Tag Archives: topiramate

2025 Pediatric Cyclic Vomiting Syndrome Guidelines

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K Karrento et al. J Pediatr Gastroenterol Nutr. 2025;80:1028–1061. Open Access! North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition 2025 guidelines for management of cyclic vomiting syndrome in children

This is an excellent CVS guideline (36 pages). There is a lot of information and advice that is not easily summarized. Some important points:

  • Epidemiology: “The prevalence of pediatric CVS is estimated between 1.9% and 2.3% with an incidence of 3.2 per 100,000 children/year.1–3, 16 CVS peaks among school-aged children and often evolves into migraine headaches in adolescent years…17 56% of children experience resolution of CVS during a median follow-up of 29 months (range 6 months to 7 years)…A long-term follow-up study demonstrated progression to migraine in 26% of those with pediatric CVS.1“
  • Autonomic dysfunction: “An underlying autonomic dysregulation is also supported by clinical features during attacks (diaphoresis, listlessness, palpitations, and peripheral vasoconstriction), and a study shows that 40% of pediatric patients with CVS develop chronic dysautonomia during adolescence.18“
  • Cannabinoid hyperemesis syndrome: “CHS is considered a probable subtype of CVS that presents after prolonged and excessive cannabis use…26 Topical capsaicin, benzodiazepines, and droperidol or haloperidol have all been proposed as possible treatments for acute CHS episodes…50 Adult guidelines recommend that CHS patients be offered the same therapies as CVS patients…Complete cannabis cessation is the only known effective long-term treatment for CHS.”
  • Sato-variant: “This subtype manifests elevated levels of adrenocorticotropin hormone, cortisol, antidiuretic hormone, catecholamines, and prostaglandin E2, consequently presenting with hypertension and profound lethargy.25 While there is no published data for guidance, electrolyte monitoring is warranted, and episodic hypertension is generally managed by short-acting agents such as lisinopril or labetalol.”
  • L-carnitine: “The panel did not find evidence of efficacy other than when used in combination with coenzyme Q10 and cautioned against use based on concerns for atherosclerosis in animals.”
  • Propranolol: “The panel cautioned for use in patients with reactive airway disease…Retrospective studies showed high long-term efficacy of propranolol (57%–81%) when used as a first-line agent for pediatric CVS.155, 156 Two prospective, observational studies in pediatric CVS showed a high response rate to propranolol (77%–93%).157, 158 A larger (n = 81) randomized (uncontrolled and unblinded) trial demonstrated long-term effects of propranolol 1 mg/kg/day on both frequency and severity of CVS attacks with a 92% response rate and superiority over amitriptyline (53% response rate).159“
  • Cyproheptadine: “Using criteria of ≥50% improvement in outcomes of interest (episode frequency and duration), 55%–75% (retrospective to randomized) met this threshold. In pediatric migraine, 83% had a positive response.”
  • Aprepitant: “The use of aprepitant two or three times per week for prophylaxis resulted in significant improvement in several essential outcomes, including episode frequency, duration, intensity, symptom-free periods, hospitalization rates, and school attendance.69, 169 At the 12-month follow-up, 82% of children [n=95] achieved either partial or complete treatment response.”
  • Tricyclic Antidepressants (TCAs): “The panel suggests that this medication be reserved for those with more frequent and severe disease who have not responded to therapies with more favorable side effect profiles. Caution for possible behavioral changes, including suicidality, is indicated in all children and adolescents….Using the common criteria of ≥50% improvement as definition of response (complete or partial), 57% of pediatric and 81% of adult CVS patients responded.”
  • Anticonvulsants: “The guideline panel suggests not using anticonvulsants (e.g., topiramate or valproate) for preventing CVS episodes in children and adolescents, except for refractory CVS.”

My take: While data for CVS remains limited, these guidelines are likely to influence how CVS is managed in children.

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#NASPGHAN19 Selected Abstracts (Part 1)

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Link to full NASPGHAN 2019 Abstracts.

Here are some abstracts that I found interesting at this year’s NASPGHAN meeting:

NAFLD:

  1. Off-label use of topiramate may be helpful in stabilizing weight and improving NAFLD
  2. Socioeconomic barriers are frequent in NAFLD patients (the 2nd poster did not appear to show a control population):

Primary Sclerosing Cholangitis -Use of Vedolizumab for PSC did not appear to help

Eosinophilic Esophagitis

  1. EoE is four times more likely in this cohort with inflammatory bowel disease
  2. 2nd poster describes very early-onset EoE

Inflammatory Bowel Disease:

  1. Use of infliximab in VEO IBD.  Used in 46/122 (38% of patients) and 50% had persistent use 3 years later

Enteral nutrition –poster from our group describing good tolerance of plant-based formula (with Ana Ramirez).

Celiac disease.  This poster indicates low yield of additional serology for celiac disease besides TTG IgA and serum IgA. This includes testing in young patients (< 2 years) with celiac disease.

Two new drugs for obesity

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Undoubtedly, a safe, effective medication for obesity would be a pharmaceutical blockbuster.  The record so far on previous medications has been dismal.  Many have been abandoned due to safety concerns, including sibutramine (myocardial infarction and stroke) as well as dexfenfluramine/fenfluramine (valvulopathy).  Two new FDA-approved agents have shown promise but caution in their use will be needed (NEJM 2012; 367: 1577-79).  Neither agent has approval for pediatric usage.

Belviq (lorcaserin) is a selective agonist of the serotonin 5-HT-2C receptor and Qsymia (phentermine with topiramate) is a combination sympathomimetic amine (anorectic agent) with an antiepileptic drug.

In studies with lorcaserin, three studies (1-year placebo-controlled) have shown that the number of patients losing >5% of body weight was increased compared to placebo.  Mean percentage body weight loss with lorcaserin was -5.8% in first two studies and -4.5% in third study.  In contrast, placebo patients who received lifestyle counseling lost  -2.5% and -1.5% respectively.  Overall, up to 47% of patients receiving medication lost more than 5% body weight.

Potential safety concerns with lorcaserin:  initially there were concerns due to increased incidence of tumors in rats and possible valvulopathy (eg. mitral or aortic valve regurgitation).  However, the FDA has concluded that it is unlikely that these are likely to occur in humans.

With phentermine/topiramate, two placebo-controlled studies have shown an increase in patients losing >5% of body weight compared to placebo.  In the first study, the mean percentage change in body weight was -10.9% combination (dosage 15 mg/92 mg) compared with -1.6% for placebo.  In the second study, this dosage led to a -9.8% reduction compared with -1.2% in placebo patients. Overall, up to 70% of patients receiving medication lost more than 5% body weight.

With regard to safety, it is known that topiramate is teratogenic and increases the risk of orofacial cleft.  Due to this, approval for this combination requires a risk evaluation and mitigation strategy (REMS) which permits only specially-certified pharmacies to dispense along with formal training for prescribers. In addition, this combination has been associated with mildly increased heart rate. Due to favorable changes in blood pressure, the FDA concluded that this medication had a good benefit-risk balance.  But, the manufacturer recommends against it use in patients with cardiac issues or cerebrovascular disease.

With both new medications, other safety concerns include the risk of increased psychiatric effects.  In addition, specific recommendations include the following:

  • Only recommended in adults with BMI ≥30 or adults with BMI ≥27 with at least one weight-related comorbidity
  • With both medications, if weight loss not adequate after 12 weeks then discontinue medication.  With lorcaserin, if weight loss is not ≥5%, then discontinue.  With phentermine/topiramate, if weight loss is not ≥3% at 12 weeks (with 7.5 mg/46 mg), consider dosage increase and/or discontinuation.

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