CVS generally results in severe discomfort, dehydration and disability, and despite prophylactic therapy substantial numbers of patients continue to suffer from repeated vomiting episodes. Our result of 72% efficacy (defined by compound measure) in those taking prophylactic amitriptyline agrees with the 52 to 73% efficacy rates reported in four previous studies [4
]. This result also supports the overall validity of our on-line survey methodology. Our data is also consistent with our own clinical experience, in that overall efficacy is good (72%), yet side effects are frequent (50%), and often result in discontinuation of treatment (21%). Overall, approximately half (47%) of 134 subjects taking amitriptyline reported that the benefits outweighed the side effects of treatment. Furthermore, our data regarding the preventative treatment of CVS with Co-Q is consistent with our clinical experience, in that overall efficacy is good (69%), with side effects being rare (0/22). Three-quarters (77%) of subjects taking Co-Q reported that the benefits outweighed the side effects, a significantly higher portion than that with amitriptyline.
There are substantial child versus adult-related differences in clinical CVS, such as longer and more frequent episodes and more severe inter-episodic nausea among adults [29
]. Furthermore, a strong association with the 16519T and 3010A mtDNA polymorphisms was noted in child-onset (< age 12 years), but not in adult-onset (≥18 years) cases [30
]. Although the numbers of subjects in some categories were small, overall efficacy rates for both amitriptyline (70% v. 72%) and Co-Q (71% v. 71%) were very similar among subjects with child (<12 years) and adult (≥18 years) onset, respectively. Thus, our data do not suggest that the choice of either treatment should differ between pediatric or adult patients.
The limitations of this study are the subjective nature of retrospective subject/parent-completed questionnaires, the lack of validation data for our questionnaire, the lack of a proof of a physician-confirmed diagnosis of CVS, the self-selection bias in Internet questionnaire studies, the relatively small number of subjects reporting treatment with Co-Q, and the wide range of treatment durations, dosages, and in the case of Co-Q, brands and preparations (gel capsules, liquids, tablets, etc.) utilized. Interestingly, both amitriptyline and Co-Q seem to affect different parameters in different people, including episode frequency, episode duration, number of emeses, and severity of nausea. Neither therapy appears to affect the prodrome (data not shown). This information is important in the design of future prospective clinical trials in that complex end points for efficacy are needed. The failure to find a dose-response is expected as only the highest dosage attempted was queried, and thus the high-dose group may contain treatment failures that are not recorded as failures on lower doses.
The authors' clinical practice for treatment of CVS with Co-Q is 10 mg/kg/day divided bid, up to 200 mg bid (either in liquid or gel capsule formulation). It also includes obtaining a blood Co-Q level in the case of an inadequate response, and increasing the dose for blood levels less than 3 mg/L. Additional mitochondrial-targeted dietary supplements have also been used to prevent CVS attacks including L-carnitine, which has demonstrated efficacy in CVS in one small open-label study [31
] (authors' practice: 100 mg/kg/day divided BID, up to one gram BID or TID), and riboflavin, which has demonstrated efficacy in migraine headache [32
] (authors' practice: 100-400 mg/day, or one "B100" tablet a day). Anecdotally, in the authors' practice while some CVS patients respond well to cofactor therapy alone, many patients require drug therapy (generally amitriptyline) in addition. While this combination may have synergy based on anecdotal observations, the numbers of subjects in the current study are inadequate to address this question. This is another question for a prospective clinical trial.