Top 10 Brain Posts 2015: Binge Eating and IBS

I have been highlighting the Brain Post blogs with the highest number of pageviews for 2015.

The third highest accessed post involved a review of a study involving binge eating disorder and irritable bowl syndrome or IBS.

You can access the original post 

HERE

Irritable bowel syndrome is a common disorder affecting up to 4% of men and 8% of women.

This study found that individuals with binge eating disorder had higher rates of IBS even controlling for potential confounding effects of obesity.

The authors noted this finding may be due to a common predisposing factor for both disorders. Additionally, they noted consumption of large quantities of food in short periods of time may put stress on the gastrointestional system that produces IBS symptoms (abdominal pain, bowel frequency disturbances).

Follow the author on Twitter WRY999

Photo of eel and reflection at the Oklahoma Aquarium is from the author's files.

Drug Development for Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a common and chronic gastrointestinal disorder.  Symptoms include abdominal pain and cramping accompanied by diarrhea and/or constipation.  Estimated to effect 10 to 15% of the population, current drug treatment modalities are fail to relieve symptoms in many patients.  There is considerable interest in novel drugs that might more effectively control symptoms while producing limited side effects. 

A recent review of treatments for irritable bowel syndrome has been authored by Chang and Talley from the Mayo Clinic.  Dr. Chang works in a program identified as Enteric NeuroScience.  This designation highlights the importance of neuroscience issues in IBS.  Here are my notes from the review:

FDA Approved Drugs in the U.S.
Alosetron (Lotronex)--nerve receptor agonist initially approved for women with IBS and severe diarrhea and then removed from market due to risk of constipation, bowel obstruction and ischemic colitis.  Now re-approved but only by prescription from a limited number of physicians participating in monitoring program.
Lubiprostone (Amitiza)--chloride channel activator approved only in women with IBS accompanied by constipation

Nonapproved Drugs
Anticholinergic (antispasmodic)
    Scopoloamine also known as hyoscine is an alkaloid drug that has muscarinic antogist effects.  Effective in reducing cramping in some IBS patients.  May cause dry mouth and blurred vision especially at higher doses.
    Peppermint oil: a natural product that appears to have some scientific support for reducing cramping in IBS. 
Antidepressants
Tricyclic antidepressants: older antidepressants such as imipramine and doxepin reduce IBS symptoms in some individuals.  Effect may be due to anticholinergic effect seen with these older antidepressants.
Selective serotonin re-uptake inhibitors: new selective serotonin re-uptake inhibitors help some with IBS, but also can worsen diarrhea and cramping.
Serotonin norepinephrine re-uptake inhibitors--combine re-uptake blocking of both the serotonin and norepinephrine.  Limited study of these agents in IBS but may be promising as they appear to reduce pain in other clinical conditions.  Duloxetine (Cymbalta) clinical trial results pending

Drug development targets in IBS
Treatment of visceral hypersensitivity
    Kappa-opioid receptor agonists-k-opioid receptor stimulus reduces pain from the gut while not producing constipation characteristic of other opioid
    Endocannabinoids- cannabinoids receptors CB1 and CB2 potential targets as activation may reduce pain and hypermotility
    Transient receptor potential vanilloid type 1 (TRPV1)-a receptor that is located throughout nervous system and mediates sensation and pain
    Beta 3 adrenoreceptor agonists-activation inhibits cholinergic GI contractions and increases release of somatostation.  Potentially helpful for inhibiting diarrhea
    Neurokinin antagonists-Neurokinin 1 receptor antagonists reduce IBS subjects emotional response to rectosigmoid distention
Centrally acting agents
    Dextofisopam-benzodiazepine receptor binding agent that modulates autonomic function
Cholecystokinin (CCK) antagonists 
   CCK1 antagonism stimulates GI motility and may be helpful in treating IBS associated with constipation
Inflammatory drug targets
    Protease-activated receptors-Mast cells release serine proteases that stimulate GI receptors and may play role in visceral hypersensitivty and inflammatory bowel diseases and IBS

A review of clinical trials for IBS at ClinicalTrials.gov shows the following:
Completed trials: duloxetine, mosapride citrate, dextofisopam, crofelemer, itopride HCL, renzapride, asimadoline, alosetron, BMS-562086, mesalazine, St. Johns wort, talnetant
Recruiting: Saccharomyces boulardii, JNJ-27018966, Probaclac, Probiotic

Model of the chemical scopolamine shared under auspices of  Creative Commons Attribution-Share Alike 3.0 Unported by author Giorgiogp2

Chang JY, & Talley NJ (2010). Current and emerging therapies in irritable bowel syndrome: from pathophysiology to treatment. Trends in pharmacological sciences, 31 (7), 326-34 PMID: 20554042

CBT for Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a common functional gastrointestinal syndrome characterized by abdominal pain and bowel disturbances (diarrhea and/or constipation).  It is estimated to affect 10 to 20% of the population and treatment approaches are often unsatisfactory. 

Irritable bowel syndrome can be viewed as a neuroscience problem from several perspectives.  Abnormal gastrointestinal motility and hypersensitivity has been identified in IBS--these functions are related to gut nervous system function.  The rates of depression and anxiety are high in IBS populations.  Pain perception is a central nervous system function.  Psychotropic medications appear to be helpful in controlling IBS symptoms in some patients.

An additional neuroscience perspective is the evolving evidence for cognitive behavioral therapy to reduction distress and suffering in IBS.  Moss-Morris and colleagues from the UK and New Zealand recently demonstrated the effectiveness of a CBT-self management program for IBS in primary care.

A series of sixty-four primary care patients were randomized to manualized CBT or a treatment as usual control condition.  The CBT group completed a seven week program using a manual, one sixty minute face-to-face therapy session and two sixty minute telephone sessions.

The key elements of the CBT program for IBS in primary care included:
1. IBS education--autonomic nervous system interacts with gut, interaction between thoughts, feelings and behaviour and how these can impact stress levels and GI symptoms
2. Assess symptoms and self-monitoring--daily diary of IBS symptoms linked to stress and eating behaviors
3. Managing IBS symptoms--behavioral management of diarrhea or constipation, set goals for managing symptoms
4. Managing unhelpful thoughts-introduction to concept of negative automatic thoughts and their relationship to IBS
5. Personal expectations and activity patterns--perfectionism and other unhelpful personal expectations reviewed
6. Relaxation and stress management-basis stress management and sleep hygiene review--relaxation CD provided
7. Managing flare-ups and the future--probability of flare-ups reviewed, skill use to manage flare-ups and ongoing symptoms emphasized

The key outcome findings for the study:
Symptom relief across all three assessment periods (77% for CBT vs 21% of controls)
At 8 months the CBT group had superior ratings on an IBS symptom severity measure (83% vs 49% of control with clinically significant change)

The authors note that CBT was well accepted with good adherence to treatment.  A majority of subjects felt CBT was more effective than any previous treatment they had received.  The model is relatively inexpensive compared to a standard 12 to 16 week individual CBT therapy course offered by a psychotherapist.

There is need for identifying ways to incorporate this type of model in the U.S.  Adoption of cost-effective treatments is important in this common, chronic disorder associated with significant distress and health care utilization.

Photo of young dik dik from Sudan courtesy of Sarah Yates

Moss-Morris R, McAlpine L, Didsbury LP, & Spence MJ (2010). A randomized controlled trial of a cognitive behavioural therapy-based self-management intervention for irritable bowel syndrome in primary care. Psychological medicine, 40 (1), 85-94 PMID: 19531276