Jackson JL et al. – Botulinum toxin A compared with placebo was associated with a small to modest benefit for chronic daily headaches and chronic migraines but was not associated with fewer episodic migraine or chronic tension–type headaches per month.

• A search of MEDLINE, EMBASE, bibliographies of published systematic reviews, and the Cochrane trial registries between 1966 and March 15, 2012.
• Inclusion and exclusion criteria of each study were reviewed.
• Headaches were categorized as episodic (<15 headaches per month) or chronic (≥15 headaches per month) migraine and episodic or chronic daily or tension headaches.
• Randomized controlled trials comparing botulinum toxin A with placebo or other interventions for headaches among adults.
• Data were ed and quality assessed independently by 2 reviewers.
• Outcomes were pooled using a random–effects model.

• Pooled analyses suggested that botulinum toxin A was associated with fewer headaches per month among patients with chronic daily headaches (1115 patients, –2.06 headaches per month; 95% CI, –3.56 to –0.56; 3 studies) and among patients with chronic migraine headaches (n = 1508, –2.30 headaches per month; 95% CI, –3.66 to –0.94; 5 studies).
• There was no significant association between use of botulinum toxin A and reduction in the number of episodic migraine (n = 1838, 0.05 headaches per month; 95% CI, –0.26 to 0.36; 9 studies) or chronic tension–type headaches (n = 675, –1.43 headaches per month; 95% CI, –3.13 to 0.27; 7 studies).
• In single trials, botulinum toxin A was not associated with fewer migraine headaches per month vs valproate (standardized mean difference [SMD], –0.20; 95% CI, –0.91 to 0.31), topiramate (SMD, 0.20; 95% CI, –0.36 to 0.76), or amitriptyline (SMD, 0.29; 95% CI, –0.17 to 0.76).
• Botulinum toxin A was associated with fewer chronic tension–type headaches per month vs methylprednisolone injections (SMD, –2.5; 95% CI, –3.5 to –1.5).
• Compared with placebo, botulinum toxin A was associated with a greater frequency of blepharoptosis, skin tightness, paresthesias, neck stiffness, muscle weakness, and neck pain.