Adderall and Adderall XR — ADHD
Adzenys and Adzenys XR — ADHD
Aripiprazole (Abilify) — Aggression, Agoraphobia, Irritability, Mood Disorders, Self-Injurious Behavior
Atomoxetine (Strattera) — ADHD
Benztropine (Cogentin) — Saliva Reduction
Brexpiprazole (Rexulti) — Aggression
Bupropion (Wellbutrin) — Anxiety
Buspirone (Buspar) — Anxiety
Carbamazepine (Tegretol) — Aggression
Citalopram (Celexa) — Anxiety
Clonazepam (Klonopin) — Anxiety
Clonidine (Catapres) — ADHD, Anxiety (see Alpha-2 Agonists), Sleep Problems
Clozapine — Aggression
Desvenlafaxine (Pristiq) — Anxiety
Dexmethylphenidate (Focalin) — ADHD
Diphenhydramine (Benadryl) — Sleep Problems
Duloxetine (Cymbalta) — Anxiety
Dyanavel XR — ADHD
Escitalopram (Lexapro) — Anxiety, OCD
Fluoxetine (Prozac) — Selective Mutism, Social Anxiety
Guanfacine (Tenex) — ADHD, Anxiety (see Alpha-2 Agonists)
Hydroxyzine (Vistaril) — Sleep Problems
Lamotrigine (Lamictal) — Aggression, Mood Disorders
Lisdexamfetamine (Vyvanse) — ADHD, Obesity or to Avoid Weight Gain
Lithium — Mood Disorders
Lorazepam (Ativan) — Anxiety
Lurasidone (Latuda) — Aggression
Melatonin — Sleep Problems
Metformin — Obesity or to Avoid Weight Gain
Methylphenidate (Ritalin, Concerta) — ADHD
Mirtazapine (Remeron) — Sleep Problems
Mydayis — ADHD
Naltrexone/Bupropion (Contrave) — Obesity or to Avoid Weight Gain
Olanzapine (Zyprexa, Zyprexa Zydis) — Aggression, Self-Injurious Behavior
Pimavanserin (Nuplazid) — Aggression
Propranolol (Inderal) — Anxiety
Quetiapine (Seroquel) — Aggression, Self-Injurious Behavior, Sleep Problems
Risperidone (Risperdal) — Aggression, Self-Injurious Behavior
Risperidone (Risperdal M-TAB) — Aggression
Sertraline (Zoloft) — Anxiety
Suvorexant (Belsomra) — Sleep Problems
Temazepam (Restoril) — Sleep Problems
Topiramate (Topamax) — Obesity or to Avoid Weight Gain
Trazodone (Desyrel) — Anxiety, Sleep Problems
Valproic Acid (Depakote) — Aggression
Venlafaxine (Effexor) —Anxiety
Ziprasidone (Geodon) — Aggression, Self-Injurious Behavior
Zolpidem (Ambien) — Sleep Problems
Important Information
Note and Disclaimer: The National Fragile X Foundation (NFXF) does not provide medical or legal advice or services. Rather, the NFXF provides general information about Fragile X as a service to the community. The information provided in this document is not an endorsement of any resource, therapeutic method, or service provider and does not replace the advice of medical, legal, or educational professionals. The NFXF has not validated and is not responsible for any information or services provided by third parties. Use independent judgment, request references, and seek the advice of or consult your physician when considering any information or treatment related to Fragile X.
The following information includes available data wherever possible, but much of the current approach to treatment relies on expert opinion. The core behaviors discussed below are commonly seen in FXS, and individuals with FXS may have one or more of the listed behaviors.
It is important to remember that individuals with FXS may:
- Be more sensitive to medication effects
- Respond to smaller doses than the general population
- Have side effects at dosing lower than expected to cause such effects. If side effects occur, the medication may need to be discontinued in consultation with the doctor.
General Recommendations for Adults: It is important to avoid adding new medications every time an adult has a crisis, and it’s important to make every attempt to avoid adults being overmedicated with high dosages and with many medications at once.
Dosing: An important general principle with all medication treatment in FXS is to start at low doses and raise the dose gradually and systematically until the desired benefit is achieved or until intolerable side effects occur.
- Adults are defined as 18 and older.
- Youth are defined as children and teenagers between the ages of 5 and 18.
- Some 3- to 5-year-olds may take medications under close supervision of their doctor.
- Where medication dosage is based on weight, it will be noted.
At all times, dosing level should be discussed with the individual’s doctor. Do not make changes to medications or supplements (increasing OR decreasing) without the guidance of the individual’s doctor.
If dosing levels are not provided for a medication listed below, it is because the medication is not recommended for use in individuals with FXS. In those instances, medications are only listed in case they are suggested by a doctor.
Medication Names: Medications appearing here are introduced using their generic name followed by the most common brand name (with a few exceptions) in parenthesis, for example: aripiprazole (Abilify). Otherwise, the generic name is used as many are available under multiple brand names.
Introduction
Many individuals with Fragile X syndrome exhibit delays in development and can also have challenging behaviors, both of which can impact academic and daily functioning. Medications are at times helpful to facilitate the individual’s ability to attain optimal life skills and allow for better integration into educational, adult, and social environments.
Psychopharmacological (medication) treatment in FXS is recommended in appropriate individuals as a treatment to be used in conjunction with therapeutic services, including:
- Behavioral intervention
- Speech and language therapy
- Occupational therapy
- Individualized educational support
It is also important to set up the environment, to the extent possible, for success. Examples might include:
- Setting up a routine
- Using visual schedules
- Allowing time for transitions
- Minimizing sensory stimuli
There are several common symptoms and psychiatric conditions in individuals with Fragile X syndrome that are treated with the same medications used in the general population and in individuals with other developmental disabilities. These medications have been reported to be effective for individuals with Fragile X syndrome in retrospective clinical studies.
However, it’s important to note that there is limited formal research or clinical trial data to demonstrate the best approach to the use of medication specifically in the Fragile X syndrome population.
ADHD (Attention Deficit Hyperactivity Disorder)
Attention-deficit and hyperactivity symptoms are among the most prevalent behaviors in individuals with FXS. Individuals with FXS, especially males, have challenges in shifting and sustaining attention. Attention difficulties and response inhibition deficiencies such as impulsivity are thought to be mediated by reduced dopamine activity in frontal cortical regions.
The mainstay of treatment for these problems is stimulant medication (methylphenidate and mixed amphetamine salts classes of medication).
It is preferable to start most patients on short-acting forms of stimulant medication to fully understand an individual’s therapeutic window at which the drug works best, and to get a sense of how long the drug works.
However, long-acting modified-release stimulant preparations may be preferable in the end as they tend to minimize “peaks and valleys” in blood levels of the medications, which can potentially aggravate mood lability in sensitive individuals with FXS. Long-acting preparations also may alleviate the disruption to the school day associated with a visit to the nurse’s office for a midday dose.
Stimulant Medications
Stimulants work well for many individuals with FXS. Many doctors report that a majority of people with FXS who receive stimulants for ADHD or impulsive behavior show improvement.
Once the individual with FXS reaches adulthood, especially as they move into middle age, stimulant medications may no longer be needed.
Central Nervous System Stimulants
Methylphenidate (Ritalin, Concerta) comes in long acting and immediate release (short acting) forms and comes in liquid, tablet, capsule with time-release beads, transdermal patch, chewable, and oral disintegrating tablet forms.
Dosing:
- Adults and Youth: Typically dosed up to a general maximum of 2 mg per kilogram (2.2 pounds) of body weight per day.
Research Note: Quillivant and Quillivant ER – long-acting methylphenidate derivative. Dr. David Hessl, from the University of California in Davis, received funding from the U.S. National Institutes of Health (NIH) to conduct a study of Quillivant across neurodevelopmental disorders, including FXS.
Dexmethylphenidate (Focalin, Focalin XR) is a similar compound to methylphenidate, but it may have less appetite suppression and less effect on tics or sleep if these are issues with methylphenidate. It also comes in short- and long-acting forms.
Focalin Dosing:
- Adults and Youth: Typically dosed in the range of 5 mg to 20 mg daily, divided in two doses.
Focalin XR Dosing:
Focalin XR is an extended-release (long-acting) Focalin.
- Adults: Typically dosed in the range of 10 mg to 40 mg per day.
- Youth: Typically dosed in the range of 10 mg to 30 mg per day.
Mixed Amphetamine Salts (Dextroamphetamine/Amphetamine)
Dextroamphetamine/Amphetamine (Adderall and Adderall XR)
Adderall XR is an extended-release Adderall.
Dosing:
- Adults and Youth: Typically dosed up to a general maximum of 1 mg per kilogram (2.2 pounds) of body weight per day.
Dextroamphetamine/Amphetamine (Mydayis) is a newer medication for use in individuals 13 years of age to adult. Mydayis lasts up to 16 hours.
Dosing:
- Adults and Youth: Typically dosed up to a general maximum of 1 mg per kilogram (2.2 pounds) of body weight per day.
Amphetamine Salt
Lisdexamfetamine (Vyvanse)
A long-acting amphetamine salt. It comes as a capsule that can be opened and sprinkled in food or liquid and lasts about 8–10 hours. It also comes as a chewable tablet.
Dosing:
- Adults and Youth: Typically dosed up to a general maximum of 1 mg per kilogram (2.2 pounds) of body weight per day.
Amphetamines
Adzenys XR-ODT is an extended-release amphetamine.
Dosing:
- Adults and Youth: Typically dosed in the range of 3.1 mg to 18.8 mg per day.
Dyanavel XR is a liquid-form extended-release amphetamine.
Dosing:
- Adults and Youth: Typically dosed in the range of 2.5 mg to 20 mg daily.
Possible Side Effects of Stimulant Medications
Individuals may experience appetite reduction (sometimes a desirable side effect) or sleep disruption, if a stimulant medication is taken too late in the day. Some patients cannot tolerate stimulants at all due to aggravation of irritability, aggression, or perseveration, or even induction of a depressive withdrawn state.
Irritability and other behavioral problems by stimulants have been seen and can occur at any age.
Non-Stimulant Medications
Alpha-2 Agonists
If stimulants for ADHD are not tolerated for the individual with FXS, non-stimulant alpha-2 agonists such as clonidine (Catapres) and guanfacine (Tenex) can be considered. These are FDA-approved non-stimulant ADHD medicines that are often used if stimulants are not working well.
Aggression
Medications mentioned in this section:
- Aripiprazole (Abilify)
- Brexpiprazole (Rexulti)
- Carbamazepine (Tegretol)
- Clozapine (Versacloz, FazaClo, and Clozaril)
- Lamotrigine (Lamictal)
- Lurasidone (Latuda)
- Olanzapine (Zyprexa, Zyprexa Zydis)
- Pimavanserin (Nuplazid)
- Quetiapine (Seroquel)
- Risperidone (Risperdal, Risperdal M-TAB)
- Valproic Acid (Depakote)
- Ziprasidone (Geodon)
Aggression in Fragile X syndrome can present at an early age, often closely associated with intense anxiety and generalized irritability. Features of autonomic arousal including tachycardia (rapid heart rate) and diaphoresis (sweating), may indicate an underlying anxiety or panic attack and can help guide the types of interventions likely to help.
Antipsychotic medications are used in children, adolescents, and adults exhibiting severe behavioral disturbances such as aggression or self-injurious behavior that interfere with daily functioning or pose a significant threat to the affected individual or others.
Antipsychotic Medications
These medications have FDA approval for use in treating irritable and aggressive behaviors associated with autism spectrum disorder (ASD) in youth ages 5 and up. However, in cases where extreme behavior dysfunction exists, these medications have been used to treat children as young as 3 years old, though great caution should be exercised in this age group due to variable responses and side effects.
Those frequently used include:
Aripiprazole (Abilify) is reported to have response rates of ~70% in Fragile X syndrome. In an open-label prospective study, this medication targeted distractibility, anxiety, mood instability, aggression, and self-injurious behavior.
Dosing:
- Adults: Typically dosed in the range of 2 mg to 30 mg total per day with some individuals responding at lower dosing. Dosing normally occurs one or two times per day.
- Youth: Typically dosed in the range of 2 mg to 15 mg per day with larger adolescents generally following adult dosing guidelines.
Possible Side Effects:
- Tolerance: Some individuals cannot tolerate this medication because it has dopamine agonist activity and its side effects can be similar to those seen with the use of stimulants, including exacerbation of agitation or aggravation of aggressive, irritable, and perseverative behaviors.
- Metabolic Issues: Metabolic issues such as weight gain can develop within weeks, especially with aripiprazole, risperidone, and olanzapine. These medications can potentially cause glucose intolerance due to increased insulin resistance.
Long-Term Use:
- Weight Gain: Weight gain is the biggest concern with aripiprazole and risperidone, because if an individual gains a lot of weight, there can be issues with a higher diabetes risk (type 2), high blood pressure, and high cholesterol.
- Extrapyramidal Movements Disorders: There is also a small risk of extrapyramidal movement disorders developing and caregivers should watch for abnormal movements. It’s important to monitor for these movements as, rarely, they can become permanent (tardive dyskinesia) if not addressed. They can potentially occur after years of use and can happen out of nowhere.
Medication Interactions:
- Sertraline and fluoxetine can increase the blood levels of aripiprazole.
- In a few individuals with FXS treated with the combination of buspirone and aripiprazole, the emergence of tics has been seen so this combination should be used with caution watching for this side effect.
Risperidone (Risperdal)
Dosing:
- Adults: Typically dosed in the range of 0.5 mg to 8 mg total per day with dosing typically divided two to three times daily.
- Youth: Typically dosed in the range of 0.5 mg to 4 mg per day in divided doses, with significant dosing variation from low to high based on size and age within childhood.
Possible Side Effects:
- Prolactic Increase: Risperidone can increase prolactin, which often has a calming effect. It’s the endogenous neurohormone that causes milk letdown or lactation in women after they give birth. Very rarely, it can cause lactation in women, and rarely it can cause breast tissue development in males. It is not seen very often, but it is something that professionals watch for and is treatable.
- Metabolic Issues: Metabolic issues such as weight gain can develop within weeks, especially with aripiprazole, risperidone, and olanzapine. These medications can potentially cause glucose intolerance due to increased insulin resistance.
Long-Term Use:
- Weight Gain: Weight gain is the biggest concern with aripiprazole and risperidone, because if an individual gains a lot of weight, there can be issues with a higher diabetes risk (type 2), high blood pressure, and high cholesterol.
- Extrapyramidal Movements Disorders: There is also a small risk of extrapyramidal movement disorders developing and caregivers should watch for abnormal movements. It’s important to monitor for these movements as, rarely, they can become permanent (tardive dyskinesia) if not addressed. They can potentially occur after years of use and can happen out of nowhere.
Olanzapine (Zyprexa)
Dosing:
- Adults: Typically dosed in the range of 5 mg to 40 mg per day often divided in two to three doses.
- Youth: Typically dosed in the range of 2.5 mg to 15 mg per day often in divided doses, with larger adolescents dosing into the adult dosing range.
Possible Side Effects:
- Metabolic Issues: Metabolic issues such as weight gain can develop within weeks, especially with aripiprazole, risperidone, and olanzapine. These medications can potentially cause glucose intolerance due to increased insulin resistance.
Side Effects of Antipsychotic Medications
At any age, antipsychotic medications can cause significant side effects.
When first starting the medication — within days to 1-2 weeks at any specific dose:
- Akathisia — restlessness
- Extrapyramidal movement disorders — abnormal movements that are repetitive and involuntary
- Oculogyric reaction — spasm movement of the eyeball or spasm of the mouth or neck — is rare but can occur within days of initiation of the treatment
After having been on a medication for an extended period of time, side effects can sometimes occur:
- Tardive Dyskinesia: Tardive dyskinesia can occur after an extended period of time. Tardive dyskinesia causes stiff, jerky movements of the face and body that the person cannot control and do not lessen even when the offending drug is stopped. There is currently no cure for tardive dyskinesia. See below for a list of antipsychotic medications least likely to cause tardive dyskinesia.
- Metabolic Issues: Issues such as weight gain can develop within weeks, especially with aripiprazole, risperidone, and olanzapine. These medications can potentially cause glucose intolerance due to increased insulin resistance.
- Other Side Effects: Lethargy and worsening of coordination.
Long-term use of aripiprazole and risperidone:
- Weight Gain: Weight gain is the biggest concern with aripiprazole and risperidone, because if an individual gains a lot of weight, there can be issues with a higher diabetes risk (type 2), high blood pressure, and high cholesterol.
- Extrapyramidal Movement Disorders: There is also a small risk of extrapyramidal movement disorders developing and caregivers should watch for abnormal movements. It’s important to monitor for these movements as, rarely, they can become permanent (tardive dyskinesia) if not addressed. They can potentially occur after years of use and can happen out of nowhere.
Because of these issues, careful clinical monitoring is required consisting of blood tests as indicated for glucose, liver function, electrolytes, and lipid profiles, particularly in individuals with substantial weight gain.
Antipsychotic Medications Least Likely to Cause Tardive Dyskinesia
If the individual with FXS is having abnormal movements, the following antipsychotic medications can be considered:
Quetiapine (Seroquel) sees lower rates of weight gain and abnormal movements, though some risk of abnormal movements does exist.
Dosing:
- Adults: Typically dosed in the range of 25 mg to 1000 mg per day total, often divided in two to three doses
- Youth: Typically dosed in the range of 50 mg to 400 mg per day, often in divided doses with larger adolescents dosing into the adult dosing range
Pimavanserin (Nuplazid) is an option for adolescents and adults who have had a lot of movement issues. Pimavanserin is a new medication that is FDA approved for psychosis associated with Parkinson’s disease. The drug often requires prior authorization due to its expense.
Dosing:
- Adults: Typically dosed in the range of 17 mg to 34 mg per day
- Youth: No dosing use information available
Clozapine (Versacloz, FazaClo, Clozaril) is one antipsychotic medication that does not cause tardive dyskinesia. However, it is associated with:
- Significant weight gain
- A lower seizure threshold resulting in the appearance or increase in seizures in some individuals
- A (rare) drop in white blood cell counts to zero, requiring blood counts every week for six months, then every other week, and then monthly
Given these associations, clozapine use remains limited in Fragile X syndrome.
Other Antipsychotic Medications
Ziprasidone (Geodon) is for those where weight gain is an issue. It can also help with self-injury, aggression, and severe tantrums. It is in a capsule form and individuals are supposed to swallow it, however there are reports of caregivers who sprinkle it on food in cases where the individual with FXS is unable to swallow the capsule.
Dosing:
- Adults: Typically dosed in the range of 20 mg to 80 mg per dose given twice daily
- Youth: Typically dosed up to adult dosing based on size and age of the youth
Lurasidone (Latuda) is a newer generation antipsychotic. It has not been specifically studied for its use in FXS. There has been a negative study for its use in treating aggression and irritability in autism.
Brexpiprazole (Rexulti) is a new form of aripiprazole (already mentioned above) for people who have tolerability issues. No systematic data has been generated to date describing its use in FXS.
Other Medications (Non-Antipsychotic)
Selective Serotonin Reuptake Inhibitors (SSRIs)
If aggressive or self-injury behavior is the result of the individual’s anxiety, treatment using a medication for anxiety, such as selective serotonin reuptake inhibitors (SSRIs) medication, can be effective. SSRIs have been used in children with Fragile X syndrome as young as 3 years of age.
See the full list of SSRIs in the Anxiety section.
Anticonvulsants
Anticonvulsants are used to target mood instability. Medications such as carbamazepin (Tegretol), lamotrigine (Lamictal), and valproic acid (Depakote), can occasionally be effective for aggressive and self-injurious behaviors, and thus should be considered as an additional option for therapy if SSRIs or the antipsychotic medications are not tolerated or effective.
Carbamazepine (Tegretol)
Dosing:
- Adults: Starting dose would be about 400 mg twice a day with titration (continuous measurement and adjustment) up to as much as 1200 mg twice a day (can be divided into three doses a day).
- Youth: Starting dose 10 mg/kg per day divided twice a day.
Possible Side Effects: Carbamazepine can cause the blood counts to drop and blood testing for a CBC and liver functions should be done initially after 4 weeks on the medication and then every 6 months. It can sometimes be activating and increase impulsive behavior and hyperactivity.
Lamotrigine (Lamictal)
Dosing:
- Adults and Youth: Lamotrigine must be started slowly and titrated (continuously measured and adjusted) up gradually to avoid allergic rashes. The dose is based on weight and the other medications the patient is on and specific guidelines are available for lamotrigine titration. It is typically dosed twice a day after titration.
Possible Side Effects: Lamotrigine can aggravate sleep problems and if it seems to be causing sleep difficulties, the second dose can be moved to the afternoon, which will in some cases resolve the sleep problems.
Valproic Acid (Depakote) dosing:
- Adults and Youth: Dosing is based on following blood levels with a goal blood level between 50 and 125 units of Depakote. Therefore, flexibly dosed, and blood levels should be closely monitored. Typically, this is started at 10 mg/kg per day divided twice or three times a day and titrated (continuously measured and adjusted) up to as much as 40 mg/kg per day monitoring liver functions, CBC for platelets, and the level.
Quick Acting Medications
There are two quick acting medications that are sometimes used with individuals with Fragile X syndrome, under the guidance of a medical doctor.
Risperidone (Risperdal M-TAB)
Risperidone also has Risperdal M-TAB that dissolves in the mouth. It is also available in a liquid, which is easy and quick to take, and the dosage can be more easily adjusted.
Dosing:
- Adults: Typically dosed in the range of 0.5 mg to 2 mg per dose used as needed and as directed.
- Youth: Typically dosed in the range of 0.25 mg to 1 mg based on age and size.
Olanzapine (Zyprexa Zydis)
Olanzapine also has Zyprexa Zydis, which is a rapidly dissolving melt-in-the-mouth antipsychotic that can be used as needed to treat severe behaviors.
Dosing:
- Adults: Typically dosed in the range of 5 mg to 10mg as needed or as directed.
- Youth: Typically dosed starting as low as 2.5 mg or even 1.25 mg, based on age and size.
Other Medication: There is also a dissolving form of aripiprazole, but itʼs used less often than the medications above
Agoraphobia
Agoraphobia is an anxiety disorder that can cause intense fear in situations where the person feels escape may be difficult or help hard to access. For some people with FXS, agoraphobia can cause the individual to not want to leave their house.
If agoraphobia leads to aggression when trying to get the individual with FXS to leave the house or their room, or results in them hurting themselves (or others) or breaking and throwing things, then medicines for anxiety (SSRIs) may help. If symptoms persist, medications for aggression are added, such as aripiprazole or risperidone.
For many agoraphobia challenges, behavioral supports can also be helpful.
Anxiety
Classes of medications covered in this section:
- Selective serotonin reuptake inhibitors — SSRIs
- Sertraline (Zoloft)
- Citalopram (Celexa)
- Escitalopram (Lexapro)
- Serotonin-norepinephrine reuptake inhibitors — SNRIs
- Duloxetine (Cymbalta)
- Venlafaxine (Effexor)
- Desvenlafaxine (Pristiq)
- Antipsychotics
- Serotonin receptor antagonists and reuptake inhibitors — SARIs
- Trazodone (Desyrel)
- Norepinephrine and dopamine reuptake inhibitors — NDRIs
- Bupropion (Wellbutrin)
- Antianxiety Agents, Anxiolytics, Nonbenzodiazepines
- Buspirone (Buspar)
- Benzodiazepines
- Clonazepam (Klonopin)
- Lorazepam (Ativan)
- Beta Blockers
- Propranolol (Inderal)
- Alpha-2 Agonists
- Tricyclic antidepressants — TCAs
Many patients with FXS begin to show signs of anxiety at a very early age, often by 2-4 years. Serotonin is one of the most important neurotransmitters in the brain involved in regulating mood and affect. SSRIs can be very effective in treating symptoms of anxiety and depression. They work by increasing levels of serotonin — the key hormone that stabilizes our mood — within the brain. SSRIs have been used on an empirical basis in affected patients with FXS as young as toddlerhood.
Selective Serotonin Reuptake Inhibitors (SSRIs)
SSRIs increase levels of serotonin in the brain, which helps regulate mood.
Learn more about SSRIs from MedLinePlus
The most commonly used SSRIs in the treatment of FXS are sertraline (Zoloft), citalopram (Celexa), and escitalopram (Lexapro), all listed below.
Once children get to school age, there is more use of citalopram and escitalopram, which have limited drug-drug interactions and are generally used interchangeably compared to sertraline use.
Sertraline (Zoloft)
Dosing:
- Adults: Typically dosed in the range of 12.5 mg up to 200 mg per day
- Youth: Typically dosed as low as 5 mg per day, with larger adolescents dosing into the adult dosing range
The best data on the use of sertraline in FXS is the result of the work of Dr. Randi Hagerman (NFXF founder and Distinguished Professor of Pediatrics at the University of California Davis Medical Center, among many other things) who has published on the potential for the drug to facilitate communication in young children — A Randomized, Double-Blind, Placebo-Controlled Trial of Low-Dose Sertraline in Young Children with Fragile X Syndrome — including young children ages 2-6 years old. This study demonstrated improvements in non-verbal cognition, fine motor skills, and visual perception compared to placebo, but improvements in expressive language only occurred in those who had autism. Sertraline is also available in a liquid formulation.
Also see OCD and Speech and Language in Toddlers sections.
Citalopram (Celexa)
Dosing:
- Adults: Typically dosed in the range of 10 mg to 40 mg per day.
- Children: Typically dosed as low as 5 mg per day, with larger adolescents dosing into the adult dosing range.
Escitalopram (Lexapro)
Dosing:
- Adults: Typically dosed in the range of 5 mg to 20 mg per day.
- Youth: Typically dosed as low as 2.5 mg per day, with larger adolescents dosing into the adult dosing range.
Side Effects of SSRIs
Behavioral activation, which can include sleep difficulties, is an increase in activity level that generally does not include any real change in mood, impulse control, or a change in the child’s demeanor or other behaviors. It can be managed by dose reduction or medication discontinuation.
At times, the activation can be more significant and results in agitation, though this is a rare side effect. However, at times it is difficult to get the dose low enough to actually get rid of the activation and keep the clinical benefit.
Additional side effects may include nausea, diarrhea, and dizziness.
Long-Term Use of SSRIs
There is a small risk of disinhibition, more so in people with autism who do not have FXS, manifested as getting overly energized or increasingly agitated. SSRIs are considered safe with no known long-term organ toxicity.
Which SSRI Do I Start With?
The most commonly used in FXS are sertraline, citalopram, and escitalopram. Check if other family members have taken one and had tolerability issues. This is a discussion to best have with the individual’s doctor.
Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)
SNRIs increase levels of serotonin and norepinephrine in the brain. Serotonin helps regulate mood and norepinephrine helps improve energy and attentiveness. The SNRIs are the next choice if the SSRIs are not effective. Usually, after trying at least two SSRIs the doctor may move to:
Duloxetine (Cymbalta) is used most often, of the SNRIs.
Dosing:
- Adults: Typically dosed in the range of 30 mg to 120 mg per day.
- Youth: Similar dosing to adults used in children based on age and size, with maximum dosing typically at 60 mg per day.
Possible Side Effects: The most common side effect is upset stomach, which is relatively rare. As a side condition, it treats neuropathic pain, and also has an indication in treating fibromyalgia.
Venlafaxine (Effexor)
Dosing:
- Adults: Typically dosed in the range of 37.5 mg to 300 mg per day.
- Youth: Half of adult dosing level, with maximum dosing of 150 mg in youth, with the exception of some adolescents who may move toward full adult dosing levels.
Desvenlafaxine (Pristiq) is a newer version of venlafaxine (Effexor), sometimes better tolerated.
Dosing:
- Adults: Typically dosed in the range of 25 mg to 100 mg per day.
- Youth: No significant experience in children to establish dosing.
Antipsychotic Medications
Data from the FORWARD project notes that some caregivers report antipsychotic medications being used for anxiety. These tend to be more for adolescent age where anxiety, aggression, and self-injury may be present.
Note: Antipsychotic medications should not be the first-choice drugs in treating anxiety.
Other classes of antidepressants may be considered in instances in which SSRIs are not clinically effective or are not tolerated due to side effects such as when there is behavioral activation that could not be managed by dose reduction.
Serotonin Receptor Antagonists and Reuptake Inhibitors (SARIs)
Trazodone (Desyrel)
Typically used at bedtime for insomnia, though use in individuals with FXS has found they are not becoming sedated when taking trazodone during the day.
Dosing:
- Adults: Typically dosed starting at 25 mg per dose with 2 to 4 doses a day, increase over time by 25 mg per dose, with a maximum total daily dose of 300 mg per day.
- Youth: Similar dosing guidelines in youth using up to 150 mg, with older and larger youth moving up to maximum adult dosing levels.
Possible Side Effects: Trazodone can cause tiredness and, rarely, persistent erections. It is important to be aware of the possibility of this side effect so as not to be upset if this happens.
Norepinephrine-Dopamine Reuptake Inhibitors (NDRIs)
Bupropion (Wellbutrin) can lower the seizure threshold and should not be used when there is an active seizure disorder. It’s a better treatment for depression than it is for anxiety and therefore its general use in FXS is more limited, although it can be helpful for attention in patients who cannot tolerate stimulants.
Dosing:
- Adults: Typically dosed in the range of 75 mg to 450 mg daily with immediate-release formulation given multiple times a day versus extended-release versions given one time daily.
- Youth: Dosing variable based on the age and size of the individual but usually starting at 25 mg for young children and at 50 mg for those ages 10 and up.
Antianxiety Agents, Anxiolytics, Nonbenzodiazepines
Buspirone (Buspar) may, in some cases, reduce anxiety either alone or in combination with an SSRI. Buspirone is also generally well tolerated.
Dosing:
- Adults: Typically dosed in the range of 15 mg up to 90 mg daily, given in three divided doses.
- Youth: Dosing generally follows adult dosing guidelines with higher dosing levels reached for larger adolescents.
Benzodiazepines
Benzodiazepines are a type of medication known as tranquilizers. Familiar names include Valium and Xanax.
Learn more about benzodiazepines from NIH
Benzodiazepines may be used in an emotional crisis accompanied by a high level of anxiety or anxiety attacks. They should be avoided for long-term treatment as they can interfere with memory, increase confusion, and/or cause paradoxical excitation (the opposite effect) with a significant increase in hyperactivity and disinhibition. They can also be addictive, meaning they can be difficult to be weaned off.
There is also an issue of induced tolerance where increasing doses are needed to attain the desired effects. Therefore, they must not be discontinued abruptly after long-term use due to the risk of withdrawal seizure.
However, benzodiazepines may be used in single doses to assess for paradoxical excitation (the opposite effect of what is expected) and if absent may be used on an as-needed basis to help with high-stress situations such as dental visits or airplane trips.
The most often used benzodiazepines in FXS are:
Clonazepam (Klonopin)
Dosing:
- Adults: Typically dosed in the range of 0.25 mg to 1 mg per dose.
- Youth: Typically, dosing starts as low as 0.125 mg with larger and older adolescents reaching adult dosing levels.
Possible Side Effects: Clonazepam is one of the more sedating benzodiazepines and can cause increased drooling.
Lorazepam (Ativan)
Dosing:
- Adults: Typically dosed in the range of 0.5 mg to 2 mg per dose.
- Youth: Typically, dosing starts as low as 0.25 mg with larger and older adolescents reaching adult dosing levels.
Beta Blockers
Propranolol (Inderal) is a beta blocker, a high blood pressure medicine. It can have some anxiety benefit, though the aggression benefit is less impressive. If other traditional anxiety medicines are not helping, it is a secondary option. It is also a relatively inexpensive medication.
Propranolol is relatively benign, but it requires blood pressure and pulse monitoring. It decreases the blood pressure in those with high blood pressure but doesn’t do much for those with normal blood pressure. Bradycardia (slower than normal heart rate) can be an issue but is rarely seen.
Propranolol has shown to be good for aggression in autism spectrum disorder (ASD).
Dosing:
- Adults: Typically dosed in the range of up to a few hundred milligrams a day in adults but should be gradually adjusted. There is a broad dosing range for this medicine from 20 mg to 240 mg with dosing adjusted over time while being careful to not provoke low pressure periods with dose increases. The drug is also already in a time-release form that enables daily versus divided two or three times per day dosing.
- Youth: Limited dosing information established in younger children, with adolescents, and in particular larger adolescents, reaching established adult dosing guidelines.
When using propranolol, adjust dosing slowly over time, and follow pulse and blood pressures to be sure they are not dropping. As long as they are not dropping, use may be continued.
Possible Side Effects: Watch for headaches or dizziness; dizziness in individuals with FXS is sometimes hard to appreciate, but one way is to look for differences in how an individual is walking. One should not stop propranolol suddenly as this might cause problems with high blood pressure and withdrawal symptoms.
Note: Propranolol is contraindicated (should not be used) in individuals with asthma or chronic obstructive pulmonary disease (COPD).
Also see Asthma section.
Alpha-2 Agonists
Clonidine (Catapres) and guanfacine (Tenex) have also been used to treat anxiety-like symptoms, particularly those related to hypersensitivity to environmental sensory stimuli, but they are probably not meaningfully effective for other forms of anxiety. Guanfacine has more of a calming effect for hyperarousal, and clonidine can help with treatment of insomnia. See Non-Stimulant Medications in the ADHD section.
Note: The following medications are not recommended without the guidance of a doctor who specializes in FXS. Contact us for assistance with locating a Fragile X specialist.
Tricyclic Antidepressants (TCAs)
For severe anxiety, tricyclic antidepressants may be considered to treat anxiety that is resistant to SSRI or SNRI therapy. They include:
- Imipramine (Tofranil)
- Clomipramine (Anafranil)
- Nortriptyline (Pamelor)
The tricyclic drugs have overall worse tolerability than SSRIs and SNRIs and may require periodic EKGs for safety monitoring.
Asthma
People with Fragile X can take traditional asthma medicines, whether it is an albuterol inhaler, a steroid inhaler, or oral meds. It’s important to note that albuterol tends to make one’s pulse faster and may cause the user to become more hyper, but asthma should be treated similarly to how it is treated in typically developing individuals.
Sometimes, propranolol, which is a beta blocker, is used to treat anxiety. However, this should not be taken by people with asthma as it can cause bronchospasm.
Depression
Depression can be difficult to diagnose and treat in individuals with developmental issues. It is especially challenging to understand in individuals with communication challenges, but it can certainly happen, and it’s something to think about if the individual with FXS is having a pattern in their behavior that is changing. Signs of depression are:
- Not doing activities like they used to
- Changes in sleep
- Eating more or less
- Crying spells
- Acting differently in general, out of their norm
Depression is treated with SSRIs and SNRIs. See the Anxiety section.
Handling Changes and Transitions
Even with planning, preparing, using a visual schedule, and allowing plenty of time, individuals with FXS can have difficulty with changes and transitions. Such difficulties can include behavior challenges such as significant anxiety, agitation, aggression, and self-injurious behavior.
If either anxiety or agitation becomes interfering, refer to medication approaches for anxiety or aggression for guidance on possible medication management to address these situations.
Hyperarousal
Hyperarousal in individuals with FXS is hard to measure, but through the use of EEGs, it has been found that the brain at rest in individuals with FXS has increased high-frequency electrical activity. There are currently studies underway to evaluate this, but at this point, treatment recommendations include the use of relaxation and calming strategies, along with the use of SSRIs and SNRIs. See the Anxiety section.
Alpha-agonists have been used if SSRIs and SNRIs are activating.
Impulsive Behaviors
See the ADHD section.
Introverted or Prefers Isolation
Some individuals like to stay in their rooms and will not come out when people come over to visit. Again, relaxation-related techniques and other therapeutic approaches are extremely helpful for caregivers and affected individuals, together and individually. The use of these techniques, in conjunction with anxiety medications, is often helpful.
See the Anxiety section.
Irritability
Irritability is frequently seen in individuals with FXS, and the cause can be difficult to determine. Irritability is defined by the FDA as aggression, self-injurious behavior, and severe tantrums. Irritability also can represent oppositional interactions that may not adhere to the FDA use of this term.
SSRIs can be helpful in managing these irritable symptoms in higher functioning individuals with FXS if they appear to relate mostly to social anxiety, rigid behaviors, obsessions, or to some extent, perseverative behaviors. A go-very-slow approach is associated with the fewest side effects, especially in lower functioning individuals.
If SSRIs are not helpful, or irritable behavior does not seem specifically related to anxiety or perseverative behavior, antipsychotics such as aripiprazole or risperidone can work well thus targeting the FDA defined nature of irritability.
See the Anxiety and Aggression sections.
Mood Disorders
Examples of mood disorders include up and down behaviors such as crying, upset and sad, then happy, and then back to being sad. Typically, mood stabilizers are used to treat mood disorders in individuals without FXS. Antipsychotics such as aripiprazole or risperidone may be used as mood stabilizers.
See the Aggression section.
Mood Stabilizers
Lithium (Eskalith, Eskalith-CR, Lithobid) works well in individuals with FXS; however, a potential problem is the narrow therapeutic dosing range and associated toxicity profile. It can cause thyroid dysfunction and long-term use can cause kidney dysfunction. It can cause some issues with hydration status, and it can sometimes cause tremors.
It is not necessarily the safest or easiest medicine to use, however there are people with FXS who do not tolerate other medications and who take lithium and do really well.
Dosing:
- Adults and Youth: Lithium is dosed to a certain level in the blood where response can be expected and below the blood levels typically associated with toxicity. Often a lithium level in the blood in the 0.6 to 1.2 range (that is in milliequivalents per liter (mEq/L)) is a common goal of treatment, often dosed two to three times per day.
Other Medications
There is less success — in treating behavior issues — with the other categories of mood stabilizers, such as the anti-epileptic drugs, including valproic acid (Depakote), oxcarbazepine (Trileptal), or lamotrigine (Lamictal). Those are mood stabilizers that also treat seizures and bipolar disorder and are sometimes used in people with FXS for behavior, but overall, the general consensus is that there has not been a strong positive response in the majority of patients.
Obesity or to Avoid Weight Gain
Metformin
Metformin appears to be helpful in addressing weight gain associated with other drugs whose use increases weight and is, therefore, used in instances where an individual is gaining a lot of weight or has out-of-control eating. Metformin also lessens type 2 diabetes risk.
In summary, the use of metformin may allow the individual with FXS to stay on a medicine that is really helping their behavior, but that was resulting in serious weight gain.
Metformin
Careful consideration must be given to dosing with using metformin. Typically, the dose is twice a day, at breakfast and dinner, unless someone is taking extended-release metformin which can be taken one time daily.
Dosing:
- Adults and Adolescents: Typically, doses start at 500 mg once per day, increasing to twice a day (morning and evening), then up to 1000 mg twice a day, or 2000 mg once a day, under the guidance of a medical doctor.
- Youth: Usually started on doses as low as 125 mg to 250 mg per day, under the guidance of a medical doctor.
Possible Side Effects: Metformin may take some time to be associated with positive effects and it may cause an upset stomach or diarrhea (see more below). Sometimes adverse effects including gastrointestinal symptoms improve with a dose reduction or may improve over time.
Metformin Clinical Trials
There is some evidence metformin helps Fragile X brain connectivity in lab animal models. There is currently a clinical trial ongoing that is scheduled to end May 2022. Results will follow. See published articles below.
Metformin Recalls
The recalls to date have been specific to specific manufacturers, meaning there was a bad batch. There is nothing inherent in metformin — the molecule — that has been found to be bad. So again, the recent metformin recalls are associated with specific manufacturers and not the drug.
Metformin and Diarrhea
Diarrhea or loose bowel movements occurs in 20% to 25% of people treated with metformin. Diarrhea is by far the most common treatment-limiting side effect. Dosing adjustments, or giving it a little bit of time, may solve this issue. Therefore, it is recommended to start low and go slow with the dosing. If the diarrhea does not improve with dose adjustments, it may need to be stopped.
If the individual with FXS is prone to be constipated, and is taking medicine for constipation, and there is then breakthrough diarrhea on metformin, it is recommended to remove the medicine for constipation. Otherwise, metformin is typically well tolerated and general laboratory monitoring is usually not required. Metformin has been around a long time and has been used over the last 10 years with good results on decreasing excessive weight gain.
Published Articles
- Metformin as Targeted Treatment in Fragile X Syndrome
- Metformin Treatment in Young Children with Fragile X Syndrome
Other Medications
Options to consider as alternatives to metformin to limit weight gain associated with other medications.
Amphetamine Salt
Metformin
Careful consideration must be given to dosing with using metformin. Typically, the dose is twice a day, at breakfast and dinner, unless someone is taking extended-release metformin which can be taken one time daily.
Dosing:
- Adults and Adolescents: Typically, doses start at 500 mg once per day, increasing to twice a day (morning and evening), then up to 1000 mg twice a day, or 2000 mg once a day, under the guidance of a medical doctor.
- Youth: Usually started on doses as low as 125 mg to 250 mg per day, under the guidance of a medical doctor.
Possible Side Effects: Metformin may take some time to be associated with positive effects and it may cause an upset stomach or diarrhea (see more below). Sometimes adverse effects including gastrointestinal symptoms improve with a dose reduction or may improve over time.
Anticonvulsants
Topiramate (Topamax)
A seizure medicine that lowers weight in many people. It can also help with headaches.
Dosing: Wide dose range based on age and size and intended use of the drug, speak with the prescriber for direction.
Possible Side Effects: It rarely causes kidney stones. It sometimes can make people tired.
Anorexiants (Appetite Suppressants)
Naltrexone/Bupropion (Contrave) is an FDA-approved medication for weight management; it is a combination of naltrexone and bupropion. It is an expensive medication that may be hard to get insurance approval.
An alternative is to use a combination of bupropion low dose and naltrexone low dose.
Dosing:
- Adults: Typically dosed in the range of 8 mg naltrexone/ 90 mg bupropion, one to four tablets per day use as directed.
- Youth: No information available.
OCD (Obsessive-Compulsive Disorder)
OCD is usually characterized by repetitive behavior and is one of the anxiety disorders. It can be treated with medications used for other anxiety disorders but often requires higher dosing than needed for other anxiety disorders.
Medications often used for OCD include the SSRI medications sertraline (Zoloft), escitalopram (Lexapro), and citalopram (Celexa). See the SSRI information in the Anxiety section.
Repetitive and Perseverative Behaviors
Perseverative speech and actions, ritualistic behavior, constant chewing of clothing or other objects, hair-pulling, and a general love of routine and repetition are frequently seen in patients with FXS.
Although obsessive-compulsive behaviors may be mediated predominantly by the serotonin system, perseverative repetitive behaviors and stereotypies* may be more closely linked to dopamine systems.
*What are stereotypies?
Repetitive, ritualistic, purposeless movements, postures, or speech. For example, tapping feet or pacing back and forth.
Thus, either SSRI’s or antipsychotics (especially if associated with irritable behaviors) may be helpful for this category of behaviors. However, perseverative behaviors and stereotypies can be difficult to eliminate and there are no medications yet that target them well.
See the Anxiety and Aggression sections.
Saliva Reduction
If drooling associated with other needed medications such as antipsychotics is a problem, benztropine can be used.
Benztropine (Cogentin)
When treating excessive salivation from antipsychotics, also reduces abnormal movement risk in the short term (but not the long term as is the case with tardive dyskinesia).
Dosing:
- Adults: Typically dosed in the range of 1 mg to 3 mg per day, divided two to three times a day.
- Youth: Typically, half the adult dosing: 0.5 mg to 1.5 mg per day, divided two to three times a day.
Seizures
Individuals with FXS who experience seizures should be seen and treated by a neurologist who specializes in seizures. Seizures are generally quite treatable by FDA-approved agents, and they often go away over time.
Medications for seizures are listed in our treatment recommendation, Seizures in Fragile X Syndrome.
Selective Mutism
Selective mutism is an anxiety disorder in which the individual with FXS does not speak in situations that are unfamiliar or uncomfortable or with people the individual does not know very well. The individual often communicates better in a familiar setting or with family members. It is often treated with medications for anxiety. Also see:
Fluoxetine (Prozac) can be quite helpful for girls with this condition because it is activating. This may be the most helpful SSRI for selective mutism and for girls with substantial social withdrawal.
Dosing:
- Adults: 20 mg to 80 mg per day
- Youth: Start at 10 mg per day and may increase gradually after a minimum of one month to evaluate effect up to a max of 60 mg to 80 mg per day based on age and size.
Self-Injurious Behavior
Many individuals with FXS engage in self-injurious behaviors, the most common of which is hand biting and finger chewing, though head banging is also seen. Behavioral assessment and treatment are the mainstays for these behaviors though sometimes medication is used as well.
It is usually treated similarly to treatments for aggression, with use of antipsychotic medications, unless it is felt to be due to anxiety.
Antipsychotics used may include:
- Aripiprazole (Abilify)
- Risperidone (Risperdal)
- Quetiapine (Seroquel)
- Ziprasidone (Geodon)
For more information, see the Aggression section.
Sensory Sensitivities
In addition to behavioral and occupational therapies, anxiety medicines, for example, SSRIs, tend to help some individuals with sensory sensitivities. The SSRIs may reduce anxiety, and the individual with FXS may be less hypervigilant and hyperresponsive without being too sleepy. See the Anxiety section.
These medications should be used in conjunction with an occupational therapist (OT), the child’s school staff (for a school-aged child), and a behavioral psychologist.
Sleep Problems
Sleep problems are a frequent complication of FXS and are most commonly caused by hyperarousal and inability to settle down either when trying to fall asleep in the evening or after awakening in the middle of the night.
The first step in managing sleep problems should be implementation of behavioral strategies such as consistent bedtimes and sleep schedules, bedtime routines, and calming strategies for bedtime and middle-night awakenings, however, these strategies may be insufficient and may need to be combined with medication treatment.
It is also important to be sure there is not a medical problem causing night awakenings such as obstructive sleep apnea. If the individual has loud snoring, pauses in breathing, or is very restless in sleep, discuss thiin sleep, discuss with a health care provider.
Here is a suggested sleep algorithm (process) to follow:
Melatonin is the first medication recommended. Melatonin comes in short- and long-acting forms. If the individual wakes too early with the short-acting form, the long-acting form may be helpful.
Long-term use of melatonin is okay. The general recommendation is to take it 30 or 45 minutes, or up to an hour or two, prior to desired sleep time.
Dosing:
- Adults and Youth: 3 mg to 8 mg (some take up to 10 mg) at night.
Short-Term Sleep Medications
Note: Diphenhydramine (Benadryl) and hydroxyzine (Vistaril), listed below, are suggested for short-term use only. It is advised to go to clonidine (Catapres) if melatonin does not work.
Diphenhydramine (Benadryl)
If melatonin is ineffective, diphenhydramine can be tried. Note that a small percentage of people may become hyperactive on diphenhydramine.
Dosing:
- Adults and Youth: Suggest 25 mg to 50 mg at bedtime, following directions on diphenhydramine packaging.
Hydroxyzine (Vistaril) can be used for both potential sleep and anxiety throughout the day.
Dosing:
- Adults and Youth: Suggest 25 mg to 50 mg per dose given up to every 4-6 hours, lower dosing generally in youth depending on age on size./
Prescription Medicines
The most commonly used prescription medications for insomnia include:
Clonidine (Catapres)
A rapid-acting traditional blood pressure medicine that is also good for sleep.
Dosing:
Dosing usually occurs at bedtime.
- Adults: Typically dosed in the range of 0.1 mg to as high as 0.3 mg or 0.4 mg (0.4 mg is pretty high).
- Youth: Typically, half the dosing of adults. The range of 0.05 mg to 0.15 mg. Dose will also depend on the age and size of the individual.
Trazodone (Desyrel)
An old antidepressant that is good for sleep. It is better at keeping people asleep.
Dosing: See trazodone (Desyrel) in the Anxiety section.
If clonidine and trazodone do not work, the following may be considered:
Mirtazapine (Remeron)
Used to treat symptoms of depression. Sometimes mirtazapine can increase appetite and should be monitored.
Dosing:
- Adults and Youth: Low dose of 7.5 mg at bedtime, but it increases appetite so that is a secondary negative for a lot of patients.
If mirtazapine does not work, zolpidem (Ambien) and temazepam (Restoril) can be considered. Note: They are technically a controlled substance.
Zolpidem (Ambien)
Dosing:
- Adults: Typically dosed in the range of 7.5 mg to 30 mg at bedtime.
- Youth: Limited data exists describing dosing in youth, with youth dosing up to adult dose levels based on age and size of the child.
Temazepam (Restoril)
Dosing:
- Adults: Typically dosed in the range of 7.5 mg to 30 mg at bedtime
- Youth: Limited data exists describing dosing in youth, with youth dosing up to adult dose levels based on age and size of the child.
If other sleep medicines fail:
Quetiapine (Seroquel)
Can be used at bedtime for insomnia.
Dosing:
- Adults and Youth: Typically dosed in the range of 12.5 mg to 100 mg range, depending on age, at bedtime.
Suvorexant (Belsomra)
A new medicine for people with terrible sleep. It is a good, FDA-approved sleep aid, however, it is expensive and requires insurance prior authorizations every time, but it has been reported to be very effective for people with poor sleep.
- Adults: Typically dosed in the range of 5 mg to 20 mg at bedtime.
- Youth: No data available.
Note: Caregivers should keep in mind that if the individual has a lot of anxiety, their sleep is not going to be great. So, treating underlying anxiety, while also potentially taking medicine as a sleep aid, is probably going to be the most helpful. See the Anxiety section.
Sleep in Children With Fragile X Syndrome
Sleep problems can be more frequent in children with developmental disabilities, including Fragile X syndrome. Ongoing support can play an important role. Depending on the presentation and primary disorder, treatment may include behavioral, pharmaceutical, and surgical interventions.
Social Anxiety
Social anxiety is present to some extent in the vast majority of individuals with FXS. This can range from shyness to a clinical diagnosis of social anxiety disorder.
When evaluating social responsiveness, individuals with FXS are often motivated to be social, but become overwhelmed by the intensity of the social interaction and expectations, which causes a negative or avoidant reaction.
Some triggers for social anxiety include:
- Being put on the spot
- Forced eye contact
- Standing up in front of people
- Making phone calls
- Attending a party or large gathering
- Meeting new people
Fluoxetine (Prozac) may be used for girls with severe social anxiety and shyness. Also see the Anxiety and Selective Mutism sections
Speech and Language in Toddlers
If a toddler is very anxious, and the anxiety is treated, improved communication may result.
If a toddler is exceptionally hyperactive and impulsive, or really anxious, or has a lot of sleep issues, it is recommended that those issues be treated aggressively because it will help them developmentally, especially in the communication area.
Sertraline (Zoloft): There is some published data on the use of sertraline (Zoloft), but it is not uniformly used with toddlers. The results of a randomized, double-blind, placebo-controlled trial of low-dose sertraline in young children with FXS provides helpful information.
Frequently Asked Questions
When should medication be considered and at what age?
Medication can potentially be part of overall treatment, when combined with non-medication therapies, and should be considered when behavioral symptoms significantly interfere in the individual’s ability to participate in daily activities including, therapy, school, or family life, or are causing some kind of risk to the individual with Fragile X syndrome or to other people around them.
Caregivers should ask: What is the behavior? How is it causing a problem? Is it a tangible issue? If treated using medication, would it improve quality of life and open up opportunities?
In the Fragile X syndrome field, medication has been utilized with children who are in kindergarten, first, or second grade age and are either showing anxiety or the beginnings of ADHD symptoms. On rare occasions, medications have been utilized to treat severe anxiety and sometimes severe ADHD in preschool and toddler age children.
Lastly, it should be emphasized that every individual is different, and that medication should not be utilized in isolation of other interventions.
Can you use two medications for two different symptoms simultaneously? For example, anxiety and ADHD?
The short answer is yes. There are many individuals who may, for example, take an SSRI for anxiety and a stimulant for ADHD, and they do quite well.
The key is — what are you treating with each medicine and are you seeing benefit?
Do not start both these classes of medicines at the same time; do them one at a time to get a sense of what’s doing what, but they are totally compatible, potentially, together.
How long does it take before I can tell if the medicine is working?
With each medication class, there is a different time frame that is needed to see if it is going to have an effect.
- For an antipsychotic, effects should be seen in about a week
- For an SSRI or an SNRI, effects may not be seen for about a month
- For a stimulant, it only takes two or three day
Different medication classes take different amounts of time to evaluate at any one dose.
Symptom Rating Scale
For Parent and Caregiver Use. Which symptoms are the biggest problems? Check all that apply. We also have a printable version of this form.
| Target Symptom | Not a problem | Is a problem |
|---|---|---|
| Aggression | ||
| Agoraphobia | ||
| Anxiety | ||
| Asthma | ||
| ADHD | ||
| Handling Changes & Transitions | ||
| Impulsive Behaviors | ||
| Irritability | ||
| Mood Disorders & Mania | ||
| Obesity | ||
| OCD | ||
| Repetitive & Perseverative Behaviors | ||
| Saliva | ||
| Seizures | ||
| Selective Mutism | ||
| Self-Injurious Behavior | ||
| Sensory Sensitivities | ||
| Sleep Problems | ||
| Social Anxiety | ||
| Speech & Language in Toddlers |
Related Recommendations
Assessment of Fragile X Syndrome — For Clinicians
Taken together, the clinical assessment of individuals with FXS must be comprehensive, accommodate the unique aspects and range of the FXS phenotype, and utilize tools that are appropriate (feasible, scorable, and valid) for use in FXS and commensurate with their developmental level.
Genetic Counseling and Family Support
Genetic counseling includes family and medical histories to assess the chance of carriers (premutations) throughout a family’s lineage.
Behavioral Challenges in Fragile X Syndrome
The most common behavioral challenges seen in FXS include those associated with generalized anxiety, social interaction difficulties, ADHD, self-injury, and aggression.