Background Persistent and intractable hiccup is a distressing symptom seen in patients with underlying diagnosis of cancer or end stage systemic disease.

Objective Find and appraise the evidence for different interventions used in the management of persistent and intractable hiccups in adults.

Design Systematic review.

Data source Electronic databases, reference lists of studies, authors and experts.

Methods Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) retrieved through search were assessed for inclusion in the review. Data extraction and quality assessment were carried out. Meta-analyses were not feasible due to lack of comparable controlled studies and therefore a narrative synthesis was carried out. Uncontrolled studies conducted with a sample size of five or more were also analysed due to small number of controlled trials retrieved.

Results One RCT and three uncontrolled studies conducted with Baclofen reported successful results. Three studies conducted with Gabapentin and four studies conducted using acupuncture were uncontrolled and showed positive therapeutic effects. Successful results were reported by two RCTs conducted using acupoint injection of Vitamin B6 and electric needling of Tianding. Significant improvement of hiccup was reported in two CCTs conducted with magnetic needle therapy and acupuncture and auricular plaster therapy. Other interventions reported to be potentially successful in uncontrolled studies included Valproic acid, Metoclopramide, Nifedipine, breathing pacemakers, linearly polarised near-infrared irradiation, cervical phrenic nerve block and electro-acupuncture.

Conclusion Review suggests many possible pharmacological and non-pharmacological interventions including Baclofen, Gabapentin and different variants of acupuncture. Most studies were uncontrolled, underpowered and lacked comprehensive data and therefore recommendations are made cautiously.Well designed RCTs are essential to generate guidelines in clinical practice. The implementation of interventions in palliative care population should be a main consideration in designing future studies. Treatment of intractable and persistent hiccup is based on patients and clinicians preferences until more evidence from RCTs is available.