SSRIs in Rett syndrome

To the Editor

Rett syndrome is a severe neurodevelopmental X-linked disorder, with a prevalence of 1 per 10,000 people (Chapleau et al., 2013). Most cases are associated with methyl CpG binding protein 2 (MeCP2) gene mutations (Pan and Tsai, 2012). Reduced levels of brain-derived neurotrophic factor (BDNF) have been implicated (Chapleau et al., 2013; Pan and Tsai, 2012). While initially thought to result in significantly reduced life expectancy, it is observed that many survive into adulthood (Percy, 2014). Currently no curative treatment exists, with management focusing on addressing symptomatology (Pan and Tsai, 2012). Here we present a case of behavioural disturbance in a child with Rett syndrome, who had a significant response to a selective serotonin reuptake inhibitor (SSRI).

An 11-year-old girl with Rett syndrome, living with her supportive family, was referred with a 12-month history of sleep disturbance and self-harming behaviour. She has motor, language and social skill difficulties, characteristic hand-wringing movements and loss of acquired purposeful hand skills.

Her parents described head-banging and self-hitting, lasting up to 30 minutes and occurring at home and school. Severe sleep difficulties, primarily early awakening, were present. She would often sleep for only 4 hours a night. MRI and blood tests were normal. EEG showed epileptiform discharges, although no clinical seizures have been observed. Careful evaluation did not identify psychosocial stressors or specific triggers for self-harm.

Head banging and sleep disturbance continued despite treatment with anti-migraine and anti-epileptic medications. Risperidone, olanzapine and clonidine were used without sustained benefit. A trial of escitalopram was initiated following parental request, based on their own investigation on a Rett syndrome Internet forum. An immediate benefit was noted which lasted for 3 months. Head-banging episodes reduced significantly in frequency and duration. She was sleeping for 11 hours each night. Unfortunately, she developed SSRI-induced bruxism. As the escitalopram dose was reduced, bruxism reduced but behavioural issues and sleep disturbances increased.

To our knowledge this is the first case report demonstrating the success of escitalopram in managing behavioural problems associated with Rett syndrome. SSRIs may assist through different mechanisms. Fluoxetine increases MeCP2 expression in rat brains (Chapleau et al., 2013; Pan and Tsai, 2012). SSRIs have been shown to enhance BDNF expression (Chapleau et al., 2013; Pan and Tsai, 2012). Patients with Rett syndrome and mice null for MeCP2 show reduced levels of brain serotonin, thus by adjusting serotonin levels, SSRIs might improve mood and behavioural disturbance (Chapleau et al., 2013; Percy, 2014). Larger animal and human trials are needed to empirically validate the effectiveness of SSRIs in moderating behavioural and sleep disturbance in Rett syndrome.