Intravenous metoclopramide plus diphenhydramine is a more effective way to reduce headaches in pregnant women than codeine and is worth the extra cost, new research shows.
Results from the study support the use of this regimen to “break the cycle of headache pain,” said Katherine Scolari Childress, MD, from Saint Louis University in Missouri.
And both agents “are safe and nonaddictive,” she toldMedscape Medical News.
Dr Scolari Childress presented the study results here at the American Congress of Obstetricians and Gynecologists Annual Clinical Meeting 2015, where it was named First Prize Paper.
Headaches affect 15% to 20% of pregnant women, but few researchers have explored treatments, said Dr Scolari Childress.
Previous studies have shown that some antiemetics, such as metoclopramide, often in combination with antihistamines, can soothe the acute headaches of nonpregnant patients in the emergency department.
Because metoclopramide and diphenhydramine are relatively inexpensive, widely available, and considered to be safe for pregnant women, some clinicians use these drugs to treat headaches, Dr Scolari Childress explained.
Nonaddictive
The researchers looked at the effectiveness of a combination treatment of metoclopramide and diphenhydramine in a previous randomized controlled trial (NCT02295280) and found it to be more effective than codeine in providing headache relief in pregnant women.
They reanalyzed the data for the current study to see if the combination is more or less expensive than codeine.
They studied normotensive women in their second or third trimester who experienced primary headache not relieved by oral acetaminophen 650 to 1000 mg.
The women were randomly assigned to one of two treatments. In the combination group, 23 women received metoclopramide 10 mg plus diphenhydramine 25 mg, administered intravenously. In the monotherapy group, 21 women received codeine 30 mg.
Demographic characteristics, parity, gravidity, and gestational age were similar in the combination and codeine groups, as were rates of obesity, hypertension, and tobacco use.
Outcomes were better with the metoclopramide plus diphenhydramine combination than with codeine monotherapy.
Table. Study Outcomes
| Outcome | Combination Group, % | Codeine Group, % | P Value |
| Full headache relief | 65.2 | 28.6 | <.05 |
| Perceived relief with one dose | 100.0 | 61.9 | .01 |
| Would use the medication again | 95.7 | 37.1 | <.01 |
| Headache recurrence | 42.9 | 57.1 | .17 |
| Adverse effects | 43.5 | 37.5 | .24 |
Time spent in triage and time to perceived headache relief were not significantly different between the two groups.
As expected, an intravenous catheter was required by more women in the combination group than in the codeine group (23 vs 7).
The average cost of therapy was higher for the combination than for codeine ($1.54 vs $0.84); however, the combination is worth the additional cost because of its greater effectiveness, said Dr Scolari Childress.
“We are considering future studies looking at a regimen of oral metoclopramide and diphenhydramine,” she reported. In addition, the team wants to assess the combination in patients with elevated blood pressure, “who were excluded from this study.”
“This is a very interesting study,” said Sharon Phelan, MD, from the University of New Mexico in Albuquerque.
“Many women come in with a headache,” Dr Phelan told Medscape Medical News. “It used to be very common that everyone would just give narcotics. They work, but there is increasing concern about prescription drug abuse.”
Dr Phelan said she is disappointed that the combination studied was administered intravenously because this increases the cost and might deter some patients.
In addition, it is difficult to account for the placebo effect in a study when one treatment is given intravenously and the other is given mostly orally. “Some people think if they get something IV, it must be more potent,” she pointed out.
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