Disulfiram safety in alcohol use disorders: Experience from an addiction treatment center in India.

Sir,

Alcohol use disorders constitute a public health concern in India. Disulfiram, approved by the Food and Drug Administration for alcohol use disorders in 1947, is a deterrent agent, producing disulfiram-ethanol reaction when used with alcohol due to the accumulation of acetaldehyde. Disulfiram is cost-effective with proven superiority to other treatments in multiple trials.[1] Despite its success, disulfiram therapy is riddled with problems of compliance and safety. Multiple adverse drug reactions (ADRs) have been reported with disulfiram over the years in the form of case reports and limited systematic studies, mostly published during the 1990s.[234] Nausea, drowsiness, abdominal pain, and diarrhea were common adverse effects, whereas psychiatric (psychotic features, catatonia, and altered consciousness) and neurological complications (convulsions) were reported to be the most important.[345] Our center routinely prescribes supervised disulfiram to patients with alcohol use disorders, number of patients ranging from 30 to more than 50/month. Considering the need for renewed research on adverse effects associated with disulfiram and the paucity of data-based studies on the topic, we sought to assess ADRs reported by patients who received disulfiram for the treatment of alcohol use disorders using a prescription-based audit spanning over 15 months from January 1, 2019, to March 31, 2020, during which approximately 614 patients were prescribed disulfiram.

A total of 69 ADR reports, containing 132 ADRs, were obtained. No data regarding adherence to disulfiram was collected for this study. The case files of the patients contain records of adherence disulfiram based on family members’ and self-report. The mean age of the population was 37.1 (±7.8) years, and all participants were males. The profile of various ADRs reported is presented in Table 1. The most common ADR reported was decreased appetite (n = 13, 18.8%) followed by headache (n = 11, 15.9%) and metallic taste in the mouth (n = 11, 15.9%). All reported ADRs, when classified according to the Medical Dictionary for Regulatory Activities Terminology system, indicated that gastrointestinal disorders were the most common (n = 37, 53.6%), followed by nervous system disorders (n = 22, 31.9%), skin and subcutaneous tissue disorders (n = 16, 23.2%), psychiatric (n = 16, 23.2%), respiratory, (n = 11, 14.5%), and musculoskeletal and connective tissue disorders (n = 5, 7.2%).

Table 1

Adverse drug reactions reported in patients who were prescribed disulfiram (n=69)

Variable	Number of reports, n (%)
Adverse drug reaction
Decreased appetite	13 (18.8)
Headache and metallic taste in mouth	11 each (15.9)
Nasal congestion	9 (13.0)
Localized numbness	8 (11.6)
Gastritis, constipation, pruritic rash, and diarrhea	6 each (8.7)
Restlessness	5 (7.2)
Abdominal pain, diarrhea, skin eruptions, and sedation	4 each (5.8)
Hypersalivation, lethargy, and myalgias	3 each (4.3)
Tingling, vertigo, flushing, increased sweating, irritability, palpitations, dry mouth, and limb pain	2 each (2.9)
Tremors, urticaria, dyspnea, dry cough, painful red eye, low mood, and postural hypotension	1 each (1.4)
Additional treatment required	8 (11.6)
Disulfiram dose
Withdrawn	10 (14.5)
Reduced	2 (2.9)
Continued as usual	57 (82.6)
Recovery
Complete	38 (55.1)
Partial	7 (10.1)
No	5 (7.2)
Unknown	19 (27.5)
Causality assessment
Probable	60 (87.0)
Possible	9 (13.0)

Two ADRs were severe and the rest were mild. Eight (11.6%) participants required additional treatment for their ADRs. Disulfiram was withdrawn in 10 (14.5%) participants, dose was reduced in 2 (2.9%) and continued unaltered in 57 (82.6%) reports. In terms of outcome, 38 (55.1%) participants reported complete recovery, 7 (10.1%) recovered partially and 5 (7.2%) did not recover. According to the WHO Uppsala Monitoring Center system for standardized case causality assessment, 60 ADRs were classified as probable and 9 as possible. Out of 132 reported ADRs, 7 ADRs were unlabelled, i.e., hitherto unreported for disulfiram. These were uploaded to the online ADR monitoring software.

Our findings indicate decreased appetite as the most common ADR, in contrast with earlier studies that reported nausea to be the most common. Lack of appetite may impact patients’ trajectory of recovery as weight gain is expected during abstinence from alcohol. Furthermore, the greater number of neuropsychiatric ADRs was seen as compared to older studies. Thus, it is recommended that clinicians inform patients of ADRs while prescribing disulfiram with efforts toward their recognition, management, and reporting.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.