Botulinum toxin for wrinkles: effects and side effects

How does it smooth wrinkles?

Wrinkles form through a combination of thinning of the dermis and repeated contraction of the facial muscles beneath it ^[1]. Botulinum toxin is a neurotoxin that blocks the release of acetylcholine where nerves meet muscles, and when a small amount is injected into a specific overactive muscle, that muscle relaxes locally and the skin above it smooths out ^[1].

It is often called by the name of a particular brand, but the correct name is botulinum toxin. Several products are on the market, and the Cochrane review stated that pooled analysis was difficult because the studies differed in the type of product, dose, number of treatments, and area treated ^[2].

Which wrinkles is it used for?

At the time of a 2014 review, the areas approved by the US Food and Drug Administration (FDA) for cosmetic use were the frown lines between the brows and crow's feet, and it was also commonly used for horizontal forehead lines ^[1]. The review stated that the effect is more pronounced for dynamic wrinkles, which appear when the muscles move, than for static wrinkles, which are visible even at rest ^[1].

A 2023 narrative review named dynamic wrinkles between the brows, on the forehead, around the eyes, on the bridge of the nose, and around the mouth as indications, and summarized injection sites and techniques separately for Asian and white patients ^[4]. This means that the injection plan may differ depending on ethnicity and facial structure. The microdroplet method, in which very small droplets are injected into shallow layers of the skin, is also used to treat fine lines without a frozen expression, but because it is a relatively new method, knowledge about dilution, dose, and depth is still limited ^[6].

Evidence on effectiveness

A 2021 Cochrane systematic review analyzed 65 randomized controlled trials with 14,919 participants ^[2]. Most participants were women aged 18 to 65, studies treating the area between the brows were the most common at 43, and 36 studies compared botulinum toxin with a placebo ^[2].

The review concluded that botulinum toxin reduced wrinkles within 4 weeks of treatment but is likely to increase the risk of drooping eyelids ^[2]. The certainty of the evidence on effectiveness ranged from high to low, and the certainty of the evidence on side effects ranged from very low to moderate ^[2]. It should also be kept in mind that not a single study was rated as having a low risk of bias in every domain ^[2].

When does the effect appear, and how long does it last?

A 2014 review explained that it takes about 2 weeks for the effect to develop fully and that it lasts 3 to 4 months ^[1]. On the other hand, the Cochrane review pointed out that evidence is lacking on how long the effect lasts, the effect of repeated treatments, and the frequency of major side effects ^[2]. How long it lasts can vary depending on muscle strength, the injection site, and your individual response.

Side effects and complications

Mild bruising can occur, and temporary drooping of the eyelid or brow is described as rare and dependent on the practitioner's technique ^[1]. The major side effect reported in the Cochrane review was mainly drooping eyelids, and the review noted that risks of misaligned eyes (strabismus) and abnormal sensation in the eyelids are also known ^[2].

A 2022 review of upper face treatment named drooping of the eyelids or brows, asymmetry of the brows, double vision, inability to close the eyes completely, the lower eyelid turning outward, and more noticeable under-eye bags as the main complications ^[3]. It stated that avoiding these requires knowledge of the anatomy and an individualized plan tailored to the patterns of the muscles of the forehead, between the brows, and around the eyes, and that staying within safe zones can greatly reduce the likelihood of complications ^[3].

What to check before injection

It is not injected in people who are prone to keloid scars, people with neuromuscular diseases such as myasthenia gravis, people who are allergic to ingredients of the product, or people with body dysmorphic disorder ^[1]. Men are described as needing different injection techniques because they tend to have larger skulls, more muscle mass, and deeper wrinkles ^[5]. Because the effect and how long it lasts vary from person to person, it is a good idea to make a plan through an examination.

• Any history of neuromuscular disease, allergies, or keloids
• Whether the wrinkles to be treated are dynamic or static
• When you last had treatment and how you responded
• What will be done if side effects such as drooping eyelids occur