Medications

‘Stimulant’ medications are methylphenidate and dexamfetamine. Atomoxetine and guanfacine are referred to as ‘non-stimulant’. 

Other medications, such as clonidine, imipramine and bupropion, are used off-label for the management of ADHD if the commonly used medications have been ineffective or not tolerated. Monotherapy is the gold standard but occasionally, two medicines are used to achieve symptom control.

Methylphenidate is highly effective, with a response rate of 70-85 per cent in clinical studies. The effects of methylphenidate are apparent very quickly (in a matter of hours) but the full effect may take a few weeks. 

Clinicians may exceed the licensed dose in some patients up to a total daily dose of 2.1mg/kg (maximum of 90mg per day of immediate release or equivalent dose of modified release). This would be off-label but is supported by NICE guidance. 

It is important that Medikinet XL is administered with some food (typically breakfast) to preserve its prolonged release effect. All other preparations can be taken with or without food.

Modified release tablets must be swallowed whole – this can be problematic for patients who find it difficult to swallow solid dosage forms. Capsule preparations may be swallowed whole or opened and the content sprinkled. Due to differences in the release profile of the modified release preparations, they should always be prescribed by brand, even for the ‘12-hour’ preparations which are marketed as bio-equivalent.  

Dexamfetamine is indicated for refractory ADHD and therefore is reserved as a second-line treatment. It is an effective second-line option since 80 per cent of patients who fail to respond to methylphenidate will respond to dexamfetamine. 

Lisdexamfetamine (Elvanse) is a pharmacologically inactive prodrug. Following oral administration, lisdexamfetamine is rapidly absorbed from the gastrointestinal tract and hydrolysed primarily by red blood cells to dexamfetamine, the active drug. 

Onset of action is one to two hours and duration of action is up to 13 hours. The capsule may be swallowed whole; for patients with swallowing difficulties (e.g. younger children), it can be opened and the contents emptied and mixed with a soft food such as yoghurt. Alternatively, it can be mixed with a glass of water or orange juice, stirred and taken immediately.

Atomoxetine (Strattera) provides up to 24 hours’ cover and has less potential for drug abuse, however, a major drawback is that it takes about four weeks to start working and may take up to three months to take full effect. During the start of atomoxetine treatment, the clinician may decide to overlap with methylphenidate and then slowly withdraw the latter. 

The safety of atomoxetine has been studied to 1.8mg/kg/day but evidence for efficacy above 1.2mg/kg/day is lacking. Atomoxetine should be given once daily in the morning. If tolerability or response is not satisfactory, the dose can be split to be given in the morning and late afternoon or early evening.  

Guanfacine (Intuniv) provides up to 24 hours’ cover. Its onset of action is quicker than atomoxetine (around three weeks) but weekly dose titration of 1mg to an optimal dose takes time and requires weekly blood pressure and pulse check with each change. Dose reductions need to be gradual. Dosing is based on patient’s weight with the maintenance dose ranging between 0.05- 0.12mg/kg/day rounded up to the nearest dosage form available.

Melatonin is a hormone thought to regulate our wake-sleep cycle. Melatonin may be prescribed in patients with ADHD if their insomnia is causing daytime impairment. Typically, doses of between 1-10mg at night are utilised to help initiate or maintain sleep. Rarely, higher doses of up to 14mg have been used. 

The range of melatonin preparations licensed in under-18s and specifically for ADHD is an area of growth. Adaflex tablets is a recent example, and a licensed liquid preparation is going to enter the market soon.