What are the next step recommendations for an adolescent patient with anxiety and Attention Deficit Hyperactivity Disorder (ADHD) on Strattera (atomoxetine) and Remeron (mirtazapine), who is sleeping better but still experiencing anxiety?

Management of Persistent Anxiety in an Adolescent on Strattera and Remeron

Add an SSRI, specifically sertraline 25 mg daily for one week then increase to 50 mg daily, as the first-line pharmacologic intervention for this adolescent's persistent anxiety, while simultaneously initiating cognitive behavioral therapy (CBT) for combined treatment. 1, 2

Rationale for Adding an SSRI

• SSRIs are the evidence-based first-line treatment for anxiety disorders in adolescents, with sertraline specifically recommended by the American Academy of Child and Adolescent Psychiatry for generalized anxiety disorder, social anxiety disorder, separation anxiety, and panic disorder 1

• While atomoxetine (Strattera) effectively treats ADHD and has some anxiolytic properties, it is not sufficient as monotherapy for primary anxiety disorders 3, 4

• Mirtazapine (Remeron) has improved sleep but is not a guideline-recommended treatment for anxiety disorders in adolescents; it lacks the robust evidence base that SSRIs possess 5

Specific SSRI Dosing Protocol

• Start sertraline at 25 mg daily for the first week to minimize initial anxiety or agitation, then increase to 50 mg daily after week 1 2

• Target therapeutic dose range is 50-200 mg/day, with dose increases every 1-2 weeks in small increments as tolerated 1, 2

• Allow 6-12 weeks at therapeutic dose before declaring treatment failure, as statistically significant improvement may begin by week 2, clinically significant improvement by week 6, and maximal benefit by week 12 1, 2

Critical Monitoring Requirements

• Monitor closely for suicidal thinking and behavior, especially in the first months and after dose changes, with pooled risk of 1% versus 0.2% placebo (NNH = 143) 2

• Common early side effects include nausea, headache, insomnia, nervousness, and initial anxiety/agitation, which typically resolve with continued treatment 2

• The bidirectional relationship between sleep and anxiety means improved sleep (already achieved with mirtazapine) should facilitate anxiety treatment response 5

Essential Combination with Psychotherapy

• Combining sertraline with CBT provides superior outcomes to either treatment alone for anxiety disorders in adolescents, as demonstrated in the Child-Adolescent Anxiety Multimodal Study 1, 2

• Recommend 12-20 structured CBT sessions targeting anxiety-specific cognitive distortions and exposure techniques 2

• Individual CBT is preferred over group therapy for superior clinical effectiveness 2

Alternative SSRI Options if Sertraline Not Tolerated

• Escitalopram 10-20 mg/day or fluoxetine 20-40 mg/day are reasonable alternatives 2

• Avoid paroxetine and fluvoxamine due to higher discontinuation syndrome risk and potentially increased suicidal thinking compared to other SSRIs 2

Addressing the Current Medication Regimen

• Continue atomoxetine (Strattera) for ADHD management, as it is particularly useful for patients with comorbid anxiety and does not exacerbate anxiety symptoms like stimulants might 6, 7, 4

• Atomoxetine combined with an SSRI is well-tolerated, though monitor for additive effects on blood pressure and pulse 3

• Consider whether mirtazapine remains necessary once the SSRI reaches therapeutic effect, as SSRIs can address both anxiety and sleep when optimized 1

Common Pitfalls to Avoid

• Do not escalate SSRI doses too quickly—allow 1-2 weeks between increases to assess tolerability and avoid overshooting the therapeutic window 2

• Do not abandon treatment before 12 weeks, as full response requires patience due to the logarithmic response curve of SSRIs 2

• Do not use benzodiazepines for chronic anxiety management in adolescents due to concerns about disinhibition, dependence, and potential worsening of long-term outcomes 5

• Do not discontinue sertraline abruptly if it becomes necessary to stop; taper gradually to avoid withdrawal symptoms 2

Expected Timeline and Outcomes

• Expect initial improvement in anxiety symptoms by week 2, clinically meaningful improvement by week 6, and maximal benefit by week 12 1, 2

• Continue SSRI therapy for a minimum of 9-12 months after achieving remission to prevent relapse 2

• The combination of improved sleep (already achieved), ADHD control (with atomoxetine), and targeted anxiety treatment (with SSRI + CBT) addresses all three domains affecting this adolescent's quality of life 5