Cyclic Vomiting Syndrome Episodes Research Articles

Clinical characteristics and long-term outcomes in patients with cyclic vomiting syndrome: A 15-year experience at a tertiary referral center.

Cyclic vomiting syndrome (CVS) is a disorder of gut-brain interaction (DGBI) characterized by recurrent episodes of nausea and vomiting. Most children outgrow their CVS symptoms and develop migraine headaches, but there are limited data in adults. We thus sought to determine the natural history of CVS in adults. We conducted a retrospective analysis of patients at a specialized tertiary care clinic. Frequency of CVS episodes, emergency department (ED) visits, and hospitalizations were recorded at the index visit and at follow-up. Of 455 CVS patients with complete data, mean age was 33 ± 13 years, 294 (65%) were female, and 392 (86%) were Caucasian. Mean duration of follow-up was 47.4 ± 37.2 months. There was a significant reduction in frequency of CVS episodes/year (18 to 6.8), ED visits (6.1 to 2), and hospitalizations (2.3 to 0.7) (all p-values < 0.001) but only 88 (19%) of patients had complete resolution of episodes at follow-up. On multivariable regression analysis, non-white race [0.33 (0.11-0.98) p = 0.01], comorbidity count [0.77 (0.62-0.95) p = 0.01], cannabis use [0.36 (0.2-0.65) p = 0.0007], and aprepitant use [0.2 (0.08-0.005) p < 0.001] were associated with a reduced odds of complete resolution of CVS episodes. Of note, 19 patients (4%) died. While most adults with CVS improved with specialized care, in contrast to children, only a small subset (~1 in 5) had complete resolution of symptoms. Reasons for the effects of race, cannabis use, and comorbidity burden on outcomes in CVS are unclear and warrant further investigation.

Efficacy of aprepitant as a prophylactic medication in adults with cyclic vomiting syndrome.

Aprepitant is a neurokinin-1 receptor antagonist, and recent guidelines by the American Neurogastoenterology and Motility Society recommend its use as prophylaxis in moderate-to severe cyclic vomiting syndrome (CVS). Data are limited to small studies in children. We aimed to determine its efficacy in adults with CVS. A retrospective review of CVS patients diagnosed using Rome criteria at a tertiary referral center was conducted. Drug response was defined as >50% reduction in symptoms and/or healthcare utilization. An intent-to-treat (ITT) analysis was conducted. Of 96 patients prescribed aprepitant, 26 (27%) were unable to start due to cost/lack of insurance coverage. Of 70 receiving therapy, mean age was 33 ± 11 years; 51 (73%) were female and 56 (80%) Caucasian. The majority (93%) were refractory to other prophylactic medications. Aprepitant was taken thrice weekly in 51 (73%), daily in 16 (23%) and a few times a month in 3 (4%) due to cost. Fifty (71.4%) had a global symptom response to aprepitant. There was significant reduction in the number of CVS episodes (14.5± 11.7 to 6.2± 8.0, p< 0.0001), emergency department visits (4.2± 7.7 to 1.8± 3.4, p= 0.006), and hospital admissions (1.6± 3.9 to 0.8± 2.1, p= 0.02) in patients treated with aprepitant. Seven (10%) discontinued the drug due to minor side effects. Aprepitant is a safe and effective prophylactic medication in adults with refractory CVS. Adequate insurance coverage is a major barrier preventing its use.

Retrospective review of patients treated for cyclic vomiting syndrome with topiramate.

Practice guidelines recommend topiramate as second-line treatment for the prevention of moderate-severe cyclic vomiting syndrome (CVS) in adults. However, data are limited to small studies in children. To characterise the response to topiramate as prophylactic therapy in adults with CVS. We conducted a retrospective review of patients with CVS. Clinical characteristics, number of CVS episodes, emergency department (ED) visits, and hospitalisations the year before and after initiating topiramate were recorded. Response was defined as a global improvement in symptoms or >50% reduction in the number of CVS episodes, ED visits or hospitalisations. Sixty-five percent (88/136) of patients responded to topiramate in an intent-to-treat analysis. There was a significant decrease in the annual number of CVS episodes (18.1 vs 6.2, P<0.0001), CVS-related ED visits (4.3 vs 1.6, P=0.0029), and CVS-related hospitalisations (2.0 vs 1.0, P=0.035). Logistic regression revealed that higher doses of topiramate, longer use of topiramate (≥12months) and topiramate as monotherapy were associated with a response to treatment. Anxiety was associated with non-response to topiramate. Fifty-five percent of patients experienced side effects, and 32% discontinued the medication as a result. The most common side effects were cognitive impairment (13%), fatigue (11%) and paresthesia (10%). This represented a refractory group with topiramate being initiated in patients (92%) who had failed treatment with tricyclic antidepressants (TCAs). Topiramate may be an effective second-line prophylaxis for patients with moderate-severe CVS, but its use is limited by side effects. Efforts to develop better-tolerated therapies for CVS are warranted.

Cyclic vomiting syndrome: A narrative review and guide to management.

Cyclic vomiting syndrome (CVS) is a disabling disorder of gut-brain interaction manifested by stereotypical and severe episodes of nausea and vomiting. Prevalence data indicate that CVS affects 1-2% of children and there has been a recent dramatic rise in diagnosed adults. This narrative review summarizes relevant literature pertaining to pediatric and adult CVS and provides a guide to management based on extensive clinical experience. More timely diagnosis is facilitated by an expert consensus diagnostic approach and limited testing. Some diagnostic tests of exclusion remain essential. These include an upper gastrointestinal (GI) contrast study to exclude intestinal malrotation and basic laboratory screening. An abdominal ultrasound is recommended to exclude renal hydronephrosis in children and biliary disease in adults. Exclusion of metabolic/genetic conditions is warranted in those with specific warning signs, presentation in infants/toddler age, and in those with refractory disease. In the absence of chronic GI symptoms, referral to a GI specialist for upper endoscopy is generally not necessary in children but recommended in adults. A large subset termed migraine-equivalent CVS display strong clinical and genetic features of migraine. A unifying pathophysiologic core concept involves neuronal hyperexcitability and aberrant central modulation of autonomic signals. This is coupled with multiple susceptibility factors including mitochondrial dysfunction/cellular energy deficits, a hyper-responsive hypothalamic-pituitary-adrenal axis and many comorbidities that increase vulnerability to triggering events. CVS episodes are frequently triggered by stressors and intercurrent illnesses. Lifestyle and non-pharmacological interventions thus play a pivotal role in successful management. Pharmacological therapies are categorized into abortive, supportive/rescue, and prophylactic treatments. The majority respond particularly well to migraine-focused treatment strategies. Despite improved characterization and understanding, CVS remains classified as a functional disorder of brain-gut interaction that is often disjointly managed by generalists and subspecialists. Early recognition, evaluation, and management will facilitate care and improve outcomes. Further research into its natural history with common progression to migraine headaches, neuroendocrine mechanisms, and the pathophysiologic relation to migraine diathesis is much needed.

Sumatriptan as abortive treatment in cyclic vomiting syndrome: A cross-sectional study

Cyclic vomiting syndrome (CVS) is characterized by episodic vomiting and shares similarities with migraine headache. Guidelines recommend using triptans as abortive therapy in CVS, but there are limited data on its efficacy. Methods: We thus sought to characterize sumatriptan use and performed a cross-sectional study of adults with CVS episodes within the previous 6 months. Questionnaires about demographics, clinical characteristics, and response to sumatriptan (defined as &gt;50% reduction in symptoms) were administered via e-mail. We investigated differences between responders and nonresponders, using χ 2 and Student’s t test. Results: Of 101 participants (age 41 ± 15 years, 74% female, 83% Caucasian), 39 (38%) used sumatriptan during their last CVS attack. Most reported an improvement in nausea (55%), vomiting (59%), and abdominal pain (43%) within 2 h and at 24 h (67%, 73%, and 67%) respectively. Eighteen (46%) reported that sumatriptan helped them avoid emergency department visits and 20 (51%) avoided being hospitalized. Nonresponse to sumatriptan was associated with depression ( p = 0.01), current cannabis use ( p = 0.02), use of benzodiazepines ( p = 0.04), and opioids (0.02) during an episode. No serious side effects were noted. Conclusions: Sumatriptan use reduced symptoms of CVS but did not abort them. Prospective studies to determine its independent effects are needed.

Patterns of Cannabis Use in Patients With Cyclic Vomiting Syndrome

Some patients with cyclic vomiting syndrome (CVS) use cannabis to relieve stress and for its antiemetic properties. However, chronic cannabis use has been associated paradoxically with cannabinoid hyperemesis syndrome (CHS) and some patients with CVS are thought to have CHS. We sought to characterize patterns of cannabis use by patients with CVS and identify those who could be reclassified as having CHS. We performed a cross-sectional study of 140 patients with CVS (72% female; mean age, 37 ± 13 y) seen at a specialized clinic. Patients were screened for cannabis use with the cannabis use disorder identification test. Patients were classified as regular (use ≥4 times/wk) or occasional users (<4 times/wk). Forty-one percent of patients were current cannabis users, with 21% reporting regular use. Regular users were more likely to be male and to report an anxiety diagnosis, and smoked cannabis with higher tetrahydrocannabinol content and for a longer duration. Most users reported that cannabis helped control CVS symptoms. Among all cannabis users, 50 of 57 (88%) reported that they had abstained for longer than 1 month, but only 1 user reported resolution of CVS episodes during the abstinence period. This patient subsequently resumed using cannabis but remains free of symptoms. Cannabis is used commonly among patients with CVS-patients report relief of symptoms with use. We found 21% of patients with CVS to be regular users, but only 1 met the Rome IV criteria for CHS. Longitudinal studies are needed to determine the relationships among cannabis use, hyperemesis, and mood symptoms.

Family Health-related Quality of Life in Pediatric Cyclic Vomiting Syndrome.

The aim of the study was to evaluate the relationship of disease characteristics and child anxiety symptoms to family health-related quality of life (FHRQoL) in youth with cyclic vomiting syndrome (CVS). Forty-two parents of youth ages 8 to 18 years diagnosed with CVS completed the Family Impact Module of the PedsQL, a measure of the impact of the child's illness on the family. We evaluated the relationship of disease characteristics and child and parent proxy reports of anxiety symptoms on the Screen for Childhood Anxiety and Related Emotional Disorders to FHRQoL. Parent report of child anxiety symptoms and missed school days (mean = 11.93, standard deviation = 14.62) were the strongest predictors of FHRQoL (r = 0.33, df = 1.39, F = 8.51, P = 0.006). Other disease characteristics, including frequency, duration, chronicity of CVS episodes, and delay in initial CVS diagnosis were not significantly associated with the FHRQoL total score. Child anxiety symptoms by either parent and/or child report were associated with subscales of the FHRQoL, including family physical functioning, family communication, and family daily activities. HRQoL for the families assessed in this study was associated with anxiety symptoms to a greater extent than disease characteristics, indexing the importance of a biopsychosocial approach to CVS management. Screening for anxiety symptoms and support for school absences due to illness are indicated to help lessen the impact of CVS on the family as a whole.

Anxiety and physiological responses to the Trier Social Stress Test for Children in adolescents with cyclic vomiting syndrome.

This study compared anxiety and physiological responses during the Trier Social Stress Test for Children (TSST-C) in adolescents. 38 subjects (26 females) were enrolled: 11 cyclic vomiting syndrome (CVS), 11 anxiety, and 16 controls. Salivary cortisol, α-amylase and heart rate variability (HRV) were assessed during the TSST-C. Anxiety was measured by the Screen for Childhood Anxiety Related Emotional Disorders (SCARED), Anxiety Disorders Interview Schedule, and State-Trait Anxiety Inventory for Children (STAI-C). 11 anxiety and 7 CVS subjects had ≥1 anxiety disorder. 82% in the anxiety and CVS groups met criteria for an anxiety disorder on the SCARED. Combining groups, cortisol increased from baseline to recovery during the TSST-C (p=0.0004) and the stressor to recovery (p=0.005). α-amylase did not differ during the TSST-C for the total sample, but increased for anxiety compared to controls from baseline to recovery (p=0.01). HRV decreased during the stressor (p=0.0001) and increased at recovery (p=0.004). No associations were found between biomarkers and trait anxiety. Associations were found between baseline HRV and pre-test state anxiety (r=-0.406, p=0.012) and between recovery HRV and post-test state anxiety (r=-0.501, p=0.002) for the total sample. Anxiety is prevalent in CVS warranting screening. HRV may serve as a biomarker for evaluating stress as a potential trigger for CVS episodes. State but not trait anxiety was associated with changes in HRV, suggesting acute anxiety may be more relevant in linking stress and CVS episodes.

Anxiety Measures Predict Health-Related Quality of Life in Children and Adolescents with Cyclic Vomiting Syndrome

To evaluate the relationship between anxiety and health-related quality of life (HRQoL) in children and adolescents with cyclic vomiting syndrome (CVS). Forty children aged 8-18 years diagnosed with CVS and 40 parents completed the Screen for Child Anxiety Related Emotional Disorders (SCARED) and the child and parent forms of the Pediatric Quality of Life Generic Core Scale, a measure of HRQoL. Eleven of the 40 children (27%) by self-report and 6 of 40 (15%) by parent-proxy report met the clinical cutoff for an anxiety disorder on the SCARED. Parent and child SCARED ratings were moderately correlated (intraclass correlation coefficient 0.68; P < .001). Child-rated HRQoL (mean ± SD, 74.3 ± 15.2) and parent-rated HRQoL (mean, 72.1 ± 14.6) were lower than healthy norms (P < .001). Disease severity (mean duration of CVS episodes, 3 ± 2.4 days), annual frequency of CVS episodes (mean, 8.2 ± 15.3), chronicity of CVS (mean, 5.8 ± 3.4 years), and delay in diagnosis (mean, 2.4 ± 1.9 years) were not associated with child-reported HRQoL; however, child SCARED scores accounted for approximately 50% of the variance in child-reported HRQoL (adjusted R(2) = 0.49; df = 1, 38; P < .001). Children and adolescents with CVS appear to be at increased risk for anxiety. Anxiety symptoms are a stronger predictor of HRQoL than disease characteristics in children and adolescents with CVS. Assessment and treatment of anxiety in children and adolescents with CVS may have a positive impact on HRQoL.

Cyclic vomiting syndrome: A common, underrecognized disorder

To increase recognition and present symptom assessment strategies for treating cyclic vomiting syndrome (CVS). Clinical experience, a range of pediatric, gastroenterological, emergency medicine research, survey, and literature review reports on CVS. Improved efforts to recognize, diagnose, and treat CVS will help patients manage their symptoms and may reduce both the morbidity and costs of hospitalizations associated with this illness. If promptly diagnosed and appropriately treated, CVS episodes can be aborted. Patients inappropriately treated must often be hospitalized because of complications associated with symptoms. Lifestyle changes, prophylactic and abortive migraine therapy, and supportive care are important to prevention.

Health-Related Quality of Life in Children and Adolescents with Cyclic Vomiting Syndrome: A Comparison with Published Data on Youth with Irritable Bowel Syndrome and Organic Gastrointestinal Disorders

To evaluate health-related quality of life (HRQoL) in children with cyclic vomiting syndrome (CVS) and to compare child self-reports with those of their parents and with published reports of children with irritable bowel syndrome (IBS), children with organic gastrointestinal disorders, and a healthy control group. Sixty-eight children aged 5-18 years with CVS confirmed in a gastroenterology clinic completed the Pediatric Quality of Life Inventory (PedsQL). Eighty-two parents completed the parent-proxy PedsQL for children aged 2-18 years. These results were compared with published data for children with IBS, organic gastrointestinal disorders, and a healthy control group using ANOVA. Intraclass correlation was used to evaluate concordance between child and parent reports of HRQoL. HRQoL reported on the PedsQL by children with CVS was lower than that reported by children with IBS (P < .01) and healthy controls (P < .001), but did not differ from that reported by children with organic gastrointestinal disorders. Children with CVS also had lower HRQoL compared with healthy controls by parent-proxy report on the PedsQL (P < .001). Correlations between HRQoL reports by parents and children were moderate to good (intraclass correlation coefficients, 0.504-0.805; P < .01). Duration of CVS episodes, delay in CVS diagnosis, and number of school days missed due to CVS were associated with lower parent-rated HRQoL (P = .01). Children with CVS reported lower HRQoL compared with those with IBS, and both parents and children reported lower HRQoL compared with healthy controls. Parent and child ratings of HRQoL converged. Improved recognition of CVS and school support might help mitigate the impact of CVS on HRQoL.

Efficacy of Tricyclic Antidepressant Therapy in Adults With Cyclic Vomiting Syndrome

To investigate the effects of prolonged tricyclic antidepressants (TCAs) therapy on the frequency and duration of episodes of cyclic vomiting syndrome (CVS) in adults, and the global assessment of clinical improvement and the number of emergency department (ED) visits and/or hospitalizations. An open labeled study was conducted in adult CVS patients treated with a TCA and followed for up to 2 years. Demographic data, TCA dosage, duration and frequency of CVS episodes, ED visits, and hospitalizations at baseline and during TCA therapy were recorded, and patients were monitored for any adverse events. Forty-six patients initially met the inclusion criteria and 41 patients (22 male) with mean age of 35 years (range: 18 to 63 y) on TCA were able to be followed for 1 year and 23 were evaluated for 2 years. Mean age of onset of CVS symptoms was 26 years (range: 10 to 52 y) and mean age for making the diagnosis of CVS was 32 years (range: 15 to 63 y). The frequency and duration of an episode and ED visits related to CVS were all significantly reduced after both the first and second year of TCA therapy (P<0.05). Eighty-eight percent reported an improved clinical status by subjective global assessment. Mild side effects were reported in 34% not necessitating stoppage of the TCA. Long-term TCA therapy significantly reduces the frequency and duration of CVS episodes, ED visits, and hospitalizations (P<0.05), and improves overall clinical well-being providing evidence that they are effective therapy for adult CVS.

Who are the nonresponders to standard treatment with tricyclic antidepressant agents for cyclic vomiting syndrome in adults?

Cyclic vomiting syndrome in adults is a disorder characterized by recurrent and stereotypic episodes of severe nausea and vomiting separated by symptom-free periods. To investigate the demographic and clinical characteristics of adult cyclic vomiting syndrome patients not responding to standard tricyclic antidepressant (TCA) therapy. A total of 132 adults (62 men) with cyclic vomiting syndrome were followed for a mean of 1.6 years. Of these, 17 (eight men) patients were identified as nonresponders based on the criteria of unchanged, increased or minimally changed (<25%) frequency/duration of episodes and/or emergency department visits/hospitalizations. Demographic and clinical characteristics at baseline and annually up to 4 years were investigated. The nonresponders were receiving TCAs at an average dose of 90 mg/day compared to a mean dose of 85 mg/day in responders. Compared with the responders, the nonresponders were significantly more likely to have a history of migraine (P < 0.05); co-existing psychological disorders (P < 0.05); chronic marijuana use (P < 0.05) and reliance on narcotics for pain control between cyclic vomiting syndrome episodes (P < 0.05). (1) Nonresponse to standard therapy in adult cyclic vomiting syndrome patients occurs in approximately 13% and is not explained by under dosing with TCA therapy. (2) The main risk factors for nonresponse are: co-existing migraine headache, psychiatric disorder, chronic narcotic and marijuana use, which should be addressed aggressively when symptom exacerbations continue during attempts to induce remission in cyclic vomiting syndrome with high-dose TCA therapy.

Efficacy of Long Term Treatment Regimens on Cyclic Vomiting Syndrome in Adults

Purpose: Cyclic vomiting syndrome (CVS) is a disorder characterized by recurrent and stereotypic episodes of severe nausea and vomiting separated by symptom-free periods. It is now diagnosed more in adults than children. It's recurrent and disabling character requires more preventive and therapeutic options to reduce emergency department (ED) visits and hospitalizations and improve quality of life in these patients. Methods: In an open labelled study of 45 patients diagnosed with CVS based on Rome III criteria, we investigated the long term efficacy of tricylclic antidepressant (TCA) alone or in combination with Propranolol or Keppra on frequency and duration of CVS episodes and frequency of ED visits or hospitalizations during one and two years follow up. All received detailed information about the disorder, psychological support and help in identifying the trigger events as well as standard back ground support with Alprazolam for anxiety, Dicyclomine for abdominal pain and Promethazine for back up nausea. Demographic data, TCA dosage, duration and frequency of CVS episodes, ED visits and hospitalizations and subjective global assessment at baseline and during TCA therapy were recorded. Adverse effects with TCA were monitored. 5 stopped the medication, 2 within 3 months and 1 after 12 months, as their symptoms had completely resolved, 1 because of a lack of response and 1 due to severe hallucinations. Results: The results are summarized in Table. We followed 40 patients (19 female), mean age 35 years (18–63) on TCA and or TCA plus Keppra (N = 1) or Propranolol (N = 1) for one year and 23 for two years. 37 were on amitriptyline, 2 on nortriptyline and 1 on doxepine. Mean age of symptoms onset was 26 years and 32 years for making the diagnosis of CVS. The goal dose of TCA was 1 mg/kg and the actual doses achieved were 25–200 mg (average 90 mg, qhs). Side effects were reported in 35 percent of our patients and included: dry mouth, somnolence, constipation, postural hypotension, chronic fatigue, blurred vision, and mild hallucinations. 86 percent reported an improved quality of life by subjective global assessment.Table: Effect of Tricyclic Antidepressant therapy on Cyclic Vomiting Syndrome Charecteristics.Conclusion: Long-term TCA therapy significantly reduces the frequency and duration of CVS episodes, ED visits & hospitalizations and improves quality of life. (P < 0.05) These data indicate that TCAs are the treatment of choice for adult CVS patients. Their efficacy could be explained by the hypothesized role of the brain-gut axis in the pathogenesis of this disorder.

The Cyclic Vomiting Syndrome Described

Cyclic vomiting syndrome (CVS) consists of discrete episodes of nausea and vomiting lasting hours or days, separated by symptom-free intervals of similar or varying lengths. The disorder is not caused by underlying organic disease. The episodes tend to be similar in time of onset, duration, and symptomatology specific for each patient and are self-limited. The majority of patients can identify experiences or conditions that may precipitate episodes, the commonest being heightened emotional states and infections. The onset of CVS most often occurs during preschool or early school years, although it may begin at any age, from infancy to mature adulthood. CVS episodes can recur for months or decades, and their subsidence cannot be predicted.

The Cyclic Vomiting Syndrome Described

Summary:Cyclic vomiting syndrome (CVS) consists of discrete episodes of nausea and vomiting lasting hours or days, separated by symptom‐free intervals of similar or varying lengths. The disorder is not caused by underlying organic disease. The episodes tend to be similar in time of onset, duration, and symptomatology specific for each patient and are self‐limited. The majority of patients can identify experiences or conditions that may precipitate episodes, the commonest being heightened emotional states and infections. The onset of CVS most often occurs during preschool or early school years, although it may begin at any age, from infancy to mature adulthood. CVS episodes can recur for months or decades, and their subsidence cannot be predicted.