What are the prescribing guidelines for Attention Deficit Hyperactivity Disorder (ADHD) medications in adults in Canada?

ADHD Prescribing Guidelines for Adults in Canada

First-Line Pharmacological Treatment

Stimulant medications—specifically methylphenidate and amphetamines (including dexamphetamine, mixed amphetamine salts, and lisdexamfetamine)—are the gold standard first-line pharmacological treatment for moderate to severe ADHD in adults, with response rates of 70-80%. 1

Stimulant Options and Dosing

Methylphenidate:

• Start with 5-20 mg three times daily 1, 2
• Can use extended-release formulations for once-daily dosing to improve adherence 1
• Titrate based on response and tolerability 3

Dexamphetamine:

• Start with 5 mg three times daily, titrate to 20 mg twice daily 1, 2, 4
• Weekly dose escalations recommended during initial titration 4

Mixed Amphetamine Salts:

• Dosing ranges from 12.5 mg/day to 80 mg/day 5
• Typical maintenance doses range from 10-50 mg daily 2

Lisdexamfetamine:

• Start at 30 mg once daily 6
• Titrate weekly by 20 mg increments as tolerated 6
• Maximum dose 70 mg/day 6
• Particularly effective in adults, with meta-analyses suggesting amphetamines may be preferred over methylphenidate for adult ADHD 1

Comparative Efficacy

• Approximately 70% of adults respond to either methylphenidate or amphetamines alone 4
• Nearly 90% respond if both medication classes are tried sequentially 4
• Lisdexamfetamine and mixed amphetamine salts show small-to-moderate effect sizes (SMD -1.06 and -0.80 respectively) for reducing ADHD symptoms 5
• Methylphenidate shows small-to-moderate effects (SMD -0.37 to -0.42) on ADHD symptom reduction 3

Second-Line Pharmacological Treatment

When stimulants are contraindicated, not tolerated, or ineffective, atomoxetine is the primary second-line option recommended by the Canadian ADHD Resource Alliance (CADDRA). 1

Non-Stimulant Options

Atomoxetine:

• Most extensively studied non-stimulant with demonstrated efficacy in adult ADHD 7
• Recommended as second-line by CADDRA guidelines 1
• Particularly useful when substance abuse history exists 4

Bupropion:

• Anecdotally beneficial for adult ADHD 1
• Can be used as monotherapy or added to stimulants for persistent symptoms 2
• Starting dose: 100-150 mg daily (SR) or 150 mg daily (XL) 2
• Maximum dose: 450 mg per day 2
• Critical warning: Avoid concurrent use with MAO inhibitors due to risk of hypertensive crisis 2

Guanfacine Extended-Release:

• Approved in Canada only for children/adolescents aged 6-17 years 1
• Limited data on efficacy in adults 1
• Starting dose: 1 mg once daily, titrate by 1 mg weekly to target range of 1-7 mg/day 1

Other Options with Limited Evidence:

• Clonidine, viloxazine (not available in Canada), tricyclic antidepressants (second-line at best) 1, 2

Treatment Algorithm Based on Clinical Presentation

For Primary ADHD with Mild or No Comorbidities:

1. Begin with stimulant trial (methylphenidate or amphetamine) 2
2. Rapid onset allows quick assessment of response within days 2
3. If first stimulant ineffective, switch to the other class 4
4. If both stimulant classes fail, switch to atomoxetine 7

For ADHD with Comorbid Depression:

1. If depression is severe or primary: Treat depression first 1, 2
2. If depression is less severe or secondary to ADHD: Start with stimulant trial first 1, 2
3. Reduction in ADHD-related functional impairment often improves depressive symptoms 1
4. If ADHD symptoms improve but depression persists, add SSRI or consider bupropion 1, 2
5. No single antidepressant effectively treats both ADHD and depression 1, 2

For ADHD with Comorbid Anxiety:

1. Stimulants remain effective even with comorbid anxiety 1
2. Consider non-stimulants (atomoxetine, guanfacine) if stimulants exacerbate anxiety 4

For ADHD with Substance Use Disorder:

1. Exercise extreme caution with stimulants 1, 2, 4
2. Prefer long-acting formulations with lower abuse potential if stimulants are necessary 2, 4
3. Consider atomoxetine or bupropion as first-line alternatives 4, 7
4. Implement urine drug screening to monitor compliance and detect substance use 2
5. Schedule monthly follow-up visits 2

Monitoring and Safety Considerations

Common Stimulant Side Effects:

• Loss of appetite, insomnia, anxiety 1
• Increased blood pressure and heart rate 2
• Monitor cardiovascular parameters at baseline and during treatment 4

Reasons for Treatment Discontinuation:

• Stimulants are associated with higher attrition due to adverse events (RR 2.69) 5
• Overall retention rates are similar between stimulants and placebo 5

Contraindications and Warnings:

• Never combine MAO inhibitors with stimulants or bupropion due to severe hypertension risk 2
• Avoid stimulants in patients with active substance abuse without close monitoring 1, 2
• Combination of bupropion and stimulants may increase seizure risk at higher doses 2

Psychotherapy Integration

For moderate to severe ADHD, combine pharmacotherapy with psychotherapy for optimal outcomes. 1

Evidence-Based Psychotherapy Options:

Cognitive Behavioral Therapy (CBT):

• Most extensively studied psychotherapy for adult ADHD 1
• Targets executive functioning skills, time management, organization, and planning 1
• Effectiveness increases when combined with medication 1

Mindfulness-Based Interventions:

• Recommended by CADDRA guidelines as non-pharmacologic intervention 1
• 8-week programs (MBCT or MBSR) show improvements in inattention, emotion regulation, executive function, and quality of life 1
• Particularly beneficial during perinatal period for self-compassion and parental self-efficacy 1

Critical Pitfalls to Avoid

• Do not assume bupropion or any single antidepressant will treat both ADHD and comorbid depression effectively 1, 2
• Do not prescribe immediate-release stimulants to patients with substance abuse history without careful risk-benefit assessment 1, 2
• Do not combine MAO inhibitors with stimulants or bupropion 2
• Do not discontinue effective ADHD treatment during pregnancy without weighing risks of untreated ADHD against medication exposure 1
• Do not rely solely on patient self-report for treatment response in adults, as they are unreliable reporters 1