Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2017 Jan 24;1(1):CD011128.
doi: 10.1002/14651858.CD011128.pub2.

Pharmacological treatment for antipsychotic-related constipation

Susanna Every-Palmer  1   2 , Giles Newton-Howes  3   4 , Mike J Clarke  5
Affiliations
Meta-Analysis

Pharmacological treatment for antipsychotic-related constipation

Susanna Every-Palmer et al. Cochrane Database Syst Rev. .

Abstract

Background: Antipsychotic-related constipation is a common and serious adverse effect, especially for people taking clozapine. Clozapine has been shown to impede gastrointestinal motility, leading to constipation, and has been reported in up to 60% of patients receiving clozapine. In rare cases, complications can be fatal. Appropriate laxatives should be prescribed to treat constipation in people taking antipsychotics, but there is a lack of guidance on the comparative effectiveness and harms of different agents in this population. An understanding of the effectiveness and safety of treatment for antipsychotic-related constipation is important for clinicians and patients alike.

Objectives: To evaluate the effectiveness and safety of pharmacologic treatment (versus placebo or compared against another treatment) for antipsychotic-related constipation (defined as constipated patients of any age, who are treated with antipsychotics, regardless of dose, in which constipation is considered to be an antipsychotic-related side effect).

Search methods: We searched the Cochrane Schizophrenia Group's Trials Register (15 June 2015), which is based on regular searches of MEDLINE, Embase, CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and registries of clinical trials, grey literature, and conference proceedings. There are no language, date, document type, or publication status limitations for inclusion of records in this register. We also handsearched bibliographies and contacted relevant authors for additional information.

Selection criteria: We included all published and unpublished randomised controlled trials (RCTs) investigating the efficacy of pharmacological treatments in patients with antipsychotic-related constipation. Pharmacological treatments included laxatives and other medicines that could reasonably be used to combat constipation in this population (e.g. anticholinergic agents, like bethanecol).

Data collection and analysis: Two review authors independently extracted data from all included studies and assessed trials for risk of bias. A third author reviewed 20% of trials. We analysed dichotomous data using relative risks (RR) and the 95% confidence intervals (CI). We assessed risk of bias for included studies and used GRADE to create a 'Summary of findings' table. We discussed any disagreement, documented decisions, and attempted to contact study authors when necessary.

Main results: We identified two relevant Chinese studies (N = 480) that contributed data to this review. Both studies were over ten years old and poorly reported, lacking descriptions of contemporary CONSORT reporting prerequisites, such as sequence generation, allocation concealment, blinding, participant flow, how the sample size was determined, or how outcomes were measured. The studies also did not report trial registration, pre-specified protocols, consent processes, ethical review, or funding source. We were unsuccessful in making contact with the authors to clarify the missing details. We classified both studies as having an overall high risk of bias.One study compared glycerol suppository with the traditional Chinese medicine (TCM) approaches of tuina massage and acupuncture. Compared to tuina massage, glycerol laxative was less effective in relieving constipation at both two days after treatment (1 RCT; N = 120; RR 2.88, 95% CI 1.89 to 4.39; very low-quality evidence), and three days (1 RCT; N = 120; RR 4.80, CI 1.96 to 11.74, very low-quality evidence). Favourable results were also seen for acupuncture at two days (1 RCT; N = 120; RR 3.50; 95% CI 2.18 to 5.62; very low-quality evidence), and at three days (1 RCT; N = 120; RR 8.00, 95% CI 2.54 to 25.16; very low-quality evidence).The other study compared mannitol, an osmotic laxative, with rhubarb soda or phenolphthalein. Mannitol was more effective than rhubarb soda or phenolphthalein in trelieving constipation within 24 hours of treatment (1 RCT; N = 240; RR 0.07; 95% CI 0.02 to 0.27, very low-quality evidence).No data were reported for our other important outcomes: need for rescue medication, bowel obstruction (a complication of antipsychotic-related constipation), quality of life, adverse events, leaving the study early, and economic costs.

Authors' conclusions: We had hoped to find clinically useful evidence appraising the relative merits of the interventions routinely used to manage antipsychotic-related constipation, a common and potentially serious adverse effect of the use of these drugs. The results were disappointing. There were no data comparing the common pharmacological interventions for constipation, such as lactulose, polyethylene glycol, stool softeners, lubricant laxatives, or of novel treatments such as linaclotide. Data available were very poor quality and the trials had a high risk of bias. Data from these biased studies suggested that mannitol, an osmotic laxative, was more effective than rhubarb soda and phenolphthalein in relieving constipation, and a two-week course of glycerol suppositories was less effective than the TCM approaches of tuina massage and acupuncture.Overall, there is insufficient trial-based evidence to assess the effectiveness and safety of pharmacological interventions for treating antipsychotic-related constipation, due to limited, poor quality data (few studies with high risk of bias and no meta-analyses). The methodological limitations in the included studies were obvious, and any conclusions based on their results should be made with caution. Methodologically rigorous RCTs evaluating interventions for treating antipsychotic-related constipation are needed.

PubMed Disclaimer

Conflict of interest statement

None declared.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Glycerol laxative versus Tuina massage, Outcome 1 Global or clinical change in constipation: change in frequency of defecation.
2.1
2.1. Analysis
Comparison 2 Glycerol laxative versus acupuncture, Outcome 1 Global or clinical change in constipation: change in frequency of defecation.
3.1
3.1. Analysis
Comparison 3 Mannitol versus phenolphthalein or rhubarb soda, Outcome 1 Global or clinical change in constipation: change in frequency of defecation.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD011128

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

References to studies included in this review

Fan 2004 {published data only}
    1. Fan Y, Luo W. Clinical study on treatment of constipation caused by antipsychotic drugs with acupuncture and Tuina combined with laxative suppository. Journal of Acupuncture and Tuina Science 2004;2(3):51‐4.
Wang 1995 {published data only}
    1. Wang SM, Cui XP, Wang Y. Oral administration of 10% mannitol treatment of psychiatric drug‐induced constipation. Journal of the Zhangjiakou Medical College 1995;12(1):16.

References to studies excluded from this review

Chukhin 2013 {published data only}
    1. Chukhin E, Takala P, Hakko H, Raidma M, Putkonen H, Rasanen P, et al. In a randomized placebo‐controlled add‐on study orlistat significantly reduced clozapine‐induced constipation. International Clinical Psychopharmacology 2013;28(2):67‐70. - PubMed
Ding 1998 {published data only}
    1. Ding Z. Study on the best therapy for neuroleptic‐induced astriction. Journal of Nursing Science [护理学杂志] 1998;13(4):197‐9.
Li 2002 {published data only}
    1. Li KQ. Chinese medicine treatment of antipsychotic chlorpromazine due to gastrointestinal adverse reactions. Efficacy 2002:188‐91.
Li 2004 {published data only}
    1. Li L, Xu H. A study on orally taking mannitol to treat psychosis patients with constipation. ECA 2004;18(6):1001‐2.
Li 2007 {published data only}
    1. Li Y, Guo Y, Jin S. Investigation on qihuangkongxian capsule in the treatment of slavering and constipation. Chinese Journal of Health Psychology 2007;15(9):836.
Lin 2006 {published data only}
    1. Lin MR. The effect of 'sit ups' on constipation in patients with schizophrenia. International Journal of Nursing 2006;25(1):58‐9.
Lin 2010 {published data only}
    1. Lin SL, Zhang SQ, Lin GL. Health education intervention on the impact of schizophrenia patients with constipation. General Nursing 2010;8(7C):1891‐3.
Lu 2001 {published data only}
    1. Lu BL, Chen CP. The clinical efficacy observed of homemade Chinese medicine treatment of antipsychotic gastrointestinal side effects. China Medicine Bulletin 2001;11:52‐4.
Lu 2002 {published data only}
    1. Lu BL, Chen CP. The homemade Chinese medicine treatment of antipsychotic induced gastrointestinal adverse reactions effect observed. Journal of Nursing Science 2002;17(5):361‐3.
Wang 2004 {published data only}
    1. Wang Y. Clinical observation of the effect on constipation by nursing intervention for hospitalized patients with psychosis. Journal of Nurses Training 2004;19(11):982‐4.
Wei 2010 {published data only}
    1. Wei B, Huang J, Xiao ZC. Life skills training activities of daily living in patients with schizophrenia and constipation. Modern Clinical Nursing 2010;9(5):63‐4, 27.
Yue 2002 {published data only}
    1. Yue S, Xu L, Sun X. A study of used abdominal massage therapy combined with physical exercise and hydropathy on treating constipation induced by antipsychotic drugs. Chinese Journal of Nursing 2002;37(8):568‐70.

References to studies awaiting assessment

Liang 2002 {published data only}
    1. Liang Y, Shuai S, Lin J. Therapeutic effects of rhubarb powder in the treatment of antipsychotic medication‐induced constipation. Journal of Nursing Science 2002;1(1):47‐8.
Zhang 2004 {published data only}
    1. Zhang ZC, Gao HZ. Therapeutic effects of aloe‐paste in the treatment of antipsychotic medication‐induced constipation. Journal of Qilu Nursing 2004;10(6):419‐20.

Additional references

Altman 1996
    1. Altman DG, Bland JM. Detecting skewness from summary information. BMJ 1996;313(7066):1200. - PMC - PubMed
Andresen 2007
    1. Andresen V, Camilleri M, Busciglio IA, Grudell A, Burton D, McKinzie S, et al. Effect of 5 days linaclotide on transit and bowel function in females with constipation‐predominant irritable bowel syndrome. Gastroenterology 2007;133(3):761‐8. - PubMed
Baptista 2015
    1. Baptista T, Carrizo E, Fernandez E, Connell L, Servigna M, Parra A, et al. Colonic transit diagnostic test shows significant gastrointestinal hypomotility in clozapine‐treated patients in comparison with subjects treated with other antipsychotics. Schizophrenia Research 2015;166:207‐11. - PubMed
BCC Research 2010
    1. BCC Research. Antipsychotic drugs: technologies and global markets. Report code: PHM063A. www.bccresearch.com/market‐research/pharmaceuticals/antipsychotic‐drugs‐... (accessed June 2010). [http://www.bccresearch.com/report/PHM063A.html. ]
Beal 2000
    1. Beal MW. Acupuncture and Oriental body work: traditional and biomedical concepts in holistic care: history and basic concepts. Holistic Nursing Practice 2000;14(3):69‐78. - PubMed
Bekelman 2003
    1. Bekelman JE, Li Y, Gross P. Scope and impact of financial conflicts of interest in biomedical research. Journal of the American Medical Association 2003;289(4):454‐65. - PubMed
Berk 2007
    1. Berk M, Fitzsimons J, Lambert T, Pantelis C, Kulkarni J, Castle D, et al. Monitoring the safe use of clozapine. CNS Drugs 2007;21(2):117‐27. - PubMed
Bickerstaff 1988
    1. Bickerstaff LK, Harris SC, Leggett RS, Cheah KC. Pain insensitivity in schizophrenic patients. A surgical dilemma. Archives of Surgery 1988;123(11):49‐51. - PubMed
Bland 1997
    1. Bland JM. Statistics notes. Trials randomised in clusters. BMJ 1997;315:600. - PMC - PubMed
Bleser 2005
    1. Bleser S, Brunton S, Carmichael B, Olden K, Rasch R, Steege J. Management of chronic constipation: recommendations from a consensus panel. Journal of Family Practice 2005;54(8):691‐8. - PubMed
Boissel 1999
    1. Boissel JP, Cucherat M, Li W, Chatellier G, Gueyffier F, Buyse M, et al. The problem of therapeutic efficacy indices. 3. Comparison of the indices and their use [Apercu sur la problematique des indices d'efficacite therapeutique, 3: comparaison des indices et utilisation. Groupe d'Etude des Indices D'efficacite]. Therapie 1999;54(4):405‐11. [PUBMED: 10667106] - PubMed
Boley 1969
    1. Boley SJ, Agrawal GP, Warren AR, Veith FJ, Lebowitz BS, Treiber W, et al. Pathophysiologic effects of bowel distension on intestinal blood flow. American Journal of Surgery 1969;117(2):228‐34. - PubMed
Brandt 2005
    1. Brandt LJ, Prather CM, Quigley EM, Schiller LR, Schoenfeld P, Talley NJ. Systematic review on the management of chronic constipation in North America. American Journal of Gastroenterology 2005;100(Suppl 1):S5‐S21. - PubMed
Camilleri 2008
    1. Camilleri M, Kerstens R, Rykx A, Vandeplassche L. A placebo‐controlled trial of prucalopride for severe chronic constipation. New England Journal of Medicine 2008;358(22):2344–54. - PubMed
Camilleri 2009
    1. Camilleri M, Beyens G, Kerstens R, Robinson P, Vandeplassche L. Safety assessment of prucalopride in elderly patients with constipation: a double‐blind, placebo‐controlled study. Neurogastroenterology and Motility 2009;21(12):1256–63. - PubMed
Candy 2015
    1. Candy B, Jones L, Larkin PJ, Vickerstaff V, Tookman A, Stone P. Laxatives for the management of constipation in people receiving palliative care. Cochrane Database of Systematic Reviews 2015, Issue 5. [DOI: 10.1002/14651858.CD003448.pub4] - DOI - PMC - PubMed
Chey 2011
    1. Chey WD, Camilleri M, Chang L, Rikner L, Graffner H. A randomized placebo‐controlled phase IIb trial of a3309, a bile acid transporter inhibitor, for chronic idiopathic constipation. American Journal of Gastroenterology 2011;106:1803‐12. - PMC - PubMed
Coggrave 2009
    1. Coggrave M, Wiesel P, Norton CC. Management of faecal incontinence and constipation in adults with central neurological diseases. Cochrane Database of Systematic Reviews 2009, Issue 1. [DOI: 10.1002/14651858.CD002115.pub3] - DOI - PubMed
Cohen 2012
    1. Cohen D, Bogers JP, Dijk D, Bakker B, Schulte PF. Beyond white blood cell monitoring: screening in the initial phase of clozapine therapy. Journal of Clinical Psychiatry 2012;73(10):1307‐12. - PubMed
Crowell 2001
    1. Crowell MD. The role of serotonin in the pathophysiology of irritable bowel syndrome. American Journal of Managed Care 2001;7(suppl):S252‐S260. - PubMed
Damon 2004
    1. Damon H, Dumas P, Mion F. Impact of anal incontinence and chronic constipation on quality of life. Gastroentérologie Clinique et Biologique 2004;28(1):16–20. - PubMed
Deeks 2000
    1. Deeks J. Issues in the selection for meta‐analyses of binary data. 8th International Cochrane Colloquium; 2000 Oct 25‐28; Cape Town. Cape Town: The Cochrane Collaboration, 2000.
Deeks 2011
    1. Deeks JJ, Higgins JPT, Altman DG, editor(s). Chapter 9: Analysing data and undertaking meta‐analyses. In: Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.handbook.cochrane.org.
Dennison 2005
    1. Dennison C, Prasad M, Lloyd A, Bhattacharyya SK, Dhawan R, Coyne K. The health‐related quality of life and economic burden of constipation. Pharmacoeconomics 2005;23:461–76. - PubMed
Divine 1992
    1. Divine GW, Brown JT, Frazier LM. The unit of analysis error in studies about physicians' patient care behavior. Journal of General Internal Medicine 1992;7(6):623‐9. - PubMed
Donner 2002
    1. Donner A, Klar N. Issues in the meta‐analysis of cluster randomized trials. Statistics in Medicine 2002;21:2971‐80. - PubMed
Drew 1997
    1. Drew L, Herdson P. Clozapine and constipation: a serious issue. Australian and New Zealand Journal of Psychiatry 1997;31(1):149‐50. - PubMed
Drossman 2016
    1. Drossman DA. Functional gastrointestinal disorders: history, pathophysiology, clinical features, and Rome IV. Gastroenterology 2016;150(6):1262‐79. - PubMed
Dworkin 1994
    1. Dworkin RH. Pain insensitivity in schizophrenia: a neglected phenomenon and some implications. Schizophrenia Bulletin 1994;20(2):235‐48. - PubMed
Egger 1997
    1. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. BMJ 1997;315:629‐34. - PMC - PubMed
Elbourne 2002
    1. Elbourne D, Altman DG, Higgins JPT, Curtina F, Worthingtond HV, Vaile A. Meta‐analyses involving cross‐over trials: methodological issues. International Journal of Epidemiology 2002;31(1):140‐9. - PubMed
Evans 2008
    1. Evans BW, Clark WK, Moore DJ, Whorwell PJ. Tegaserod for the treatment of irritable bowel syndrome and chronic constipation. Cochrane Database of Systematic Reviews 2008, Issue 4. [DOI: 10.1002/14651858.CD003960.pub3] - DOI - PubMed
Every‐Palmer 2014
    1. Every‐Palmer S, Howick J. How evidence‐based medicine is failing due to biased trials and selective publication. Journal of Evaluation in Clinical Practice 2014;20:908‐14. [DOI: 10.1111/jep.12147] - DOI - PubMed
Every‐Palmer 2016
    1. Every‐Palmer S, Nowitz M, Stanley J, Grant E, Huthwaite M, Dunn H, et al. Clozapine associated with marked gastrointestinal hypomotility, the probable basis of life‐threatening gastrointestinal complications: a cross sectional study. EBioMedicine 2016;5:125‐34. [DOI: 10.1016/j.ebiom.2016.02.020] - DOI - PMC - PubMed
Every‐Palmer 2017
    1. Every‐Palmer S, Ellis PM, Nowitz M, Stanley J, Grant E, Huthwaite M, et al. The Porirua Protocol in the treatment of clozapine‐induced gastrointestinal hypomotility and constipation: a pre‐ and post‐treatment study. CNS Drugs 2017;31(1):75‐85. [DOI: ] - PubMed
Fishbain 1982
    1. Fishbain DA. Pain insensitivity in psychosis. Annals of Emergency Medicine 1982;11:630‐2. - PubMed
Ford 2011
    1. Ford AC, Suares NC. Effect of laxatives and pharmacological therapies in chronic idiopathic constipation: systematic review and meta‐analysis. Gut 2011;60:209‐18. - PubMed
Furukawa 2006
    1. Furukawa TA, Barbui C, Cipriani A, Brambilla P, Watanabe N. Imputing missing standard deviations in meta‐analyses can provide accurate results. Journal of Clinical Epidemiology 2006;59(7):7‐10. - PubMed
Glia 1997
    1. Glia A, Lindberg G. Quality of life in patients with different types of functional constipation. Scandinavian Journal of Gastroenterology 1997;32(11):1083–9. - PubMed
Gulliford 1999
    1. Gulliford MC. Components of variance and intraclass correlations for the design of community‐based surveys and intervention studies: data from the Health Survey for England 1994. American Journal of Epidemiology 1999;149:876‐83. - PubMed
Hasan 2012
    1. Hasan AP, Falkai T, Wobrock J, Lieberman B, Glenthoj WF, Gattaz WF, et al. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. The World Journal of Biological Psychiatry 2012;13(5):318‐78. - PubMed
Hasan 2016
    1. Hasan A. Clozapine‐induced gastrointestinal hypomotility — new objective evidence for an underestimated side‐effect. EBioMedicine 2016;31(5):12‐3. - PMC - PubMed
Hass 2007
    1. Hass DJ, Kozuch P, Brandt LJ. Pharmacologically mediated colon ischemia. American Journal of Gastroenterology 2007;102:1765‐80. - PubMed
Hibbard 2009
    1. Hibbard KR, Propst A, Frank DE, Wyse J. Fatalities associated with clozapine‐related constipation and bowel obstruction: a literature review and two case reports. Psychosomatics 2009;50(4):416‐9. - PubMed
Higgins 2003
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327:557‐60. - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Green S editor(s). Chapter 7: Selecting studies and collecting data. In: Higgins JPT, Green S, editor(s), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.handbook.cochrane.org.
Higgins 2011a
    1. Higgins JPT, Altman DG, Sterne JAC, editor(s). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.handbook.cochrane.org.
Honigfeld 1998
    1. Honigfeld G, Arellano F, Sethi J, Bianchini A, Schein J. Reducing clozapine‐related morbidity and mortality: 5 years of experience with the Clozaril national registry. Journal of Clinical Psychiatry 1998;59(3S):3‐7. - PubMed
Horsley 2011
    1. Horsley T, Dingwall O, Sampson M. Checking reference lists to find additional studies for systematic reviews. Cochrane Database of Systematic Reviews 2011, Issue 8. [DOI: 10.1002/14651858.MR000026.pub2] - DOI - PMC - PubMed
Hutton 2009
    1. Hutton JL. Number needed to treat and number needed to harm are not the best way to report and assess the results of randomised clinical trials. British Journal of Haematology 2009;146(1):27‐30. - PubMed
Jewell 2009
    1. Jewell D, Young G. Interventions for treating constipation in pregnancy. Cochrane Database of Systematic Reviews 2009, Issue 1. [DOI: 10.1002/14651858.CD001142] - DOI
Johanson 2004
    1. Johanson JF, Wald A, Tougas G, Chey WD, Novick JS. Lembo AJ, et al. Effect of tegaserod in chronic constipation: a randomized, double‐blind, controlled trial. Clinical Gastroenterology and Hepatology 2004;2(9):796‐805. - PubMed
Johanson 2004a
    1. Johanson JF. Review article: tegaserod for chronic constipation. Alimentary Pharmacology & Therapeutics 2004;20(Suppl 7):20‐4. - PubMed
Johanson 2005
    1. Johanson JF, Gargano MA, Holland PC, Patchen M, Ueno R. Multicenter open‐label study of oral lubiprostone for the treatment of chronic constipation. American Journal of Gastroenterology 2005;100(Suppl 9):S331.
Johanson 2005a
    1. Johanson JF, Gargano MA, Holland PC, Patchen M, Ueno R. Phase III study of lubiprostone, a chloride channel‐2 (ClC‐2) activator, for the treatment of constipation: safety and primary efficacy. American Journal of Gastroenterology 2005;100(Suppl 9):S328.
Johanson 2007
    1. Johanson JF, Ueno R. Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double‐blind, placebo‐controlled, dose‐ranging study to evaluate efficacy and safety. Alimentary Pharmacology & Therapeutics 2007;25(11):1351‐61. - PubMed
Johanson 2008
    1. Johanson JF, Drossman DA, Panas R, Wahle A, Ueno R. Clinical trial: phase 2 study of lubiprostone for irritable bowel syndrome with constipation. Alimentary Pharmacology & Therapeutics 2008;27(8):685–96. - PubMed
Jones 2002
    1. Jones MP, Talley NJ, Nuyts G, Dubois D. Lack of objective evidence of efficacy of laxatives in chronic constipation. Digestive Diseases and Sciences 2002;47(10):2222‐30. - PubMed
Kamm 2005
    1. Kamm MA, Muller‐Lissner S, Talley NJ, Tack J, Boeckxstaens G, Minushkin ON, et al. Tegaserod for the treatment of chronic constipation: a randomized, double‐blind, placebo‐controlled multinational study. American Journal of Gastroenterology 2005;100(2):362‐72. - PubMed
Lambert 2004
    1. Lambert TJ, Chapman LH. Diabetes, psychotic disorders and antipsychotic therapy: a consensus statement. Medical Journal of Australia 2004;181(10):544‐8. - PubMed
Lee‐Robichaud 2010
    1. Lee‐Robichaud H, Thomas K, Morgan J, Nelson RL. Lactulose versus polyethylene glycol for chronic constipation. Cochrane Database of Systematic Reviews 2010, Issue 7. [DOI: 10.1002/14651858.CD007570.pub2] - DOI - PubMed
Lembo 2010
    1. Lembo AJ, Kurtz CB, Macdougall JE, Lavins BJ, Currie MG, Fitch DA, et al. Linaclotide is effective for patients with chronic constipation. Gastroenterology 2010;138:886–95. - PubMed
Leon 2006
    1. Leon AC, Mallinckrodt CH, Chuang‐Stein C, Archibald DG, Archer GE, Chartier K. Attrition in randomized controlled clinical trials: methodological issues in psychopharmacology. Biological Psychiatry 2006;59(11):1001‐5. [PUBMED: 16905632] - PubMed
Leung 2008
    1. Leung JS, Lee CC, Lee WK, Kwong PP. Rapidly fatal clozapine‐induced intestinal obstruction without prior warning signs. Australian and New Zealand Journal of Psychiatry 2008;42(12):1073‐4. - PubMed
Lieberman 1989
    1. Lieberman JA, Kane JM, Johns CA. Clozapine: guidelines for clinical management. Journal of Clinical Psychiatry 1989;50(9):329‐38. - PubMed
Lundh 2012
    1. Lundh A, Sismondo S, Lexchin J, Busuioc OA, Bero L. Industry sponsorship and research outcome. Cochrane Database of Systematic Reviews 2012, Issue 12. [DOI: 10.1002/14651858.MR000033.pub2] - DOI - PubMed
Marshall 2000
    1. Marshall M, Lockwood A, Bradley C, Adams C, Joy C, Fenton M. Unpublished rating scales: a major source of bias in randomised controlled trials of treatments for schizophrenia. British Journal of Psychiatry 2000;176:249‐52. - PubMed
Meek 2008
    1. Meek PM, Coates SD, Norelli L, Woodcock DP, Shobola O, Dreyfus S, et al. Constipation in patients with schizophrenia: a systematic review of antipsychotic trials comparing clozapine. Gastroenterology 2008;134(4 Suppl 1A):528.
Moher 2001
    1. Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel‐group randomised trials. Lancet 2001;357(9263):1191‐4. - PubMed
Nielsen 2012
    1. Nielsen J, Meyer JM. Risk factors for ileus in patients with schizophrenia. Schizophrenia Bulletin 2012;38(3):592‐8. - PMC - PubMed
Ozbilen 2009
    1. Ozbilen M, Adams CE. Systematic overview of Cochrane reviews for anticholinergic effects of antipsychotic drugs. Journal of Clinical Psychopharmacology 2009;29(2):141‐6. - PubMed
Palmer 2008
    1. Palmer SE, Mclean R, Ellis PM, Harrison‐Woolrych M. Life‐threatening clozapine‐induced gastrointestinal hypomotility. Journal of Clinical Psychiatry 2008;69(5):759‐68. - PubMed
Panchal 2007
    1. Panchal SJ, Müller‐Schwefe P, Wurzelmann JI. Opioid‐induced bowel dysfunction: prevalence, pathophysiology and burden. International Journal of Clinical Practice 2007;61:1181‐7. - PMC - PubMed
Qu 2011
    1. Qu HB, Dengfeng W, Wu T, Marjoribanks J, Ying S, Haijun J, et al. Chinese herbal medicine in the treatment of ectopic pregnancy. Cochrane Database of Systematic Reviews 2011, Issue 7. [DOI: 10.1002/14651858.CD006224.pub3] - DOI - PubMed
Ramkumar 2005
    1. Ramkumar D, Rao SS. Efficacy and safety of traditional medical therapies for chronic constipation: systematic review. American Journal of Gastroenterology 2005;100(4):936‐71. - PubMed
Rao 2011
    1. Rao SS, Camilleri M, Hasler WL, Maurer AH, Parkman HP, Saad R, et al. Evaluation of gastrointestinal transit in clinical practice: position paper of the American and European Neurogastroenterology and Motility Societies. Neurogastroenterology & Motility 2011;23:8‐23. - PubMed
Roarty 1997
    1. Roarty TP, Weber F, Soykan I, McCallum RW. Misoprostol in the treatment of chronic refractory constipation: results of a long‐term open label trial. Alimentary Pharmacology & Therapeutics 1997;11(6):1059‐66. - PubMed
Rosenthal 1990
    1. Rosenthal SH, Porter KA, Coffey B. Pain insensitivity in schizophrenia. Case report and review of the literature. General Hospital Psychiatry 1990;12(5):319‐22. - PubMed
Rousseau 2007
    1. Rousseau A, Charbonneau M. Severe faecal impaction under clozapine, resulting in death. Journal de l' Association des Médecins Psychiatres du Québec 2007;11:16‐8.
Rungsiprakarn 2015
    1. Rungsiprakarn P, Laopaiboon M, Sangkomkamhang US, Lumbiganon P, Pratt JJ. Interventions for treating constipation in pregnancy. Cochrane Database of Systematic Reviews 2015, Issue 9. [DOI: 10.1002/14651858.CD011448] - DOI - PMC - PubMed
Schulz 2010
    1. Schulz KF, Altman DG, Moher D, CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. PLoS Medicine 2010;7(3):e1000251. [PUBMED: 20352064] - PMC - PubMed
Schünemann 2011
    1. Schünemann HJ, Oxman AD, Vist GE, Higgins JPT, Deeks JJ, Glasziou P, et al. Chapter 12: Interpreting results and drawing conclusions. In: Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Intervention. Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.handbook.cochrane.org.
Shammi 1997
    1. Shammi CM, Remington G. Clozapine‐induced necrotizing colitis. Journal of Clinical Psychopharmacology 1997;17(3):230‐1. - PubMed
Shirazi 2016
    1. Shirazi A, Stubbs B, Gomez L, Moore S, Gaughran F, Flanagan RJ, et al. Prevalence and predictors of clozapine‐associated constipation: a systematic review and meta‐analysis. International Journal of Molecular Sciences 2016;17(6):863. - PMC - PubMed
Singh 2006
    1. Singh MK, Giles LL, Nasrallah HA. Pain insensitivity in schizophrenia: trait or state marker?. Journal of Psychiatric Practice 2006;12(2):90‐102. - PubMed
Sirois 2005
    1. Sirois JF. Haloperidol‐induced ileus. Psychosomatics 2005;46:275. - PubMed
Soffer 1994
    1. Soffer EE, Metcalf A, Launspach J. Misoprostol is effective treatment for patients with severe chronic constipation. Digestive Diseases and Sciences 1994;39(5):929–33. - PubMed
Song 2010
    1. Song F, Parekh S, Hooper L, Loke YK, Ryder J, Sutton AJ, et al. Dissemination and publication of research findings: an updated review of related biases. Health Technology Assessment. 2010;14(8):1‐193. [DOI: 10.3310/hta14080] - DOI - PubMed
Sterne 2011
    1. Sterne JAC, Egger M, Moher D, editor(s). Chapter 10: Addressing reporting biases. In: Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Intervention. Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.handbook.cochrane.org.
Tack 2006
    1. Tack J, Middleton SJ, Horne MC, Piessevaux H, Bloor JS, Meyers NL, et al. Pilot study of the efficacy of renzapride on gastrointestinal motility and symptoms in patients with constipation‐predominant irritable bowel syndrome. Alimentary Pharmacology & Therapeutics 2006;23(11):1655‐65. - PubMed
Taghavi 2010
    1. Taghavi SA, Shabani S, Mehramiri A, Eshraghian A, Kazemi SM, Moeini M, et al. Colchicine is effective for short‐term treatment of slow transit constipation: a double‐blind placebo‐controlled clinical trial. International Journal of Colorectal Disease 2010;25(3):389–94. - PubMed
Talley 2003
    1. Talley NJ, Jones M, Nuyts G, Dubois D. Risk factors for chronic constipation based on a general practice sample. American Journal of Gastroenterology 2003;98:1107–11. - PubMed
Ukoumunne 1999
    1. Ukoumunne OC, Gulliford MC, Chinn S, Sterne JAC, Burney PGJ. Methods for evaluating area‐wide and organisation‐based intervention in health and health care: a systematic review. Health Technology Assessment 1999;3(5):1‐75. - PubMed
Vandenplas 1999
    1. Vandenplas Y, Belli D, Benatar A. The role of cisapride in the treatment of paediatric gastroesophageal reflux. Journal of Pediatric Gastroenterology and Nutrition 1999;28:518–28. - PubMed
Verne 1997
    1. Verne GN, Eaker EY, Davis RH, Sninsky CA. Colchicine is an effective treatment for patients with chronic constipation: an open‐label trial. Digestive Diseases and Sciences 1997;42(9):1959‐63. - PubMed
Verne 2003
    1. Verne GN, Davis RH, Robinson ME, Gordon JM, Eaker EY, Sninksy CA. Treatment of chronic constipation with colchicine: randomized, double‐blind, placebo‐controlled, crossover trial. American Journal of Gastroenterology 2003;98(5):1112‐26. - PubMed
Wald 2007
    1. Wald A, Scarpignato C, Kamm MA, Mueller‐Lissner S, Helfrich I, Schuijt C, et al. The burden of constipation on quality of life: results of a multinational survey. Alimentary Pharmacology & Therapeutics 2007;26(2):227‐36. - PubMed
Wong 2011
    1. Wong BS, Camilleri M, McKinzie S, Burton D, Graffner H, Zinsmeister AR. Effects of A3309, an ileal bile acid transporter inhibitor, on colonic transit and symptoms in females with functional constipation. American Journal of Gastroenterology 2011;106:2154‐64. - PubMed
Xia 2009
    1. Xia J, Adams CE, Bhagat N, Bhagat V, Bhoopathi P, El‐Sayeh H, et al. Loss to outcomes stakeholder survey: the LOSS study. Psychiatric Bulletin 2009;33(7):254‐7.
Young 2011
    1. Young T, Hopewell S. Methods for obtaining unpublished data. Cochrane Database of Systematic Reviews 2011, Issue 11. [DOI: 10.1002/14651858.MR000027.pub2] - DOI - PMC - PubMed

References to other published versions of this review

Every‐Palmer 2014b
    1. Every‐Palmer S, Newton‐Howes G, Clarke MJ. Pharmacological treatment for antipsychotic‐related constipation. Cochrane Database of Systematic Reviews 2014, Issue 5. [DOI: 10.1002/14651858.CD011128] - DOI - PMC - PubMed

Publication types