Olanzapine and Baclofen for the Treatment of Intractable Hiccups

Pharmacotherapy (Impact Factor: 2.66). 02/2014; 34(1):e4-8. DOI: 10.1002/phar.1378
Source: PubMed


Intractable hiccups are a relatively uncommon condition characterized by involuntary, spasmodic contractions of the diaphragm. This type of hiccups generally has a duration of more than 1 month. We describe a 59-year-old kidney transplant recipient with a complicated medical history (atrial fibrillation, chronic renal failure, type 2 diabetes mellitus, gastroesophageal reflux, gout, hypertension, hyperlipidemia, and obstructive sleep apnea) who developed intractable hiccups that significantly affected his quality of life. Despite an extensive gastrointestinal and pulmonary evaluation, and treatment failures with several different drug regimens--metoclopramide, desipramine, amantadine, cyclobenzaprine, phenytoin, and lorazepam--his hiccups were eventually controlled with a combination of baclofen and low-dose olanzapine therapy. Baclofen is a c-aminobutyric acid (GABA) analog that contains a phenylethylamine moiety. It is hypothesized that having both GABA and phenylethylamine properties activates inhibitory neurotransmitters, most notably GABA, which may in turn block the hiccup stimulus. The exact mechanism through which olanzapine is effective in patients with hiccups is not fully understood. It is thought that the effect is, in part, due to serotonin augmenting phrenic motoneuronal activity on the reflex arcs involved in the generation of hiccups within the spinal cord. In addition, since olanazapine is a dopamine antagonist, particularly a dopamine D₂-receptor antagonist, this could also have played a role in its effectiveness in treating our patient. Strong evidence for a specific treatment regimen for intractable hiccups is lacking in the primary literature. Our case report adds to the available literature, as there are currently no published data on the use of combination therapy for the treatment of intractable hiccups, and the combination of baclofen and olanzapine significantly improved our patient's quality of life.

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Available from: Julie Ehret Leal, Aug 06, 2014
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    ABSTRACT: Hiccups are familiar to everyone, but remain poorly understood. Acute hiccups can often be terminated by physical manoeuvres. In contrast, persistent and intractable hiccups that continue for days or months are rare, but can be distressing and difficult to treat. To review the management of hiccups, including a systematic review of reported efficacy and safety of pharmacological treatments. Available articles were identified using three electronic databases in addition to hand searching of published articles. Inclusion criteria were any reports of pharmaceutical therapy of 'hiccup(s)', 'hiccough(s)' or 'singultus' in English or German. Treatment of 341 patients with persistent or intractable hiccups was reported in 15 published studies. Management was most effective when directed at the underlying condition. An empirical trial of anti-reflux therapy may be appropriate. If the underlying cause is not known or not treatable, then a range of pharmacological agents may provide benefit; however, systematic review revealed no adequately powered, well-designed trials of treatment. The use of baclofen and metoclopramide are supported by small randomised, placebo-controlled trials. Observational data suggest that gabapentin and chlorpromazine are also effective. Baclofen and gabapentin are less likely than standard neuroleptic agents to cause side effects during long-term therapy. This systematic review revealed no high quality data on which to base treatment recommendations. Based on limited efficacy and safety data, baclofen and gabapentin may be considered as first line therapy for persistent and intractable hiccups, with metoclopramide and chlorpromazine in reserve. © 2015 John Wiley & Sons Ltd.
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