Multiple drug intolerance syndrome and multiple drug allergy syndrome: Epidemiology and associations with anxiety and depression

Abstract

Background: The epidemiology of multiple drug intolerance syndrome (MDIS) and multiple drug allergy syndrome (MDAS) is poorly characterized. We used electronic health record (EHR) data to describe prevalences of MDIS and MDAS and to examine associations with anxiety and depression.

Methods: Patients with ≥3 outpatient encounters at Partners HealthCare System from 2008 to 2015 were included. Patients with MDIS had intolerances to ≥3 drug classes, and patients with MDAS had hypersensitivities to ≥2 drug classes. Psychiatric conditions and comorbidities were defined from the EHR and used in multivariable logistic regression models to assess the relation between anxiety/depression and MDIS/MDAS.

Results: Of 746 888 patients, 47 634 (6.4%) had MDIS and 8615 (1.2%) had MDAS; 3171 (0.4%) had both. Anxiety (adjusted odds ratio [aOR] 1.72 [1.65, 1.80]), depression (aOR 1.46 [1.41, 1.52]), and both anxiety and depression (aOR 1.97 [1.86, 2.08]) were associated with increased odds of MDIS. Depression was associated with increased odds of MDAS (aOR 1.41 [1.28, 1.56]), but there were no clear associations with anxiety (aOR 1.13 [0.99, 1.30]) nor both depression and anxiety (aOR 1.13 [0.92, 1.38]).

Conclusion: While 6% of patients had MDIS, only 1% had MDAS. MDIS was associated with both anxiety and depression; patients with both anxiety and depression had an almost twofold increased odds of MDIS. MDAS was associated with a 40% increased odds of depression, but there was no significant association with anxiety. Psychological assessments may be useful in the evaluation and treatment of patients with MDIS and MDAS; physiologic causes for MDAS warrant further investigation.

Keywords: anxiety; depression; healthcare utilization; hypersensitivity; immunologic.

Figure 1

Hypersensitivity reactions identified in MDAS patients. 17,196 hypersensitivity reactions were identified among 8,615 MDAS patients. Other includes drug induced lupus (n=14), erythema nodosum (n=14), eosinophilia (n=10), and fixed drug eruption (n=5). *Anaphylaxis was defined by the symptoms of hypotension, shock, arrest and arrhythmia. ^† Shortness of breath was defined by the symptoms of bronchospasm, wheezing, and/or asthma. ^‡ Severe cutaneous reactions included Stevens-Johnson syndrome (n=60), erythema multiforme (n=14), toxic epidermal necrolysis (n=10), drug rash eosinophilia and systemic symptoms (n=17), and exfoliative dermatitis (n=24). ^§ Organ-specific reactions include acute interstitial nephritis (n=667), immune-mediated hepatitis (n=39), aseptic meningitis (n=6), and interstitial pneumonitis (n=5).

Figure 2

Association between number of drug class intolerances and number of drug class hypersensitivities and anxiety and depression. This figure displays the odds ratio for anxiety (and depression) according to the number of drug class intolerances (or hypersensitivities) documented in the electronic health record. MDIS patients included all patients with 3 or more drug class intolerances and MDAS included all patients with 2 or more drug class hypersensitivities. A significant trend was observed for intolerances: Patients reporting more drug class intolerances had higher odds of anxiety and depression. There was no appreciable trend for hypersensitivities.