What assessment questions should I ask for a suspected SSRI (Selective Serotonin Reuptake Inhibitor) hypersensitivity reaction?

Assessment Questions for Suspected SSRI Hypersensitivity Reaction

When evaluating a suspected SSRI hypersensitivity reaction, immediately establish the temporal relationship between drug exposure and symptom onset, focusing on whether symptoms appeared within 1-6 hours (immediate reaction) or after 1 hour to several days (non-immediate reaction), as this distinction determines the underlying mechanism and guides management. 1

Critical Timeline Assessment

• Document exact timing of SSRI initiation and symptom onset - the latent period between initial drug intake and reaction onset is typically 5-28 days for first exposure, though it may be shorter with prior exposure to the same drug 1
• Identify when the last dose was administered - immediate hypersensitivity reactions typically occur within 1-6 hours and are IgE-mediated, while non-immediate reactions occur after 1 hour and are often T-cell mediated 1
• Determine if symptoms developed within minutes to hours (usually 6-24 hours) after starting or increasing the SSRI dose, as this timeframe is characteristic of drug hypersensitivity 2

Comprehensive Drug History

• Obtain a complete medication list covering the 2 months prior to symptom onset, including all over-the-counter preparations 1
• Ask specifically about previous SSRI exposures - document any prior adverse reactions to the same or similar SSRIs, as cross-reactivity within the drug class has been reported 3
• Identify all concomitant serotonergic medications including tramadol, fentanyl, mirtazapine, buspirone, and chlorpheniramine, as these increase risk of serotonin syndrome 4
• Screen for monoamine oxidase inhibitors (MAOIs) - concomitant use is contraindicated due to serotonin syndrome risk 1
• Document any recent dose changes or missed doses - SSRI discontinuation syndrome can mimic hypersensitivity, particularly with shorter-acting agents like paroxetine 1

Cutaneous Manifestations

• Characterize the rash distribution and morphology - ask if it is morbilliform, pruritic, generalized over trunk and limbs, with or without facial involvement 3
• Assess for palm and sole involvement - this can help differentiate between reaction types 3
• Determine if there is mucosal involvement (lips, tongue, uvula swelling, oral lesions) - this suggests more severe hypersensitivity 1
• Quantify body surface area involvement - document extent of erythema and epidermal detachment separately, as this impacts severity assessment 1

Systemic Symptoms Suggesting Severe Reactions

Anaphylaxis Criteria 1

• Ask about acute onset respiratory symptoms - dyspnea, wheezing, stridor, or sensation of throat closing
• Screen for cardiovascular symptoms - lightheadedness, syncope, hypotension, or feeling faint
• Document gastrointestinal symptoms - persistent crampy abdominal pain or vomiting (not isolated nausea)

Serotonin Syndrome Features 2

• Mental status changes - agitation, confusion, restlessness, or altered consciousness
• Autonomic hyperactivity - diaphoresis, fever, tachycardia, hypertension, or mydriasis
• Neuromuscular abnormalities - tremor, muscle rigidity, hyperreflexia, or clonus (spontaneous, inducible, or ocular)
• Hyperthermia - temperature above 38°C, particularly when combined with neuromuscular findings 2

DRESS/Drug Hypersensitivity Syndrome 5

• Fever onset and pattern - persistent fever is a cardinal feature
• Lymphadenopathy - ask about swollen lymph nodes
• Facial edema - particularly periorbital swelling
• Systemic organ involvement - inquire about dark urine (hepatic), decreased urination (renal), or shortness of breath (pulmonary)

Dietary and Environmental Triggers

• Ask about chocolate consumption - case reports document that chocolate can trigger pruritic reactions in patients on SSRIs due to serotonin content 6
• Screen for other serotonin-rich foods consumed around symptom onset 6

Risk Factors for Severe Reactions

• Age and comorbidities - document chronic respiratory disease, cardiovascular disease, or mastocytosis 1
• Concurrent medications that increase anaphylaxis risk - beta-blockers or ACE inhibitors 1
• History of severe atopic disease 1
• Adolescent age group - associated with higher risk of fatal anaphylaxis 1
• Concomitant asthma, especially if severe or poorly controlled 1

Differential Diagnosis Screening

• Rule out SSRI discontinuation syndrome - characterized by dizziness, fatigue, myalgias, headaches, nausea, insomnia, and sensory disturbances, particularly with paroxetine 1
• Exclude infection - fever with rash may represent viral exanthem or mycoplasma infection 1
• Assess for anxiety/panic symptoms - these can mimic hypersensitivity reactions 1

Timing of Epinephrine Administration

• Document whether epinephrine was given and when - delayed administration is associated with worse outcomes including hospitalization and death 1
• If epinephrine was administered, note the response - improvement supports anaphylaxis diagnosis 1