Psychopharmacology in fragile X syndrome—Present and future

Abstract

In addition to cognitive disability, fragile X syndrome (FXS) is associated with behavioral problems that are often functionally limiting. There are few controlled trials to guide treatment; however, available information does suggest that medications can be quite helpful for a number of categories of behavioral disturbance in FXS. Specifically, stimulants appear to be quite useful for management of distractibility, hyperactivity, and impulsive behavior; antidepressants help with anxiety, obsessive-compulsive behaviors and mood dysregulation; and antipsychotics can reduce aggression. These medications are supportive and help minimize dysfunctional behaviors and maximize functioning. As more is learned about the neural functions of FMRP, medications in the future will be expected to target specific synaptic mechanisms dysregulated in FXS brain and thus ameliorate the cognitive deficit with resultant behavioral improvements. This article summarizes knowledge about effectiveness and approaches to management of currently available psychopharmacology for behavior in FXS and discusses early leads to future treatments for cognition.

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

“…Children and adults with FXS are regularly prescribed stimulants, antidepressants, anticonvulsants, and antipsychotics [727-729]. Psychostimulants are the most often prescribed psychoactive medication to treat FXS [730], with initial randomized controlled trial data of response to methylphenidate and dextroamphetamine suggesting moderate response rates on attention and social skills [731].…”

Serotonin dysregulation in Fragile X Syndrome: implications for treatment

“…Symptom-based treatments currently include stimulants, antidepressants (e.g. selective serotonin reuptake inhibitors; SSRIs), and atypical antipsychotics which are useful in treating symptoms such as hyperactivity, anxiety, and aggression (59,64). SSRIs are sometimes prescribed for patients with FXS to relieve symptoms of anxiety (59).…”

Therapeutic Strategies in Fragile X Syndrome: Dysregulated mGluR Signaling and Beyond

“…Males with FXS have characteristic behavioral features including hyperactivity, impulsivity, attention problems, generalized anxiety with phobias and multiple specific domains of anxiety (de Vries et al, 1996;Sullivan et al, 2007;Hagerman et al, 2009;Farzin et al, 2011), mood lability, and autistic features such as poor eye contact, shyness, self-talk, hand-flapping, hand-biting, hyperarousal to sensory stimuli, and substantial perseverative language and behavior (Berry- Kravis and Potanos, 2004;Hagerman et al, 2009;Wang et al, 2010b). A subset of these problems are common in females, including attention problems, impulsivity, shyness, selective mutism, specific phobias, social anxiety, and social deficits, often occurring even when the IQ is in the normal range (de Vries et al, 1996;Hagerman et al, 2009;Wang et al, 2010b).…”

“…Although aripiprazole is a treatment directed primarily at behavior rather than molecular mechanism, it could theoretically be targeted to dopamine deficits thought to be present in FXS (Wang et al, 2008b), given its dopamine agonist activity at lower doses. Aripiprazole has shown good success when used empirically in FXS clinic populations (Berry-Kravis and Potanos, 2004;Hagerman et al, 2009), and has resulted in improvement in the ABC Irritability subscore, other ABC subscores, and other behavioral rating scales in a pilot open-label trial in 15 individuals with FXS (Erickson et al, 2011a). Plans are underway to initiate a double-blind placebo-controlled trial of aripiprazole in FXS.…”