Olfactory Reference Syndrome Responding to Amisulpride

Olfactory reference syndrome (ORS) is a rare and frequently underrecognized psychiatric condition characterized by a persistent false belief of emitting an offensive body odor.¹ The condition is commonly associated with marked distress, social avoidance, and significant functional impairment.² Because its phenomenology overlaps with psychotic and obsessive-compulsive spectrum disorders, ORS is often misdiagnosed, leading to prolonged untreated illness.¹ We report a case of ORS presenting with prominent referential beliefs and poor insight, closely resembling a first-episode psychosis, and discuss its diagnostic and therapeutic implications for clinical practice.

Case Report

A 22-year-old woman, originally from Cape Verde and living in Portugal since childhood, was referred for psychiatric evaluation in February 2025 because of long-standing social withdrawal and distressing beliefs concerning body odor. She lived with her mother, was in a stable romantic relationship, and was enrolled in an undergraduate law program. There was no history of substance use, relevant medical illness, or known family history of psychiatric disorders.

The patient reported that symptoms began in early adolescence, around 2013, when she started noticing what she perceived as unusual reactions from others, including nose rubbing, coughing, grimacing, or physical distancing. Initially experienced as puzzling, these observations gradually acquired personal significance. Over time, she developed the conviction that others were reacting to an unpleasant odor emanating from her body.

Throughout adolescence and early adulthood, the belief became increasingly fixed and emotionally salient. She reported overhearing indirect comments that she interpreted as confirmation of her belief, which persisted despite meticulous personal hygiene and was not confined to specific situations. Progressive avoidance behaviors emerged, including social withdrawal and reduced academic engagement. Although she recognized the distress associated with the belief, she remained fully convinced of its accuracy. Secondary depressive symptoms developed, characterized by hopelessness, low self-esteem, and anxiety in social contexts.

On mental status examination, she was cooperative and fully oriented, with coherent and goal-directed thought processes. Her mood was depressed. A single, circumscribed belief of emitting a foul odor was evident, accompanied by prominent ideas of reference. These referential interpretations included perceiving others coughing, rubbing their noses, or stepping away from her in public spaces as evidence that they were reacting to her odor. On several occasions, she interpreted overheard comments or gestures as indirect confirmation of this belief. Given the fixed conviction and lack of doubt regarding these interpretations, the referential beliefs were considered closer to delusions of reference rather than mere ideas of reference, consistent with phenomenological descriptions of ORS. No hallucinations, additional delusions, or first-rank psychotic symptoms were identified. Insight into the pathological nature of the belief was markedly impaired.

Relevant medical conditions were excluded. Differential diagnoses included schizophrenia spectrum disorders, obsessive-compulsive disorder, and body dysmorphic disorder. Based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision diagnostic criteria, a diagnosis of ORS was established. Initial trials of risperidone and aripiprazole were discontinued due to poor tolerability. Treatment was subsequently initiated with amisulpride at a dose of 200 mg/day, which was well tolerated.

Over the following weeks, there was a gradual reduction in both the conviction and affective salience of the olfactory belief. Referential interpretations resolved, depressive symptoms remitted, and social and academic functioning returned to premorbid levels. At follow-up, the patient was considered clinically asymptomatic.

Discussion

This case highlights several clinically relevant aspects of ORS. First, it illustrates the insidious onset and chronic course that often characterize untreated ORS, with symptom emergence in early adolescence and substantial delays before appropriate psychiatric intervention. Such delays contribute to cumulative psychosocial burden and are frequently reported in the literature.¹

Second, the case underscores the diagnostic complexity of ORS, particularly when poor insight and prominent referential interpretations create a presentation resembling first-episode psychosis. Although phenomenology alone rarely distinguishes ORS from primary psychotic disorders, the presence of a single, circumscribed belief, absence of additional psychotic features, and favorable response to antipsychotic treatment supported the diagnosis in this patient.

Third, the favorable clinical outcome with antipsychotic monotherapy reinforces evidence that dopamine-blocking agents may be effective in ORS presentations characterized by delusional conviction.³ Medication tolerability was a decisive factor in treatment selection, emphasizing the importance of individualized pharmacologic strategies.

Patients with ORS often first present in primary care or general psychiatric settings. Increased awareness of this condition may facilitate earlier referral, reduce prolonged untreated illness, and help prevent long-term functional impairment and suicide risk.⁴

Article Information

Published Online: September 17, 2026. https://doi.org/10.4088/PCC.26cr04191
© 2026 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord 2026;28(5):26cr04191
Submitted: January 18, 2026; accepted March 17, 2026.
To Cite: Lopes JR, Siopa C, Simões I. Olfactory reference syndrome responding to amisulpride.
Prim Care Companion CNS Disord 2026;28(5):26cr04191.
Author Affiliations: Unidade Local de Saúde de Santa Maria, Lisbon, Portugal (all authors).
Corresponding Author: João Revez Lopes, MD, Unidade Local de Saúde de Santa Maria, Lisbon, Portugal ([email protected]).
Financial Disclosure: None.
Funding/Support: None.
Patient Consent: Consent was received from the patient to publish the case report, and information, including dates, has been de-identified to protect anonymity.