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 Table of Contents    
LETTERS TO EDITOR  
Year : 2020  |  Volume : 62  |  Issue : 6  |  Page : 736-738
Acute dystonic reaction due to a combination of chloroquine and doxycycline in an emergency psychiatry setting


1 Department of Psychiatry, TNMC and BYL Nair Charitable Hospital, Mumbai, Maharashtra, India
2 Department of Psychiatry, KEM Hospital and Seth GS Medical College, Mumbai, Maharashtra, India

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Date of Submission19-Nov-2019
Date of Decision28-Nov-2019
Date of Acceptance08-Jul-2020
Date of Web Publication12-Dec-2020
 

How to cite this article:
Nachane HB, Nayak AS. Acute dystonic reaction due to a combination of chloroquine and doxycycline in an emergency psychiatry setting. Indian J Psychiatry 2020;62:736-8

How to cite this URL:
Nachane HB, Nayak AS. Acute dystonic reaction due to a combination of chloroquine and doxycycline in an emergency psychiatry setting. Indian J Psychiatry [serial online] 2020 [cited 2021 Jan 22];62:736-8. Available from: https://www.indianjpsychiatry.org/text.asp?2020/62/6/736/303183




Sir,

Acute dystonic reactions are extrapyramidal side effects that are seen after the initiation or a rapid increase in the dose of neuroleptic drugs, mainly typical antipsychotics, and have a varied presentation, such as torticollis, trismus, “mouth opening” dystonia, grimacing, dysarthria, oculogyric crisis, blepharospasm, and swallowing difficulties.[1] They frequently present to clinicians in an emergency setting and may sometimes be tricky to handle. Drug-induced movement disorders usually have a clear temporal relationship between medication initiation and symptom onset (some typically occurring with first dose).[1] They are also dose – dependent, and with the exception of tardive syndromes, have a complete resolution after discontinuation of the offending agent.[1] Mechanisms underlying drug-induced movement disorders involve blockade, facilitation, or imbalance of dopamine, serotonin, noradrenaline, and cholinergic neurotransmission in the basal ganglia.[1] Chloroquine is a drug commonly used for the treatment of malaria and has been reported to have gastrointestinal problems, headaches, blurring of vision, and itching as the common side effects.[2] Dystonia induced by chloroquine, although rare, is not really new and is mentioned in patient information leaflets.[2] However, such incidents are rare and mainly have been reported with the first dose. No case reports on acute dystonic reactions with a stable dose of chloroquine or with doxycycline are available. In view of current coronavirus disease pandemic, several combinations of antibiotics and antivirals are being tried and this report necessitates an exercise of caution for possible adverse drug reactions.


   Case Report Top


A 23-year-old man presented to an emergency psychiatry setting with the complaints of difficulty in lowering his gaze, up-rolling of eyeballs, and difficulty in jaw opening for the last 2 h. On examination, the patient was conscious, cooperative, and oriented. He had difficulty in opening his mouth and lowering his gaze. He appeared to have an acute dystonic reaction presenting with trismus and oculogyric crisis. Other aspects of his general examination were unremarkable. His systemic examination, which included an exhaustive neurological examination, was normal. All baseline investigations, including complete blood counts, serum electrolytes, liver and renal function tests, and random blood glucose, were within normal limits. His resting electrocardiogram was also normal. There was no past history of similar complaints or of any transient ischemic attack, and he had neither a family history of dystonia nor a history of alcohol ingestion, cigarette smoking, or use of illicit drugs or history of taking psychotropic medications.

On enquiry, the patient yielded that he had fever for the past 3–4 days, for which he was taking some medications from a physician. All his blood parameters were normal, and he had tested negative for dengue and malaria. However, as it is a common practice in India to empirically start a patient on antibiotics, he had been started on chloroquine (500 mg once daily dosing) and doxycycline (100 mg twice a day). It was after his third dose that he had developed an acute dystonic reaction. Immediately, an injection of promethazine 50 mg was administered intramuscularly. After 15 min, there was some relief in his symptoms. Later on, after giving an injection of intravenous diazepam 5 mg, the patient's symptoms improved considerably. He was kept was observation for 2–3 h and later discharged on oral diazepam 5 mg once daily for 3 days. He was asked to discontinue the antibiotics, and on follow-up, the patient had no further complaints and reported 100% improvement.


   Discussion Top


Rampant use of antibiotics and their amalgamations has concerning effects such as antimicrobial resistance and higher occurrence of adverse side effects. While most side effects appear nonchalant, there are a few which could be life-threatening, such as acute dystonic reaction. Oculogyric crisis is the only form of acute dystonia that may occur, while the patient is receiving a stable dose of an antipsychotic drug; it may be provoked by alcohol, emotional stress, fatigue, or suggestion.[3] Given the paucity of literature on chloroquine- and doxycycline-induced acute dystonic reactions, we report a case of an acute dystonic reaction presenting as oculogyric crisis with trismus in a patient who was on a stable dose of chloroquine and doxycycline, being empirically treated for fever with a combination of antimalarial and broad-spectrum antibiotic. At a standard dose for malaria treatment, the common adverse effects of chloroquine include gastrointestinal problems, headaches, nightmare, blurring of vision, and itching. Using the Naranjo algorithm, the patient appeared to have probable adverse drug reaction when chloroquine was considered as a cause (score = 6). If doxycycline is considered as a cause alone, the score would be 5 indicating probable adverse drug reactions due to it. The difference of scoring occurs only on the first question of the algorithm as no report mentions dystonia due to doxycycline. This also sheds light on the importance of the first question of the Naranjo algorithm and the need to report such possible adverse reactions. Acute dystonic reactions usually result due to dopamine receptor-2 (D2) blockade in the nigrostriatal pathway, which results in an excess of striatal cholinergic output.[1] The pathophysiological mechanism underlying chloroquine-associated acute dystonic reaction suggests a reduction in the forebrain catecholamine levels and an inhibition of neuronal calcium uptake.[4] Gamma aminobutyric acid has been postulated to play a role in the pathophysiology of acute dystonic reactions, and this is supported by the effectiveness of benzodiazepines in reducing chloroquine-induced acute dystonic reactions.[1] This also explains why our patient improved with diazepam and promethazine had minimal effect on him. There is no available literature on doxycycline-induced acute dystonic reactions, and whether this drug had a contribution in the development of oculogyric crisis in our patient is uncertain. The combination of chloroquine and doxycycline has been shown to be synergistic in the treatment of malaria with increased efficacy of chloroquine on addition of doxycycline.[5] This could perhaps also predispose patients on this combination to develop rare side effects such as dystonia. Doxycycline has been shown to protect dopaminergic neurons and increase levels of dopamine in certain areas of the brain and can theoretically lead to dystonia.[6] Hence, we advocate an index of suspicion for oculogyric crisis whenever these drugs are being prescribed, especially in combination.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Burkhard PR. Acute and subacute drug-induced movement disorders. Parkinsonism Relat Disord 2014;20 Suppl 1:S108-12.  Back to cited text no. 1
    
2.
Busari OA, Fadare J, Agboola S, Gabriel O, Elegbede O, Oladosu Y. Chloroquine-induced acute dystonic reactions after a standard therapeutic dose for uncomplicated malaria. Sultan Qaboos Univ Med J 2013;13:E476-8.  Back to cited text no. 2
    
3.
FitzGerald PM, Jankovic J. Tardive oculogyric crises. Neurology 1989;39:1434-7.  Back to cited text no. 3
    
4.
Achumba JI, Ette EI, Thomas WO, Essien EE. Chloroquine-induced acute dystonic reactions in the presence of metronidazole. Drug Intell Clin Pharm 1988;22:308-10.  Back to cited text no. 4
    
5.
Taylor WR, Widjaja H, Richie TL, Basri H, Ohrt C, Taufik E, et al. Chloroquine/doxycycline combination versus chloroquine alone, and doxycycline alone for the treatment of Plasmodium falciparum and Plasmodium vivax malaria in northeastern Irian Jaya, Indonesia. Am J Trop Med Hyg 2001;64:223-8.  Back to cited text no. 5
    
6.
Cho Y, Son HJ, Kim EM, Choi JH, Kim ST, Ji IJ, et al. Doxycycline is neuroprotective against nigral dopaminergic degeneration by a dual mechanism involving MMP-3. Neurotox Res 2009;16:361-71.  Back to cited text no. 6
    

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Correspondence Address:
Hrishikesh B Nachane
Department of Psychiatry, TNMC and BYL Nair Charitable Hospital, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/psychiatry.IndianJPsychiatry_712_19

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