Turn That Frown Upside Down

Believe it or not, botulinum toxin might be a future psychiatric treatment.

Posted Dec 26, 2018

Good old botulism. An anaerobic bacteria, Clostridium botulinum, that lives all over but flourishes in low-oxygen environments (such as improperly canned foods) and produces seven different types of deadly nerve toxin,* most of which can kill you in microscopic amounts. After ingesting even a small bit, after 12 to 36 hours, fatigue, blurred vision, vertigo, and difficulty swallowing and speaking is followed by profound weakness that descends through the body until respiration is affected, which can be deadly. Treatment requires an early proper diagnosis and the administration of antitoxin along with respiratory care to protect the airway.

Botulinum toxin as a temporary (months-long) nerve paralysis agent has a lot of uses in medicine. From migraines to torticollis (a type of muscle spasm or tightening of the neck) to wrinkles, to too much sweating, careful administration of the deadly toxin can smooth the skin and ease spasm and pain. You may have a received a coupon for some BOTOX as a holiday gift this year. But can this toxin help any psychiatric diagnosis?

The facial feedback hypothesis, first put forth by Charles Darwin, reverses the common sense thinking about emotions and facial expressions. Clearly it’s true that happiness will make us smile while anger and sadness will make us frown or cry. The reverse, it seems, is also true (to a much lesser extent). Just the act of smiling can briefly brighten the mood, whereas grimacing or frowning can make you feel irritable, upset, or mad.

Flickr creative commons
Source: Flickr creative commons

Botulinum toxin administered to that little creasing frowny spot between the eyebrows and just above them (the glabellar region) prevents you from having a full-faced frown. In rats, botulinum toxin injected into the face causes increases in neurotransmitters associated with good feelings, like serotonin and norepinephrine. Back in 2012, Wollmer published a study giving the toxin or placebo (sterile saline) to 30 patients who were being treated for depression. After 6 weeks, those who received the toxin had a better response to treatment for depression than those who received placebo, and the effect wore off after 12 weeks (which is about how long a skin injection of botulinum toxin lasts). Later studies with more patients and a longer, crossover design achieved similar or even better results. Allergan, the maker of BOTOX, is going forward with more studies for depression.

Side effects can occur… some folks are allergic, and if it is administered incorrectly, the eyelids can droop for months and you can get double vision. If you somehow get a blood vessel with the needle, you can give yourself good old-fashioned botulism poisoning. However, with the small amounts used for cosmetic purposes and particularly in the front part of the forehead, it would take a very incompetent administration to cause systemic problems. The other drawbacks to these studies is that most people can tell if their forehead wrinkles have disappeared or not, so blinding in the placebo controlled studies usually fails. Also, the vast majority of the folks studied have been women, so it’s unclear if the treatment would work for men as well, and if part of the treatment isn’t the “facial feedback hypothesis” at all, but just that getting rid of wrinkles makes us feel better in general.** 

Despite the drawbacks, botulinum toxin has been studied in other psychiatric populations, showing the most promise in those with more profound agitation (historically a population that is a bit more difficult to treat). The idea is that chronic paralysis of the lower forehead can modestly attenuate negative emotions in general, not just in depression, but in other states as well.

At the moment, BOTOX is not FDA approved for the treatment of major depressive disorders or any other psychiatric disease. But the fact that chemically turning a frown upside down might well improve psychiatric symptoms… well, we can use all the help we can get. That coupon for a cosmetic treatment might well have a double benefit.

Flickr creative commons
Source: Flickr creative commons

*botulinum toxin works by inhibiting the release of acetylcholine at the presynaptic motor neurons in the neuromuscular junction for those of you facing biology tests or medical board exams

**as a clinician, I don’t always care why it works as long as it does.

Copyright Emily Deans MD