Laxative AbuseEpidemiology, Diagnosis and Management

James L. Roerig,1,2 Kristine J. Steffen,2 James E. Mitchell1,2 and Christie Zunker2

1 Department of Clinical Neuroscience, University of North Dakota School of Medicine and Health

Sciences, Fargo, North Dakota, USA

2 Neuropsychiatric Research Institute, Fargo, North Dakota, USA

Contents

Abstract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14871. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14882. Gastrointestinal Functioning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14893. Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1490

3.1 Eating Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14903.2 Habitual Laxative Abuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1490

4. Presentation/Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14915. Types of Laxatives. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1493

5.1 Stimulant Laxatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14935.1.1 Diphenylmethane Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14935.1.2 Anthraquinone Derivatives. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14945.1.3 Castor Oil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14945.1.4 Colorectal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1495

5.2 Bulk-Forming Laxatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14955.3 Saline Laxatives. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14955.4 Osmotic Laxatives. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14955.5 Surfactants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14965.6 Lubricants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1496

6. Medical Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14966.1 Electrolyte Disturbances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14966.2 Metabolic Disturbances. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14976.3 Bowel Disturbances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14976.4 Kidney Disturbances. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14976.5 Miscellaneous Disturbances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1498

7. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14988. Summary and Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1499

Abstract Laxatives have been used for health purposes for over 2000 years, and formuch of that time abuse or misuse of laxatives has occurred. Individuals whoabuse laxatives can generally be categorized as falling into one of four groups.By far the largest group is made up of individuals suffering from an eatingdisorder such as anorexia or bulimia nervosa. The prevalence of laxative abusehas been reported to range from approximately 10% to 60% of individuals inthis group. The second group consists of individuals who are generally middleaged or older who begin using laxatives when constipated but continue tooveruse them. This pattern may be promulgated on certain beliefs that daily

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bowel movements are necessary for good health. The third group includesindividuals engaged in certain types of athletic training, including sports withset weight limits. The fourth group contains surreptitious laxative abuserswho use the drugs to cause factitious diarrhoea and may have a factitiousdisorder.

Normal bowel function consists of the absorption of nutrients, electrolytesand water from the gut. Most nutrients are absorbed in the small intestine,while the large bowel absorbs primarily water. There are several types oflaxatives available, including stimulant agents, saline and osmotic products,bulking agents and surfactants. The most frequently abused group of laxa-tives are of the stimulant class. This may be related to the quick action ofstimulants, particularly in individuals with eating disorders as they may er-roneously believe that they can avoid the absorption of calories via the re-sulting diarrhoea.

Medical problems associated with laxative abuse include electrolyte andacid/base changes that can involve the renal and cardiovascular systems andmay become life threatening. The renin-aldosterone system becomes acti-vated due to the loss of fluid, which leads to oedema and acute weight gainwhen the laxative is discontinued. This can result in reinforcing furtherlaxative abuse when a patient feels bloated and has gained weight.

Treatment begins with a high level of suspicion, particularly when a pa-tient presents with alternating diarrhoea and constipation as well as othergastrointestinal complaints. Checking serum electrolytes and the acid/basestatus can identify individuals who may need medical stabilization and con-firm the severity of the abuse. The first step in treating laxative misuse once itis identified is to determine what may be promoting the behaviour, such as aneating disorder or use based on misinformation regarding what constitutes ahealthy bowel habit. The first intervention would be to stop the stimulantlaxatives and replace them with fibre/osmotic supplements utilized to estab-lish normal bowel movements. Education and further treatment may be re-quired to maintain a healthy bowel programme. In the case of an eatingdisorder, referral for psychiatric treatment is essential to lessen the reliance onlaxatives as a method to alter weight and shape.

1. Introduction

For more than 2000 years, purgative use hasbeen an important element in medical therapy.However, laxatives are increasingly used as amethod of weight control.[1] Individuals whoabuse laxatives can generally be categorized asfalling into one of four groups. The first includesthose with eating disorders, a group of patientswho are well known to have a high prevalence oflaxative abuse.[2] In light of the high prevalence oflaxative abuse in this group, reported to rangefrom approximately 10% to 60%, we review it indetail. The second group consists of individuals

who are generally middle aged or older who beginusing laxatives when constipated, but who con-tinue to overuse them to the point that theirbowel becomes relatively refractory to the laxa-tives.[3] Considering that normal stool frequencyon a Western diet is at least three times a week,excessive use may begin with the belief that dailybowel evacuation is necessary for good health.[4]

It can also be the result of increased constipationassociated with a variety of causes including poordiet, decreased mobility or concomitant drugtherapy. As these patients become dependent onlaxatives, it becomes increasingly hard to inter-vene. Both of these use patterns are associated

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with medical complications that may have a sig-nificant impact on the health of the patient, andhighlight the need for early detection and inter-vention. The third group includes individualsengaged in certain types of athletic training,including sports with set weight limits. The sub-group here that has perhaps been best char-acterized includes wrestlers, who take laxatives asa way to drop weight.[5] The fourth group con-tains surreptitious laxative abusers who use thedrugs to cause factitious diarrhoea and may havea factitious disorder.[6,7]

Eating disorder patients constitute the largestgroup of individuals who abuse laxatives and arecertainly the best characterized. These patientsmay initially take laxatives in response to con-stipation. This is particularly true of patients withanorexia nervosa who, because of low food in-take and dehydration, frequently have problemswith constipation. However, most eating disorderpatients take laxatives to induce diarrhoea in or-der to feel thinner, and in an attempt to get rid ofunwanted calories and lose weight. Often, laxa-tives are misused following eating binges, whenthe individual mistakenly believes that the laxa-tives will work to rush food and calories throughthe gut before they can be absorbed and, thus,will prevent calorie absorption and weight gain.[8]

Obviously, these individuals are very concernedabout weight and shape, and see laxative abuse asone method of controlling their bodyweight. Thisabuse sets up a vicious cycle in which they becomedehydrated because of fluid loss, retain fluid be-cause of the renin-angiotensen response to dehy-dration, gain fluid weight and then need to usethe laxatives again to dehydrate themselves. Also,because their bowels become relatively refractoryto laxatives, they need to escalate the dose to getthe same effect, and eventually develop patternsof using large amounts of laxatives.[9] The goal ofthis review is to acquaint the practitioner with theepidemiology, presentation and management oflaxative abuse.

2. Gastrointestinal Functioning

The main function of the gastrointestinal (GI)tract is the extraction of fluid and nutrients from

the contents present in the lumen. Nutrients areabsorbed mainly by the small intestine and theright colon absorbs mainly water and electro-lytes. As faecal matter moves into the left colon,it becomes more formed.[10] Control of the GItract involves intrinsic and extrinsic innervation.The intrinsic innervation involves the entericnervous system,[11-13] and comprises myenteric,submucosal and mucosal neuronal layers. Nor-mal functioning of these layers involves inter-neurons and utilizes neurotransmitter aminesand/or peptides, including acetylcholine, vaso-active intestinal peptide, opioids, noradrenaline(norepinephrine), serotonin, adenosine triphos-phate and nitric oxide. The myenteric plexusregulates smooth-muscle function. The submu-cosal plexus regulates secretion, fluid transportand vascular flow.[14,15] The extrinsic innerva-tion of the GI tract involves the parasympatheticautonomic nervous system which modulatesmotor and secretory functions. The excitatoryneurotransmitters controlling motor function areacetylcholine and the tachykinins, such as sub-stance P.

Ultimately, fluid content is important in thedetermination of stool consistency and volume,with water accounting for 70–85% of total stoolweight. A balance exists between the ingestionand secretion of water and electrolytes into theGI tract and the absorption over its length. Eightto ten litres of fluid enter the small intestine daily.Due to osmotic gradients, absorption of water inthe small intestine reduces the fluid presented tothe large bowel to only 1–5L. The colon extractsmost of the remaining fluid, leaving about100mL of faecal water daily. This process can bealtered by neurohumoral mechanisms, pathogensand drugs. The extent of water absorption is alsoinfluenced by the GI transit time. Colon motilityis made up of two types of contractions: non-propulsive contractions provide a mixing func-tion and propulsive contractions move thecontents of the bowel toward the rectum. SlowedGI motility results in a slower GI transit time,allowing more water to be absorbed, which canlead to constipation. Rapid transit time results inless water absorption, with the potential for re-sulting diarrhoea.[14,15]

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Various drugs can affect this system. The useof anticholinergic drugs such as benztropine ordiphenhydramine results in a slowing of the GItract with the potential for constipation. On theother hand, a variety of drugs have a prokineticeffect on the bowel. These include cholinergicagents (bethanechol), acetylcholinesterase inhibi-tors (neostigmine or donepezil), dopamine-receptorantagonists (metoclopramide), serotonin enhancingdrugs such as selective serotonin reuptake inhibi-tors, and motilin receptor agonists (erythromycinand other macrolide antibiotics).[16-18]

3. Epidemiology

3.1 Eating Disorders

Studies investigating the prevalence of laxativeabuse are complicated. Virtually all investiga-tions rely on self report and many have used dif-ferent criteria to define laxative abuse. Overall,the lifetime occurrence of laxative abuse has beenreported to be 4.18% in the general popula-tion.[19] However, the authors reported that therates are substantially higher in people who sufferfrom an eating disorder. The lifetime occurrenceamong individuals with bulimia nervosa was14.94%, greater than a 3-fold increase over theprevalence in the general population. Other stud-ies have reported that laxative abuse amongpatients with bulimia nervosa range from 18% to75%.[20-22] In a consecutive series of 100 patientswith bulimia nervosa, Mitchell et al.[23] reportedfinding that 36% had abused laxatives for weightcontrol purposes during the month prior to eva-luation. More recently, Steffen et al.[24] reportedthat laxatives had been used at some point tocontrol weight or ‘‘get rid of food’’ by 67% of 39eating disorder patients surveyed. Of these, 31%reported abuse of laxatives during the monthprior to evaluation. Phelps et al.[1] studied theprevalence of laxative abuse over time in adoles-cent females. They surveyed students on threeoccasions (1984, 1989 and 1992). Prevalence oflaxative use for weight control remained rela-tively stable over the time period, ranging from3.2% to 5.5% of those in high school and 0–1.8%of those in middle school (ages 13–15 years).

Recently, Steffen and colleagues[25] explored theuse of herbal laxatives and found that of 100participants with eating disorder symptoms, 26%reported having used a herbal laxative at somepoint in time.

A difference in the prevalence of laxativeabuse between eating disorder diagnoses mayexist. A study compared subjects with bulimianervosa – purging subtype (BN-P) and eatingdisorders not otherwise specified – purging only(EDNOS-P) with controls.[26] Laxative abuse wasutilized significantly more frequently in theEDNOS-P group than by BN-P subjects (62% vs27%; p < 0.04) as their purging method, whilevomiting was more frequently used in the BN-Pgroup than by EDNOS-P subjects (86% vs 38%;p < 0.001). A study in adolescents diagnosed withanorexia nervosa examined laxative use via self-report and biochemical laboratory evaluation,which included serum electrolytes, calcium,magnesium and phosphate levels, and urinarylaxative screening for the stimulant laxativesbisacodyl, phenolphthalein and rhein.[27] Cau-tion should be utilized when monitoring laxativeuse via laboratory assessment; difficulties withassays for senna and bisacodyl have recentlybeen reported.[9] The frequency of laxative usefrom self-report alone was 12% and when com-bined with urine screening was 19%. With pro-spective follow-up, the frequency of laxativeuse increased to 32%. By all accounts, laxativeabuse is not uncommon in patients with eatingdisorders.

3.2 Habitual Laxative Abuse

Unfortunately, the prevalence of chroniclaxative use is difficult to quantify in light of thecondition often being overlooked or the diag-nosis being made only after extensive investiga-tions have proven negative.[28,29] Studies suggestthat the prevalence of constipation is as high as50% in the elderly, which increases to 74% ofnursing home residents using daily laxatives.[30-32]

However, this probably under-represents the trueimpact of constipation and subsequent medicaluse, as many people either do not seek medicalattention or use over-the-counter remedies (either

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alone or in combination with those prescribed bytheir physician).

The elderly are a group of individuals withunique health challenges and different medicalneeds than their younger counterparts. The highfrequency of laxative use in the elderly may becaused, in part, by underestimation of stool fre-quency.[30] This can lead them to plan theirschedules around their bowel movements. Un-fortunately, laxative treatments in these patientsoften precipitate loose stools and incontinence.Subsequently, they may present to their health-care provider with diarrhoea of unknown origin.Habitually used laxatives constitute an importantcause of chronic diarrhoea in these patients.[33]

Extensive medical investigations and an increasein the lengths of hospital stays are associated withdiarrhoea of unknown origin. However, there aremany people who are well served by chroniclaxative use, such as patients with chronic con-stipation due to slow colonic transit or pelvicfloor dysfunction.

4. Presentation/Diagnosis

The most important factor in making thediagnosis of laxative abuse is a high index ofsuspicion on the part of the clinician. If possible,objective evidence for laxative abuse should beobtained. However, laxative use is often carriedout in secret and patients may be less thanforthcoming regarding self report. The only signthat has been found to be suggestive of chroniclaxative use is melanosis coli, a non-pathological,reversible, pigmentation of the colon associatedwith anthraquinone use.[34] A pattern of diar-rhoea alternating with constipation, as well asother GI symptoms, may be reported. A varietyof laboratory tests are helpful in determining thediagnosis. Serum hypokalaemia in eating dis-order patients has been suggested to be definitiveevidence of purging, including by laxative use.[35]

In the presence of culture-negative diarrhoea,faecal electrolytes can aid in diagnosis.[33] Thisanalysis includes quantification of the osmolality,the electrolyte composition and the pH level ofstool water, with the calculation of the osmoticgap.[36-38] Diarrhoea caused by stimulant laxa-

tives (such as bisacodyl), is associated with anosmotic gap that is small; in patients with ele-vated magnesium levels, the gap is much greater.Faecal magnesium concentration testing can aidin determining the presence of abuse with amagnesium-containing laxative. Fine and collea-gues[39] reported that the upper limits of faecaloutput of soluble magnesium and faecal magne-sium concentration in healthy volunteers were14.6mmol/day and 45.2mmol/L, respectively.They defined a concentration of magnesium above50mmol as diarrhoeogenic. For pure magnesium-induced diarrhoea (without additional laxativessuch as phenolphthalein), stool magnesium con-centration in excess of 100mmol indicate the useof amagnesium-containing laxative such asmilk ofmagnesia. Laboratory tests for the presence oflaxatives themselves are found in table I.

Many patients report that the feeling of havingemptied themselves is associated not only withgratification resulting from the apparent weightloss but also with a sense of purification.[41] Eatingdisorder patients also believe that laxatives canreduce nutrient absorption. However, most nu-trient absorption occurs in the small intestine.[42]

Nutrient absorption has been reported to be re-duced by only 12% by laxative use.[43] The patient’sweight may be reduced slightly by the expulsion ofwater leading to a temporary mood-elevating ef-fect further reinforcing the laxative use.[8]

Several publications have suggested thatlaxative abuse may characterize a more ill sub-group of patients with eating disorders, and anumber of investigations support this observa-tion in patients diagnosed with anorexia nervosa.A group of anorexia nervosa patients who abuse

Table I. Laboratory screening for laxative abuse[40]

Analyte Duration of detection

Anthraquinones – cascara,

danthron, senna (mg/mL)

150 mg dose: 32 hours post dose

Bisacodyl (mg/mL) 5 mg dose: 32 hours post dose

Oxyphenisatin (mg/mL)a 10 mg dose: 18 hours post dose

Phenolphthalein (mg/mL)a 150 mg dose: 32 hours post dose

Magnesium (mg/L) Faecal water sample

Phosphorus (g/L) Calculated normal: 0.3–1.1 g/La No longer on the market.

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laxatives have been reported to have higherscores on histrionic personality assessments.[44]

Kovacs and Palmer[41] assessed 117 patients di-agnosed with anorexia nervosa. They found that22 (18.8%) used laxatives for weight control.Subjects abusing laxatives were rated higher onthe Ineffectiveness, Body Dissatisfaction andDrive for Thinness subscales of the Eating Dis-order Inventory, and on the depression, somati-zation and global scores on the SymptomChecklist-90-Revised. They also scored higher onthe Rosenberg Self-Esteem Scale (RSES),[45]

suggesting lower self-esteem. In this series ofadults, logistic regression revealed that in subjectswith anorexia nervosa, body dissatisfaction(p< 0.002) andRSES scores (p< 0.033) were signif-icant predictors of laxative abuse. Furthermore,the association of lower ‘self-liking’ in subjectssuffering from anorexia nervosa and laxativeabuse and self-induced vomiting has recentlybeen reported.[46] A multiple regression was thenperformed to determine the relative contributionsof each of these purging methods. Laxative abusewas determined to be the sole contributor tolower self-liking. These results suggest the possi-bility that laxative abuse is distinct from othertypes of purging by its association with self-likingrather than self-competence. This is in line withdata indicating a significant association betweenlaxative abuse and lower self-esteem.[41] The di-rection of this association has yet to be elucidated.

In patients diagnosed with bulimia nervosa,there is ample data associating more severesymptomology with laxative use. Bryant-Waughand colleagues[47] examined laxative use in 201consecutive patients in an outpatient eating dis-order population. Those who misused laxativeswere compared with those who did not. Fifty-three (26.4%) patients had misused laxatives inthe month before assessment. Those whomisusedlaxatives scored higher on measures of anorecticbehaviours and cognitions, restraint, and weightand shape concerns. A history of use was asso-ciated with anorectic behaviours, depression andan increase in clinical severity, regardless ofdiagnosis. In a study of 23 bulimia nervosapatients who purged with laxatives and 17 whopurged by vomiting, women who abused laxa-

tives had higher levels of state anxiety than non-laxative-abusing women after laxative use wasdiscontinued.[48] This study also found that thepatients who abused laxatives were more likely tobe treated with an antianxiety medication. Fifty-nine percent of a sample of 280 bulimia nervosapatients were found to abuse laxatives.[44] In thissample, patients with a laxative abuse historywere found to demonstrate greater perfectionismand avoidant personality features. Subsequently,40 ‘multi-impulsive’ bulimia nervosa patientswere compared with 177 non-impulsive sub-jects.[49] A significantly greater likelihood oflaxative abuse was found in the impulsive group.Another study evaluated the association of im-pulsivity and compulsivity in 125 patients withbulimia nervosa.[50] Laxative abuse was demon-strated to be associated with the impulsivedimension. Thus, impulsivity appears to be a per-sonality characteristic that is frequently found inpatients who abuse laxatives.

In a large community sample of young adultwomen (n = 5255), the 39 individuals who mis-used laxatives were found to be older, perceivedthemselves to be in poorer physical health andwere less likely to have sought treatment specifi-cally for a problem with eating than those whoengaged in self-induced vomiting.[51] However,they found little evidence that young adult womenwho engage in self-induced vomiting differ fromthose whomisuse laxatives with respect to levels ofeating disorder psychopathology, health-relatedquality of life and general psychological distress.

In contrast, recent findings suggest that mea-sures of greater illness were associated with thenumber of purging methods used and not asso-ciated with the type of purging method.[52] In thisstudy, the authors reported similar levels of pa-thology between subjects who used a singlemethod of purging (vomiting or laxative abuse)and greater eating pathology in those who usedboth methods. Behavioural co-morbidity foundin laxative-abusing individuals may include af-fective disorders,[8,53,54] substance abuse,[22,55-57]

self-destructive behaviours,[54] collateral purgemethods[22] and general life impairments.[58]

A group of 43 adolescents diagnosed with an-orexia nervosa was investigated in terms of eating

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symptomology.[27] The results showed that laxa-tive use was associated with a longer duration ofdisease and with higher scores on the EatingConcern subscale of the Eating Disorders Exam-ination (EDE). Laxative abuse has also beenshown to predict lower quality of life in eatingdisordered samples,[59] and to be associated with anumber of other variables suggestive of greaterseverity, including increased rates of self-harmand suicidal behaviours and increased rates ofborderline personality disorder (BPD).[2,60] Anal-ysis of symptoms revealed that specific featuresof BPD, including suicidality and self-harm, andfeelings of emptiness and anger, were moststrongly associated with laxative abuse.[2]

While urinary screening for laxatives mayincrease the detection of laxative use, so can mon-itoring for medical complications such as hypo-kalaemia. Monitoring serum electrolytes as wellas faecal electrolytes, such as magnesium, may bemore cost effective.[61] Turner and colleagues[27]

reported performing 144 screens for laxatives,which yielded only 26 positive results.

In summary, the abuse of laxatives appears tobe a marker for high rates of co-morbidity andother problematic behaviours among individualswith eating disorders. These patients will oftennot wish to reveal their laxative abuse and it fallson the clinician to investigate the possibility ofthis condition. Serum and faecal electrolytes rep-resent an effective screening tool in patients whopresent with diarrhoea and additional GI com-plaints. Urine analysis for individual laxativesmay be best reserved for more difficult cases. Asindicated earlier, caution should be utilized whenmonitoring laxative use via laboratory assess-ment in light of recent difficulties with assays forsenna and bisacodyl.[9]

5. Types of Laxatives

Table II lists commonly used laxatives, theironset of effect and daily dose. Laxatives generallyact in one of the following ways: (i) enhancingretention of fluid by hydrophilic or osmoticmechanisms; (ii) decreasing net absorption offluid by effects on small and large bowel fluid andelectrolyte transport; or (iii) altering motility by

either inhibiting segmenting (nonpropulsive)contractions or stimulating propulsive contrac-tions.[64] All of the agents, with the exception ofdocusate calcium, reduce the transit time throughthe small bowel. Most of the agents enhancepropulsive contractions in the large bowel andvariably increase the amount of stool water. Ofthe laxative classes, stimulant types appear to bethe most commonly abused agents.[42,65] Thispreference for stimulant agents may be related tothe rapid, high-volume faecal discharge asso-ciated with these products. Of the 248 productssurveyed by Steffen et al.,[24] 89 (36%) contained anonprescription stimulant laxative (not includingaloe-containing compounds). In their sample oftreatment-seeking patients with bulimia nervosa,ex-lax� was the most commonly used laxative.This agent currently contains sennosides.

5.1 Stimulant Laxatives

There are two pharmacological classes of stimu-lant laxatives: diphenylmethane derivatives (bisaco-dyl) and anthraquinones (senna and cascara). Someauthors also include castor oil in the stimulant class.

5.1.1 Diphenylmethane Derivatives

Previously, many of the over-the-counterlaxative preparations utilized phenolphthalein asthe active ingredient; however, concerns overcarcinogenicity led the US FDA to ban it fromlaxative preparations in 1997. Ironically, twosubsequent case-controlled studies could notidentify an association of phenolphthalein andovarian cancer.[66,67] These discrepant findingsmay be explained by the dosage (3–1000 times thehuman dose) used in the animal studies uponwhich the FDA based its ruling.[68,69] Currently,the only diphenylmethane agent in use is bisaco-dyl. This agent stimulates peristalsis by directlyirritating the smooth muscle of the intestine. Italso alters water and electrolyte secretion, produc-ing net intestinal fluid accumulation. Bisacodyl iswell tolerated; adverse effects include mildabdominal cramps, nausea, vomiting and rectalburning. The tablets are manufactured with apH-sensitive coating so the agent will not dissolvein the stomach or upper GI tract. If taken with

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dairy products or antacids, the coating will dis-solve while the dose is in the stomach and upperGI tract; any action of bisacodyl in these areaswill produce cramping.

5.1.2 Anthraquinone Derivatives

Anthraquinones (senna and cascara) are me-tabolized by gut bacteria to active agents. Adistinguishing effect of these compounds is acolouring of the bowel referred to as pseudome-lanosis coli or melanosis coli. Its presence isassociated with 9–12 months of anthraquinoneuse and can be used to identify abuse of theseagents.[70] A controversial link between pseudo-melanosis coli and colorectal cancer has been re-ported.[71] In fact, the anthraquinone laxative

danthron was withdrawn from the market be-cause of tumour formation in laboratory ani-mals. Both agents are well tolerated. Senna cancause abdominal cramps, diarrhoea, nausea andvomiting. Cascara has similar adverse effects andcan discolour the urine (reddish, pink or brown).

5.1.3 Castor Oil

Castor oil is derived from the bean of the cas-tor plant, Ricinus communis. It contains twonoxious ingredients: an extremely toxic protein,ricin, and an oil composed chiefly of the trigly-ceride of ricinoleic acid. These agents can pro-duce a strong laxative effect with accompanyingabdominal pain.

Table II. Selected laxatives[25,62,63]

Agent Onset of action Daily dose

Stimulant laxatives

Diphenylmethane derivatives

Bisacodyl Oral: 6–8 hours

Rectal: 1 hour

Oral: 10–15 mg daily

Rectal: 10 mg daily

Anthraquinone derivatives

Senna 8–12 hours Varies by product

Cascara sagrada 8–12 hours

Ricinus communis

Castor oil 2–6 hours 15–60 mL/day (90 mL for emulsion)

In fasting patient, 4 mL may be effective

Bulk-forming laxatives

Psyllium preparations Days Typically 1 tablespoon, 1–3 times daily

Methylcellulose Days 1 tablespoon, 1–3 times daily

Calcium polycarbophil 12–24 hours 1 g, 1–4 times daily

Maximum daily dose 5 g/day

Saline laxatives: watery evacuation

Sodium phosphates 1–6 hours 20–45 mL/day

Magnesium sulfate 3–6 hours 30–60 mL/day of the 400 mg/5 mL suspension

Magnesium hydroxide (milk of magnesia) 6–24 hours 30–60 mL/day of the 400 mg/5 mL suspension

Magnesium citrate 3–6 hours 150–300 mL (usually used preprocedure)

Osmotic laxatives: watery evacuation

Lactulose 6–48 hours Oral: 30–45 mL, 3–4 times daily

Polyethylene glycol <4 hours 4 L preprocedure

Surfactant laxatives: softening of faeces

Docusates 12–72 hours Docusate sodium: 50–200 mg daily

Docusate calcium: 240 mg daily

Lubricants

Glycerin 0.5–3 hours One suppository (3 g) daily

Mineral oil 6–8 hours 15–45 mL once or twice daily

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5.1.4 Colorectal Cancer

Concerns have been voiced regarding the as-sociation of long-term use of stimulant laxativesand the development of colorectal cancer. Long-term administration of bisacodyl has been re-ported to be toxic to the GI tract. Disturbedcytoplasmic and nuclear structure have been dem-onstrated in rat small-intestinal enterocytes.[72] Ameta-analysis did find an association betweencolorectal cancer and constipation and catharticuse.[73] However, it appears that these data wereconfounded by the underlying dietary habits ofthe subjects. A case-controlled study involvingmiddle-aged adults[74] found an association be-tween constipation and laxative use and an in-creased risk of colorectal cancer. However, theassociation with laxatives disappeared when thedata were adjusted for constipation. The asso-ciation remained for constipation when adjustedfor laxative use. Thus, it appears that the factorincreasing the risk of colorectal cancer is con-stipation and not the laxative abuse. Additionalstudies question the colorectal cancer associa-tion. An investigation by Nusko and collea-gues[75] found no association between colorectalcancer and melanosis coli or laxative use. Theresults of a 26-week study in the transgenic micestrain p53+/- revealed neither drug-related neo-plasm nor micronuclei in polychromatic ery-throcytes, and did not induce transformations inthe in vitro Syrian hamster embryo assay.[76]

Subsequent studies have also not found an asso-ciation;[73,74,77-81] hence, the FDA has categorizedbisacodyl as category I (safe and effective). Thehuman evidence appears not to support an asso-ciation between stimulant cathartics and colo-rectal cancer. Various authors also question thetoxic potential of stimulant laxatives,[82,83]

particularly neuronal toxicity leading to catharticcolon.

5.2 Bulk-Forming Laxatives

Bulk, softness and hydration of faeces dependon the fibre content of the diet. Fibre is the part offood that does not undergo enzymatic digestion.It reaches the colon largely unchanged. Colonicbacteria ferment fibre to varying degrees, depen-

ding on its chemistry and water solubility. Mostof the bulk laxative formulations include a deri-vative of semi-synthetic fibre (methylcellulose),psyllium or polycarbophil (a hydrophilic resin).Others contain fibre or bran products. Theseagents are usually manufactured as a powder tobe mixed with fluids (water or juice). They absorbwater in the intestine to form a viscous liquid thatpromotes peristalsis and reduces transit time.Insoluble, poorly fermentable fibres have thegreatest effect on increasing bulk.

Bulk-forming laxatives soften the faeces.[15,84]

Bile acid binding such aswith psylliummay reducethe production of low-density lipoprotein.[85-87]

Bulk-forming laxatives have a slow onset of ac-tion (between 12 and 72 hours) and substantialrelief from constipation may take several monthsof continued use. Due to the longer onset of ac-tion, eating disorder patients find these agentsinadequate to control weight. Adverse effectswith these agents are generally mild and includebloating, allergic reactions and flatulence.[71]

Specific contraindications exist, including use inpatients with obstructive symptoms and in thosewith megacolon or megarectum.[15]

5.3 Saline Laxatives

Many saline laxatives contain magnesiumsalts. Their use results in an increase in osmoticpressure in the bowel, which aids in water reten-tion. In addition, magnesium salts may stimulatethe secretion of cholecystokinin, which increasesintestinal secretion and motility.[15] The onset ofaction is dose dependent, with lower doses havingan onset of effect in 6–8 hours. The onset of effectfor higher doses can be less than 3 hours, such aswith the use of magnesium citrate to evacuate thebowel prior to surgical and diagnostic proce-dures.[15] Adverse effects of these agents includehypotension, hypermagnesaemia, abdominalcramps, diarrhoea, gas formation and respiratorydepression (see section 6).

5.4 Osmotic Laxatives

An increase in osmotic pressure in the gut lu-men is also caused by osmotic laxatives. Theyremain unabsorbed and are not digested in the

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small intestine. Lactulose is metabolized to formfructose and galactose then converted to lactate,acetate and formate. Lactulose helps to reducethe intestinal absorption of ammonia. It has fre-quently been used to manage hepatic encephalo-pathy associated with hepatic failure, although itsefficacy for this purpose is controversial.[88] Thisagent is generally well tolerated, and adverse ef-fects including flatulence, cramping, abdominaldiscomfort, nausea and vomiting. Larger dosescan cause diarrhoea, fluid loss, hypokalaemiaand hypernatraemia.

Polyethylene glycol (PEG) is an osmotic laxa-tive supported by good-quality evidence that hasdemonstrated efficacy and safety in the treatmentof patients with chronic constipation. While lac-tulose is more effective in relieving constipationthan placebo, it is less effective than PEG. PEG isused prior to procedures such as a colonoscopy.Patients are instructed to drink 4L of a PEG so-lution, which results in a watery bowel evacua-tion. Fluid and electrolyte status is not altered.Adverse effects include urticaria, abdominalbloating, cramping, diarrhoea, flatulence andnausea.[89]

5.5 Surfactants

The docusate compounds are often used asstool-softening agents. They may be combinedwith other laxatives such as the stimulant com-pounds. Docusate calcium reduces the surfacetension of the oil-water interface of the stool. Thisresults in the incorporation of water and fat, withresultant stool softening. These agents have lim-ited, if any, efficacy in most cases of constipa-tion.[15] Adverse effects of these compounds aremild and include abdominal cramps, rashes andnausea.

5.6 Lubricants

Mineral oil acts as a laxative by decreasingwater absorption in the colon, as well as lubricat-ing the intestine. Onset of action is approximately6–8 hours if administered orally and 2–5 minuteswith rectal administration. This agent is not re-commended for use in the elderly as aspirationmay occur with resulting lipid pneumonitis.

Glycerin is a trihydroxy alcohol that acts as ahygroscopic agent and lubricant when given re-ctally as a suppository, and results in defecationin about 30 minutes. Adverse reactions associatedwith glycerin suppositories include local discom-fort, burning or hyperaemia, and (minimal) bleed-ing. Some glycerin suppositories contain sodiumstearate, which also can cause local irritation.

6. Medical Complications

Medical complications stemming from laxa-tive ingestion depend on the severity of abuse, aswell as the frequency, duration and type of agentused. Problems may be confined to the GI tractor involve systemic features. The most frequentcomplication of laxative abuse is obviously diar-rhoea. GI cramping and pain may present withthe diarrhoea due to stool volume and a directeffect of the laxative on intestinal motility. Fre-quency of stools may reach 15–20 per day.[3]

Medical complications can be divided into dis-turbances involving electrolytes, metabolic is-sues, bowel, kidney and miscellaneous effects.

6.1 Electrolyte Disturbances

Medical complications of laxative abuse areoften a result of chronic diarrhoea and the asso-ciated severe electrolyte disturbances. Potassiumis the primary electrolyte in stool water(70–90mmol/L), with lower concentrations of so-dium and chloride (30–40 and 15mmol/L, respec-tively). With the development of hypokalaemia,the patient may present with generalized muscleweakness and lassitude.[90] Additionally, the pre-sentation may include skeletal muscle paralysis,or rhabdomyolysis with renal impairment, andnerve palsies. More severe hypokalaemia can re-sult in cardiac arrhythmias with an increased riskof sudden death.[3,91] Severe hypokalaemia hasbeen associated with distal renal tubular acidosisin laxative abuse.[92,93] With the expulsion of anadded volume of stool water, dehydration, hypo-tension, tachycardia, postural dizziness and syn-cope may occur. Renin secretion with secondaryhyperaldosteronism can develop with chronicdehydration. Hypermagnesaemia associated with

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large doses of magnesium-containing laxatives haspresented with quadriparesis and neuromuscularjunction defects.[94] Recently, it has been reportedthat patients with congestive heart failure (CHF)but normal renal function who presented withhypermagnesaemia had a lower rate of 3-year sur-vival than patients with normal magnesium levels.These subjects also had a greater antacid/laxativeuse profile: 82.7% versus 24.8% (p < 0.0001).[95]

Patients with pre-existing renal dysfunction are atan increased risk of adverse effects with salinelaxatives. However, acute phosphate nephro-pathy is an accepted complication of the use ofphosphate preparations in patients about to un-dergo to colonoscopy. Patients’ CHF may beexacerbated due to the sodium content.

6.2 Metabolic Disturbances

Acid-base disturbances are possible withlaxative use. Metabolic alkalosis is the mostcommon acid-base disturbance associated withlaxative use, and is related to hypokalaemia,volume contraction and secondary hyper-aldosteronism. Concomitant purging by vomit-ing may increase the risk of developing metabolicalkalosis. Additional acid-base disturbances in-clude hypochloraemic metabolic alkalosis andsecondary complications such as increased renalammoniagenesis,[96] which promotes bicarbonatereabsorption in the renal tubule. Laxative abusehas also been reported to cause GI dysfunction,particularly pancreatic damage.[97] In a smallstudy, Brown et al.[98] compared 18 recoveredanorexia nervosa patients with age- and weight-matched controls. Ten of the 18 anorexia nervosapatients had a history of laxative abuse; thesesubjects showed a more gradual increase and de-crease in insulin secretion in response to astandard meal, but no differences in glucose res-ponse or hunger ratings. The authors concludedthat the difference in insulin response is due tochanges in the enteroinsular axis induced bychronic laxative abuse.

6.3 Bowel Disturbances

Bowel dysfunctions including colonic mucosainflammation and ulceration, ileocaecal sphincter

dilation, colonic neuropathy, steatorrhoea andprotein-losing gastroenteropathy have been re-ported with laxative abuse.[99-106] Other presen-tations include GI bleeding[107] and dehydrationwith various electrolyte abnormalities.[108] Diar-rhoea may alternate with periods of constipation,which causes the patient to enter a vicious cyclealternating between the two.

Direct toxicity to the small intestinal mucosamay be a GI complication of laxative use thatleads to steatorrhoea. Rarely, fat-soluble vitaminmalabsorption leads to osteomalacia and pseu-dofractures.[3] Progressive laxative dosing ob-served in some laxative users may be attributed tohypofunctioning in bowel processes, loss of in-trinsic innervation action and laxative toleranceeffects.[100] However, controversy exists regard-ing the effect of senna laxatives on bowel in-nervation and function. The adverse effects andtoxicity of stimulant-type laxatives often includeconstipation[102] and cathartic colon, which isdefined as a loss of colonic myenteric neurons,atrophy of smooth muscle, loss of haustralmarkings, increased submucosal fat, fibrosis andhypertrophy of the muscularis mucosae.[3,103,109]

Barium enema procedures have shown the term-inal ileum to be smooth, without a normal mu-cosal pattern.[8] However, contrary to the widelyheld belief, stimulant laxatives, which promoteintestinal motility, do not seem to lead to bowelinjury.[83,109] Recently, Morales and collea-gues[110] concluded that there is no convincingevidence that the long-term use of senna causes astructural and/or functional alteration of the en-teric nerves or the intestinal smooth muscle.Supporting these findings is the absence ofreports of cathartic colon since the removal ofphenolpthalein from clinical use. They also re-port that current evidence does not show thatthere is a genotoxic risk for patients who takelaxatives containing senna extracts or sennosides.

6.4 Kidney Disturbances

Prolonged laxative abuse is also associatedwith chronic kidney disease and can lead torenal failure.[111] Renal function is reduced by acombination of several factors, including severe

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hypokalaemia, volume depletion, rhabdomyolysisand hyperuricaemia. In addition, some laxativesare nephrotoxic and cause renal tubular damage.[3]

Urolithiasis has also been reported in conjunctionwith laxative abuse.[112] Wright and DuVal[92] re-ported five cases of laxative-associated renal da-mage with electrolyte abnormalities.

6.5 Miscellaneous Disturbances

Recently, laxative use has been reported as acomplication in four of seven patients with rectalprolapse and the diagnosis of bulimia nervo-sa.[113] Causality in these cases was uncertain.A patient intermittently abusing cascara over2 years was reported to have developed gastricmelanosis.[114] Recently, paraesthesias and fasci-cular and ventricular tachycardia were reportedto be associated with an Ayurveda bowel regi-men.[115] The preparation included substratesfrom the Aconitum species, Aconitum hetero-phyllum (atvish), Aegle marmelos (bilwa), Pavo-nia adorata (suganda bala), Cyperus rotundus(musta), Picrorrhiza kurrooa (kutki) and Holar-rhena antidysenterica (vatsaka). A. heterophyllum(atvish), also known as aconite, monkshood orwolfsbane, was thought to be the most likely of-fending agent in this combination. Aconite rootscontain aconitine, mesaconitine, hypaconitineand other aconitum alkaloids, which are knowncardiotoxins and neurotoxins.[115,116]

7. Treatment

The best technique for withdrawing individualsfrom laxatives has not been systematically ascer-tained. Whether a patient is habitually abusinglaxatives or using them surreptitiously, the maingoals of treatment are to stop the laxative use andmaintain healthy GI function. However, as a firststep, the patient’s beliefs regarding the laxativeuse have to be determined. If the patient is ex-pressing erroneous beliefs regarding the normalnumber and frequency of bowel movements,education is essential. If the person is sufferingfrom an eating disorder, an appropriate treat-ment plan for the particular eating disordershould be enacted. In addition, eating disorder

patients have been reported to have difficultieswith increasing anxiety with laxative discontinua-tion.[48] This may be related to the retention offluid with a subsequent increase in weight. Thepatient may also experience further constipation,which may result in a strong drive to continue totake laxatives. Close supervision is requiredduring this time to ensure that the laxative with-drawal is successful.

Another risk that needs to be appreciated inlaxative withdrawal is the development of CHF.This problem is illustrated by the case of a60-year-old woman who presented with hypoka-laemia and weakness.[117] She was consuming alaxative combination of phenolphthalein andrhubarb in doses above the package recom-mendation. On presentation her potassium was2.6mmol/L. She had no signs of CHF at thattime. The laxatives were withdrawn and oral po-tassium supplements started. Over the next10 days she began to experience oedema, a weightgain of 15 kg and breathlessness. By day 10, herchest radiograph showed cardiomegaly and bi-lateral pleural effusions. Furosimide and capto-pril were initiated. She recovered over the next2 weeks. The depletion of sodium and waterthrough diarrhoea leads to an increase in reninsecretion with secondary hyperaldosteronism.Water retention develops with oedema and, inthis case, the development of CHF. Oedema fol-lowing laxative withdrawal is not uncommon,but usually subsides over a period of weeks assodium balance becomes re-established.

Several protocols have been published regard-ing the interventionmethods designed to reduce andeliminate the use of laxatives. Harper et al.[118]

reported a 6-month prospective trial evaluatinga pharmacist-supervised, blinded withdrawal pro-tocol. Ten eating disorder patients were enrolledin the trial and seven completed the study. Five ofthe seven reduced their laxative intake by at least50%. Three of the seven withdrew completelyfrom laxative use. Their protocol called for dis-continuation of all stimulant laxatives with thesubstitution of docusate calcium, psyllium andfruit lax, a mixture of natural ingredients (sennaleaves, pitted prunes, figs, pitted dates, dark rai-sins), as tolerated. In addition, a combination of

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30mL of Magnolax� (formula per mL: magne-sium hydroxide 60mg and mineral oil 0.25mL)and 30mL of cascara was initiated in a dose thatwas based on the patient’s previous dose of bisa-codyl or an equivalent. The liquid was reduced by5mL every 3–7 days until no longer needed (seetable III). The withdrawal protocol includedpatient education concerning normal eating andbowel habits.

Colton et al.[119] reported on the results of theirlaxative withdrawal protocol at 3 and 20 months’follow-up. Subjects included all patients admittedfor laxative withdrawal in their eating disordersprogramme between 1993 and 1995. They wereassessed with a shortened version of the EDE.[120]

Their programme consists of the following com-ponents: initial contact, which includes abruptdiscontinuation of the laxative; an immediatewithdrawal stage (before the first normal bowelmovement), involving the provision of non-laxa-tive aids to normal bowel function and psycho-education; and, lastly, the desensitization stage(after the first normal bowel movement). The fi-nal stage initially includes visiting a pharmacywith a staff member and no money with which tobuy laxatives, and progresses through to visitingthe pharmacy alone with money and not pur-chasing laxatives. Aids to normal bowel functionprogress over the month and initially includebulk-forming agents with fluids, stool softenersand glycerin suppositories. In the second half ofthe month, if need be, they progress to a smallclear-water enema and, ultimately, the additionof an irrigation agent. This programme resultedin 57% of patients being abstinent from laxativesat follow-up and significant reductions in laxative-related symptom variables.

8. Summary and Conclusion

Abuse of laxatives is not an uncommon oc-currence in the general population and is quitefrequent among certain groups, such as in thosewith eating disorders. Both patients with anor-exia nervosa and bulimia nervosa utilize laxativesin an attempt to reduce weight and remove un-wanted calories, neither of which is possible withlaxatives. Other groups that may utilize laxativesin an unhealthy way include athletes, middle-aged adults and the elderly. The motivation in theelderly group is often based on rigid and some-times false conceptions about the need for dailybowel movements. This type of use can be diffi-cult to identify as the individual may start out withlegitimate constipation related to other diseasestates or concomitant medication use. However,when the frequency and duration of use exceedsthe need, medical complications may occur.

Stimulant laxatives are the more frequent typeof laxative used in the eating disorder population.Also, the presence of laxative abuse has been re-ported to be associated with greater psycho-pathology by some, but not all, investigators.Certainly, the use of such a drastic purgingmethod places these patients at greater risk than aperson who does not purge.

In severe cases, the individual may presentwith electrolyte and acid/base changes that caninvolve the renal and cardiovascular systems andmay become life threatening. Due to the loss offluid, the renin-aldosterone system becomes ac-tivated, which leads to oedema and acute weightgain when the laxative is discontinued.

Treatment begins with a high level of suspi-cion, particularly when a patient presents withalternating diarrhoea and constipation as well asother GI complaints. Checking serum electrolytesand the acid/base status can identify individualswho may need medical stabilization. At times, itmay also be helpful to check the stool water forelectrolytes, particularly magnesium, which maybe associated with abuse of magnesium-contain-ing laxatives. Once stable, any stimulant laxativesshould be discontinued and a fibre/osmotic supple-ment utilized to establish normal bowel movements.Health education is of paramount importance in

Table III. Laxative taper used in a pharmacist supervised blinded

withdrawal protocol (reproduced from Harper et al.,[118] with per-

mission)

Magnolax�/cascara Previous laxative dose

Magnolax� 30 mL/cascara 30 mL <20 bisacodyl 5 mg tablets/day

Magnolax� 45 mL/cascara 45 mL 20–40 bisacodyl 5 mg tablets/day

Magnolax� 60 mL/cascara 60 mL 40–60 bisacodyl 5 mg tablets/day

Magnolax� 90 mL/cascara 90 mL >60 bisacodyl 5 mg tablets/day

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order to enable patients to alter their diet andbowel habits so as to avoid the need for futurelaxative use. In the case of a suspected or con-firmed eating disorder, the patient should bereferred for psychiatric treatment to lessen thereliance on laxatives as a method to alter weightand shape.

Acknowledgements

No sources of funding were used to assist in the prepara-tion of this review. James Mitchell has received a researchgrant from GlaxoSmithKline to study orlistat (Alli�). Theother authors have no conflicts of interest that are directlyrelevant to the content of this review.

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Correspondence: Professor James E. Mitchell, President,Neuropsychiatric Research Institute, 120 8th St South,Fargo, ND 58102, USA.E-mail: jmitchell@nrifargo.com

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