The poor-insight feature of PI-OCD makes it a difficult condition for therapists. Obsessions and delusions have been traditionally viewed as dichotomous phenomena, with obsessions defined as 'intrusive, egodystonic thoughts with the patient maintaining insight'. By contrast, delusions have been defined as false beliefs firmly held by the patient without insight into the irrationality of the belief. However, obsessions and delusions may be better conceptualised as existing on a continuum of insight that ranges from good insight (overvalued ideation, as in typical OCD) to poor insight/no insight (delusional thinking) as in the course of PI-OCD [9]. When 'psychotic features' are present in the course of OCD, treatment is often difficult, requiring high doses of standard OCD medication and frequently requiring augmentation strategies with both proserotonergic drugs and antipsychotics, especially second generation compounds associated with more favourable general side-effect profiles [11]. As a consequence, such high doses of drugs (often beyond in-label ranges), can be associated with unpleasant side effects, including nausea as one the most frequent occurrences [12]. Furthermore, no univocal pharmacological management of PI-OCD and potential iatrogenic effects exists. This is essentially due to a relatively low prevalence [2] of the disorder and difficulty in detection of related clinical features.

Fluoxetine (in-label doses for depression and anxiety disorders range between 20-80 mg/day) is an SSRI antidepressant stimulating 5-HT2A postsynaptic receptors and desensitising 1A receptors; it also acts as a 5-HT2C antagonist, increasing norepinephrine and dopamine neurotransmission at the prefrontal cortex [13]. Both 5-HT2A and 5-HT2C actions may play a major role in its antiobsessive actions, although 5-HT2A stimulation can induce nausea, especially at higher doses [13], conversely reducing striatal dopaminergic neurotransmission [2].

Amisulpride is an atypical antipsychotic possibly acting as a dopamine stabiliser and dopamine partial agonist. Although not a first-line choice antipsychotic augmentation strategy for PI-OCD cases unresponsive to serotonergic monotherapy, it may be considered when dysthymia is also present, as it was in our case. While low doses (for example, 50 mg/day) of amisulpride may be suggested for dysthymia (disinhibiting presynaptic D2 receptors), higher doses (blocking postsynaptic D2 receptors) may be required in case of negative symptomatology (50-300 mg/day) or positive symptoms (400-800 mg/day for schizophrenia). Additionally, the gastrointestinal D2 blockade may contribute to an antiemetic effect of amisulpride or other benzamides (for example, metoclopramide) with potential gastroprokinetics actions at high doses (possibly also from 5-HT3 receptor antagonism).

Nonetheless, as apparently occurred in our case, 5-HT2A stimulation may prevail on the atypical antipsychotic '5-HT2A > D2' blockade, inducing nausea eventually unresponsive to standard antiemetic medications. In such cases, a slight reduction of the SSRI dose may be made, suggesting an add-on therapy with a second antidepressant medication as the α2 antagonist, dual serotonin and norepinephrine agent (NaSSA) mirtazapine (for example, at 30 mg/day) [14], which may help in anti-obsessive and antiemetic management via 5-HT3 antagonism and 5-HT2A blockade [13, 15]. Switching amisulpride to olanzapine (for example, at 10 mg/day) may also help since the antipsychotic action may be coupled to a strong 5-HT3 blockade, whereas olanzapine 5-HT2C blockade should be an optimal complement to fluoxetine in the management of affective, anxious and cognitive symptoms [13].

Interestingly, blocking the ligand-gated ion channel 5-HT3 receptor [13] may not only exert an antiemetic effect but also a putative intrinsic antiobsessive action, as suggested by the efficacy of ondansetron (a potent 5-HT3 antagonist used for chemotherapy-induced nausea) augmentation in treatment-resistant OCD [16, 17], whereas olanzapine and mirtazapine 5-HT3 blockade has been considered for cancer chemotherapy-related nausea and cachexia (due to the H1 blockade) [18].

Indeed, both compliance issues related to the total number of medications and anti-OCD therapeutic implications should not support the choice of non-psychiatric 5-HT3 blockers in favour of proven anti-OCD psychopharmacological agents sharing the 5-HT3 antagonist property. Finally, while more research is needed in this direction, mirtazapine and olanzapine could play a major role in PI-OCD augmentation strategies for patients taking high (sometimes off-label) doses of SSRIs, and their 5-HT3 blockade may substantially contribute to the management of drug-induced nausea, even if as in this case it remains unclear which one of the two medications might have had most contribution to cessation of nausea or contribution to compliance lasting for at least 1 year.