RTT girls suffer periods of abnormal behavior from early infancy, including irritability and sleep disorders or anxiety in the first years of life, and a more depressed mood after adolescence, all of which influences their quality of life. An association between emotional and behavioral disorders and various neurochemical changes in the synapses of cortical and subcortical brain regions has been established; also, cortisol levels in the blood vary during stress. The main purpose of this study was to improve mood and behavior disorders in RTT patients with venlafaxine (SNRI), and compare the results with citalopram (SSRIs) during 6 - 8 weeks, to determine which drug offered greater efficacy and fewer side effects, as well as to compare them to risperidone, and to correlate cortisol levels in saliva with stress and drug response. Eleven patients, aged 5 to 26 years old, agreed to participate in this study; neuropsychological tests (Mullen and Vineland scales), quality of life and quality of sleep scales, blood tests, EKG and EEG were performed before and after treatment. Only 2 patients completed the three months trial. Improvement in mood and behavior was not statistically significant for patients; differences in neurodevelopment and quality of life or sleep scales were not significant either; no serious adverse effects were observed. Cortisol levels in saliva decreased in 50% of the patients after the first month of treatment, although this was not statistically significant.