What is the recommended treatment for a patient with low energy, low mood, and motivational anhedonia, with a history of ADHD traits, perimenopause, and caregiver stress, and a PHQ-7 score of 8, already on HRT and with stimulants contraindicated?

Treatment Recommendation for Low Energy, Motivation, and Mood in Perimenopause with ADHD Traits

Start bupropion SR 100-150 mg daily as first-line pharmacotherapy, titrating to 150-300 mg daily based on response, since stimulants are contraindicated and this patient presents with subsyndromal depression (PHQ-7=8), motivational anhedonia, and residual ADHD symptoms. 1, 2

Rationale for Bupropion as Primary Treatment

• Bupropion is the only antidepressant consistently shown to promote weight loss and has proven efficacy for both depression and ADHD symptoms, making it ideal for this clinical presentation where stimulants cannot be used 2

• The American Academy of Child and Adolescent Psychiatry recommends bupropion as a second-line option when stimulants are contraindicated or not tolerated, which directly applies to this case 1

• Bupropion is a norepinephrine and dopamine reuptake inhibitor that has been shown to be more effective than placebo in adults with ADHD 3

• For patients with ADHD and comorbid depressive symptoms where stimulants are not an option, bupropion effectively addresses both conditions simultaneously 1, 4

Dosing Strategy

• Start with bupropion SR 100-150 mg daily or XL at 150 mg daily 1

• Titrate to maintenance doses of 100-150 mg twice daily (SR) or 150-300 mg daily (XL) 1

• Maximum recommended dose is 450 mg per day 1

• Unlike stimulants which work within days, bupropion requires 2-4 weeks to achieve full therapeutic effect, so set appropriate expectations with the patient 1

Monitoring Requirements

• Screen for suicidality, particularly given the comorbid depressive symptoms and caregiver stress 2

• Monitor for common side effects including headache, insomnia, and anxiety, especially during the first 2-4 weeks 1, 2

• Assess response at 4-week intervals using standardized validated instruments to monitor symptom relief, side effects, and satisfaction with treatment 4

• Monitor blood pressure and pulse, though cardiovascular effects are less pronounced than with stimulants 1

Managing Potential Side Effects

• For insomnia (if it emerges), consider low-dose trazodone or non-pharmacological interventions like sleep hygiene education and cognitive behavioral therapy 2

• If anxiety worsens despite no baseline anxiety, consider adjunctive treatments like buspirone augmentation or mindfulness-based stress reduction techniques 2

• The activating properties of bupropion may actually help with the low energy and motivational anhedonia in this case 2

Alternative Non-Stimulant Options if Bupropion Fails

• Atomoxetine (60-100 mg daily) is the only FDA-approved non-stimulant for adult ADHD, though it requires 2-4 weeks to achieve full effect and carries a black box warning for suicidal ideation requiring close monitoring 1

• Alpha-2 agonists (guanfacine 1-4 mg daily or clonidine) are additional options with 2-4 weeks until effects are observed, particularly useful if sleep disturbances emerge 1

• Viloxazine is a newer non-stimulant option that has shown significant efficacy in treating ADHD in adults 3, 2

Augmentation Strategy if Mood Symptoms Persist

• If ADHD-related symptoms improve with bupropion but depressive symptoms persist after 4-6 weeks, add an SSRI to the regimen, as there are no significant drug-drug interactions between bupropion and SSRIs 1

• SSRIs remain the treatment of choice for depression and are weight-neutral with long-term use 1

Treatment Duration

• Continue antidepressant treatment for 4-9 months after achieving satisfactory response in a first episode of major depression, with longer duration for patients with recurrent episodes 4

• Given the chronic caregiver stress (3+ years), plan for extended treatment duration 4

Critical Safety Considerations

• Never use MAO inhibitors concurrently with bupropion due to risk of hypertensive crisis - at least 14 days should elapse between discontinuation of an MAOI and initiation of bupropion 1

• The combination of bupropion with any future stimulant therapy (if contraindication resolves) may increase the risk of seizures, particularly at higher doses of bupropion 1

• Avoid benzodiazepines for any emerging anxiety, as they may reduce self-control and have disinhibiting effects 1

Adjunctive Non-Pharmacological Interventions

• Dialectical Behavior Therapy (DBT) has been modified for adult patients with ADHD and shows decreased ADHD symptoms, improved neuropsychological functioning, and reduction of co-existing anxiety and depression 3

• The four DBT modules address: mindfulness skills (poor concentration), distress tolerance (disorganization), interpersonal effectiveness (caregiver stress management), and emotion regulation (mood symptoms) 3

• Mindfulness interventions during this life transition may improve self-compassion and various dimensions of mindfulness 3

Special Considerations for Perimenopause

• The patient is already on HRT which has helped with vasomotor symptoms - continue this as it provides positive effects on mood, particularly in the younger perimenopausal age group 5

• Combined HRT and antidepressant therapy (like bupropion) has shown high efficacy in relief from menopausal symptoms 6

• HRT has a positive impact on cognition and mood when administered in the perimenopausal or early postmenopausal period, supporting continuation of current HRT 5