Adding 5-hydroxytryptamine receptor type 3 antagonists may reduce drug-induced nausea in poor insight obsessive-compulsive patients taking off-label doses of selective serotonin reuptake inhibitors: a 52-week follow-up case report

Abstract

Poor-insight obsessive-compulsive disorder (PI-OCD) is a severe form of OCD where the 'typically obsessive' features of intrusive, 'egodystonic' feelings and thoughts are absent. PI-OCD is difficult to treat, often requiring very high doses of serotonergic drugs as well as antipsychotic augmentation. When this occurs, unpleasant side effects as nausea are common, eventually further reducing compliance to medication and increasing the need for pharmacological alternatives. We present the case of a PI-OCD patient who developed severe nausea after response to off-label doses of the selective serotonin reuptake inhibitor (SSRI), fluoxetine. Drug choices are discussed, providing pharmacodynamic rationales and hypotheses along with reports of rating scale scores, administered within a follow-up period of 52 weeks. A slight reduction of fluoxetine dose, augmentation with mirtazapine and a switch from amisulpride to olanzapine led to resolution of nausea while preserving the anti-OCD therapeutic effect. Mirtazapine and olanzapine have already been suggested for OCD treatment, although a lack of evidence exists about their role in the course of PI-OCD. Both mirtazapine and olanzapine also act as 5-hydroxytryptamine receptor type 3 (5-HT3) blockers, making them preferred choices especially in cases of drug-induced nausea.

Fluvoxamine combination therapy with tropisetron for obsessive-compulsive disorder patients: A placebo-controlled, randomized clinical trial

“…Evidence for the use of ondansetron for monotherapy is poor, nevertheless, it caused additional OCD symptom relief when added to an SSRI in clinical trials (Serata et al, 2015). Antipsychotic drugs with prominent 5-HT 3 antagonistic properties, olanzapine and mirtazapine, have also been used to control nausea induced by high doses of fluoxetine (Fornaro and Martino, 2010). However, in spite of the common direction of results in studies, which is toward 5-HT 3 antagonists having beneficial effects for OCD, the evidence is not yet totally conclusive (Serata et al, 2015).…”

Are 5‐HT3 antagonists effective in obsessive–compulsive disorder? A systematic review of literature

“…The range of ondansetron doses used in these studies (1-8 mg/day) was lower than the one used in schizophrenia (4-16 mg/day; Bennett and Vila, 2010). Because the antiemetic equivalence of the oral formulations of the two drugs is 1 mg granisetron to 32 mg ondansetron (Fox-Geiman et al, 2001), the dose of granisetron used by Askari et al (2012) is rather high. The ondansetron dose is related to side effect appearance, as there were none (Pallanti et al, 2009) or very few in the lowest-dose studies (Pallanti et al, 2014), whereas open administration of 3 mg/day ondansetron (Hewlett et al, 2003) was associated with 18 adverse events in eight patients (ratio = 2.25), with constipation dominating the scene (Table 2).…”

“…The 5‐HT 3 antagonist properties of olanzapine and mirtazapine, which induced improvement in nausea induced by inappropriately high doses of fluoxetine in one case of poor insight OCD (Fornaro and Martino, ), hardly constitute an indication for OCD. However, specific 5‐HT 3 antagonists may nonspecifically increase treatment adherence to SSRIs, which have as their principal side effects nausea and vomiting; this could indirectly facilitate the therapeutic effects of SSRIs.…”

Granisetron-mediated augmentation of sertraline therapeutic effect in obsessive-compulsive disorder: a double-blind placebo-controlled, randomized clinical trial

“…Moreover, nausea is one of the important adverse effects of serotonin reuptake inhibitors (SSRIs) and it can reduce compliance to medication. Using 5-HT3 blockers, as augmentation therapy maybe the preferred choice especially in cases of drug-induced nausea[ 23 ].…”