Emerging Treatments for Chronic Constipation and Defecation Disorders

Constipation is a common gastrointestinal problem afflicting 15% of people of all ages worldwide.¹ Characterized by difficult, less frequent, or incomplete passage of bowel movements, it leads to symptoms including straining, hard stools, use of digital maneuvers, incomplete evacuation, bloating, and abdominal pain. Constipation poses a significant healthcare burden. The 2020 estimate of over-the-counter laxatives alone was approximately $1.5 billion.² About one-third of constipated patients also suffer from anxiety and depression.³

The condition is broadly classified as primary constipation—pathophysiologic dysfunction of the colon and rectum due to the overlapping subtypes slow-transit constipation, dyssynergic defecation, and irritable bowel syndrome with constipation (IBS-C)—and secondary constipation due to disorders that affect gut motility or cause colon obstruction, other causes including certain drugs,⁴ and occasional constipation.⁵

Although over-the-counter treatments such as fiber supplements, laxatives, and dietary changes have been the mainstay for managing mild constipation, patients with chronic symptoms may respond better to prescription second-tier drugs such as linaclotide (Linzess, AbbVie), lubiprostone, plecanatide (Trulance, Salix), and prucalopride (Motegrity, Takeda).² However, many patients are unable to take these drugs because of adverse effects, costs, or insurance constraints. Several emerging or recently approved treatments can offer more effective and targeted relief of symptoms. In this review article, we explore the latest developments related to nondrug treatments for constipation.

Kiwifruit

Although the importance of a high-fiber diet/supplement to control constipation-related symptoms has been well established, recent randomized controlled trials (RCTs) on kiwifruit have shown that eating 2 kiwifruit per day may be beneficial for patients with constipation (Table 1).^6-8 In a recent study, Gearry et al compared kiwifruit with psyllium in 184 patients with functional constipation or IBS-C and found that kiwifruit resulted in significant improvements in the number of complete spontaneous bowel movements (CSBMs) in patients with functional constipation, IBS-C, or both.⁶ Kiwifruit ingestion also was associated with improvement in scores on the Gastrointestinal Symptom Rating Scale, the Bristol Stool Form Scale, and the IBS Quality of Life (QOL) instrument, as well as in straining symptoms. In an international multicenter RCT, Bayer et al found that consumption of kiwifruit significantly improved measures of GI comfort and resulted in at least 1.5 CSBMs per week, although they found no significant difference between kiwifruit and psyllium.⁷ Chey et al noted similar results, showing that the use of kiwifruit produced significant improvement in CSBMs, stool consistency, and symptoms of straining and bloating but finding no significant difference between kiwifruit, psyllium, and prunes.⁸

Table 1. RCTs Assessing Kiwifruit
Study	Patient group	Intervention dose/duration	Primary end point	Results
Gearry et al 2023	184 patients: 60 FC, 61 IBS-C, 121 FC + IBS-C (Rome III), 63 healthy controls	2 kiwifruit (˜6 g of fiber) vs 7.5 g of psyllium daily for 4 wk	=1 CSBMs/wk from baseline at 4 wk	Mean increase in CSBMs/wk in FC (1.53; P<0.0001), IBS-C (1.73; P<0.0003), and FC + IBS-C groups (1.69; P<0.0001) No difference between treatments
Bayer et al 2022	56 patients: 11 FC, 13 IBS-C (Rome IV), and 32 healthy controls	2 kiwifruit (2.5 g of fiber) vs 1.5 teaspoons of psyllium (˜2.5 g of fiber) daily for 4 wk	GSRS scores	Kiwifruit significantly reduced mean scores in FC (–1.08; 95% CI, 0.60 to –1.57) and IBS-C (–0.03; 95% CI, 0.48 to –0.54) groups Psyllium significantly reduced mean scores in FC (–0.44; 95% CI, 0.05 to –0.94) and IBS-C (–0.45; 95% CI, 0.06 to –0.97) groups No difference between treatments
Chey et al 2021	FC and IBS-C (Rome IV)	2 green kiwifruit, 100 g of prunes, or 12 g of psyllium daily for 4 wk (all provided 6 g/d of fiber)	=1 CSBMs/wk for 2 of 4 treatment wk	45% of the kiwifruit group, 67% of the prune group, and 64% of the psyllium group responded No significant difference between groups
CSBM, complete spontaneous bowel movement; FC, functional constipation; GSRS, Gastrointestinal Symptom Rating Scale; IBS-C, irritable bowel syndrome with constipation; RCT, randomized controlled trial. Based on references 6-8.

Vibrating Capsules

An innovative new approach to address constipation has been the development of a vibrating capsule (Vibrant) that helps to mechanically stimulate the intestines directly and induce local peristalsis and augment the natural circadian rhythm.^9,10 The capsule can be programmed to vibrate according to a fixed schedule, and the number of vibrations also can be adjusted. Patients reported that CSBMs occur closely with the scheduled vibrations of the pill (Table 2).^9,10

Table 2. RCTs Assessing Vibrating Capsule Against Placebo For Patients With Constipation and Defecation Disorders
Study	Patient groups	Intervention dose/duration	Outcomes assessed	Primary end points	Results
Rao et al 2023	312 patients with CIC (Rome III), with an average of =1 SBM/wk and =2.5 SBMs/wk	Capsule vs placebo: 1 capsule 5 times per wk for 8 wk (capsule was programmed to induce 2 separate vibration cycles over a 2-d period, 16 h after ingestion, with each cycle lasting 2 h and comprised 3 s of stimulation and 16 s of rest)	CSBMs, SBMs, BMs, straining, BSFS, bloating, PAC-QOL, physical, psychosocial, satisfaction	Proportion of patients with an increase of =1 CSBM (CSBM1) per wk, or with an increase of =2 CSBMs per wk (CSBM2), during at least 6-8 wk of treatment compared with baseline	Significantly higher responder rate in capsule group vs placebo (39.3% vs 22.1%; P=0.01 for CSBM1 and 22.7% vs 11.4% for CSBM2) Significant improvements also seen in straining, stool consistency, and QOL measures 11% experienced vibrating sensation
Zhu et al 2022	117 patients with FC (revised Rome IV)	Capsule vs placebo: 1 capsule every 3-4 d for 6 wk; total of 12 capsules (vibrations began after 8 h and lasted for 6 h)	CSBMs >1/wk, change in CSBM/6 wk, PAC-QOL, PAC-SYM, SBMs, BSFS, rescue medications	Proportion of patients with an increase of =1 CSBMs/wk	Significantly higher responder rate in capsule group vs placebo (64.2% vs 35.8%; P=0.005) Mean PAC-QOL + PAC-SYM scores improved significantly from baseline (P<0.0001) Most common adverse event was abdominal discomfort (3.7%)
BM, bowel movement; BSFS, Bristol Stool Form Scale; CIC, chronic idiopathic constipation; CSBM, complete spontaneous BM; FC, functional constipation; GSRS, Gastrointestinal Symptom Rating Scale; IBS-C, irritable bowel syndrome with constipation; PAC-QOL, Patient Assessment of Constipation Quality of Life; PAC-SYM, Patient Assessment of Constipation-Symptoms; RCT, randomized controlled trial; SBM, spontaneous BM. Based on references 11 and 12.

In a phase 3 RCT comparing the Vibrant capsule administered 5 times per week with a sham capsule, there was significant improvement in constipation symptoms and QOL measures.⁹ The primary outcome measure of an increase in 1 or more CSBMs per week or at least 2 CSBMs per week was significantly higher with the Vibrant capsule than with the sham capsule. Stool consistency, straining effort, and the number of patients with at least 3 CSBMs per week also improved significantly in the Vibrant capsule group. Adverse events included a sensation of vibration, which 11% of patients reported, but none of the patients withdrew from the trial due to the sensation. No diarrhea was seen.

Another recent study showed that vibrating capsule stimulation in the gut (normal and enhanced) is perceived in the parieto-occipital region, and the gastric evoked potentials showed intensity-dependent correlation with gut perception.¹⁰ These findings suggest that the Vibrant capsule–induced evoked potentials may provide insights into how the brain processes gut sensations.¹⁰

The Vibrant capsule is approved by the FDA for treatment of chronic idiopathic constipation and could prove to be a significant advance in our approach to managing constipation. In the future, it may be possible to change the vibration settings and personalize delivery of vibration for each patient.¹¹

Zhu et al evaluated another vibrating capsule (Vibrabot, Ankon Medical) in a phase 2 study and found that it improved the number of BMs and was safe.¹² In this trial, the investigators were allowed to use 2 different vibration modes based on the patient’s tolerance.

Neuromodulation Therapies

Neuromodulation is a broad term that refers to the use of various techniques to modulate or alter the activity of the nervous system. In the context of constipation, neuromodulation techniques can be employed to influence the nerve signals that control bowel function and motility. Multiple approaches to neuromodulation are under investigation, each with variable efficacy and adverse effects (Figure and Table 3).

Figure. Types of neuromodulation therapies under investigation for the treatment of constipation.

Table 3. Neuromodulation Treatment Options Under Investigation for Patients With Constipation
Intervention	Methodology
Interferential current therapy	Cutaneous delivery of medium-frequency electrical stimulation to the upper abdomen (below costal margins) and low back (T9-L2 vertebrae)
Percutaneous tibial nerve stimulation	Electrical stimulation of the tibial nerve either via needles placed above the medial malleolus (percutaneous) or on the skin surface behind the medial malleolus
Trans-cutaneous tibial nerve stimulation	Electrical stimulation of the tibial nerve via electrodes placed on the skin behind the medial malleolus
Sacral nerve stimulation	Implantation of an electronic pacemaker to stimulate the sacral nerves
Trans-cutaneous sacral nerve stimulation	Electrical stimulation delivered through surface electrodes to the lower sacral region (S2-S3)

Interferential Current Therapy

Interferential current therapy (IFC) is a noninvasive and nonpharmacologic treatment that delivers medium-frequency electrical current to stimulate deep tissue nerves without activating cutaneous nerves. IFC works by producing 2 out-of-phase medium-frequency alternating currents. Since they are out of phase, the stimulations interfere with each other, creating a sinusoidal modulation, or an alternating current.¹³

Initially studied in children, IFC has been evaluated for adult chronic constipation in 3 studies (Table 4).^13-15 Vitton et al performed a phase 3 sham versus placebo trial in 185 patients and found no significant improvement in their primary end point of at least 3 CSBMs per week at the end of 8 weeks (IFC, 67.1% vs sham, 73.2%).¹³ They found significant improvement in the Patient Assessment of Constipation-Symptoms (PAC-SYM) questionnaire but no change in Patient Assessment of QOL (PAC-QOL). In another study comparing sham versus IFC in 33 patients, the investigators found a significant improvement in 53% (9/17) of the IFC group.¹⁴ An earlier pilot study evaluating 11 patients showed significant improvement in stool frequency per week and scores on the Knowles–Eccersley–Scott Symptom and Gastrointestinal QOL Index questionnaires.¹⁵

Table 4. RCTs Assessing IFC Against Sham
Study	Patient group	Intervention dose/duration	Primary end point	Results
Vitton et al 2023	185 patients with =2 CSBMs/wk for 6 mo (97 IFC; 88 sham)	4-kHz carrier frequency with a beat frequency of 80-160 Hz and an intensity <33 mA delivered for 1 h/d for 8 wk	=3 CSBMs per wk during last 4 wk of 8-wk period	Response rate: 73.2% IFC vs 67.1% sham (6.1%; 95% CI, –8% to 20.0%; P=0.405)
Moore J et al 2020	33 female patients with <2 SBMs/wk for >6 mo (17 IFC; 16 sham)	4-kHz carrier frequency with a beat frequency of 80-160 Hz delivered for 1 h/d for 6 wk	=3 SBMs/wk for 6-8 wk	Response rate: 53% IFC vs 12.5% sham (P=0.02)
Queralto et al 2013	11 patients with <3 BMs/wk plus a CTT with radiopaque markers >100 h	4-kHz carrier frequency with a beat frequency of 80-160 Hz and an intensity of <33 mA delivered for 1 h/d for 3 mo at home	Median stools/wk, KESS score, CCCS, GIQLI	Median number of stools decreased from 0.66 to 1.66 (P=0.007) KESS score decreased from 30-19 (P=0.005) CCCS decreased from 103-98 (P=0.02) GIQLI score increased from 60-95 (P=0.005)
BM, bowel movement; CCCS, Cleveland Clinic Constipation Score; CSBM, complete spontaneous BM; CTT, colon transit time; GIQLI, Gastrointestinal Quality of Life Index; IFC, interferential current therapy; KESS, Knowles–Eccersley–Scott Symptom; RCT, randomized controlled trial. Based on references 13-15.

Tibial Nerve Stimulation

Posterior tibial nerve stimulation (PTNS) uses electrical stimulation to activate the sacral nerves retrogradely and improve bowel function.¹⁶ Percutaneous PTNS (pPTNS) involves percutaneous electrical impulses delivered to the tibial nerve using needles placed under the skin near the ankle, whereas transcutaneous PTNS (tPTNS) involves placing surface electrodes near the medial malleolus region.¹⁷ Table 5 reviews the studies on pPTNS and tPTNS.^18-21

Table 5. RCTs Assessing pPTNS and tTPNS for Patients With Constipation and Defecation Disorders
Study	Patient groups	Intervention dose/duration	Primary end point	Results
pPTNS
Kumar et al 2015	30 patients with slow CTT (STC), RED (BET> 30 s), or both who failed biofeedback and laxative therapy	12 outpatient PTNS sessions 1 wk apart, each lasting 30 min	WCS change of =5 or score =15	No significant improvement in patients with STC (21.3 vs 20.2; P=0.34) and RED + STC (20.9 vs 21.4; P=0.63) Significant improvement in RED patients (21.2 vs 18.4; P=0.004)
Collins et al 2011	18 patients (Rome II) with constipation who had failed biofeedback therapy and had STC	12 sessions (1-3/wk), each lasting 30 min (study duration varied from 4-12 wk)	WCS change of =5	33% of patients responded on WCS
tPTNS
Gokce et al 2022	105 FC patients (Rome IV) nonresponsive to dietary changes and stool softeners	3 sessions/wk, each lasting 30 min (pulse width, 200 mcs; frequency, 10 Hz); stimulations weekly for 6 wk	Defecation time, stool softener use, CSI	Defecation time >5 min reduced from 97.1% to 17.1% (P<0.001) Stool softener use reduced from 76.2% to 20% (P=0.001) Total CSI score reduced from 51.4-19.1 (P<0.001)
Gokce et al 2020	44 patients aged >65 y with constipation (Rome III)	3 sessions/wk for 6 wk, each lasting 30 min (pulse width, 200 mcs; frequency, 10 Hz)	Defecation time, stool softener use, CSS	Defecation time >5 min reduced from 95.4% to 18.2% (P=0.05) Stool softener use reduced from 63.6%-15.9% (P<0.001) Total CSS score reduced from 503-216 (P<0.828)
-Madbouly et al 2017	36 patients with “-evacuation disorder” with no anatomic obstruction and refractory to medical therapy and biofeedback	3 sessions/wk for 6 wk, each lasting 30 min (pulse width, 200 mcs; frequency, 10 Hz)	MODS	47% responded (>75% with a MODS score change from 15.1 [95% CI, 13.9-16.2] to 5.1 [95% CI, 4.4-5.7]; P<0.0001)
Iqbal et al 2016	15 FC patients (Rome III) nonresponsive to biofeedback	Daily sessions for 6 wk, each lasting 30 min (pulse width, 200 mcs; frequency, 10 Hz)	PAC-QOL, PAC-SYM	PAC-QOL improvement <1; 60% responded PAC-QOL improved =1; 26% responded PAC-SYM =1; 13% of patients improved
Zhang et al 2014	14 sham vs treatment with constipation (Rome III) refractory to medical therapy and biofeedback	Twice-daily 1-h sessions for 2 wk, then crossover period (pulse width, 0.5 ms; pulse frequency, 25 Hz; amplitude, 2-10 mA; on time, 2 s; off time, 3 s)	Spontaneous defecation, defecation time	Significant improvement in spontaneous defecation from 1.1 to 3.7 BMs/wk (P<0.001) Defecation time was reduced significantly (12.6-8.2; P<0.02)
BET, balloon expulsion time; BM, bowel movement; CSBM, complete spontaneous BM; CSI, Constipation Severity Instrument; CSS, Constipation Scoring System; CTT, colon transit time; FC, functional constipation; MODS, Modified Obstructed Defecation Score; PAC-QOL, Patient Assessment of Constipation Quality of Life; PAC-SYM, Patient Assessment of Constipation-Symptoms; pPTNS, percutaneous posterior tibial nerve stimulation; RED, rectal evacuation disorder; STC, slow-transit constipation; tPTNS, transcutaneous PTNS; WCS, Wexner Constipation Score. Based on references 17-23.

The data on pPTNS have been mixed.^18,19 In 2011, Collins et al studied a cohort group of 18 patients, and found a significant improvement in the Wexner Constipation Score (WCS), colonic transit time (CTT), the PAC-QOL, and median change in BMs per week.¹⁸ However, in 2015, Kumar et al evaluated 30 patients and found no significant changes in the WCS and CTT and balloon expulsion time.¹⁹

tPTNS overcomes the invasiveness of the pPTNS method. Gokce et al evaluated the effect of tPTNS on defecation time (group 1, <5 minutes; group 2, 5-11 minutes; group 3, >11 minutes). tPTNS significantly reduced the defecation time to less than 5 minutes in the majority of patients (82.9% vs 61.9% at baseline).²⁰ Stool softener use, Constipation Severity Instrument (CSI) scores, and anal pain also were significantly reduced. Gokce et al also previously evaluated tPTNS in a geriatric cohort with significant reduction in defecation time, CSI scores, and use of stool softeners.²¹ However, standard outcome measures such as the CSBM rate were not reported.

In another study of bilateral tPTNS, 47% were responders whereas 53% were nonresponders, with tPTNS resulting in no significant change in patents with functional outlet obstruction and constipation who failed medical management and biofeedback therapy.²² Iqbal et al evaluated tPTNS use in 15 patients and found no improvement in bowel symptoms but significant improvement on the PAC-QOL (<1 difference from baseline).¹⁷ However, 66% of the patients required rescue laxatives. Zhang et al conducted a sham versus tPTNS crossover trial of 12 patients and showed a significant improvement on spontaneous defecation, defecation time, and PAC-SYM parameters.²³

Although these small uncontrolled studies demonstrate mixed results, larger RCTs with standard objective measures are necessary to establish the efficacy and safety of PTNS. One large multicenter RCT failed to demonstrate benefit of PTNS in fecal incontinence.²⁴

Sacral Nerve Stimulation

Sacral nerve stimulation (SNS), or sacral neuromodulation, has been tested for chronic constipation that has not responded to conservative treatments.²⁵ SNS involves electrical stimulation of the S2 and S3 nerves and implantation of a small device under the skin in the low back or buttock area. SNS implantation typically is done in 2 stages. In the first stage, a temporary wire is inserted to assess the patient’s response to therapy; if results are positive, a permanent device is implanted in the second stage.

SNS has shown conflicting results (Table 6). Although a large open-label study showed significant improvements in patients with constipation refractory to other therapies,²⁶ recent RCTs have revealed no significant improvement.^27-29 In a cohort of 11 patients, Thomas et al reported improvement in 2 of 10 outcomes for patients, using different combinations of SNS stimulation for each patient and comparing with standard therapy in a crossover trial.²⁷ Likewise, in larger RCTs, Dinning et al²⁸ and Zerbib et al²⁹ found no significant improvements in QOL measures, CTT, and bowel symptoms. There was a higher incidence of adverse events in these trials, namely pain (2.7%-44%), explantation of the device (8.3%), and wound infection (2.7%-20.3%).^28,29 Given the costs and lack of benefit, SNS is unlikely to be approved for constipation.

Table 6. RCTs Assessing SNS Against Sham for Patients With Constipation and Defecation Disorders
Study	Patient groups	Intervention dose/duration	Primary end point	Results
Dinning et al 2015	Patients with CSBMs <3 d/wk, slow CTT (STC), no dyssynergia, and anatomic obstruction	All active arms delivered 14-Hz, 300-mcs pulse width parameters	CSBMs >2 d/wk, in a 2- to 3-wk period	No significant change in end point in the stimulation group (29.6% vs 20.8% in sham group; P=0.23)
Thomas et al 2015	11 patients with constipation and previous suboptimal response to SNS treatment	Patients exposed to 5 combinations of stimulation, with frequency ranging from 14-31 Hz and pulse width ranging from 90-210 mcs	Number of digitations performed per defecation, CCCS, PAC-SYM	Significant improvement in CCCS and PAC-SYM for group 1 (standard), and in number of defecation digits for group 5
Zerbib et al 2017	=2 of the following symptoms: <3 CSBMs, straining (>25% of time), sensation of incomplete evacuation (>25% of time refractory to standard therapies)	8-wk period of either subsensory active stimulation or sham stimulation followed by a 2-wk washout and crossover	Responsive patients included =1 of the following: increase in evacuation frequency from <2-3 BMs/wk; =50% reduction in BMs with straining; or =50% decrease in BMs with a sense of incomplete evacuation	12/20 patients responded during the on cycles and 11/20 during the off cycles
BM, bowel movement; CSBM, complete spontaneous BM; CCCS, Cleveland Clinic Constipation Score; CTT, colon transit time; PAC-SYM, Patient Assessment of Constipation-Symptoms; RCT, randomized controlled trial; SNS, sacral nerve stimulation; STC, slow-transit constipation. Based on references 27-29.

Transcutaneous SNS

The sacral nerve also may be stimulated using surface electrodes placed near the sacral region of the spinal cord (S2-S3). RCTs with a small sample size (<30 patients) have been conducted with mixed results (Table 7).^30-32 With a 6-week treatment protocol and cohort of 15 participants, Kim et al found transcutaneous SNS (tSNS) to significantly increase BMs per week and the Constipation Assessment Scale (CAS) score.³⁰ However, the inclusion criteria for participants were not based on standard diagnosis. Iqbal et al evaluated a cohort of 16 patients and found no significant changes in PAC-SYM parameters, stool frequency, Cleveland Clinic Constipation Score, and the PAC-QOL.³¹ However, the treatment protocol differed from that used by Kim et al. Lastly, Yang et al evaluated 28 patients (14 sham and 14 tSNS) and showed a significant improvement in CAS score and number of bowel movements (BMs) per week, as well as reduced abdominal pain.³² Further studies with a larger sample sizes are required to evaluate whether tSNS can improve symptoms in chronic constipation.

Table 7. RCTs Assessing Transcutaneous SNS Against Sham For Patients With Constipation and Defecation Disorders
Study	Patient groups	Intervention dose/duration	Primary end point	Results
Yang et al 2017	28 women with STC	14 patients randomized to treatment and 14 to sham; stimulation performed for 20 min 3 times/wk for 4 wk	CAS score, abdominal pain, number of BMs/wk	Significant improvement in CAS score, abdominal pain, and evacuation frequency per week
Iqbal et al 2016	16 FC patients (Rome III)	Continuous electrical stimulation (device worn continuously for 12 h/d) (frequency of 40 Hz, a pulse width of 220 mcs, work cycles of 99 s with 2 s rest)	PAC-SYM	No significant changes in PAC-SYM when documenting
Kim et al 2014	15 patients with CAS score >4 points and <3 BMs/wk	Stimulation performed for 20 min 3 times/wk for 6 wk (frequency of 50 Hz with burst intervals of 3 and 6 s)	BMs/d, BMs/wk, CAS score	Significant improvement in BMs/d and BMs/wk
BM, bowel movement; CAS, Constipation Assessment Scale; FC, functional constipation; PAC-SYM, Patient Assessment of Constipation Symptoms; RCT, randomized controlled trial; SNS sacral nerve stimulation; STC, slow-transit constipation. Based on references 30-32.

Exoperistalsis Treatment

Abdominal massage, specifically colon massage, may alleviate symptoms of chronic constipation. An open-label study evaluated an exoperistaltic device that delivered intermittent massage therapy for 20 minutes up to 3 times daily for 4 weeks in a cohort of 92 patients with neurogenic bowel dysfunction or idiopathic constipation.³³ Patients experienced a significant improvement in the number of complete BMs per week, with reduced use of laxatives and improved QOL measures. However, CTT and stool consistency were unchanged. Although exoperistalsis may seem like a promising treatment for constipated patients, further RCT studies are required to establish efficacy, particularly compared with a sham device.

Acupuncture

Acupuncture is an ancient Chinese medical practice that involves inserting thin needles into specific points on the body. Multiple studies suggest that traditional or electroacupuncture may help improve bowel function and alleviate constipation symptoms.³⁴ However, these studies evaluate different sites and regimens and modes of treatment (ie, electrical vs traditional), producing considerable heterogeneity within the studies.

Jie et al and Zhang et al reviewed studies assessing electroacupuncture.^35,36 Jie et al’s review included studies that had substantial heterogeneity and evaluated different etiologies of constipation, such as post-stroke constipation, diabetic constipation, opioid-induced constipation, and constipation in patients with Parkinson’s disease.³⁵ Of the 13 studies in Jie et al’s review, 2 were analyzed and showed a significant improvement in CSBMs, with a mean difference of 0.42 (P=0.001) and I², 0 (P=0.58). Zhang et al’s meta-analysis included 5 RCTs that only evaluated use of electroacupuncture, with similar sites of puncture, in patients with functional constipation.³⁶ They showed a significant improvement in CSBMs per week at 4 weeks, with a mean difference of 0.8 (P<0.0001) and I², 87% (P<0.00001); at 12 weeks the mean difference was 1.25 (P<0.0001) and I², 92% (P<0.00001).

Table 8 reviews 3 RCTs of electroacupuncture.^37-39 Zheng et al conducted a large study of 650 patients with 4 arms: Shu-Mu, He, and He-Shu-Mu acupuncture sites and mosapride (not available in the United States). The primary outcome assessed was an increase in spontaneous BMs at the end of 4 weeks. There was no significant improvement in this measure at 4 weeks, but at week 8, there was a significant mean change of 2.4 in the He group, 2.3 in the Shu-Mu group, and 2.1 in the He-Shu-Mu group compared with 1.4 in the mosapride group (P=0.005).³⁷ In another study, Wu et al compared mosapride with low- and high-current intensity acupuncture at the Qu chí and Shàng jù xu sites and found no significant differences between the groups on primary and secondary outcomes.³⁸ Lastly, in one of the most robust studies, Liu et al evaluated 1,075 patients from 15 centers, comparing electroacupuncture with sham electroacupuncture and found significant improvements in primary outcome. The change in CSBMs from baseline between electro- and sham acupuncture was 0.9 at the end of 8 weeks of treatment (P<0.0001). For secondary outcomes, the mean difference was marginal: 0.24, –0.31, and –0.24 for stool consistency, PAC-QOL score, and straining, respectively (P<0.0001).³⁹

Table 8. RCTs Assessing Acupuncture Against Sham For Patients With Constipation and Defecation Disorders
Study	Patient groups	Intervention dose/duration	Primary end point	Results
Zheng et al 2018	684 patients with FC (Rome III), 172 He, 171 Shu-Mu, 171 He-Shu-Mu, and 170 mosapride	16 sessions of acupuncture over 4 wk	Mean weekly SBMs at 4 wk	Mean changes of SBMs at 4 wk were 2.7, 2.7, 2.2, and 2.4 times/wk in He, Shu-Mu, He-Shu-Mu, and mosapride groups, respectively (P=0.226)
Wu et al 2017	190 patients with FC (Rome III); 58 LCI, 65 HCI, and 67 mosapride	16 sessions of acupuncture over 4 wk	=3 SBMs/wk and an increase of =1 SBMs/wk from baseline for 3- to 4-wk treatment period	53.5%, 66.2%, and 52.2% of the patients in LCI, HCI, and mosapride groups reached primary outcome (P>0.05)
Liu et al 2016	1,075 FC (Rome III); 536 in electroacupuncture, 536 in sham	28 sessions over 8 wk	Change in mean CSBMs/wk from baseline	Change in mean CSBMs/wk was 1.76 (95% CI, 1.61-1.89) in the electroacupuncture group and 0.87 (95% CI, 0.73-0.97) in the sham group (0.90; 95% CI, 0.74-1.10; P<0.001)
CSBM, complete spontaneous bowel movement; FC, functional constipation; HCI, high current intensity; LCI, low current intensity; RCT, randomized controlled trial; SBM, spontaneous BM. Based on references 37-39.

Treatment for Dyssynergic Defecation

Constipation can be due to multiple etiologies; therefore, different treatment options are needed to target individual pathophysiologic mechanisms. For patients with dyssynergic defecation who are unable to perform coordinated movements of the rectum, puborectalis, and anal sphincter to facilitate stooling, biofeedback therapy has been shown to be an effective treatment.^40,41 The American Neurogastroenterology and Motility Society and the European Society of Neurogastroenterology and Motility have given this treatment a Grade A recommendation.⁴² Biofeedback therapy involves using specialized equipment to measure various physiologic parameters related to bowel muscle function, such as rectal and anal sphincter muscle pressures during attempted defecation. Through biofeedback sessions, patients can learn how to regain voluntary control over their BMs and improve muscle coordination, leading to more effective, coordinated emptying of their bowels.^40-43

Home Biofeedback Therapy

Although biofeedback therapy is safe and efficacious, it can be difficult to access medical centers providing biofeedback therapy and skilled personnel to perform traditional office-based biofeedback therapy. Home biofeedback has been developed, in which patients are given the tools and guidance to administer biofeedback treatment from the comfort of their home.⁴³ The advantages of home biofeedback therapy are numerous. It is a cost-effective method for patients to receive readily available treatment, bypassing the difficulty of logistical issues such as transportation and time off work. In addition, it allows patients to access a greater number of treatments according to their own schedules.⁴⁰ Particularly in cases in which office biofeedback may not be a possibility due to lack of infrastructure, home biofeedback can provide a viable alternative.

In an RCT of 100 patients, Rao et al showed that home biofeedback therapy is effective and safe and was noninferior to office biofeedback therapy.⁴³ Using a rigorous objective outcome measure composed of normalization of dyssynergia pattern plus an increase in 1 or more CSBMs per week, they showed that 68% of patients who received home biofeedback met the primary outcome compared with 70% who received office biofeedback. Satisfaction with bowel function and balloon expulsion time also improved significantly in both groups. In addition, home biofeedback was more cost-effective than office biofeedback and improved QOL domains. However, there is no standardized equipment or protocol or commercial equipment for performing home or office biofeedback therapy. This has handicapped the delivery of biofeedback therapy to patients with pelvic floor disorders. Clearly there is an urgent need for development of innovative biofeedback instruments, and there is early promise.⁴⁴

Treatment for Rectal Sensory Disorders

Recent studies have highlighted that disorders of rectal sensation play an important role in the pathogenesis of anorectal disorders,^45,46 including rectal hyposensitivity, in which there is poor awareness of stooling sensation,^45,47 and rectal hypersensitivity, which leads to urgency to defecate even in the presence of a small amount of stool or abdominal pain and is often associated with IBS.^48,49

Two recent innovative treatments have been tested in RCTs. In one study, barostat-assisted sensory training (BAST) was compared with syringe-assisted sensory training in patients with rectal hyposensitivity.⁴⁸ This showed that BAST was superior, with a higher responder rate and greater ease of treatment administration.⁴⁸ In another study, a novel approach termed sensory adaptation therapy, which involves placing a highly compliant barostat balloon in the rectum and performing gentle, stepwise balloon inflations, led to greater improvement in rectal hypersensitivity and bowel symptoms and was better tolerated than the selective serotonin inhibitor escitalopram.⁴⁹ Further studies are needed to confirm the beneficial effects of these treatments and other approaches to treat these disorders.

Conclusion

As research and medical advancements continue to expand our understanding of gastrointestinal health, emerging treatments for constipation offer new hope for individuals struggling with this condition. With options from kiwifruit to vibrating pills as well as nonpharmacologic approaches such as biofeedback and neuromodulation therapies, the future looks bright for more effective and personalized treatment options for constipation. However, it is essential to remember that any new treatment should be discussed with qualified healthcare professionals because individual responses to therapies can vary. With ongoing research and continued commitment to improving bowel health, we can look forward to a future where constipation becomes a more manageable and less disruptive problem.

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Emerging Treatments for Chronic Constipation And Defecation Disorders

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