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Baclofen for treatment of persistent hiccups in HIV-infected patients

D'Alessandro, D. J.; Dever, L. L.


D.J. D'Alessandro and L.L. Dever, Division of Infectious Diseases, Department of Veterans Affairs Medical Center, East Orange, and Department of Medicine, University of Medicine and Dentistry at New Jersey, New Jersey Medical School, Newark, New Jersey, USA.

Date of receipt: 14 January 1997; revised: 10 February 1997; accepted: 18 February 1997.

Hiccups are associated with many conditions including those that involve the central nervous system, the vagus and phrenic nerves, the mediastinum, the diaphragm, the gastrointestinal tract, and peripheral nerves [1]. Although usually innocuous, they can be associated with significant morbidity when present and may interfere with eating and sleep. We have found persistent hiccups to be a relatively common complaint in our HIV-infected patient population. Baclofen, a gammaamino butyric acid agonist, is a skeletal muscle relaxant used for management of spasticity in disorders such as multiple sclerosis. It also has been reported to be effective in the treatment of chronic or intractable hiccups [2–7]. Our experience with oral baclofen for the treatment of hiccups in HIV-infected patients is presented.

Patient 1 was a 45-year-old man with CD4 lymphocyte count of 608 × 106/l who developed intractable hiccups following an episode of bacterial pneumonia requiring intubation. The patient's hiccups became increasingly more severe over a 2-month period. No abnormalities were found on physical examination or chest radiographs to explain the source of his hiccups. Treatment with baclofen at a dosage of 5 mg every 6 h was initiated with a reduction in frequency of hiccups. Increase in dosage to 10 mg every 6 h resulted in complete resolution of his hiccups. Subsequent attempts to reduce the dosage or discontinue the drug resulted in recurrence of hiccups. Baclofen was discontinued after a 4-month period without recurrence of hiccups.

Patient 2 was a 34-year-old man with a CD4 lymphocyte count of 11 × 106/l and a history of HIV encephalopathy and peripheral neuropathy. The patient complained of intermittent hiccups for 6 months that had become increasingly more frequent. Amitriptyline, chlorpromazine, metoclopramide, and clonazepam failed to reduce the frequency of hiccups. Therapy with baclofen at a dosage of 5 mg every 8 h led to resolution of his hiccups. Baclofen was discontinued after 3 months without recurrence of hiccups. Four months later his hiccups recurred but again responded to treatment with baclofen.

Patient 3 was a 45-year-old man with a CD lymphocyte count of 260 × 106/l who presented with an acute exacerbation of asthma and a 1-month history of frequent hiccups. Chest radiographs were normal. The patient's asthma responded to treatment with inhaled bronchodilators; however, he continued to experience frequent hiccups. The patient was treated with chlorpromazine without improvement. Therapy with baclofen at a dosage of 10 mg every 6 h resulted in complete resolution of hiccups. Discontinuation of baclofen or reduction of dosage resulted in return of hiccups. The patient continued on baclofen for 9 months without adverse effects.

Patient 4 was a 56-year-old man with a CD4 lymphocyte count of 71 × 106/l who was receiving palliative radiation therapy for adenocarcinoma of the lung with metastasis to the brain. The patient's persistent hiccups failed to respond to treatment with metoclopramide, chlorpromazine, or phenytoin. Baclofen therapy at a dosage of 5 mg every 6 hours resulted in prompt and complete resolution of his hiccups. The patient received 2 weeks of therapy but complained of drowsiness related to baclofen, and therapy was discontinued. Intermittent episodes of hiccups occurred following discontinuation of drug but he did not wish further treatment.

The treatment of hiccups was the subject of a recent review by Friedman [8]. Many anecdotal treatments for hiccups have been described, but limited data are available regarding their effectiveness. Classes of drugs that have been often used in the treatment of hiccups include tranquilizers, muscle relaxants, anticonvulsants, and narcotics. The only blinded controlled cross-over study of baclofen for the treatment of hiccups involved only four patients and tailed to demonstrate objective improvement in hiccup frequency [9]. Interestingly, patients did report symptomatic relief that was doserelated. The authors suggested that subjective improvement noted by the patients may be a result of lessening of the intensity of the hiccups and therefore a reduced perception that hiccups had occurred.

Our patients had a variety of presentations and the cause of their hiccups was not precisely defined. However, it is likely that patients 1 and 3 had a pulmonary or thoracic abnormality responsible for their hiccups. HIV encephalopathy or peripheral neuropathy may have been the cause of hiccups in patient 3; patient 4 had tumor involving both the chest and brain, either of which may have been responsible for his hiccups. Three of our patients failed to respond to treatment with a variety of drugs including metoclopramide, chlorpromazine, amitriptyline, clonazepam, and phenytoin. Baclofen appeared to be effective in eliminating hiccups in all of our patients. The most convincing evidence that baclofen may have had some beneficial effect is that patients complained that hiccups returned when the dosage of baclofen was reduced in frequency or discontinued. The only patient-reported side-effect was sedation, which occurred in patient 4 and led to discontinuation of therapy. Although controlled trials are needed, baclofen appears to be a safe and useful agent in the treatment of hiccups in HIV-infected patients.

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