Systematic reviews and meta-analyses of system and component efficacy
Three systematic reviews and meta-analyses published in 2005 and 2009 specifically addressing acupuncture and/or acupressure in chemotherapy-induced nausea and vomiting were identified.4-6 All three generally agree with the findings described in the individual studies below on efficacy although one was limited to acupressure alone, whereas another included injections in acupuncture points and observational studies, and was not only limited to chemotherapy-induced nausea and vomiting, but also included treatment of other conditions such as post-operative pain.6 In the review that was limited to acupressure (n=10), six of the seven studies showing positive results assessed systemic efficacy (i.e. comparing acupressure to no treatment or other treatment).
The other reviews included all stimulation methods of the relevant acupoints, mainly P6.4-5 A similar difference between systemic and component efficacy for acupuncture and acupressure was also seen in these reviews. The summary indicators of effect suggest effect on certain aspects of the nausea and vomiting associated with chemotherapy, but additional studies are needed to pinpoint the specific areas of clinical applicability.
Clinical trials
Acupuncture
Component efficacy (acupuncture compared to placebo treatment)
Acupuncture of P6 has been compared to placebo treatment in two trials.7-8 The first trial consisted of 104 “high-risk” breast cancer patients undergoing standard chemotherapy.7 They were randomized to three treatment arms: low-frequency electroacupuncture, minimum needling at control points, and no adjunct needling. The results showed that the electroacupuncture group experienced significantly fewer five-day emesis episodes when compared to the minimum needling group (10 versus 15).
The other trial included 80 cancer patients treated with high-dose chemotherapy and autologous peripheral stem cell transplantation receiving ondansetron to reduce nausea and vomiting.8 In a single-blind placebo-controlled design the patients were randomized to either verum or placebo (telescopic needle) acupuncture. The results show no difference in the severity of nausea and the number of bouts of vomiting when acupuncture was given in addition to ondansetron.
One additional study9 was not included in the evaluation because they had added up three sub-trials (among them a pilot study) into one combined trial.
Systemic efficacy (acupuncture compared to no treatment or other treatments):
Acupuncture of P6 has been compared to no treatment in four clinical trials.7,10-12 One cross-over trial11 included only eleven pediatric patients receiving antiemetic medication who were randomized to start treatment with or without additional acupuncture, and was not evaluated further.
In the second trial 39 rheumatologic patients receiving cyclophosphamide were treated with ondansetron to reduce nausea and vomiting.10 In a design where patients acted repeatedly as their own controls, they were also treated with acupuncture during some of their chemotherapy sessions. The results show that both the severity of nausea and the number of bouts of vomiting were significantly lower when acupuncture was given in addition to ondansetron. Seventy-two hours after the cyclophosphamide infusion, 20% of the patients who were not receiving acupuncture still had severe vomiting and 10% experienced 10 to 25 bouts of vomiting per day, while only 8% had severe vomiting and none experienced 10 to 25 bouts of vomiting when they were also given acupuncture.
The third trial consisted of 104 “high-risk” breast cancer patients undergoing standard chemotherapy.7 They were randomized to three treatment arms: low-frequency electroacupuncture, minimum needling at control points, and no adjunct needling. The results showed that the electroacupuncture group experienced significantly fewer five-day emesis episodes when compared to the no needling group (5 versus 15).
In the fourth trial, 23 children between 6 and 18 years of age with different cancer diagnoses were randomized to receive acupuncture concurrently with their chemotherapy treatment.12 The trial followed a cross-over design and showed that during acupuncture treatment the children required less rescue medication (primary endpoint), but the results were only statistically significant with regard to phenothiazines. Retching/vomiting episodes (secondary endpoint) were statistically significantly reduced by approximately 50% in the periods where acupuncture was in use.
Acupressure
Component efficacy (acupressure compared to placebo treatment)
Acupressure of P6 has been compared to placebo treatment in five trials.13-17 Two of these analyzed results for less than ten patients in each treatment group, and were not evaluated further.13,17
The third trial included 49 cancer patients with a variety of diagnoses undergoing standard chemotherapy.16 The intervention group wore an acupressure wristband, while the control group wore an identical-looking inactive wristband. The intervention group did significantly better during the five-day follow-up on severity of nausea and vomiting (1.54 versus 3.1 on a scale from 0 to 10), and retching episodes (1.4 versus 3.6).
In the fourth trial, 107 women with breast cancer 18 years of age or older were randomized to wristbands with electrical stimulation at either P6, at a sham point on the dorsal side of the forearm, or to no wristband at all.14 The results were analyzed using ANCOVA comparing all three groups, and no significant differences were found neither in the primary endpoint (delayed nausea) nor in any secondary endpoints.
The fifth trial included 160 breast cancer patients undergoing chemotherapy.15 The participants were randomized to self-acupressure of P6 (active) or S13 (“placebo” controls) or usual care. A statistically significant reduction in delayed nausea and vomiting was found in the active group compared separately with the “placebo” group and with the usual care group.
Systemic efficacy (acupressure compared to no treatment or other treatments):
Acupressure of P6 has been compared to no treatment, or other treatment, in seven trials.13-15,18-21 Two trials included less than ten patients in every treatment group, and were not evaluated further.13,20
The third trial included 739 patients with mainly breast and haematological cancers undergoing chemotherapy.18 Patients randomized to receive an acupressure wristband experienced significantly less severe nausea on the first day of treatment compared to the no treatment group (2.6 versus 3.0 on a scale from 1 to 7), but no difference was seen on the subsequent days.
The fourth trial included stomach cancer patients (n=40) undergoing chemotherapy and treated with standard anti-emetic treatment.19 The intervention group applied self-acupressure manually, while the controls received no therapy. The intervention group did significantly better during the five-day follow-up. On the 5th day they experienced less severe nausea and vomiting (6.05 versus 9.55 on a scale from 0 to 10), shorter duration of nausea and vomiting (1.70 versus 4.25 hours), and less frequent nausea and vomiting (0.3 versus 0.9 times).
The fifth trial included 54 patients with breast cancer undergoing their first cycle of chemotherapy and receiving standard anti-emetic treatment.21 Patients randomized to an acupressure wristband experienced statistically significant less severe combined nausea, retching and vomiting measured on a five-point scale (for each item) over five days compared to controls receiving antiemetics alone. This sum difference was in the order of 2.5 to 3 except for the third day when only minimal differences were seen.
In the sixth trial 107 women with breast cancer aged ≥18 years were randomized to wristbands with electrical stimulation at either P6, at a sham point on the dorsal side of the forearm, or to no wristband at all.14 The results were analyzed using ANCOVA comparing all three groups, and no significant differences were found neither in the primary endpoint (delayed nausea) nor in any secondary endpoints.
The seventh trial included 160 breast cancer patients undergoing chemotherapy.15 The participants were randomized to self-acupressure of P6 (active) or S13 (“placebo” controls) or usual care. A statistically significant reduction in delayed nausea and vomiting was found in the active group compared separately with the “placebo” group and with the usual-care group.
Acupuncture and acupressure combined
A protocol combining acupuncture and subsequently applied acupressure of P6 has been compared to placebo treatment in one cross-over trial.22 The trial included 28 cancer patients with a variety of cancer diagnoses undergoing standard chemotherapy. The intervention group received acupuncture and wore an acupressure wristband, while the control group wore an identical-looking inactive wristband. The intervention group did significantly better during the five-day follow up on severity of nausea and vomiting (1.54 versus 3.1 on a scale from 0 to 10), and retching episodes (1.4 versus 3.6).
Animal studies
Electroacupuncture at P6 in combination with antiemetic drugs were better than either treatment alone in alleviating early emesis episodes in ferrets.23 The emesis episodes were induced by venous injection of cyclophosphamide.
Biologic mechanism
Three human studies measuring gastric myoelectric activity and tachyarrhythmia showed a statistically significant increase in “slow waves” or “period dominant power” when the subject was undergoing P6 electroacupuncture or acupressure.1-2,24
The fourth study failed to show any statistically significant difference.25 Transient lower esophageal sphincter relaxations have also been shown to be statistically significantly lower when the P6 acupuncture point was stimulated by transcutaneous electric nerve stimulation (TENS).26 fMRI suggests that the cerebellum serves as an important activation loci during acupuncture stimulation of P6.27
A study on a dog model monitoring gastroduodenal motor activity by four implanted force transducers on the serosal surfaces of the gastric body, antrum, pylorus, and duodenum, showed that stimulation by electroacupuncture of P6 significantly suppressed vasopressin-induced retrograde peristaltic contractions.28 The anti-emetic effect was abolished by pre-treatment with naloxone but not naloxone methiodide. It is therefore suggested that the anti-emetic effect of acupuncture is mediated via the central opioid pathway.