Non-stimulant use in ADHD

This article is about the use of Non-Stimulants in Attention Deficit Hyperactivity Disorder (ADHD). Clinicians carefully consider the use of these medications, and the treatment should be guided by experienced clinicians familiar with them.

Disclaimer: This article is written to inform you and share my clinical experience and shouldn’t replace the advice from your treating clinician. Clinicians practice based on their clinical judgement and expertise, and clinicians often hold differing views.  There is no correct answer, but the crucial aspect is the safe use of medication.

Common drug names may be used in the article. I have no affiliation with any drug companies.

Clonidine

Clonidine is increasingly used in children with ADHD, particularly when aggression, oppositional behaviour, or sleep disturbances are present, and when stimulant medications like methylphenidate (Ritalin) are unsuitable or insufficient. It reduces hyperactivity, impulsiveness, inattention, and aggression, especially in children with comorbid oppositional disorders or tic disorders. It is often used adjunctively with stimulants when aggression or sleep problems persist.

It can offer benefits for sleep onset and maintenance difficulties, particularly in children whose sleep is disrupted by stimulants or by ADHD itself. It may be considered as a primary agent in children under 6 years, where stimulants are not recommended.

Dosing and Administration – General Principles

Clonidine is available as tablets. Small evening doses are frequently used for sleep and behavioural symptoms, starting low and titrating gradually to achieve the desired effect. Example dilution: 100 micrograms in 10 ml (1 ml = 10 mcg) allows for careful incremental increases. Tablets may need to be divided into quarters or halves for accurate dosing in pediatric patients.

Depending on their severity and timing, clonidine can be given two to four times daily for daytime symptoms. For sleep onset, a single dose 1 hour before bedtime is standard, with gradual increases as needed. The therapeutic effect may be seen within days, but full benefit can take 2–3 months. Dose adjustments should be made slowly to minimise side effects and monitor efficacy.

Before starting clonidine for sleep, address sleep hygiene: avoid screens, caffeine, and colas in the evening. Melatonin (short-acting for sleep onset, extended-release for sleep maintenance) is typically tried before clonidine for sleep issues.

Monitoring and Side Effects:

Blood pressure should be monitored periodically, as clonidine can cause hypotension. Dizziness may indicate low blood pressure. Other side effects include headache, fatigue, dry mouth, constipation, and, rarely, worsening aggression at higher doses.

Some children may initially experience increased aggression, which often improves after 2–3 weeks or with dose adjustment. This is relatively common in clinical practice. If higher doses worsen aggression, reducing the dose may resolve the issue. Clonidine is less likely than stimulants to cause appetite suppression or irritability, but may cause sedation, particularly when starting or increasing dose.

All the medications used in ADHD need to be safely stored out of reach of children. Instances of Clonidine overdose are seen in clinical practice, with a common presentation being low blood pressure.

Withdrawal and Discontinuation:

Clonidine must be weaned off gradually over 2–3 weeks to avoid rebound hypertension. Doses under 50 mcg can generally be stopped without tapering, but always follow a physician’s guidance.

Guanfacine (Intuniv)

Guanfacine (brand name: Intuniv) is a non-stimulant, extended-release medication approved for the treatment of ADHD in children and adolescents aged 6–17 years. It is particularly useful when aggression, oppositional behaviour, temper tantrums, and impulsiveness are prominent. It is often used when stimulant medications are insufficient, not tolerated, or to counteract stimulant-induced insomnia.

Guanfacine’s action is similar to that of clonidine, but it has a more selective profile, leading to fewer sedative and hypotensive effects. Guanfacine can be used alone or in combination with stimulant medications. It is especially beneficial for managing oppositional symptoms in ADHD, with clinical trials showing significant improvements compared to a placebo.

Dosing and Administration

It is available as extended-release tablets in various strengths. It’s a once-daily medication, and the effect will likely last throughout the day. Tablets should not be crushed or chewed, as this affects the extended-release mechanism and absorption. Fatty foods can reduce absorption, so consistent timing with or without food is recommended.

The Initial effects are generally seen after 2 weeks at a stable dose, with full benefit in 2–6 weeks. Doses above 1 mg should be increased gradually and weaned slowly over 2–3 weeks to avoid withdrawal and rebound hypertension.

Monitoring and Side Effects

Blood Pressure and Heart Rate: Check before starting, after each dose change, and after the initial dose; then every 3–6 months; and as determined by the treating clinician. Common Side Effects include drowsiness, dizziness, low blood pressure, headache, abdominal pain, fatigue, and sedation. These are typically most pronounced during titration and often improve with time. Abrupt discontinuation can cause rebound hypertension; tapering is essential for doses above 1 mg.

Atomoxetine (Strattera)

Atomoxetine (brand name: Strattera) is a non-stimulant medication prescribed for attention-deficit hyperactivity disorder (ADHD) in children, adolescents, and adults. It offers an alternative to stimulant medications, particularly for patients who experience undesirable side effects from stimulants or have certain coexisting conditions.

It is most effective for symptoms of impulsivity and hyperactivity, with somewhat less impact on attentional difficulties compared to stimulant medications. For some patients, atomoxetine may be added to stimulant therapy if symptoms are not fully controlled.

Atomoxetine typically takes several weeks to show noticeable effects, with full benefits often seen after 2–3 months of consistent use. It is usually taken once daily in the morning, and its effects last throughout the day and into the evening. Capsules should be swallowed whole and not broken, crushed, or chewed.

The medication should be taken at the same time each day for best results.

Side Effects and Precautions

Common Side Effects include indigestion, nausea, vomiting, stomach pain, constipation, dry mouth, decreased appetite, weight loss, drowsiness or excessive tiredness, dizziness, headache, mood swings and irritability, especially in children and teenagers.

Suicidal thoughts or behaviours, particularly in children, adolescents, and young adults, during the first few months of treatment or after dose changes, are possible. Liver toxicity is a known side effect, and it’s essential to watch for symptoms such as dark urine, yellowing of the skin or eyes (jaundice), upper abdominal pain, or flu-like symptoms. Atomoxetine can also be associated with aggressive behaviour, hostility, or new behavioural problems. It can also be associated with severe allergic reactions, including swelling, rash, or difficulty breathing.

Regular medical follow-up is recommended to monitor for side effects, child growth, and blood pressure and heart rate changes. Patients and families should be alert for any changes in mood or behaviour, especially signs of depression, suicidal ideation, or aggression, and report these promptly to a healthcare provider.

Atomoxetine is a valuable non-stimulant option for managing ADHD, particularly for patients with significant impulsivity and hyperactivity or those who cannot tolerate stimulants. However, it requires careful monitoring for potential psychiatric, hepatic, and cardiovascular side effects. This is not a common medication I use in my clinical practice.