A 34-year-old married female reported in the outpatient unit, Department of Psychiatry, Medical College and Hospital, Kolkata, with complaints of decreased sleep, anger outburst, suspiciousness, social impairment, irritable mood increasing gradually for last 2 months. She reported of experiencing a similar episode 3 years ago. She was diagnosed as a case of bipolar affective disorder (F-31) according to International Classification of Disease: Clinical Descriptions and Diagnostic Guidelines-10. Young Mania Rating Scale (YMRS) scored 34 which further corroborated the diagnosis. She was initiated on lithium 600 mg/day and risperidone 3 mg/day. Serum lithium level was estimated on the day 5. The lithium level was found to be slightly higher than upper therapeutic range, so the physician decided to taper the dose to 300 mg/day. After 2 weeks on follow-up, the symptoms of agitation and insomnia were still persisting, and the quetiapine 100 mg/day and clonazepam 0.5 mg/day were added.
After 3 weeks follow-up, the patient showed significant improvement with a repeat YMRS score of 8 and risperidone dose was reduced to 1 mg daily. One month after the initiation of the therapy, the patient complained of bothersome incidence of pedal edema that, on examination, was described as bilateral 2+ pitting edema reaching up to the level of her mid calves.
She was reviewed by a physician and no physical cause for the edema was found. All hematological and biochemical profiles, including full blood count, serum albumin, lipid profile, liver function tests, thyroid function tests, urea, and electrolytes, were normal. Her blood pressure was normal; cardiac investigations such as electrocardiogram, cardiac echocardiogram troponins, and creatinine kinase were found unremarkable. Pulmonary examinations were benign. A complete metabolic profile, including albumin and thyroid-stimulating hormone, to determine etiology of her edema was found to be within normal limits. To exclude allergic etiology, immunology testing consisting of C3, C4, and IgE were normal.
Risperidone was discontinued by the psychiatrist owing to its propensity to cause pedal edema. However, the condition remained unresolved even after 2 weeks, and the edema progressed to 3+, gradually reaching her calves [Figure 1]. The dose of quetiapine was tapered to 50 mg/day. The patient started showing gradual improvement in edematous condition (Grade 2+). Quetiapine was slowly discontinued. Furosemide 20 mg/d for 10 days was prescribed symptomatically for edema, which resolved over the course of approximately 3 weeks. No further recurrence of edema occurred, and hence, no further medication changes were implemented.
Naranjo adverse drug reaction probability scale gave a score of 7 which denotes "probable" adverse drug reaction. Pedal edema was found to be resolved within weeks of dechallenge of the regimen. No rechallenge was attempted by the physician, after the withdrawal of the medication.
The temporal relationship between AAP and this incidence of pedal edema was thus established.