How should I manage a 22-year-old patient with attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), generalized anxiety disorder (GAD), severe vitamin D deficiency, mild subclinical hypothyroidism (elevated thyroid‑stimulating hormone [TSH]), and iron deficiency?

Management of a 22-Year-Old with ADHD, MDD, GAD, Severe Vitamin D Deficiency, Subclinical Hypothyroidism, and Iron Deficiency

Initiate high-dose vitamin D supplementation (50,000 IU weekly for 8 weeks), start levothyroxine 25 mcg daily for the elevated TSH, replace iron stores, and optimize psychiatric treatment with FDA-approved stimulant medication for ADHD combined with an SSRI for depression/anxiety, as these metabolic abnormalities directly worsen executive function, mood, and attention symptoms. 1, 2, 3, 4

Immediate Metabolic Corrections

Vitamin D Deficiency (Level 9 ng/mL)

• Severe deficiency at 9 ng/mL requires aggressive repletion with 50,000 IU vitamin D weekly for 8 weeks, followed by maintenance dosing of 1,000-2,000 IU daily. 5
• Vitamin D deficiency is directly associated with elevated anxiety, depression, and internalizing problems in patients with neurodevelopmental conditions, and correction may reduce psychiatric symptom burden. 5
• Recheck 25-OH vitamin D levels 8 weeks after initiating supplementation to confirm adequate repletion (target >30 ng/mL). 5

Subclinical Hypothyroidism (TSH 4.579 mIU/L)

• Start levothyroxine 25 mcg daily given the TSH in the upper quartile of normal range, which is associated with worsened executive function deficits, increased inattention, cognitive slowing, and elevated ADHD symptoms. 1, 6
• TSH concentrations in the upper quartile of the normal range (even when technically "normal") are associated with lower cognitive function, higher risk for attention deficit symptoms, and decreased memory and quantitative skills in young adults. 6
• In patients at risk for hyperactivity, start at one-fourth the recommended full replacement dosage (approximately 6.25-12.5 mcg daily) and increase weekly by one-fourth until reaching 25-50 mcg daily to minimize risk of exacerbating hyperactive symptoms. 2
• Monitor TSH and free T4 at 6-8 weeks after initiation, then adjust dosage to normalize TSH to lower half of reference range (0.5-2.5 mIU/L). 2
• TSH elevation within the normal reference range (≥upper 25th percentile) is positively associated with recurrent depression, higher number of depressive episodes, and increased suicide attempts in patients with major depression. 7

Iron Deficiency (Iron 33 mcg/dL)

• Initiate oral iron supplementation with ferrous sulfate 325 mg (65 mg elemental iron) daily on an empty stomach, as iron deficiency worsens restless symptoms, fatigue, and cognitive function. 1
• Recheck serum iron, ferritin, and complete blood count in 8-12 weeks to assess response and guide continued supplementation.

Psychiatric Medication Optimization

ADHD Treatment

• Prescribe FDA-approved stimulant medication as first-line treatment (methylphenidate 18 mg extended-release or lisdexamfetamine 20-30 mg once daily), as stimulants achieve 70-80% response rates and have the largest effect sizes from over 161 randomized controlled trials. 3, 4
• Titrate methylphenidate by 18 mg weekly up to 54-72 mg daily maximum, or lisdexamfetamine by 10-20 mg weekly up to 70 mg daily maximum, based on symptom response and tolerability. 4
• Obtain baseline blood pressure and pulse before initiating stimulants, then monitor at each dose adjustment and quarterly during maintenance. 4
• Screen for substance use at baseline and monitor throughout treatment, as untreated ADHD increases risk for substance use disorders, early death, suicide, lower educational achievement, and incarceration. 8, 1

Depression and Anxiety Treatment

• If depressive/anxiety symptoms persist after 4-6 weeks of optimized ADHD treatment, add an SSRI (sertraline 25-50 mg daily, titrating to 100-200 mg daily) to the stimulant regimen, as there are no significant drug-drug interactions and this combination is well-established. 4
• SSRIs remain the treatment of choice for depression and anxiety, are weight-neutral with long-term use, and can be safely combined with stimulants. 4
• Do not assume a single antidepressant will effectively treat both ADHD and depression—no single antidepressant is proven for this dual purpose, requiring separate targeted treatments. 4

Treatment Sequencing Algorithm

• Begin with stimulant monotherapy for ADHD, as treatment of ADHD alone may resolve comorbid depressive or anxiety symptoms in many cases without additional medication, and stimulants work rapidly (within days) allowing quick assessment of efficacy. 4
• If ADHD symptoms improve but depression/anxiety remain at moderate-to-severe levels after 4-6 weeks, add SSRI to stimulant regimen rather than switching medications. 4
• Treat depression first only if it is severe with suicidal ideation or psychotic features; otherwise, prioritize ADHD treatment as functional impairment from untreated ADHD persists despite mood improvement. 3, 4

Comprehensive Behavioral Interventions

• Implement cognitive-behavioral therapy (CBT) specifically developed for ADHD as the most extensively studied psychotherapy, with increased effectiveness when combined with medication for treating ADHD with comorbid depression and anxiety. 4
• Parent training in behavior management (if living with family) and behavioral interventions addressing organizational skills, time management, and emotion regulation are essential components. 3
• Manage this patient following chronic care model principles with ongoing monitoring for emergence of new comorbidities, bidirectional communication with educational/occupational settings, and periodic re-evaluation of treatment effectiveness. 8, 1

Critical Monitoring Parameters

Ongoing Surveillance

• Screen for suicidality at every visit, particularly during the first few months of SSRI treatment or at dose changes, as both depression and ADHD medications carry monitoring requirements. 4
• Monitor blood pressure, pulse, weight, sleep quality, and appetite at each visit during stimulant titration, then quarterly during maintenance. 4
• Reassess TSH and free T4 every 6-8 weeks until stable, then every 6-12 months or with any change in clinical status. 2
• Track functional improvement across home, work/school, and social settings using standardized rating scales. 3

Red Flags Requiring Immediate Attention

• Never use MAO inhibitors concurrently with stimulants or bupropion due to risk of hypertensive crisis; maintain at least 14-day washout period. 4
• Avoid stimulants if uncontrolled hypertension, symptomatic cardiovascular disease, or active psychosis develops. 4
• If manic or hypomanic symptoms emerge, immediately discontinue stimulants and refer to psychiatry, as stimulants can precipitate mood episodes in patients with underlying bipolar vulnerability. 4

Common Pitfalls to Avoid

• Do not delay ADHD treatment while waiting for metabolic abnormalities to fully correct—initiate concurrent treatment of all conditions, as thyroid dysfunction and vitamin D deficiency exacerbate but do not contraindicate stimulant therapy. 1, 6
• Do not use bupropion as first-line treatment for ADHD—it is explicitly positioned as second-line, to be considered only when two or more stimulants have failed or caused intolerable side effects. 4
• Do not prescribe benzodiazepines for anxiety in this population, as they may reduce self-control, have disinhibiting effects, and are not recommended for chronic anxiety treatment in ADHD patients. 4
• Do not assume current 22q11.2DS guidelines apply to this patient unless genetic testing confirms this diagnosis—the provided evidence on 22q11.2DS is not relevant to a typical 22-year-old with ADHD, MDD, and GAD. 8