Clomipramine as an alternative to selective serotonin reuptake inhibitors for patients at haemorrhagic risk

Abstract

Selective serotonin reuptake inhibitors (SSRIs) can cause haemorrhage secondary to decreased platelet aggregation thus limiting pharmacological treatment options in Obsessive-compulsive disorder (OCD) patients with bleeding tendency (Laporte et al., 2017). We report a case where Clomipramine was better tolerated than SSRIs in a patient with recurrent epistaxis and recommend it as an alternative to SSRIs in patients susceptible to haemorrhagic complications. EL is a 59-year-old male, with a 15-year history of schizophrenia stable on Paliperidone 3 monthly depot and a 10-year history of OCD that responded well to Fluvoxamine but was selfceased due to recurrent epistaxis. In February 2021, EL was admitted to an acute psychiatric inpatient ward with obsessive ruminations about past social interactions where he would ‘replay conversations’ in his mind incessantly. The associated anxiety led to reduced self-care, isolation and disengagement with community mental health services. The psychotic symptoms were not dominant. EL was commenced on Sertraline 25 mg and titrated to 50 mg, but subsequently experienced recurrent episodes of severe epistaxis, which resolved with cessation. Naranjo Adverse Drug Reaction Probability Scale was applied to Sertraline and in retrospect to Fluvoxamine (Naranjo et al., 1981). The SSRIs scored 7 and 8, respectively, indicating probable adverse drug reaction (ADR). Further exploration of the aetiology of his epistaxis also revealed a nasal septal defect and Polycythemia Rubra Vera (PCV) for which he was commenced on Aspirin 100 mg/day and Hydroxyurea 1000 mg mane. PCV increases the risk of thrombosis and haemorrhage and Aspirin increases the risk of bleeding. Subsequent treatment with an SSRI would have further increased this risk. We therefore initiated a trial of Clomipramine which has a theoretical advantage over SSRIs of increased platelet aggregation (Alvarez et al., 1999). Clomipramine was gradually uptitrated to 175 mg/day with no further epistaxis during the admission. EL’s OCD symptoms improved with his Yale-Brown Obsessive Compulsive Scale score reducing from 22 at admission to 14 at discharge. He exhibited improved selfcare, social interactions and mood. Clomipramine is a third-line pharmacological treatment for OCD. Like SSRIs it can also increase the risk of haemorrhage via decreased platelet aggregation However, unlike SSRIs, Clomipramine is distinctly a 5-HT2 receptor antagonist which is proposed to lead to compensatory up-regulation of 5-HT2 receptors promoting platelet aggregation (Alvarez et al., 1999). It is possible that this mechanism helped prevent epistaxis in EL and led to better clinical outcome. To our knowledge, this is the first report comparing clomipramine and SSRIs in patients with haemorrhagic complications and provides the clinicians a safer alternative in such cases.