Editorials

The changed image of botulinum toxin

Its unlicensed use is increasing dramatically, ahead of robust evidence

Over the past decade botulinum toxin has had a makeover. Earlier it was known as one of the most potent biological neurotoxinsin botulism it blocks the release of acetylcholine at the neuromuscular junction and can cause fatal muscular paralysis. Today botulinum toxin is widely known as a pharmaceutical agent with multiple uses and has been propelled into the public eye after it was widely reported in the lay press as an antiwrinkle drug for facial cosmetic enhancement. This has established its new image as a glamour drug. Botulinum toxin is reported to be useful in more than 50 conditions, with indications spanning many specialties.¹ But the toxin is licensed for only a few specific conditions, based on clear scientific evidence of its efficacy and safety. Some "off licence" indications are substantiated by some evidence, but its efficacy in several other conditions is based on anecdote and observations made in small numbers of patients.

Botulinum toxin is licensed in the United Kingdom for blepharospasm and hemifacial spasms, cervical dystonia, spasticity, and axillary hyperhidrosis, and evidence of its efficacy in these conditions is notable. Trials for cervical dystonia done in 1988-95 show that it works in 80% of patients; the effect appears in 5-7 days and lasts for 10-12 weeks. In these studies the incidence of side effects such as dysphagia due to weakness of the pharyngeal muscles varied between 9% and 90%, and for excessive neck muscle weakness between 3% and 31%.² This wide variation in side effects is due to the wide variation in the dose of the toxin used and stresses the need for using appropriate dosing. Fortunately systemic side effects are rare.³

A recent large multicentre randomised controlled trial of botulinum toxin for glabellar lines showed a significant reduction in the lines compared with placebo.⁴ In the United States the toxin has been licensed this year for hyperfunctional facial lines or wrinkles. An increasing amount of published data shows that botulinum toxin may be useful in several conditions for which it does not yet have a licence. These include palmar hyperhidrosis,⁵ focal limb dystonia,⁶ sialorrhoea,⁷ and anal fissures.⁸ As some of these conditions are rare studies have been done on small numbers of patients, and the evidence so far is not robust.

So far the use of botulinum toxin has been based on its effects on the blockade of the neuromuscular and neurosecretory junction. Recent reports implying its usefulness in myofascial pain and migraine speculate that benefit may be the result of an effect of the toxin on the sensory system. ^{9 10} Clearly, more trials comparing the efficacy of botulinum toxin with established treatments for these painful conditions are needed. Robust evidence for the action of botulinum toxin on sensory neurones is lacking. Animal experiments have shown that botulinum toxin affects the transmission of afferent nerves,¹¹ and a conjugated form of the toxin has been shown to play a part in inhibiting the release of neurotransmitters from dorsal root ganglia in rats.¹²

The revenue for the global sales of Botox has increased from $25m (£16m; 25m) in 1993 to $310m in 2001 and is estimated to be $430m in 2002 (personal communication, Allergan Pharmaceuticals, 2002). The biggest area of growth has probably been in dermatologythe use of the toxin for facial lines has increased by 1500% in the United States over the past four years (B Sommer. Basic and therapeutic aspects of botulinum and tetanus toxins. Presentation at an international conference in Hanover, Germany, 8-11 June 2002). Popular magazines and newspapers regularly report its use by celebrities from the film, television, and music industries. Given such hype it is unsurprising that a recent study found that 23% of patients seeking treatment with botulinum toxin at a dermatology clinic had body dysmorphic disorder, and psychotherapy was considered the more appropriate treatment for them.¹³ In this atmosphere of "Botox parties" (where champagne sipping socialites are injected with botulinum toxin), it is easy to forget that botulinum toxin is a potent neurotoxin and that its very long term effects are still unknown.

V Peter Misra, consultant clinical neurophysiologist. 

National Hospital for Neurology and Neurosurgery, London WC1N 3BG (peter.misra{at}uclh.org)

Footnotes

Competing interests: VPM has attended scientific meetings paid for by Allergan, Ipsen, and Elan Pharmaceuticals and conducted educational programmes paid for by Allergan. All these companies manufacture botulinum toxin. His research registrars have also been paid by the above companies for attending meetings and to conduct research.