Table 3. Medications for symptomatic management of pediatric patients with Fragile X syndrome.
| Indication | Medication | Considerations | Adverse Effects |
|---|---|---|---|
| Sleep disturbances | Melatonin | First line. Extended-release formulation is more effective in individuals that wake up in the middle of the night. Give before going to sleep. | Headache, daytime sleepiness, dizziness, stomach cramps, and irritability. |
| Clonidine | Second line. In older than two years. Give before going to sleep | Headache and hypotension at high doses. Infrequent: enuresis. | |
| Trazodone | For refractory cases to melatonin and clonidine. Give before going to sleep. | Consider potential interactions with other medications. Dizziness, xerostomia, nervousness. | |
| Cannabidiol | Pharmacological presentations vary from country to country. Prefer those with fixed dosing | Tiredness, diarrhea, nausea. Drug interactions, especially if hepatic metabolism via CYP enzymes. | |
| Anxiety and related disorders | Fluoxetine Escitalopram Sertraline | First line. Sertraline is the medication with more experience in children with Fragile X syndrome. Liquid presentations if sertraline are not available in some region. | Behavioral activation, sleep disturbances, hyperactivity, aggression, impulsive behavior (especially fluoxetine). Risk of suicidal ideation and behavior, especially in adolescents. |
| Trazodone | Consider in patients with sleep disturbances, depression, aggressiveness. | See above | |
| Bupropion | Contraindicated in patients with uncontrolled seizures. Does not cause weight gain. | Reduces seizure threshold at high doses. | |
| Cannabidiol | See above | See above | |
| Attention deficit and hyperactivity disorder and associated symptoms | Psychostimulants: Methylphenidate Amphetamine derivates | Secondary effects are dose-dependent. In patients ≤4 years old with poor tolerance, suspend and reinitiate at an older age. | Decreased appetite, sleep disturbances, perseveration, tics. At high doses: decrease in language, emotional lability, irritability, and agitation. Hypertension, tachycardia |
| Clonidine | Can be given in combination with psychostimulants. Hyperactivity management. Does not improve concentration. May improve tics. May improve sleep disturbances if administered at night. | Sedation | |
| Guanfancine | Can be given in children under 5yo and later in combination with psychostimulants. Less sedation than clonidine. | ||
| L-acetylcarnitine (LAC) | Positive effect in impulsive behavior and hyperactivity. | ||
| Aggression and self injurious behavior | Aripiprazole | Response rate 70% | Irritability, perseverative behavior, weight gain, dystonia |
| Risperidone | Reserved for severe cases. Administer at night. In the case of dystonia, reduce the dose or consider concomitant use of benztropine. | Sedation. Weight gain. Dystonia. Orthostatic hypotension. Parkinsonian symptoms in older patients. | |
| Quetiapine | Quetiapine is the preferred antipsychotic in older patients because less Parkinsonism. May cause significant weight gain, especially in Prader-Willi phenotype | Weight gain, sedation, dystonia | |
| Olanzapine | |||
| SSRI | Use as adjuvant in patients with aggression and anxiety associated | See above | |
| Mood stabilizers | May be used in combination with atypical antipsychotics and behavioral interventions | Weight gain | |
| Valproate | Steven-Johnson Syndrome | ||
| Lamotrigine | Kidney disease | ||
| Lithium | Hypothyroidism |