Treatment of functional dyspepsia with sertraline:A double-blind randomized placebo-controlled pilot studydr.Radias Zasra1st Journal Reading

AbstractAim To evaluate sertraline, a selective serotonin reuptake inhibitor in the treatment of patients with functional dyspepsia

METHODS Diagnosis of functional dyspepsia

Rome II criteria with Hongkong dyspepsia index (HKDI) greater than 16

PATIENTS

ethnic chinessHKDI symptom scorenormal upper endoscopyquality of lifehelicobacter pylori negatifhospital anxiety and depression (HAD) scale and global symptom relief

receive -sertraline 50 mg- placebo

-evaluated before,during and after treatment.- adverse effect were monitored during and after treatment.

RESULT patients

no difference in the primary outcome of global dyspepsia symptoms between the sertraline and placebo groups

intention to treat (ITT)193 patientsper protocol (PP) analysis150 patients

ITTPP analysisin the PP analysis by week 8 patients in the sertraline group --> statistically significant difference in HKDIno statistically significant difference in overall quality of life measure or the HAD scale related to treatmentin either the ITT or PP analysis at week 8

sertraline ( 98 patients )placebo ( 95 patients )w 0 :HKDI 26.086.19w 8 :HKDI 22.416.36HKDI 26.705.89HKDI 23.257.30

sertraline ( 74 patients )placebo ( 76 patients )HKDI : 25.836.313HKDI : 20.536.917HKDI : 27.195.929HKDI : 23.347.199

CONCLUSIONThis pilot study, the first to examine sertralinea selective serotonine reuptake inhibitor , for the management of FD did not find that it was superior to placebo

INTRODUCTION persistent or recurrent pain and/or discomfort centered in the upper abdomen for at least 12 wk in the preceding 12 mo according to the Rome criteria in the absence if structural disease.

FUNGTIONAL DYSPEPSIA (FD)The Rome criteria, published in 2006,further refines FD into epigastric pain syndrome and/orpostprandial distress syndrome with the criteria fulfilledin the last 3 mo with symptoms onset at least 6 mo priorto diagnosis, again in the absence of structural disease

The pathogenesis of FD is not known. A number of studies have shown an important role of psychological factors in the pathogenesis of this condition. We have demonstrated previously that anxiety and depression are important co-factors in its pathogenesis. There is no definitive treatment for this condition.

Visceral hypersensitivity appears to be important in the pathogenesis of FDantidepressants were investigated in FD for their ability to modulate visceral hypersensitivity.selective serotonin reuptake inhibitors (SSRIs) are more commonly used in clinical practice.The precise mechanism of action of SSRIs in the treatment of depression is not fully understood.

MATERIALS AND METHODS

Patient enrollmentPatients aged 18-80 years with symptoms of dyspepsia within two weeks prior to the endoscopy visit were eligible for the study. Informed written consent was obtained from all patients.

Patients were also required to have a dyspepsia score of greater than 16 by our validate questionnaire. and have had no prior investigations performed for this episode of dyspepsia within the 6 mo prior to the study.

EXCLUSION CRITERIA

EXCLUSION CRITERIA

1. Pregnant or breast feeding2. Had a history of alcohol or drug abuse3. Recent malignancy or significant medical illnesses or concurrent medication4. Patients with a history of or current anti-depressant use5. Patients with classical heartburn or acid regurgitation as their only symptom without epigastric discomfort or pain

Study protocolPatients were randomized to receive either sertraline 50 mg or placebo once daily for eight weeks.

Both the investigators and patients were blinded to the assigned treatment throughout the study.

Patients were given a diary in which they recorded side effects and symptoms during therapy.

After enrolment by gastroenterologists,patients returned for follow up at four and eight weeks

Study intervention

The SSRI utilized in this study was sertraline at a dose of 50 mg orally daily.

Study participants were provided with pre-sealed boxes containing either sertraline or placebo and were asked to take a capsule per day for 8 wk in total. Patient compliance was checked by counting returned study medications.

Dyspepsia scores

DISCUSSIONthere was a statistically significant improvement in the mean HKID score at week 8 in the sertraline group compared to the placebo group in the PP but not the ITT analysis. There were also no differences in measures of quality of life, depression and anxiety and subjective global symptom resolution.

the majority of the drop outs in the sertraline group occurred at week four, which could possibly be explained by the short term side effects of sertraline usually seen during the run in period of SSRIs.

We assert that our findings are important given that clinicians not uncommonly are utilizing SSRIs to treat FD despite the fact that to date, our study included, there is no strong justification for its use.

In conclusion, our data suggest that an SSRI, sertraline was not superior to placebo for the management of FD in Chinese patients

CRITICAL APPRAISAL

Is the evidence of this therapeutic aspect valid?Is the patient allocation of the treatment randomized? yesIs the observation of the patient done for enough time and completely? NoAre all of the patient be analyzed? NoAre the doctor and patient blind in the study? YesDo all of the groups get the same action? NoAre the control and treatment group similar in the initial of the study? Yes

Is the evidence of this valid therapeutic aspect important?ARR = (a/a+b) (c/c+d) = 98/193 74/150 = 0,01NTT = 1/ARR = 1/0,01 = 100

SertralinePlaseboTotal

ITT98 (a)95 (b)193 (a+b)PP74 (c)76 (d)150 (c+d)TOTAL172 (a+c)171 (b+d)343

Confidence interval (CI) 95%

NTT 1.96 ((a/a+b) x (1-(a/a+b)) + ((c/c+d) x (1-(c/c+d)) a+b c+d

= 16.67 1.96 ((98/193) x (1-98/193)) + ((74/150) x (1-74/150))193 150

= 16.67 0.003

= 16.667 - 16.673

Can we applied the evidence of these valid and important therapeutic aspect to our patient?Are our patients different from patients in the study? NoCan therapy applicated to our patients? YesDo our patients have beneficial potential effect for the patients if this therapy applicated? YesWhat is the value and expectation for the patients if the result offered?Sertraline for the management of FD, did not find that it was superior to placebo