Drug-Induced Psychosis Associated with Albendazole–Ivermectin Combination Therapy in a 10-Year-Old Child

To the Editor:

Ivermectin and albendazole are antihelminthics used alone and in combination for a wide variety of parasitic infections. The combination regime of albendazole and ivermectin is found to be a useful tool in the integrated or combined control of both lymphatic filariasis and trichuriasis, and has a more favorable tolerability profile in terms of side-effects (Belizario et al. 2003). Psychotic symptoms have not been commonly reported with ivermectin or albendazole use. To best of our knowledge, only a single case of psychosis following the use of albendazole–ivermectin combination therapy was reported in an adult until now (Sinha et al. 2012). We report the first case of psychosis following use of albendazole–ivermectin combination therapy in a 10-year-old boy.

Case Report

A 10-year-old boy with an uneventful birth and developmental history without past or family history of neurological and psychiatric illness, presented to the outpatient department with complaints of fearfulness, suspiciousness, irritability, and decreased sleep for the previous 5 days. There was no history of any substance use. No ongoing stressor could be elicited. On evaluation it was found that 24 hours before the onset of symptoms, the child had taken a single dose of albendazole 400 mg and ivermectin 6 mg combination therapy for suspected gastrointestinal worm infestation, prescribed by a general physician.

A detailed medical evaluation, including a neurological examination, revealed no significant findings. Hematological and biochemical indices were within normal limits. The patient was hospitalized and the possibility of psychosis induced by combination therapy with of albendazole and ivermectin was entertained. The patient was started on tablet lorazepam 1 mg twice daily. After 3 days, the patient's suspiciousness and fearfulness improved significantly. Over the next 7 days, his psychotic symptoms resolved completely. After 2 weeks, lorazepam was tapered and stopped gradually. The patient was discharged from the hospital, and 8 weeks after discharge was completely asymptomatic.

Discussion

In our patient, the strength of association between with albendazole–ivermectin combination therapy use and the emergence of psychotic symptoms is strengthened by factors such as the absence of a past history, family history, or substance use, the fast remission of psychotic symptoms with the stoppage of the medication even without the use of antipsychotic medication. Our patient improved completely only with use of lorazepam. Therefore, in this case, a definite causal link between albendazole–ivermectin use in combination and psychotic symptoms can be established by Naranjo adverse drug reaction probability criteria (Naranjo et al. 1991).

The exact mechanism by which the combination of these two drugs or each individual drug causes psychosis is not known. The metabolite of albendazole–albendazole sulfoxide is known to penetrate the blood–brain barrier and reach the cerebrospinal fluid, which explains its use in central nervous system infections. It is, however, not known whether ivermectin and albendazole have any action on the dopaminergic system (Edwards and Breckenridge 1988). Altered expression or function of P-glycoprotein (expressed in the brain capillary epithelial cells and responsible for limiting the brain penetration of different compounds) could conceivably allow elevation of brain concentrations of ivermectin and produce severe neurotoxicity (Edwards 2003). This might arise through a genetic polymorphism in P- glycoprotein or coadministration of ivermectin with a drug that might inhibit this efflux transporter. Although an interaction between ivermectin and albendazole could be postulated on the basis of these drugs being cosubstrates of cytochrome P450 (CYP) 3A4, it is not established that there could be an interaction at the level of P-glycoprotein. Our patient may have a genetic defect in P-glycoprotein that led to neurotoxologic effects (Mealey et al. 2001).