Is any one analgesic superior for episodic tension-type headache?
This systematic review suggests good tolerance of any given agent may be the deciding factor.
Twenty-five studies compared 1 or more types of NSAIDs with placebo,13-17,22-24,26-36,38,41-43,45-47 17 studies compared 1 or more doses of acetaminophen with placebo,17-21,25,30-34,41,44-46,48,49 7 studies compared different types of NSAIDs,15,26,28,29,35-37 9 studies compared 1 or more types of NSAIDs with acetaminophen,17,30-34,41,45,46 and 13 studies compared other analgesics with placebo.15,18,25,27,39,40,44,49,50-53
The quality score (with positive items in parenthesis) is presented in the “Notes” section of TABLE W1. The interobserver reliability of the methodological quality assessment was high (κ=0.85). There was disagreement between the 2 authors in 7.5% of the criteria, but after consensus no disagreement persisted. The median quality score was 5 (range 1–9). Using a cutoff point of 6 out of 10 criteria, 15 studies (36.6%) were considered to be of high quality.15,17,19,21,22,24,25,28-30,32-34,36
Only 1 study reported a concealed randomization method.34 Other methodological flaws, which often scored “negative” or “unclear,” were blinding of the care provider (unclear 88%) and an intention-to-treat analysis (unclear 30% and negative 60%).
Effectiveness of analgesics
TABLE 1 gives the quantitative analysis for high-quality studies, low-quality studies, and for all studies for the different comparisons of NSAIDs, acetaminophen, and placebo.
TABLE 1
Quantitative analysis for the different studies for the comparisons of NSAIDs, acetaminophen and placebo
| HIGH-QUALITY TRIALS | LOW-QUALITY TRIALS | ALL TRIALS | |||||
|---|---|---|---|---|---|---|---|
| N/n | RR (95% CI) | N/n | RR (95% CI) | N/n | RR (95% CI) | ||
| 1. NSAIDs vs placebo | 7/13 | 1.5 (1.3–1.8)* | 8/15 | 2.0 (1.4–2.7)* | 15/28 | 1.6 (1.4–2.0)* | |
| 2. Acetaminophen vs placebo | 5/6 | 1.4 (1.04–1.8)* | 3/3 | 1.6 (0.9–2.7) | 8/9 | 1.4 (1.1–1.8)* | |
| 500 mg vs placebo | 1/1 | 1.1 (0.8–1.5) | 1/1 | 1.1 (0.8–1.5) | |||
| 1000 mg vs placebo | 4/5 | 1.4 (0.97–2.0) | 3/3 | 1.6 (0.9–2.7) | 7/8 | 1.5 (1.1–2.0)8 | |
| 4. NSAIDs vs acetaminophen | 5/7 | 1.1 (0.96–1.4) | 2/2 | 2.2 (1.4–3.4)* | 7/9 | 1.3 (1.04–1.5)* | |
| 3. NSAIDs vs NSAIDs | |||||||
| Ibuprofen 400/800 mg vs aspirin 650 mg37 | 1/2 | 1.2 (0.6–2.2) | |||||
| Ketoprofen 12.5/25/50 mg vs ibuprofen 200 mg29,36 | 1/2 | 1.1 (0.8–1.5) | 1/2 | 1.5 (0.8–2.7) | 2/4 | 1.2 (0.9–1.6) | |
| Ketoprofen 12.5/25 mg vs naproxen 275 mg29 | 1/2 | 0.96 (0.7–1.3) | |||||
| Naproxen 275 mg vs ibuprofen 200 mg29 | 1/1 | 0.9 (0.7–1.2) | |||||
| Metamizol 500/1000 mg vs aspirin 1000 mg30 | 1/2 | 1.2 (0.9–1.7) | |||||
| Diclofenac 12.5/25 mg vs ibuprofen 400 mg55 | 1/2 | 1.1 (0.8–1.5) | |||||
| N/n=number of trials/total number of comparisons; RR: relative risk; CI: confidence interval. *P<.05. | |||||||
1. NSAIDs vs placebo
Twenty-five studies compared one or more types of NSAIDs with placebo, of which 10 are of high quality.15,17,22,24,29,30,32-34,36,45
Quantitative analysis. Sufficient data were available in 15 studies,13,14,29-38,41,45,47 of which 6 were of high quality.29,30,32-34,36,45 Because some trials included 3 or more treatment groups, data were available for 28 comparisons. We found a significant effect in favor of NSAIDs compared with placebo on short-term pain relief (see TABLE 1 and FIGURE W1).
Qualitative analysis. The 10 high-quality studies reported 30 comparisons, of which in 26 (86.6%) NSAIDs were significantly more effective compared with placebo for short-term pain relief (strong evidence).
Adverse events. Twenty studies reported during a 2 to 6 hours treatment period data on adverse events. For the NSAID group (n=2061) frequently mentioned side effects were nausea (4.6%), photophobia (3.1%), vomiting (2.7%), phonophobia (1.7%), aching limbs (1.2%), dizziness (1.1%), and drowsiness (1.0%). For the placebo group (n=1323), these were nausea (7.0%), photophobia (4.8%), vomiting (3.9%), phonophobia (3.4%), aching limbs (2.0%), drowsiness (1.7%), and dizziness (1.0%). The pooled RR for the number of patients reporting side effects for 14 studies with sufficient data was 0.96 (95% CI, 0.7–1.3), indicating no significant difference.
2. Acetaminophen vs placebo
Seventeen studies compared 1 or more doses of acetaminophen with placebo; 9 were high-quality studies.17,19,21,25,30-34,45
Quantitative analysis. The pooled analysis of 5 high-quality trials30,32-34,45 and 3 low-quality trials31,41,44 showed that acetaminophen was significantly more effective compared with placebo for patients on short-term pain relief (TABLE 1 and FIGURE W2). This result was due to the studies comparing acetaminophen with placebo. The only high-quality trial34 with acetaminophen 500 mg failed to show a difference in short-term pain relief compared with placebo (TABLE 1).
Qualitative analysis. The 9 high-quality studies reported 16 comparisons, of which 10 (62.5%) mentioned that acetaminophen showed significantly more pain relief than placebo (conflicting evidence). In 2 high-quality studies,17,34 we found no significant differences between acetaminophen 500 mg and placebo (strong evidence), but in the 9 high-quality studies, in 10 out of 14 comparisons (71.4%) acetaminophen 1000 mg showed significantly more pain relief compared with placebo (conflicting evidence).
Adverse events. Twelve studies reported data on adverse events. For the acetaminophen group (n=3715), frequently mentioned side effects were stomach discomfort (3.9%), dizziness (1.6%), nervousness (0.7%), nausea (0.4%), and drowsiness (0.3%). For the placebo group (n=3700), these were stomach discomfort (3.7%), nervousness (0.7%), nausea (0.6%), dizziness (0.5%), and drowsiness (0.3%). The pooled RR for the number of patients reporting side effects was 1.3 (95% CI, 0.9–1.7), indicating no significant difference.
3. NSAIDs vs acetaminophen
