Protracted Hiccups Induced by Aripiprazole and Regressed after Administration of Gabapentin

Hiccups are sudden, repeated, and involuntary contractions of the diaphragm muscle (myoclonic contraction). It involves a reflex arc that, once activated, causes a strong contraction of the diaphragm immediately followed by the closure of the glottis translating into the classic "hic" sound. Hiccups can be short, persistent, and intractable depending on the duration. The most disabling hiccups often represent the epiphenomenon of a medical condition such as gastrointestinal and cardiovascular disorders; central nervous system (CNS) abnormalities; ear, nose, and throat (ENT) conditions or pneumological problems; metabolic/endocrine disorders; infections; and psychogenic disorders. Some drugs, such as aripiprazole, a second-generation antipsychotic, can induce the onset of variable hiccups. We describe herein the cases of three hospitalized patients who developed insistent hiccups after taking aripiprazole and who positively responded to low doses of gabapentin. It is probable that aripiprazole, prescribed at a low dosage (<7.5 mg/day), would act as a dopamine agonist by stimulating D₂ and D₃ receptors at the "hiccup center" level-located in the brain stem-thus triggering the hiccup. On the other hand, gabapentin led to a complete regression of the hiccup probably by reducing the nerve impulse transmission and modulating the diaphragmatic activity. The present case series suggests the use of low doses of gabapentin as an effective treatment for aripiprazole-induced hiccups. However, our knowledge of the neurotransmitter functioning of the hiccup reflex arc is still limited, and further research is needed to characterize the neurotransmitters involved in hiccups for potential novel therapeutic targets.