Drug therapy in autism: a present and future perspective

Abstract

Autism is a neurodevelopmental disorder, with a multifactorial etiology, characterized by severe abnormalities in communications, social awareness and skills, and the presence of restrictive and stereotyped patterns of behaviors. It is traditionally considered a "static" encephalopathic disorder without any specific cure and few effective biomedical interventions. There are various factors which are involved in the etiopathogenesis of autism or autism spectrum disorder (ASD) such as impaired immune responses, neuroinflammation, abnormal neurotransmission, oxidative stress, mitochondrial dysfunction, environmental toxins and stressors. The autism is often associated with a number of genetic disorders such as fragile X syndrome, tuberous sclerosis, epilepsy and Down syndrome. The recent approaches to autism treatment included various non-pharmacological and pharmacological therapy such as food supplementation, detoxification, treatment of neuroinflammation, immunologic treatments and psychotropic medications, which are found to be effective in treating various behavioral symptoms of autism. In current practice, there is no curative treatment for autism but the recommended treatment for autism involves educational therapies: speech therapy, sensory integration therapy, auditory therapy. There are classes of different pharmacological agents which are found to be effective in improving behavioral symptoms of ASD such as neurotransmitter reuptake inhibitors (fluoxetine), tricyclic antidepressants (imipramine), anticonvulsants (lamotrigine), atypical antipsychotics (clozapine), acetylcholinesterase inhibitors (rivastigmine), etc. New classes of drugs with novel mechanisms of action should be there so that this disorder will become less prevalent in the future.

Evidence supporting an altered immune response in ASD

“…Early intensive behavioral intervention, which provides individual teaching in a structured setting with the goal of improving a child's specific deficits, has been shown to lead to improvements in behavior. When initiated at a young age (before 4) it has been shown to improve cognition, communication, and social functioning [95]. There is also a wide array of alternative therapies given to children with ASD.…”

“…There is also a wide array of alternative therapies given to children with ASD. Some examples include probiotics which are often given to children with ASD who show GI dysregulation [96] melatonin which is often given to children who show sleep disturbances [97], and nutritional supplementation with pyroxidine and magnesium [95]. As for pharmacological therapies, only two medications have been approved by the FDA for management of ASD symptoms, risperidone and aripiprazole.…”

“…[98] That being said, many medications are prescribed to children with ASD to mitigate certain symptoms. They range from anticonvulsants, to tricyclic antidepressants, to neurotransmitter reuptake inhibitors [95]. Of interest to this paper are immune-based therapies for ASD.…”

Acute dietary tryptophan manipulation differentially alters social behavior, brain serotonin and plasma corticosterone in three inbred mouse strains

“…Such markers comprise reduced 5-HT transporter binding in frontal cortex (Makkonen et al, 2008; Nakamura et al, 2010), low oxytocin and low melatonin levels (Alabdali et al, 2014, Ruggeri et al, 2014). Selective 5-HT reuptake inhibitors (SSRIs) improve autism symptoms in some patients (West et al, 2009; Kumar et al, 2012; Hollander et al, 2012; Politte et al, 2014)1, suggesting 5-HT neurotransmission may be reduced and/or brain 5-HT depleted.…”

Aspectos genéticos y neuroendocrinos en el trastorno del espectro autista

“…Con base en lo anterior, un fenómeno común observado en sujetos con TEA es la hiperserotoninemia 52 . Sin embargo, el tratamiento con inhibidores selectivos de la recaptura de serotonina (SSRI), como fluoxetina, paroxetina, fluvoxamina y venlafaxina, mostró efectos positivos en el estereotipo de conductas repetitivas, déficit social y en los problemas de comunicación 53 .…”