She was placed in foster care at the age of 6 years old due to severe neglected behaviors from her parents. She has experienced a very insecure environment leading to an early attachment disorder and anxiety disorder. During primary school, major global learning disabilities were reported. In this context, she was evaluated by a standard metric test (EXALANG 5-8 years). The initial evaluation found severe attentional and behavioral difficulties leading to poor reading and writing skills. Writing rehabilitation was prescribed but stopped due to behavioral disorders. At the age of 9 years old, the Wechsler Intelligence Scale for Children (WISC:IV) was homogeneous with intellectual disability (verbal comprehension index = 69; perceptual reasoning index = 82; processing speed index = 71; full scale IQ = 69). Rapidly, she presented severe outbursts and tantrums leading to hetero-aggressiveness and self-injuries. In the meantime, she started to exhibit many simple motor tics associated with simple verbal tics characterized by facial grimacing, arm jerk, obscene gesture, and scream compatible with Tourette syndrome. The worsening of the Tourette syndrome associated with intellectual deficiency led to many changes in her living environment and many long-term hospitalizations. She was unsuccessfully challenged by risperidone, aripiprazole, fluoxetine, propericiazine, haloperidol, zuclopenthixol, and naltrexone.
During her last admission in our specialized unit, our clinical assessment underlined the severity of her attachment disorder with severe ambitendency toward her relationship with peers and caregivers, many simple and complex motor/verbal tics, aggressiveness, strong impulsivity, and numerous self-harm behaviors. A clinical examination did not find any abnormality, and the result of a standard blood workup (CBC and liver and kidney function) was normal. Given the overall resistance to atypical and typical antipsychotics, the severity and burden of the automutilations, and the impulsivity, the off-label use of clozapine was considered legitimate by the medical team. We quickly reported low clozapine plasma levels (275 ng/mL), regardless of the progressive increase of clozapine dosage (500 mg/day). After excluding all known food or drug interactions, a pharmacogenetic testing on cytochromes was performed and identified the CYP1A2*1F/*1F genotype (see Table 1). This genotype is associated with ultra-rapid drug metabolism, therefore explaining the low clozapine plasma levels. We decided to add fluvoxamine to clozapine to inhibit the CYP1A2 subunit and to enhance the clozapine plasma level. Within the next days after fluvoxamine introduction (50 mg/day), we observed a major increase of clozapine plasma level (503 ng/mL) (see Figure 1). Clinically, we reported a drastic improvement regarding automutilations and impulsivity, with a 32% reduction in the ABC:irritability subscale and 33.3% in the ABC:hyperactivity subscale. Regarding tolerance, we did not report any side effect, and no hematological adverse event was reported (see Supplementary Figure 1).