Medications in Fragile X Syndrome | Dr Jonathan Cohen
With Dr Jonathan Cohen, specialist physician and Medical Director of Fragile X Alliance, from a webinar recording on 14 May 2026. In this session, Dr Cohen walks through the range of medications used to manage conditions associated with Fragile X Syndrome – including anxiety, ADHD, mood disorders, OCD, aggression, epilepsy, and sleep disorders – explaining how each works, what families can expect, and how medications combine with behavioural strategies for the best outcomes.
Key Takeaways
- Fragile X syndrome causes a range of conditions including anxiety, ADHD, mood disorders, OCD, aggression, epilepsy, bedwetting, and sleep disorders – each with specific medications available to help.
- Medications like SSRIs and stimulants are effective for most people with Fragile X, but work best when combined with behavioural strategies and environmental modifications.
- People with Fragile X often respond well to very low doses and may have increased sensitivity, so careful monitoring and regular medical supervision are essential.
- ADHD diagnosis requires a comprehensive assessment – including medical examination, blood tests, ECG, and evidence of symptoms across multiple settings for at least six months.
- Emerging medications like metformin show promise for some people, but are not yet standard treatment and should be discussed carefully with a qualified practitioner.
Conditions and Medications at a Glance
| Condition | Medications used |
| Anxiety | SSRIs/SNRIs (e.g. sertraline, fluoxetine, citalopram); clonidine, buspirone |
| ADHD | Methylphenidate (Ritalin, Concerta), dexamphetamine, lisdexamphetamine (Vyvanse); clonidine, guanfacine, atomoxetine |
| Aggression and self-injury | SSRIs, clonidine, mood stabilisers; antipsychotics (risperidone, olanzapine, aripiprazole) |
| Mood disorders | SSRIs/SNRIs, carbamazepine, valproate, lamotrigine |
| OCD | SSRIs/SNRIs |
| Epilepsy | Carbamazepine, valproate, lamotrigine, topiramate |
| Enuresis (bedwetting) | Desmopressin, imipramine |
| Sleep disorders | Melatonin, clonidine, mirtazapine |
All medications should only be used under the supervision of a qualified medical practitioner.
What is Fragile X Syndrome
Fragile X syndrome is the most common known inherited cause of intellectual disability and developmental delay, and the single gene cause of autism. The condition is neurodevelopmental in origin, meaning the biological wiring of the brain works differently. People with Fragile X experience a range of conditions as direct results of the genetic change – anxiety, ADHD, mood disorders, OCD, aggression, epilepsy, and sleep difficulties among them. These are biological conditions, not behavioural choices. Behavioural management strategies, environmental modifications, and medications can all help improve wellbeing for both the person and their carers.
Understanding Anxiety in Fragile X
Dr Cohen draws a clinical distinction between three separate levels that are easy to confuse – and understanding them helps with treatment decisions.
| Anxiety | Hyperarousal | Agitation |
| The emotion itself. Felt but not seen. Particularly hard to detect in females with Fragile X. | The brainstem’s fight-or-flight response – triggered by anxiety. Mediated by adrenaline and noradrenaline. | What we actually see: flushing, trembling, crying, pacing, hitting, shouting. This is not the anxiety itself. |
Anxiety disorder is diagnosed when there is excessive worry lasting at least six months that significantly interferes with daily life, and the person experiences three or more of: restlessness or feeling keyed up, being easily fatigued, difficulty concentrating, irritability, muscle tension, or sleep disturbance.
SSRIs for Anxiety and Mood
SSRIs (selective serotonin reuptake inhibitors) like sertraline are commonly used to treat anxiety, panic, OCD, aggression, and mood difficulties in Fragile X. They work by helping neurotransmitters – the brain’s chemical messengers – stay active a little longer, improving communication between nerve cells. SSRIs are effective for 60-80% of people and are taken once daily. People with Fragile X often respond well to very low doses, including pre-mutation carriers. Around 20% of people experience paradoxical activation (becoming more agitated, or occasionally mania or nausea) – if this occurs, the dose is reduced or a different medication is tried.
Stimulant Medications for ADHD
ADHD is defined by three key features: inattention, hyperactivity, and impulsivity. Stimulant medications like methylphenidate (Ritalin, Concerta) and dexamphetamine are indicated for children from 6 years of age and can significantly improve attention, concentration, impulsivity, and importantly, socialisation – people find it easier to interact with others. Short-acting versions last 2-3 hours, so timing around school start is important. Long-acting formulations last 6-8 hours. These medications are tightly controlled under Schedule 8 and require regular medical monitoring including blood pressure checks and heart assessment. A comprehensive assessment including blood tests and ECG must be completed before prescribing begins.
Mood Stabilisers and Atypical Antipsychotics
When SSRIs are not providing enough relief, mood stabilisers are the next option. These medications are also used for epilepsy – which affects around 10-13% of people with Fragile X – but a person does not need to have epilepsy to benefit from them. If mood stabilisers are not effective, atypical antipsychotics such as risperidone, quetiapine, and aripiprazole can help with agitation and hyperarousal. Despite their name, these medications are not given because someone is psychotic – they simply help settle the nervous system. People with Fragile X are sensitive to these medications, so treatment always begins with very low doses and is adjusted carefully.
Practical Tips from Jonathan
- Always start with very low doses when trialling medications in Fragile X, as people are often more sensitive than average.
- Give short-acting ADHD medications (dexamphetamine, Ritalin) just before school starts – they take 20-30 minutes to kick in and wear off after 2-3 hours.
- Combine medications with behavioural strategies and environmental modifications – the two approaches work together and the combined effect is greater than either alone.
- Before starting ADHD medication, ensure a comprehensive assessment has been completed, including medical examination, blood tests, and ECG.
- Monitor blood pressure and heart health regularly for anyone taking stimulant medications, as cardiovascular effects can occur over time.
- If someone experiences activation or increased agitation on an SSRI, reduce the dose or switch to a different medication rather than stopping abruptly.
“Medications can be great but they need to have behavioural strategies put in place to get the best results. They work really well together.”
About Jonathan
Dr Jonathan Cohen is a specialist physician with extensive clinical experience treating individuals with Fragile X Syndrome in Australia. He is Medical Director of Fragile X Alliance, and works with families to find safe, effective medication approaches tailored to each individual’s needs.
Resources Mentioned
- Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
- Royal Australian and New Zealand College of Psychiatrists – clinical practice guidelines for anxiety disorders (Aust NZ J Psychiatry 2018; 52: 1109-1172)
- Fragile X New Zealand
- Synapse Harmony Biosciences – AFQ056 (arbaclofen) research study
- Fragile X Alliance Clinic – 263 Glen Eira Rd, Caulfield North, Vic 3161
Fragile X Association of Australia’s webinars are produced with support from Alba Prime and are available on YouTube, Apple Podcasts, and Spotify.
