Parenteral treatment of episodic tension-type headache: a systematic review

Tension-type headache is highly prevalent in the general population and is a consistent if not frequent cause of visits to acute care settings. Analgesics such as nonsteroidal anti-inflammatory drugs, acetaminophen, and salicylates are considered first-line therapy for treatment of tension-type headache. For patients who present to an acute care setting with persistent tension-type headache despite analgesic therapy, it is not clear which parenteral agent should be administered. We performed a systematic review of the medical literature to determine whether parenteral therapies other than salicylates or nonsteroidals are efficacious for acute tension-type headache.

We performed a systematic review of Medline, EMBASE, CINAHL, Google scholar, and the Cochrane Central Registry of Controlled Trials from inception through August, 2012 using the search terms "tension-type headache" and "parenteral or subcutaneous or intramuscular or intravenous." Our goal was to identify randomized trials in which one parenteral treatment was compared to another active comparator or to placebo for the acute relief of tension-type headache. Parenteral was defined as intravenous, intramuscular, or subcutaneous administration. We only included studies that distinguished tension-type headache from other primary headache disorders, such as migraine. The primary outcome for this review was measures of efficacy one hour after medication administration. Data abstraction was performed by two authors. Disagreements were resolved by a third author. We assessed the internal validity of trials using the Cochrane Collaboration risk of bias tool. Because of the small number of trials identified, and the substantial heterogeneity among study design and medications, we decided that combining data and reporting summary statistics would serve no useful function. The results of individual studies are presented using Number Needed to Treat (NNT) with 95%CI when dichotomous outcomes were available and continuous outcomes otherwise.

Our search returned 640 results. One hundred eighty-seven abstracts were reviewed, and 8 studies involving 486 patients were included in our analysis. The most common reasons for exclusion of abstracts were no assessment of acute pain relief, use of nonparenteral medications only, and no differentiation of headache type. Risk of bias ranged from low to high. The following medications were more effective than placebo for acute pain (NNT, 95%CI): metamizole (4, 2-26), chlorpromazine (4, 2-26), and metoclopramide (2, 1-3). The combination of metoclopramide + diphenhydramine was superior to ketorolac (4, 2-8) The following medications were not more effective than placebo: mepivacaine, meperidine + promethazine, and sumatriptan.

Various parenteral medications other than salicylates or nonsteroidals provide acute relief of tension-type headache. Comparative efficacy studies are needed.