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.