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5. Pharmacological interventions

5.1 Starting and managing pharmacological interventions

Clinical Questions

1. What principles should clinicians follow when discussing decisions to start, adjust, or discontinue pharmacological treatment for people with ADHD?
2. Which clinicians should initiate pharmacological therapy, and continue it long term?
3. How should initial medications be titrated

Clinical practice gaps, uncertainties and need for guidance

While there are universal principles for starting, adjusting and discontinuing pharmacological treatments, guidance specific to people with ADHD is needed. Anecdotally there are inconsistencies in approaches to starting, adjusting and discontinuing pharmacological treatments in Australia. There is a need for a clear approach for commencing and managing pharmacological treatment for people with ADHD.

Summary of evidence review

An evidence review (update of NICE 2018) was conducted to explore what principles clinicians should follow when discussing decisions to start, adjust, or discontinue pharmacological treatment for people with ADHD Whilst new evidence was found, it was not integrated because the NICE analysis was already deemed to have reached saturation of thematic data. NICE identified 69 studies and conducted a qualitative review of the views of people with a lived experience of ADHD and their families. Saturation in themes was reached after five themes were identified. Clinicians should be aware of these themes in order to improve outcomes for people with ADHD and adequately support them through the pharmacological treatment process (see below).

Theme 1. Starting pharmacological treatment

For children and adolescents, there was a need for parental acceptance of the ADHD diagnosis and awareness that parental decisions on starting medication treatment were influenced by others. Parental decision-making was based on what was ‘best for the child’.

Some parents decided to use medication as a treatment option for their child’s ADHD when symptoms were severe, and it was the ‘last resort’. Strong relationships and communication by clinicians with people with ADHD and/or their parents, including providing sufficient information, could reduce delays in the initiation of medication. Some parents expressed concerns about using medication as a treatment for their child’s ADHD, such as harmful side effects. Delays in accessing services resulted in delayed initiation of treatment.

Theme 2. Monitoring pharmacological treatment

Parents regularly revisited the decision to use medication as a treatment option for their child’s ADHD. Some people with ADHD and parents of children with ADHD were reported to adjust ADHD medications, sometimes without consulting clinicians. This mainly included decreasing dosage due to side effects, experimenting with dosages to find the optimal balance between benefits and side effects, and some had periods of stopping medication used without consulting with a clinician, often due to adverse events.

This theme also identified a reluctance of some healthcare professionals regarding prescribing medication. For example, general practitioners were sometimes reluctant to prescribe ADHD medication for children.

Diversion of medications to substance misuse was another subtheme. Some people reported being approached by others wanting to take their medication, and clinicians should provide education regarding this potential occurrence.

Theme 3. Decision-making about pharmacological treatment

People involved in medication treatment decisions often had conflicting opinions about commencing, adjusting and changing medication treatment. This included different opinions between family members, the person with ADHD, and clinicians. The sharing of decision-making was varied with broad experiences across parents and people with ADHD. As adolescents matured, they became increasingly involved in medication treatment decisions.

Theme 4. Stopping pharmacological treatment

This included people discontinuing medication due to side effects or when side effects outweighed the benefit of medication. People discontinued pharmacological treatment if they felt it changed their ‘sense of self’ and caused a loss of identity. Clinicians were not necessarily informed when medication was stopped, and people expressed not having adequate support during cessation periods. Negative experiences with the healthcare system also resulted in medication discontinuation. People often wished to experience their life without medication for a period of time to decide whether to discontinue.

Theme 5. The experience of medication

People developed individual ways of interpreting the balance of benefits of treatment and side effects. A range of benefits and side effects were described, as was a loss of identity for some when taking medication. People expressed worries/concerns regarding the long-term impact of medication and addiction. Stigma from taking medication was experienced by people with ADHD. Children demonstrated an understanding of why they were taking medication.

Summary of narrative review

In titrating initial medication, different schedules have been used to optimise the dose. For methylphenidate therapy in children, titration to the maximum dose (Wang et al., 2007) and a fixed dose regimen (Mohammadi, Hafezi, Galeiha, Hajiaghaee, & Akhondzadeh, 2012) with consideration of body weight (Simonoff et al., 2013) have been used. A similar approach (bodyweight-based maximum dose estimation) has also been followed in studies involving adult participants (Biederman et al., 2006; Kooij et al., 2004) for standard-release and osmotic-release oral preparations (Biederman et al., 2010) and a fixed-dose regimen.

Different dosing methods have also been observed in studies on dexamfetamine preparations (Adler et al., 2009; Biederman, Mick, Spencer, Surman, & Faraone, 2012), clonidine (Jain, Segal, Kollins, & Khayrallah, 2011; Nair & Mahadevan, 2009), guanfacine (Scahill et al., 2001; Scahill et al., 2015; Taylor & Russo, 2001) and atomoxetine in children (Takahashi et al., 2009; Wehmeier et al., 2012) and adults (Durell et al., 2013; Wernicke et al., 2004). Studies have varied with respect to the duration of dose titration. All studies used pre-defined clinical outcomes and rated adverse effects. In a meta-analysis including 11 randomised controlled trials (RCTs) and 38 cohort studies on maximum-dose titration and safety, variations existed in the maximum treatment doses used, with lack of justification for a given dosing approach in some studies (Ching, Eslick, & Poulton, 2019).

According to NICE (2018), during the titration phase, ADHD symptoms, impairment and adverse effects should be recorded at baseline and at each dose change on standard scales by the person with ADHD, and in children, their parents and teachers, and progress regularly reviewed (for example, by telephone contact) with a specialist.

NICE recommends titration of the dose against symptoms and adverse effects until dose optimisation is achieved, that is, reduced symptoms, improvements in education, employment and relationships, with tolerable adverse effects. Dose titration should be slower and monitoring more frequent if any of the following are present in people with ADHD – other neurodevelopmental disorders (for example, autism spectrum disorder, tic disorders, learning disability [intellectual disability]), mental health disorders (for example, anxiety disorders [including obsessive-compulsive disorder], schizophrenia or bipolar disorder, depression, personality disorder, eating disorder, post-traumatic stress disorder, substance misuse), physical health disorders (for example, cardiac disease, epilepsy or acquired brain injury).

The Canadian Paediatric Guidelines (CADDRA, 2018) recommend that ADHD medication dose adjustments need to occur while monitoring therapeutic goals and side effects. These treatment goals should be monitored with standardised questionnaires and checklists completed by parents and older children (self-rating) for baseline scores and teachers for baseline and follow-up scores or self-reported by adults with ADHD. Teacher observations are important for monitoring treatment response. Dosing should be individualised based on response to careful titration to identify the optimum dose, not on the severity of presentation or (solely) on the person’s age or size. Close monitoring is essential until medication effectiveness and tolerability have been optimised.

When the initial dose is tolerated but not effective, small increments may be made at weekly, biweekly or monthly intervals until symptoms are improved or adverse effects appear. When dosage response has been optimised, monitoring every few months helps ensure the dose remains appropriate and can be adjusted as necessary. Dose adjustments must be closely tied to reports of benefits or adverse effects from the person with ADHD and/or their families and teachers.

Evidence-to-recommendation statement

Qualitative evidence highlights the experiences and needs of people with ADHD, children with ADHD and their parents when making decisions around treatment and discontinuation decisions. Evidence highlights the need to provide adequate information about the benefits and side effects of medication treatment and address any concerns around long-term effects.

Careful management of side effects and benefits is needed, particularly as these will impact adherence (see section 5.4). Evidence also highlights the need for joint decision-making for treatment planning, with this principle reflected throughout this guideline. Evidence highlights the difficulty parents may experience with decision-making around medication treatment and the need to regularly review their decision. The need to involve children and adolescents in decision-making is also reflected in the evidence reviewed and is another principle of this guideline.


Clinical considerations for implementation of the recommendations

State-based regulations will determine who should initiate pharmacological therapy (see also Principles and Assumptions). Generally, paediatricians and child psychiatrists may prescribe for persons under 18 years of age. For adults, psychiatrists are primarily authorised to prescribe psychostimulants.

In some circumstances, such as in regional/rural settings where there is no access to specialists, a general practitioner with appropriate training and authorisation may be authorised to initiate psychostimulant medication. It is noted that specialists with the appropriate expertise are best placed to determine the dosing requirement for their individual clients and as such no dosing recommendations have been included.

Assessment, discussion of options, development of a treatment plan, initiation of treatment, titration and stabilisation are all legitimate and necessary roles for a medical specialist working with individuals with ADHD. Medical practitioners may be assisted by other professionals in monitoring to decrease the frequency needed for medical appointments without compromising the quality of information about improvements and adverse events.

Australian paediatricians see more children and adolescents with ADHD than those with any other condition. Children and adolescents with ADHD are more likely to be treated by paediatricians in private settings than in public settings (Efron, Davies, & Sciberras, 2013). Adults are most commonly supported by psychiatrists in the private sector. This can result in significant out-of-pocket costs to access medication treatment.

There are also significant bottlenecks and delays in accessing experienced adult ADHD psychiatrists due to few being specialised in adult ADHD diagnosis and treatment in Australia. This results in health inequity for many Australians with ADHD. Workforce development may ensure that health inequity impacts are minimised.

Next 5.2 Medication choice