise, exposure to cold, strong emotional experiences, and sexual intercourse. There have been several reports of TGA after use of medication prescribed for erectile dysfunction (Viagra, etc.) but since there was also sex involved, the medication itself wasn’t considered a trigger. There have now been, however, two cases published where someone had TGA after taking an ED medication and NOT having sex.

Generally, theories about TGA fall into two categories: seizure and vascular events. Given the nature of the known triggers, and the known vasodilatory effects of ED medications, these reports would seem to favor a vascular explanation. We do know that Viagra and its kin have vascular effects that encourage erections (after all, that’s the point) but they often cause headache as well, implying that they are also vasoactive in the head.

Bob Dole, Viagra pitchman

TGA is a fascinating syndrome to observe and diagnose. Sufferers typically are somewhat anxious and aware that they are experiencing something unusual. Characteristically they will ask the same questions repeatedly: usually asking why they are in the hospital, how they got there, or what they did that day. They rarely become agitated, which is somewhat surprising until you realize that to become agitated one must hold onto the idea that something is wrong or upsetting. Patients with TGA are easily reassured, for a few seconds or minutes at a time. Gradually, they can hold information for longer and longer periods until their memory is essentially restored. They do not regain memory for events that happened during the episode. It is most likely that whatever vascular changes lead to TGA involve the hippocampus, both because this is where short-term memories are encoded and also because there is some MRI evidence that some TGA patients have slight tissue loss in one or both hippocampi. The best thing about TGA, compared to most things a neurologist or psychiatrist will see in the Emergency Department, is that the prognosis is excellent. Most patients are entirely  back to themselves within a day, and most will not have a repeat episode. In the past it was believed that the recovery was uniformly complete, but some studies that follow TGA patients indicate some residual but subtle cognitive impairments. TGA is fairly rare: Dr. Wikipedia gives the annual incidence in the USA as about 3 per 100,000, but that increases to 23 per 100,000 among those over 50.

You might think that this is a major side effect that would discourage use of these medications, but I have a feeling that if men can ignore concerns about vision loss, cardiac events, and prolonged painful erections, then worries about transient global amnesia won’t begin to make a dent in their blockbuster sales.