Reactions 1916, p65 - 23 Jul 2022 1

Aripiprazole/isoniazid/lorazepam XS

Worsening of agitation and psychosis following drug interaction and rebound effect in the form of increased
anxiety: case report
A 36-year-old man developed worsening agitation and psychosis following concomitant use of aripiprazole and isoniazid for
schizoaffective disorder bipolar type or latent tuberculosis. Additonally, he exhibited rebound effect in the form of increased anxiety
following decrease in the dose of lorazepam, while receiving for the treatment of schizoaffective disorder bipolar type [routes and
time to reactions onset not stated].
The man with schizoaffective disorder bipolar type was stabilised at a psychiatric hospital with treatment including aripiprazole
25 mg/day, clozapine 250 mg/day, lorazepam 4 mg/day and valproic acid 1500 mg/day. After 3 months of stability, he started
receiving isoniazid 300 mg/day and pyridoxine for latent tuberculosis. Lorazepam dose was reduced to 2 mg/day after 15 days on
isoniazid therapy with the goal of tapering and discontinuation. The next day (on day 16 of isoniazid treatment), he started acting
more disorganised with elevated mood and had difficulty following unit rules. He also expressed delusional thought content. On
day 17 of isoniazid treatment, doses of clozapine and lorazepam (3 mg/day) were increased. During next several days, he continued
to present as hypomanic, confused, irritable, paranoid and delusional with interpersonal conflicts with staff and peers along with
tachycardia, decreased appetite and self-reported anxiety. The anxiety was thought to be related to the decrease in lorazepam dose
(rebound effect). On day 22 of isoniazid therapy, drug-drug interaction was suspected leading to increased levels of aripiprazole.
Hence, the man’s aripiprazole dose was reduced to 15 mg/day. Lorazepam dose was also increased back to 4 mg/day at that time.
Aripiprazole drug levels were not measured. Within a few days and decrease in aripiprazole, stabilisation was observed. On day 35
of isoniazid therapy, a complete resolution of symptoms was observed after aripiprazole discontinuation. A few months later,
another attempt to taper lorazepam was made without reemergence of hypomania, irritability, disorganization or delusions and was
eventually discontinued. He was discharged from the hospital after completion of the treatment course with isoniazid and
pyridoxine. Worsening agitation and psychosis was thought to be related to drug-drug pharmacokinetic interaction of aripiprazole
with isoniazid (isoniazid is a weak inhibitor of cytochrome P450 3A4 (CYP3A4) and aripiprazole is significantly metabolized by
CYP3A4 enzymes leading to an increase in serum concentrations of aripiprazole).
Davis EAK, et al. Probable Interaction Between Aripiprazole and Isoniazid. Journal of Clinical Psychopharmacology 42: 420-421, No. 4, Jul 2022. Available from: URL:
http://doi.org/10.1097/JCP.0000000000001565 803685809

0114-9954/22/1916-0001/$14.95 Adis © 2022 Springer Nature Switzerland AG. All rights reserved Reactions 23 Jul 2022 No. 1916