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How Botox Injections May Reduce Depression

Botox injections may improve clinical depression.

Key points

  • A new meta-analysis suggests that, compared to baseline and placebo groups, those who receive Botox injections show reduced depression symptoms.
  • Botox injections' affect on depression may involve facial feedback.
  • The results of studies on Botox and depression need to be interpreted cautiously.
Source: Engin_Akyurt/Pixabay

A recent study by Schulze et al., published in the March issue of Journal of Psychiatric Research, suggests that Botox injections improve depression. How? Perhaps due to the facial feedback effect or “emotional proprioception.”

What is Botox?

Botulinum toxin is a potent neurotoxin, meaning it damages or impairs the functioning of the nerves.

Produced by several bacteria (mainly Clostridium botulinum), botulinum toxin is responsible for a rare but sometimes deadly disease called botulism (e.g., foodborne botulism). Foodborne botulism, of course, is usually associated with improperly canned food.

The mechanisms of botulinum toxin’s actions are complex. Put simply, they involve preventing the release of the neurotransmitter acetylcholine at the neuromuscular junction, where muscle cells and motor neurons meet. The action of the toxin can have dangerous consequences, especially when it results in blocking the transmission of messages between nerves and important muscles, such as those that help us breathe.

But what if we injected a small amount of the toxin into the muscles responsible for, say, frown lines? Indeed, many people are aware of the uses of this toxin for cosmetic purposes (as OnabotulinumtoxinA injections, known as Botox), such as for relaxing and softening the muscles that cause facial wrinkles.

What some people may not know is that Botox injections are also used for the management of other conditions including hyperhidrosis (excessive sweating), migraine headaches, urinary incontinence, certain eye conditions (e.g., lazy eye, eye twitching, crossed eyes), as well as other types of excessive muscle contraction and stiffness (e.g., cervical dystonia, which is a painful type of neck spasm).

How does Botox influence mood and depressive symptoms?

A newer use of Botox injections has been in the treatment of depression. Yes, depression.

For instance, the results of a randomized, placebo-controlled trial, published in 2014, showed that Botox injections into facial muscles (the corrugator and procerus muscles) reduced depressive symptoms. The response rate (50% or greater reduction in Montgomery-Asberg Depression Rating Scale scores), measured six weeks after the injections, was 15% in the placebo injections group but 52% in the Botox injection group.

So, how might Botox injections reduce depression? One explanation, called the facial feedback hypothesis, involves how changes in facial expressions affect the brain.

For example, when we frown, we are more likely to evaluate unpleasant stimuli (e.g., a picture of a couple arguing) more negatively than usual. Indeed, contracting facial muscles (e.g., muscles used for the emotional expression of rage or pain) can affect the autonomic nervous system activity, resulting in changes in sweating, blood pressure, heart rate, etc. Botox injections might interfere with these effects. How? By signaling to trigeminal nerve endings in the face—nerves potentially involved in sensing muscle tension and pain—“a relief of physical stress, resulting in decreased emotional stress.” In short, Botox injections break up the feedback loop from certain facial muscles—muscles communicating to the brain that one is feeling angry, sad, miserable, etc.

Note that other mechanisms for the positive effects of Botox on depression have also been suggested. These consist, among others, of the effects of Botox on the central nervous system via various direct and indirect pathways, more positive self-awareness (greater self-confidence and satisfaction due to improved appearance), and altered social interactions (e.g., those appearing more relaxed and happy being more approachable).

Meta-analysis: Botox injections for the treatment of depression

The investigation by Schulze and colleagues is a review and meta-analysis of randomized clinical trials of botulinum toxin injected into the glabella—the glabellar region is a part of the forehead between the eyebrows—for management of depression.

Of 801 records identified, five met the criteria. Sample sizes ranged from 28 to 132, with most of the participants being women. The primary outcomes were the 17-item version of the Hamilton Depression Rating Scale (HAM-D17), the Montgomery-Asberg Depression Rating Scale (MADRS), the 21-item version of the Hamilton Depression Rating Scale (HAM-D21), and the Beck Depression Inventory (BDI).

The results of three comparisons showed Botox is an effective treatment for depression:

  • The difference between placebo and Botox post-treatment: Botox group showed reduced depression (d = 0.63; 95% CI (0.27; 0.98)).
  • How symptoms of depression changed over time in the Botox treatment (baseline vs. six weeks later): Participants who received Botox injections experienced reduced depression (d = 1.47; 95% CI (1.27; 1.67)).
  • Combined analysis of the interaction between group (placebo vs. Botox) and time (baseline vs. six weeks later): Greater improvement in depression in the Botox group (d = 0.98; 95% CI (0.47; 1.49)).
Source: RobinHiggins/Pixabay


In conclusion, a meta-analysis of five randomized clinical trials found that individuals who received Botox injections showed reduced depressive symptoms. The only major side effects were short-term headaches.

The effect sizes obtained in this research agree with those of a 2019 meta-analysis, although they are smaller. Nevertheless, these effect sizes are still larger than the effects of antidepressant medications.

Does this mean Botox is a miracle drug for depression? Not quite. The above results need to be interpreted cautiously.

Given the visible effects of Botox on facial muscles, it is difficult to conduct true double-blind studies on the potential benefits of Botox injections for the treatment of depression. (See my explanation of single-blind and double-blind studies here.) In addition, participants may generally show a greater response to the use of injections as opposed to the oral route of administration (e.g., antidepressant pills). Thus, additional research is needed before Botox injections for depression could be recommended to the public.

If future research confirms that Botox is safe and effective for the treatment of depression, then it is conceivable some patients would not only want to try but even come to prefer Botox over other treatments for depression. After all, receiving Botox injections every few months means easier treatment adherence, fewer side effects (compared to some antidepressants), and even lower costs (compared to certain intensive psychotherapy interventions).