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. 2012 May 25;5:69–100. doi: 10.2147/CEG.S29023

Table 1.

Randomized controlled trials of tricyclic and selective serotonin-reuptake inhibitor antidepressants in irritable bowel syndrome: study characteristics and efficacy outcomes

Study Diagnostic criteria Sample size, type of IBS,* dosage, analysis population Study type and duration Relief of abdominal pain with or without discomfort Relief of bloating and/or distension Effect on stool frequency Effect on stool consistency Effect on urgency Global or overall IBS improvement Other efficacy assessments
Tricyclic antidepressant: amitriptyline
Rajagopalan et al1 Rome Patients: 40, age 21–65 yr, with IBS and symptoms for ≥1 yr
Treatment: amitriptyline 25–75 mg (titrated) vs placebo		 Randomized, DB, PC design; 12 wk treatment Reduction in days per wk with abdominal pain: +, P < 0.01 NA/NR 0 NA/NR NA/NR +, 63.6% with amitriptyline vs 25.9% with placebo, P < 0.01 Days felt well: +, P < 0.001
Days with satisfactory bowel movements: +, P < 0.05
Vahedi et al2 Rome II Patients: 50, mean age 36 yr, with IBS-D and symptoms for ≥12 wk during the preceding yr, 42% women
Treatment: amitriptyline 10 mg qhs vs placebo		 Randomized, DB, PC design; 2 mo treatment 0 NA/NR NA/NR Number of loose stools per day: +, P < 0.05 NA/NR Complete response: ITT +, P = 0.01 Degree of symptom improvement: +, P = 0.01; Passage of mucus: 0; Feeling of incomplete defecation: +, P < 0.05; Diarrhea: 0
Tricyclic antidepressant: desipramine
Greenbaum et al3 Clinical diagnosis (history, PE, labs, stool studies, proctosigmoidoscopy, and barium enema at screening or within previous yr) Patients: 41 (27 women) with IBS defined as ≥3 mo of abdominal pain or distress not attributed to menstruation, with diarrhea, constipation, or alternating symptoms occurring at least biweekly with no organic cause; concomitant meds allowed, including analgesics and antibiotics
Treatment: desipramine
50–150 mg qhs, atropine
0.4–1.2 mg qhs, or placebo
Analysis population:

  1. Overall completers (n = 28)

  2. IBS-D (n = 19)

  3. IBS-C (n = 9)

  4. IBS-D vs IBD-C

 DB, PC, crossover design; 3 6 wk test periods Pain index:

  1. +, P < 0.0025

  2. +, P < 0.025

  3. N too small for meaningful comparison

  4. Significant differences favoring IBS-D (P < 0.01) over IBS-C

 NA/NR Mean frequency of stools:

  1. +, P < 0.025

  2. +, P < 0.025

  3. N too small for meaningful comparison

  4. No significant differences between IBS-D and IBS-C

 Mean frequency of loose stools:

  1. 0

  2. 0

  3. N too small for meaningful comparison

  4. No significant differences between IBS-D and IBS-C

 NA/NR

  1. 15 of 26 patients with improvement while receiving desipramine

  2. 87% of patients who reported global improvement had IBS-D

 Reduction in diarrhea:

  1. 0

  2. +, P < 0.005

  3. 0

  4. Significant differences between IBS-D; (P < 0.025) and IBS-C;

Reduction in slow contractions:

  1. +, P < 0.01

  2. +, P < 0.05

  3. N too small

  4. 0

No significant differences for number of fast contractions or motility indices; Other assessments included Brief Psychiatric Rating Scale and HAM-D
Drossman et al4 Rome I and physicians’ clinical diagnosis Patients: 431 women aged >18 yr with functional bowel disorder with moderate to severe abdominal pain with or without altered bowel habit; 78% of whom had IBS on Rome I criteria; 87% had IBS diagnosis by physician
Treatment: desipramine 50–150 mg (titrated) vs placebo		 Randomized (variable-sized blocks of 6 and 12), comparator-controlled design; 12 wk treatment with CBT vs education and desipramine vs placebo (only desipramine vs placebo results presented here) McGill average daily pain:
ITT: 0		 NA/NR NA/NR NA/NR NA/NR Responder analysis:
ITT: 0
PPP: +, P = 0.02; Patients with detectable desipramine: +, P = 0.006; Global well-being:
ITT: 0		 Post-treatment satisfaction:
ITT: +, P = 0.011; IBS-QOL:
ITT: 0; Composite score:
ITT: 0
PPP: +, P = 0.03; Patients with detectable desipramine: +, P = 0.01
Tricyclic antidepressant: imipramine
Talley et al5 Rome II Patients:
34 with IBS (IBS-D 73%)
Treatment:
imipramine 25–50 mg/d, citalopram 20–40 mg/d, vs placebo (“n” represents imipramine vs placebo results presented here)		 Randomized, DB, PC, PG, pilot study; 12 wk treatment 0 NA/NR 0 NA/NR NA/NR Adequate relief of IBS symptoms at last wk: 0; Adequate relief of IBS symptoms ≥ 50% of wk: 0; CGI: 0;
BSSRS:
Disability +, P = 0.05
Distress: +, P = 0.02		 HADS: anxiety 0 and depression 0; SF-36: menta 0 and physical 0
Abdul-Baki et al6 Rome II Patients: 107 patients with IBS (42% female)
Treatment:
imipramine 25 mg qhs vs placebo		 Randomized, DB, PC study; 12 wk treatment NA/NR NA/NR NA/NR NA/NR NA/NR Global symptom relief: ITT: 0
PPP: +, P < 0.05		 QOL using SF-36: 0
SSRI: fluoxetine
Kuiken et al7 Rome I Patients: 40 adults with IBS (IBS-D 40%)
Treatment: fluoxetine 20 mg qhs vs placebo		 Randomized, DB, PC study; 6 wk treatment 0 0 NA/NR NA/NR 0 0 Flatulence: 0
Incomplete evacuation: 0
SSRI: paroxetine
Tabas et al8 Rome I Patients: 81 adults with IBS
Treatment:
HFD ± paroxetine 10 mg qd vs placebo; titration at wk 4, 8, and 11 prn; maximum dose 40 mg qd		 Randomized, DB, PC study; 12 wk treatment 0 0 NA/NR NA/NR NA/NR ++†, P = 0.01 Stool passage: +
Masand et al9 Rome II Patients: 72 adults with IBS (women 87.5%)
Treatment:
paroxetine CR 12.5 mg qd titrated biweekly to response and tolerability; maximum dose 50 mg qd		 Randomized, DB, PC study; 12 wk treatment 0 0 NA/NR NA/NR NA/NR NA/NR CGI-Severity improvement: ++, P < 0.01; Constipation, diarrhea, distress: 0
SSRI: citalopram
Tack et al10 Rome II Patients: 23 adults with IBS (women 78.3%)
Treatment:
citalopram 20 mg qd for 3 wk then 40 mg qd for 3 wk		 Crossover study; 6 wk treatment No. days per wk with abdominal pain: +, P < 0.05 +; P < 0.05 NA/NR NA/NR NA/NR NA/NR No. days with loose stools, straining, and incomplete evacuation: +, P < 0.05
Talley et al5 Rome II Patients: 33 adults with IBS (IBS-D 76%)
Treatment:
citalopram 20–40 mg/d, imipramine 25–50 mg/d, vs placebo (“n” represents citalopram vs placebo results presented here)		 Randomized, DB, PC, PG, pilot study; 12 wk treatment 0 NA/NR 0 NA/NR NA/NR Adequate IBS symptom relief at last wk: 0; CGI: 0;
BSSRS:
Disability: 0
Distress: 0		 Adequate symptom relief for ≥50% of wk: 0

Notes:

*

According to predominant stool pattern, if available;

†

Endpoint was “improvement in overall well-being.” + Indicates significant improvement over placebo; 0 represents no statistically significant difference between active treatment and placebo. If a study did not report on a particular assessment, it was noted as “not assessed.” If more than one population is assessed for a particular parameter, the populations are numbered (see sample size, type of IBS, dosage, analysis population column); subsequent efficacy values are presented to correspond to the population so designated.

Abbreviations: BSSRS, bowel syndrome severity rating scale; CBT, cognitive behavioral therapy; CGI, Clinical Global Impression scale; CR, controlled release; DB, double-blind; HADS, Hospital Anxiety and Depression Scale; HAM-D, Hamilton Rating Scale for Depression; HFD, high-fiber diet; IBS, irritable bowel syndrome; IBS-C, constipation-predominant IBS; IBS-D, diarrhea-predominant IBS; IBS-QOL, Irritable Bowel Syndrome Quality of Life Questionnaire; ITT, intent-to-treat population; NA/NR, not assessed or not reported; PC, placebo-controlled; PE, physical exam; PG, parallel group; PPP, per-protocol population; QOL, quality of life; SF-36, Medical Outcomes Study Short Form; SSRI, selective serotonin-reuptake inhibitor.