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Table of Contents
LETTER TO THE EDITOR
Year : 2020  |  Volume : 34  |  Issue : 2  |  Page : 96-97

High-dose disulfiram-induced delirium and manic features: A case report


1 Department of Psychiatry, Taoyuan Psychiatric Center, Ministry of Health and Welfare, Taoyuan City, Taiwan
2 Department of Psychiatry, Taiwan Adventist Hospital, Taipei City, Taiwan
3 Department of Psychiatry, Taoyuan Psychiatric Center, Ministry of Health and Welfare, Taoyuan City; Department of Public Health and Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University; Research Center of Big Data and Meta-analysis, Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan

Date of Submission30-Dec-2019
Date of Decision24-Feb-2020
Date of Acceptance26-Feb-2020
Date of Web Publication26-Jun-2020

Correspondence Address:
Ying- Chih Cheng
No. 71, Longshou Street, Taoyuan 33058
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/TPSY.TPSY_17_20

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How to cite this article:
Lin Y, Tsai PC, Cheng YC. High-dose disulfiram-induced delirium and manic features: A case report. Taiwan J Psychiatry 2020;34:96-7

How to cite this URL:
Lin Y, Tsai PC, Cheng YC. High-dose disulfiram-induced delirium and manic features: A case report. Taiwan J Psychiatry [serial online] 2020 [cited 2020 Jul 2];34:96-7. Available from: http://www.e-tjp.org/text.asp?2020/34/2/96/288008



Disulfiram is an aldehyde dehydrogenase inhibitor that affects the metabolism of alcohol, increasing blood acetaldehyde level to treat alcohol use disorder. Disulfiram is also known to be a dopamine-β-hydroxylase (DBH) inhibitor with potential to cause neuropsychiatric symptoms. Manic symptoms accompanied by delirium related to disulfiram are rarely reported. Here, we present a case of a patient with alcohol use disorder, who developed acute delirium and manic symptoms after receiving a high dose of disulfiram. Those neuropsychiatric symptoms were resolved gradually as discontinuation of disulfiram.


  Case Report Top


A 56-year-old female patient had a history of alcohol use disorder. She started to have excessive alcohol consumption after divorce eight years ago. She usually took 7–8 standard units of alcohol per day (30% volume concentration, 300–400 mL/day). She spent most time in drinking and quit her job because of drinking problem. She had all symptoms of DSM-5 criteria of alcohol use disorder such as tolerance, withdrawal, and craving. Her first treatment of alcohol use disorder started five years ago due to unsuccessful efforts to cut down alcohol use on her own. Except for alcohol use disorder, she also had chronic depressive symptoms and was diagnosed with persistent depressive disorder. She had received selective serotonin reuptake inhibitor (SSRI) treatment as escitalopram 10 mg/day for about three years previously. She had a history of peptic ulcer but no other medical illness. Because of several times of relapsed drinking, disulfiram 200 mg/day was administrated for total abstinence. The patient took disulfiram and benzodiazepines as lorazepam 8 mg/day for the treatment of alcohol use disorder and did not drink alcohol for seven months. But she started to take higher dose of disulfiram, which was up to 1,500 mg every day since one week before the indexed admission, due to its sedative effect. One week later, she became disoriented, being brought to the emergency department, and was hospitalized for delirium.

The patient received comprehensive workups for delirium, including brain computed tomography, electroencephalography, electrocardiography, blood tests, as well as physical and detailed neurological examination, but all results were negative. Her laboratory examinations including blood alcohol concentration had no remarkable findings (glutamic-oxaloacetic transaminase, 42 U/L; glutamic-pyruvic transaminase, 40 U/L; gamma-glutamyltransferase, 53 U/L; ammonia, 73 μg/dL; and blood alcohol level, <10 mg/dL). Brain computed tomography showed no evidence of organic lesion. Delirious symptoms were improved gradually within the next three days after stopping disulfiram use, without any further treatment for delirium. But she developed manic symptoms including elated mood, racing thoughts, grandiosity, talkativeness, and decreased need of sleep. Manic symptoms were resolved within one month under treatment of carbamazepine 600 mg/day. We prescribed carbamazepine as mood stabilizer because she was worried about gaining weight. Carbamazepine is associated with a lower risk of weight gain compared with lithium and valproic acid [1]. After being discharged, she decided not to take disulfiram and had several bouts of relapses thereafter, but no further delirium and manic symptoms recurred.


  Comment Top


We proposed that our patient's delirium and manic symptoms were related to a higher-than-normal dose of disulfiram because of the time sequence of symptoms. The possibility of alcohol withdrawal delirium was low because the patient did not take any alcohol and maintain the dosage of disulfiram as 200 mg/day for seven months. Discontinuation of disulfiram upon admission with rapid response to short-term mood stabilizer suggests that those neuropsychiatric symptoms were secondary to disulfiram misuse.

Disulfiram is known to be an inhibitor of DBH, which blocks the production of norepinephrine from dopamine, thereby causing dopamine accumulation. Many reports suggest that disulfiram may provoke psychotic symptoms or delirium through DBH inhibition [2]. Another possible pathophysiology of disulfiram-induced neuropsychiatric symptoms is the neurotoxicity due to its metabolites such as diethyldithiocarbamate (DDC) and carbon disulfide [3]. DDC can also cause the inhibition of DBH and induce psychotic symptoms, and it has also shown to block glutamate binding to receptors, further causing glutamate dysregulation [4]. Previous studies were found that even chronic administration of low doses of disulfiram can increase the extracellular level of striatal glutamate, leading to glutamate-induced neurotoxicity [3],[5]. Augmented dopamine accumulation and glutamate dysregulation can conjointly cause dysfunction in brain activity such as delirium. Although disulfiram alone is relatively nontoxic, a high-dose disulfiram may increase its metabolite, resulting in aggravating toxic effect and increased risk of neuropsychiatric symptoms.

It has been reported that disulfiram and its interaction [3],[6] with other drugs, including alcohol, may cause bipolar disorder [6],[7],[8],[9]. Disulfiram in excess of 500 mg/day can carry a high risk of inducing mood disorder [10]. The blocked norepinephrine synthesis and dopamine-accumulating effect through inhibiting of DBH with disulfiram may explain the development of manic symptoms. Disulfiram-related psychiatric complications are more prevalent in certain individuals, including those with a history of psychosis, bipolar disorder, psychostimulant abuse, old age, impaired liver function, concurrent dopaminergic medications, and overly rapid increase in dosage or greater than recommended total dosage, especially in patients from Eastern countries [6],[11]. Genetic mechanism such as DBH polymorphism may offer an additional explanation for the pathogenesis of our patients [12].

As shown in the finding in our patient, the toxicity was obviously to be dose-related, while the dosage used today is relatively safe to most patients. The effective standard maintenance dose of disulfiram is ranged from 125 to 500 mg/day. In addition, previous studies suggested that disulfiram should be used at the lowest effective dose and cautioned that it should be taken when prescribing disulfiram for patients with personal and familial antecedents of psychosis [13]. Patients taking disulfiram also require to be monitored for symptoms and signs such as hepatitis, sedation, and fatigue. Baseline liver function test must be carried out as well both before and after the prescription of disulfiram [14] because disulfiram-induced hepatotoxicity is mostly categorized as idiosyncratic [15] and hepatocellular [16].

In summary, clinicians should be aware of the neuropsychiatric symptoms and its common side effect while prescribing disulfiram higher than excess of 500 mg/day [17]. (The institutional review board at Taoyuan Psychiatric Hospital, Ministry of Health and Welfare, approved this case report for publication (protocol number = R20191120, and date of approval = November 23, 2019) without any stipulation of obtaining any signed formal consent from the patient.)


  Financial Support and Sponsorship Top


None.


  Conflicts of Interest Top


All authors declare no conflicts of interest in writing this report.



 
  References Top

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Grootens KP, Meijer A, Hartong EG, et al.: Weight changes associated with antiepileptic mood stabilizers in the treatment of bipolar disorder. Eur J Clin Pharmacol 2018; 74: 1485-9.  Back to cited text no. 1
    
2.
Cheng YC, Tsai MC, Huang MC: Delirium associated with griseofulvin and disulfiram coadministration. J Clin Psychopharmacol 2015; 35: 477-8.  Back to cited text no. 2
    
3.
Vaccari A, Ferraro L, Saba P, et al.: Differential mechanisms in the effects of disulfiram and diethyldithiocarbamate intoxication on striatal release and vesicular transport of glutamate. J Pharmacol Exp Ther 1998; 285: 961-7.  Back to cited text no. 3
    
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Gaval-Cruz M, Weinshenker D: Mechanisms of disulfiram-induced cocaine abstinence: antabuse and cocaine relapse. Mol Interv 2009; 9: 175-87.  Back to cited text no. 4
    
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Ceylan ME, Turkcan A, Mutlu E, et al.: Manic episode with psychotic symptoms associated with high dose of disulfiram: a case report. J Clin Psychopharmacol 2007; 27: 224-5.  Back to cited text no. 6
    
7.
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8.
Iruela LM, Ibañez-Rojo V, Caballero L, et al.: Buspirone-induced mania: possible interaction with disulfiram. Br J Psychiatry 1991; 159: 297-8.  Back to cited text no. 8
    
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Lacoursiere RB, Swatek R: Adverse interaction between disulfiram and marijuana: a case report. Am J Psychiatry 1983; 140: 243-4.  Back to cited text no. 9
    
10.
Li MY, Shen YC: Manic episode with psychosis following a lower than recommended dosage regimen of disulfiram. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32: 311-2.  Back to cited text no. 10
    
11.
Ewing JA, Rouse BA, Mueller RA, et al.: Can dopamine beta-hydroxylase levels predict adverse reactions to disulfiram? Alcohol Clin Exp Res 1978; 2: 93-4.  Back to cited text no. 11
    
12.
Mutschler J, Abbruzzese E, Witt SH, et al.: Functional polymorphism of the dopamine β-hydroxylase gene is associated with increased risk of disulfiram-induced adverse effects in alcohol-dependent patients. J Clin Psychopharmacol 2012; 32: 578-80.  Back to cited text no. 12
    
13.
Mohapatra S, Rath NR: Disulfiram induced psychosis. Clin Psychopharmacol Neurosci 2017; 15: 68-9.  Back to cited text no. 13
    
14.
De Sousa A: Disulfiram: side effects and toxicity. In: De Sousa A (ed.): Disulfiram: Its Use in Alcohol Dependence and Other Disorders. Singapore: Springer Singapore, 2019: 59-67.  Back to cited text no. 14
    
15.
Lee WM: Drug-induced hepatotoxicity. N Engl J Med 1995; 333: 1118-27.  Back to cited text no. 15
    
16.
Berlin RG: Disulfiram hepatotoxicity: a consideration of its mechanism and clinical spectrum. Alcohol Alcohol 1989; 24: 241-6.  Back to cited text no. 16
    
17.
Huang MC, Liu SK, Yu CM, et al.: Assessment of side effects of disulfiram in patients with alcohol addiction (in Mandarin). Taiwan J Psychiatry (Taipei) 2002; 16: 213-21.  Back to cited text no. 17
    




 

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