Protracted Hiccups Induced by Aripiprazole and Regressed afterAdministration of Gabapentin

Hiccups are sudden, repeated, and involuntary contractions of the diaphragm muscle (myoclonic contraction). It involves a reflexarc that, once activated, causes a strong contraction of the diaphragm immediately followed by the closure of the glottistranslating into the classic“hic”sound. Hiccups can be short, persistent, and intractable depending on the duration. The mostdisabling hiccups often represent the epiphenomenon of a medical condition such as gastrointestinal and cardiovasculardisorders; 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-generationantipsychotic, can induce the onset of variable hiccups. We describe herein the cases of three hospitalized patients whodeveloped insistent hiccups after taking aripiprazole and who positively responded to low doses of gabapentin. It is probablethat aripiprazole, prescribed at a low dosage (<7.5 mg/day), would act as a dopamine agonist by stimulating D2and D3receptors at the“hiccup center”level—located in the brain stem—thus triggering the hiccup. On the other hand, gabapentinled to a complete regression of the hiccup probably by reducing the nerve impulse transmission and modulating thediaphragmatic activity. The present case series suggests the use of low doses of gabapentin as an effective treatment foraripiprazole-induced hiccups. However, our knowledge of the neurotransmitter functioning of the hiccup reflex arc is stilllimited, and further research is needed to characterize the neurotransmitters involved in hiccups for potential noveltherapeutic targets