Ondansetron Compared With Doxylamine And Pyridoxine For Treatment Of Nausea In Pregnancy

Ondansetron Compared With DoxylamineAnd Pyridoxine For Treatment Of NauseaIn Pregnancy

Asty amelia (09310099)Pembimbing : dr. Eka Handayani,Sp.OG

Up to 80% of expectant women experience some degree of nausea and vomiting in pregnancy.

Many women with this condition report increased feelings of depression and believe it negatively affects their relationship with their partner. Furthermore, nearly 50% of working pregnant women believe their job efficiency was reduced and approximately 25% require time off work. The combination of pyridoxine (vitamin B6) and doxylamine is recommended by the American College of Obstetricians and Gynecologists as first-line therapy for nausea and vomiting in pregnancy. However, despite the lack of evidence, the 5-hydroxytryptamine type 3 receptor antagonist ondansetron has become the most frequently prescribed antiemetic for the treatment of nausea and vomiting of pregnancy in the United States. The objective of our study was to evaluate whether ondansetron was superior to the combination of pyridoxine and doxylamine for the treatment of nausea and vomiting of pregnancy.

MATERIALS AND METHODSWe performed a double-blind, randomized, controlled trial comparing the efficacy of ondansetron with the combination of pyridoxine and doxylamine for the treatment of nausea and vomiting in pregnancy. Patients were enrolled from October 2012 through April 2013 at a tertiary care medical center that serves beneficiaries of active duty and retired military personel. Enrollment occurred in both the emergency department and the obstetrics and gynecology clinic. Women were excluded from the study if their nausea or vomiting predated the pregnancy, hospitalization was required at the time of initial enrollment, they were already using anti-emetics (including metoclopramide, ondansetron, doxylamine, pyridoxine, or promethazine), they had an allergy to any of the study medications, they were unable to return for a follow-up visit in 1 week, or they were unable to obtain the medications on the day of enrollment.

We chose the most conservative of values (25 mm) to indicate a clinically significant reduction in nausea and vomiting on the VAS. Before initiating treatment, each patient was asked to grade the severity of nausea and emesis experienced over the previous 7 days on two separate 100-mm visual analog scales (VAS) ranging from 0 (indicating no nausea or emesis) to 100 (indicating worst nausea or emesis imaginable).

The ondansetron group was given one capsule containing ondansetron 4 mg and one placebo capsule to be taken orally every 8 hours for 5 days. The pyridoxine and doxylamine group was given one capsule containing pyridoxine 25 mg and one capsule containing doxylamine 12.5 mg to be taken orally every 8 hours for 5 days. Patients were reevaluated 5 to 7 days after initiating the drug regimen.

Statistical analysis was performed using Stata 13 software.

RESULT

Forty eligible patients were approached for enrollment and four patients declined participation. A total of 36 women were enrolled and randomized to treatment, with 30 fully completing the study (13 in the ondansetron group, 17 in the pyridoxine and doxylamine group) (Fig. 1).

Baseline characteristics for each group are reported in Table 1. No significant differences between the groups were observed with regard to demographics (gravidity, parity, or estimated gestational age) or level of nausea or vomiting before treatment.

The primary outcome was the reduction in nausea on the VAS. Patients using ondansetron reported a greater reduction in nausea than those using pyridoxine and doxylamine (median 51 mm [interquartile range 3764] compared with 20 mm [interquartile range 851]; P5.019) (Table 2 and Fig. 2).

Additionally, those who were using ondansetron reported less vomiting on the VAS as compared with the pyridoxine and doxylamine group (median 41 [interquartile range 1757] compared with 17 [interquartile range 24 to 38]; P 5.049) (Table 2 and Fig. 2).

In the ondansetron group, 12 out of the 13 patients had a clinically significant reduction in nausea (defined as a 25-mm or greater reduction in nausea on the VAS); however, in the pyridoxine and doxylamine group, only 7 out of 17 patients had a clinically significant reduction (P5.007) (Table 3 and Fig. 3). In the ondansetron group, 10 out of the 13 patients had a reduction in emesis on the VAS; however, in the pyridoxine and doxylamine group, only 6 out of 17 patients had a reduction in emesis (P5.033) (Table 3 and Fig. 4).

Significance in VAS reduction decreased 1.8% in the test of difference between groups for change in nausea attributable to treatment (P increased to .037) (Fig. 5) and increased 3.9% for change in emesis (P decreased to .010) (Table 2, Fig. 6). Significance in clinical improvement decreased 0.8% on the test of difference between groups for a change in nausea attributable to treatment (P increased to .015) and decreased 1.1% for a change in emesis (P increased to .044) (Table 3).

Fig. 1. Study recruitment and randomization process.

Table 1. Baseline Demographic Characteristics and Initial Visual Analog Scale Scores by Group

DemographicOndansentron Piridoksin dan DoxylaminGravid 2 (1-3)2 (1-3)Parity 1 (0-1)0,5 (0-1)Gestasional age (wk)8(7,1-8,9)8,1 (7,2-9,9)Baseline nasue (mm)73 (67-84)81 (68-93)Baseline emesis (mm)53 (26-74)64 (26-89)

Table 2. Change in Visual Analog Scale Score for Ondansetron and Pyridoxine and Doxylamine Groups

VariableGroupFrom missing data DBFrom imputed data DBMedian (IQR)PMedian (IQR)PChange in nauseOndansentron51 (37-64)0,1945(27-62)0,37Piridoksin dan Doxylamin20 (8-51)19(8-49)Change in emesisOndansentron41 (17-57)0,4946 (22-67)0,010Piridoksin dan Doxylamin17 (-4 to 38)12 (-9 to 37)

Fig. 2. The median reduction in nausea and vomiting on the visual analog scale (mm) for each medication regimen. CI,confidence interval.

Table 3. Clinically Significant ImprovementsTestGroupFrom missing data DBFrom Imputed data DBn/N(%)Pn/N(%)PChange in nauseaOndansentron12/13(92,2%)0,00715/18(83,3%)0,015Piridoksin dan Doxylamin7/17(41,2%)7/18(38,9%)Change in emesisOndansentron10/13(76,9%)0,03313/18(72,2%)0,044Piridoksin dan Doxylamin6/17(35,3%)6/18(33,3%)

Fig. 3. Change in nausea on the visual analog scale (mm) for each patient. A reduction of at least 25 mm on the visual analog scale is considered clinically significant.

Fig. 4. Change in emesis on the visual analog scale (mm) for each patient. A reduction of at least 25 mm on the visual analog scale is considered clinically significant

Fig. 5. Pretreatment and posttreatment visual analog scale (mm) for nausea for each individual patient for (A) ondansetron and (B) pyridoxine and doxylamine

Fig. 6. Pretreatment and posttreatment visual analog scale (mm) for emesis for each individual patient for (A) ondanstetron and (B) pyridoxine and doxylamine

DISCUSSIONOur investigation showed ondansetron to be superior to the combination of pyridoxine and doxylamine in the treatment of nausea during pregnancy. Although our sample was quite small, the strength of outcome differences suggests that it might well be considered as a possible first-line therapy. Decreasing the incidence of nausea during pregnancy will likely improve the mental and physical health of patients, allowing less time away from work, resulting in less health care expenditures on urgent visits, and increasing quality of life.