Recurrence of Panic Attacks After Brucellosis TreatmentVHighly Probable Citalopram and Rifampin Drug Interaction To the Editors: A 27-year-old woman was admitted to Imam Hospital in Tehran, Iran, be- cause of chief complaints of fever, night sweat, and arthralgias. In past medical and drug history, she had been receiving cita- lopram 20 mg daily for panic attacks since 2 years ago, and her disease was under control without any complication up to the recent hospital admission. After clini- cal evaluation and serological tests results, she was diagnosed with brucellosis in- fection and received doxycycline 100 mg twice daily and rifampin 600 mg once daily. Five days after starting the brucel- losis treatment regimen, she developed gas- trointestinal symptoms (dyspepsia, nausea, and abdominal pain), anxiety, agitation, and tachycardia. In routine review of the patient’s chart by the infectious diseases ward clinical pharmacists and based on the patient’s medical and drug history, recur- rence of panic attack symptoms after cit- alopram, a rifampin drug interaction was proposed. Propranolol with a dose of 20 mg orally twice daily was started, and citalo- pram dose was gradually increased to 40 mg daily. The patient’s symptoms gradually im- proved, and propranolol doses were tapered down. On day 20 of hospitalization, the patient was stable and discharged with cit- alopram 40 mg daily and an antibrucello- sis regimen (doxycycline and rifampin). Only 2 cases of rifampin interaction with sertraline and citalopram were reported in the literature. Relapse of panic symptoms occurred 5 days after rifampin and doxycy- cline therapy, and symptoms of our patient were controlled by doubling dose of cita- lopram. Based on patient’s chart review, clinical characteristics, presentations, and outcome, recurrence of panic attacks after interaction between rifampin and citalopram is highly probable. Drug interactions can affect the effi- cacy and safety of drug treatment. Drug interactions are the major causes of hospi- tal admissions, treatment failures, and poor patient’s compliance with drug therapy reg- imens. 1 Pharmacokinetic and pharmaco- dynamic mechanisms are 2 major types of drug-drug interactions. 2 From pharmaco- kinetic drug interactions, induction or in- hibition of the cytochrome P450 (CYP450) isoenzyme activity plays an important role in the occurrence of drug interactions. Ri- fampin is a strong CYP450 inducer that accelerates the metabolism of variety of CYP3A4 and CYP2C19 substrates and reduces serum concentrations of concomi- tant administered drugs. 3 Citalopram is a selective serotonin reuptake inhibitor anti- depressant that metabolized principally by CYP P450 enzyme subtypes 2C19 and 3A4. 4 In this report, we have described a drug-drug interaction between rifampin and citalopram that led to recurrence of panic attacks in a patient with a diagnosis of bru- cellosis. We also have done a literature re- view to find similar cases by Medline search until June 2011. Drug interactions, SSRI, rifampin, and citalopram were se- lected index terms for our search. CASE REPORT After a complete workup during 5 days of her hospitalization, clinical presentations, positive history of unpasteurized dairy pro- ducts consumption, and positive serum ag- glutination tests (Wright and combs Wright titer equal to 1/320), a diagnosis of bru- cellosis was made. The patient’s past med- ical history included episodic panic attacks (intense discomfort with symptoms of pal- pitation, sweating, shortness of breath, fell- ing of chocking, nausea, chills, and hot flash) from 2 years ago before the recent hospital admission. She had been receiving citalopram 20 mg daily for panic attacks, and her disease was under control without any complication during the recent 2 year period. After the brucellosis diagnosis, dox- ycycline 100 mg twice daily and rifampin 600 mg daily were started. Five days later, the patient complained of being light- headed, tremor, exacerbation of sweating, nausea, vomiting, agitation, tachycardia, and fear of dying. Diagnostic evaluations, such as thyroid function tests, cardiology, and gastrointestinal workup, were performed. All were within normal limits. It was con- cluded that the patient’s recent symptoms may be related to doxycycline and rifam- pin therapy. The patient was educated about doxycycline and rifampin consumption, and omeprazole 20 mg orally daily and meto- clopramide 10 mg as needed (up to 10 mg 3 times daily) were administered for con- trol of GI problems. GI symptoms partially responded to this intervention, but other symptoms (sweating, tachycardia, anxiety agitation, and fear of dying) were progres- sive. In routine review of the patient chart by the infectious diseases ward’s clinical pharmacist and based on patient’s medical and drug history, recurrence of panic attack symptoms after citalopram, a rifampin drug interaction was proposed. In coordination with the patient’s responsible consultant, propranolol with a dose of 20 mg orally twice daily was started, and citalopram dose was gradually increased to 40 mg daily. Also, the patient’s metoclopramide and ome- prazole were discontinued. After these mod- ifications, the patient’s symptoms gradually improved, and propranolol doses were ta- pered down. On day 20 of hospitalization, the patient was stable and discharged with citalopram 40 mg daily and an antibrucel- losis regimen (doxycycline 100 mg orally twice daily and rifampin 600 mg orally once daily). DISCUSSION Citalopram is a selective serotonin re- uptake inhibitors antidepressant that me- tabolized principally by CYP P450 enzyme subtypes 2C19 and 3A4. 4 Although it was reported that clinically important interac- tions with citalopram are unlikely to have happened since it undergoes metabolism by various enzyme systems and also has high drug tolerability, 5 but available data showed that cimetidine and carbamazepine can sig- nificantly affect the metabolism of citalo- pram by inhibition and induction of P450 3A4 respectively. Clearance of citalopram was increased by concomitant administra- tion of carbamazepine. 6,7 Also carbamaze- pine augmentation therapy can decrease plasma concentrations of citalopram. 7,8 Con- comitant administration of cimetidine can lead to moderate increase in the serum levels of citalopram. 6 Apart from limited inter- actions of citalopram that were reported, rifampin is a potent inducer of CYP450 enzyme system which resulted in different clinically significant drug interactions. 3 Si- multaneous administration of rifampin with neuroleptic drugs can cause therapeutic fail- ure or recurrence of patient symptoms. 3 Following literature review, only two cases of rifampin interaction with sertraline and citalopram were found. In case one, a patient with diagnosis of general anx- iety disorder that had been stable with sertraline 200 mg orally daily complained anxiety symptoms following 7 days treat- ment with rifampin and cotrimoxazole for staphylococcal skin infection. In this pa- tient sertraline serum concentration and its metabolite decreased up to 2Y3 fold following rifampin therapy. 9 In another case, rifampin-citalopram interaction was reported. 10 In this case, a 55-year-old man with diagnosis of osteomyelitis experi- enced panic attacks after treatment of his osteomyelitis with rifampin. This patient had a history of uncontrolled panic attack that had been under treatment with bupro- pion, citalopram, and lorazepam before recent episodes. After a citalopram dose increase from 20 to 40 mg daily, the Letters to the Editors Journal of Clinical Psychopharmacology & Volume 32, Number 6, December 2012 842 www.psychopharmacology.com * 2012 Lippincott Williams & Wilkins Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.