C10ANTIDEPRESSANTS

StudyParticipantsInterventions
Boerner 1988; Trial held in Germany; parallel trial; Setting: mixed.Inclusion & Exclusion criteria: Type of IBS: Mixed. IBS definition: Authors’ def. Severity of IBS symptoms: Not stated; Bloating/flatus: Not stated; Post infective: not stated. Age (range): range 22–70 years; Gender (M/F): ; Co-morbidities: some patients had depression. Translation from German; from Cochrane review. At baseline doxepine group score on HAMD (0–20) 11.7; control group 9.8.
  1. Doxepine 50mg (tricyclic); duration: 8 weeks; frequency/day: once daily; amount 50 mg (n=40).
  2. Placebo identical capsule (placebo); duration: 8 weeks; frequency/day: once daily (n=39).
Creed 2003; Trial held in UK; parallel trial; Setting: secondary care.Inclusion & Exclusion criteria: Included: duration of symptoms >6 months, failure to respond to usual treatment, severe abdominal pain. Excluded: contraindication to psychotherapy or paroxetine. Type of IBS: Mixed, IBS definition: Rome I. Severity of IBS symptoms: severe; Bloating/flatus: Not stated; Post infective: not stated. Age (range): mean 40 yrs SD=10.5. Gender (M/F): 52:205. Co-morbidities: 47% had anxiety or depression. Median duration 8 y. Refractory IBS. 29% IBS-D, 23% IBS-C. 55% >12 yrs education. 12% sexual abuse. 99% white, 47% psychiatric disorder. Concurrent dedication stopped in active interventions (author info). Follow up period had some paroxetine in all arms.
  1. Paroxetine (SSRI selective serotonin reuptake inhibitors); duration: 3 months; frequency/day: 1; amount 20 mg (n=86).
  2. One long (2 hrs) session, followed by 7 shorter (45 minutes) sessions psychotherapy (psychotherapy); duration: 3 months frequency/day: 8 sessions over 3 months; amount 8 sessions over 3 months (n=85).
  3. “Routine care” by gastroenterologist and usual care including antispasmodics, laxatives, antidiarrhoeal medication or additional analgesics for 3 months.
Kuiken 2003; Trial held in Netherlands; parallel trial; Setting: secondary care.Inclusion & Exclusion criteria: Inclusions: less than 50 points on Zung Self-rating depression scale (i.e. not depressed). Exclusions: organic disease; pregnancy; breast feeding; previous abdominal surgery. Type of IBS: Mixed. IBS definition: Rome I. Severity of IBS symptoms: Not stated; Bloating/flatus: Some patients; Post infective: not stated. Age (range): 40y (18–59). Gender (M/F): 18:22. Co-morbidities: None stated; not depressed Mean duration of symptoms 5.9y. 40% IBS-D; 28% IBS-C; 32% IBS-A. Refractory IBS. Mean Zung score 38 (range 23–48). concurrent medication discontinued. Tertiary referral centre. Sponsored by Eli Lilly (Prozac).
  1. Fluoxetine 20mg capsules at bedtime (SSRI selective serotonin reuptake inhibitors); duration: 6 weeks; requency/day: once; amount 20mg (n=19).
  2. Placebo capsule at bedtime (placebo); duration: 6 weeks; frequency/day: once (n=21).
Myren 1984; Trial held in Norway; parallel trial; Setting: mixed.Inclusion & Exclusion criteria: Excluded: organic disease. Type of IBS: Unclear. IBS definition: ‘Had IBS’; Severity of IBS symptoms: Not stated; Bloating/flatus: Not stated; Post infective: not stated. Age (range): mean 36.5 yrs (16–75). Gender (M/F): 212: 216. Co-morbidities: none gastroenterologists and GPs conducted study. 23–36% of patients had concurrent medication during the trial; 45–61% were not taking other drugs before the study started.
  1. Trimipramine (tricyclic (sedative)); duration: 6 weeks; frequency/day: 1; amount 50 mg (n=92).
  2. Placebo (placebo); duration: 6 weeks; frequency/day: unclear; amount (n=75).
  3. Trimipramine 10 mg, twice a day (10mg in the morning, 40 mg in the evening).
  4. Trimipramine 35 mg, once a day (at bedtime).
  5. Trimipramine 10 mg, 3 times a day.
Myren 1982; Trial held in Norway; parallel trial; Setting: secondary care.Inclusion & Exclusion criteria: Included: ‘patients’ with chronic symptoms lasting for several months. Excluded: organic disease. Type of IBS: Unclear. IBS definition: Authors’ def. Severity of IBS symptoms: Not stated; Bloating/flatus: Not stated; Post infective: not stated. Age (range): 38 (range not given) SD 13. Gender (M/F): 28:33. Co-morbidities: Double blind procedure described but randomisation not mentioned. Mean score at baseline on 10cm VAS depression scale and on anxiety scale was about 2. Previous treatment not stated.
  1. Trimipramine (tricyclic (sedative)); duration: 4 Weeks; frequency/day: 1; amount 25 mg (n= 30).
  2. Placebo (placebo); duration: 4 weeks; frequency/day: 1 (n= 31).
Rajagopalan 1998; Trial held in India; parallel trial; Setting: secondary care.Inclusion & Exclusion criteria: Included: Symptoms persist 1 year or more, for 3 days/ week or more. Literate; aged 21–65y. Excluded: major medical or psychiatric illnesses, previous antidepressant medication. Type of IBS: Unclear. IBS definition: Rome II. Severity of IBS symptoms: Not stated; Bloating/flatus: Some patients; Post infective: not stated. Age (range): mean 35y. Gender (M/F): 11:11. Co-morbidities: none. Mean duration: 4 and 5 years. No major medical or psychiatric illnesses. No concurrent medication.
  1. Amitriptyline initially 1 tablet (25 mg) (tricyclic (sedative)); duration: 12 weeks; frequency/day: 3; amount up to 75 mg (tapered up to end of 2nd week) (n=20).
  2. Placebo (placebo); duration: 12 weeks;frequency/day: 3 (n=20).
Steinhart 1981; Trial held in US; crossover; trial; Setting: not stated.Inclusion & Exclusion criteria: Included: adult patients with spastic colon syndrome with moderate to severe symptoms (2 episodes or more per day) for at least 6 months. Excluded: cases with known allergy, systemic disease of any kind, any gastrointestinal disease. Type of IBS: Mixed. IBS definition: Authors' def. Severity of IBS symptoms: severe; Bloating/flatus: Some patients; Post infective: not stated. Age (range): mean 41 (21 to 65). Gender (M/F): 3:11; Co-morbidities: 57% had depression and 79% anxiety. Mean duration of IBS was 5.07 years. No concurrent medication. All patients had received antispasmodics previously.
  1. Amitriptyline (tricyclic (sedative)); duration: 4 weeks; frequency/day: 1; amount 50 mg (n=14).
  2. Placebo (placebo); duration: 4 weeks; frequency/day: 1 (n=14).
Steinhart 1981; Trial held in US; crossover; trial; Setting: not stated.Inclusion & Exclusion criteria: Included: adult patients with spastic colon syndrome with moderate to severe symptoms (2 episodes or more per day) for at least 6 months. Excluded: cases with known allergy, systemic disease of any kind, any gastrointestinal disease. Type of IBS: Mixed. IBS definition: Authors' def. Severity of IBS symptoms: severe; Bloating/flatus: Some patients; Post infective: not stated. Age (range): mean 41 (21 to 65). Gender (M/F): 3:11; Co-morbidities: 57% had depression and 79% anxiety. Mean duration of IBS was 5.07 years. No concurrent medication. All patients had received antispasmodics previously.
  1. Amitriptyline (tricyclic (sedative)); duration: 4 weeks; frequency/day: 1; amount 50 mg (n=14).
  2. Placebo (placebo); duration: 4 weeks; frequency/day: 1 (n=14).
Tabas 2004; Trial held in US; parallel trial; Setting: mixed.Inclusion & Exclusion criteria: Included: failed high fibre diet. Excluded: major medical or psychiatric illnesses; breastfeeding/pregnancy; medication; allergy to paroxetine. Type of IBS: Mixed. IBS definition: Rome I. Severity of IBS symptoms: Not stated; Bloating/flatus: Not stated; Post infective: Not stated. Age (range): 18–65yrs mean 45. Gender (M/F): 60:140. Co-morbidities: 27/81 (33%) had some depression (BDI score >10) Patients recruited through physician referrals and newspaper adverts. Non-responders to high fibre diet. No industry funding apart from supply of drugs. 2.8 to 3.6 times more diarrhoea than constipation.
  1. Paroxetine (10 mg/day initially) and high fibre diet >25g per day (SSRI selective serotonin reuptake inhibitors); duration: 12 weeks; frequency/day: up to 4; amount up to 40 mg (23% 10mg; 43% 20mg; 33% 40mg) (n=38).
  2. Placebo (I pill initially) and high fibre diet >25g per day (placebo); duration: 12 weeks; frequency/day: up to 4 (n= 43).
Tanum and Malt 1996; Trial held in Norway; parallel trial; Setting: secondary care.Inclusion & Exclusion criteria: Included: patient aged 18–70 diagnosed with functional gastrointestinal disorder, with pain for at least 12 months with symptoms present for majority of the week. Excluded: pregnant/nursing women; psychopathology (Axis I); initial placebo responders. Type of IBS: Unclear. IBS definition: Manning. Severity of IBS symptoms: Not stated; Bloating/flatus: Not stated; Post infective: not stated. Age (range): mean 37 (23–63).
Gender (M/F): 15: 32; Co-morbidities: none 60% IBS, 40% NUD (non-ulcer dyspepsia). Duration of disorder 7.1 and 9.9 years. Schizophrenia, anxiety and depression excluded. Placebo responders also excluded.
  1. Tricyclic related antidepressant – miancerin hydrochloride 30 mg (1 tbl) initially (tricyclic and related antidepressants); duration: 7 weeks; frequency/day: 4; amount up to 120 mg for weeks 2–7, then tapered week 8 (n=25).
  2. Placebo (placebo); duration: 7 weeks; frequency/day: 4 (n=22).
Tripathi 1983; Trial held in India; parallel trial; Setting: secondary care.Inclusion & Exclusion criteria: Included: outpatients with vague abdominal pain, flatulence, loose motions and without any weight loss for the past 3 yrs, and not showing improvements with intestinal antiseptics.
Excluded: pregnant women; jaundice; those with organic illness. Type of IBS: Unclear. IBS definition: Authors' def.
Severity of IBS
symptoms: Not stated; Bloating/flatus: Some patients; Post infective: not stated. Age (range): 37 (13–60).
Gender (M/F): not stated. Co-morbidities: Mainly anxiety (MMPI score) in all patients. Inpatients in medical ward for 5 weeks. No other medication during the trial. Mean score at baseline on 10cm VAS depression scale and on anxiety
scale was about 1.6
  1. Trimipramine (tricyclic (sedative)); duration: 5 weeks; frequency/day: 3; amount 10 mg (n=25).
  2. Placebo (placebo); duration: 5 weeks; frequency/day: 3 (n=25).
Vij 1991; Trial held in India; parallel trial; Setting: secondary care.Inclusion & Exclusion criteria: Inclusion: IBS symptoms >3 months. Exclusions: organic disease. Type of IBS: Mixed. IBS definition: Symptoms described. Severity of IBS symptoms: mixed; Bloating/flatus: Not stated; Post infective: not stated. Age (range): 32yrs. Gender (M/F): 33/11; Co-morbidities: 57% psychiatric comorbidities IBS-D in 34; IBS-C in 10; IBS-A in 6 patients. 25/44 (57%) patients assessed to be 'probable psychiatric cases' using the GHQ. Previous treatment not stated.
  1. Doxepin 75mg (tricyclic); duration: 6 weeks; frequency/day: once daily; amount 75mg per day (n=25).
  2. Identical looking capsule (placebo); duration: 6 weeks; frequency/day: once daily (n=25).

From: Appendix C, Characteristics of included studies

Cover of Irritable Bowel Syndrome in Adults
Irritable Bowel Syndrome in Adults: Diagnosis and Management of Irritable Bowel Syndrome in Primary Care [Internet].
NICE Clinical Guidelines, No. 61.
National Collaborating Centre for Nursing and Supportive Care (UK).
Copyright © 2008, Royal College of Nursing.

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