Pharmacotherapy for Chronic & Intractable Hiccups in Palliative Care: A Mixed Methods Systematic & Umbrella Review

Chronic and intractable hiccups are a debilitating symptom in palliative care, yet the evidence for their pharmacological management is sparse and of low certainty, as certain study designs are frequently excluded from traditional systematic reviews.

To synthesize all available quantitative and qualitative evidence for the pharmacological management of chronic and intractable hiccups in adults receiving palliative care.

We conducted a mixed methods systematic review, including a rapid umbrella review, following a registered PROSPERO protocol (CRD42024514442) in accordance to the PRISMA and SWiM guidelines. Seven electronic databases, trial registries and grey literature sources were searched from inception until August 2025 for studies of any design and systematic reviews. Quantitative data on hiccup reduction or cessation following pharmacological use, and qualitative phenomena of interest on patient and clinician experiences were extracted. Studies were critically appraised via JBI and AMSTAR-2 tools, synthesized separately using a convergent segregated approach, and then integrated narratively. This was performed independently by two reviewers.

A total of 88 primary studies (85 quantitative, two qualitative and one mixed methods) and six systematic reviews were included. The quantitative synthesis, comprising 156 patients, identified gabapentin and baclofen as the most frequently reported effective agents, alongside various dopamine antagonists, benzodiazepines, medication rotation, combination therapies and novel approaches. The qualitative synthesis revealed four themes: the profound psychosocial impact of hiccups, perceived treatment ineffectiveness, a disconnect between patient experience and clinical awareness, and a patient preference for symptom management over cure.

The evidence for management of chronic and intractable hiccups in palliative care is of very low certainty and likely subject to significant publication bias. Clinical goals should be reframed from cure to "palliative control", prioritizing functional improvement and a reduction in symptom burden.