What is the appropriate first‑line pharmacologic treatment for a 14‑year‑old boy with 22q11.2 deletion syndrome and mild‑to‑moderate intellectual disability who has anxiety and a mood disorder?

Pharmacologic Treatment for Anxiety and Mood Disorder in 22q11.2DS

Standard management of anxiety and mood disorders in this 14-year-old with 22q11.2 deletion syndrome should follow general psychiatric treatment principles, but you must first rule out and correct hypocalcemia and thyroid dysfunction before initiating any psychotropic medication. 1

Critical Pre-Treatment Medical Evaluation

Before prescribing any psychiatric medication, you must obtain:

• pH-corrected ionized calcium, magnesium, parathyroid hormone, and phosphorus levels – hypocalcemia is present in approximately 80% of individuals with 22q11.2DS and can manifest with irritability and altered mental status that mimic or worsen psychiatric symptoms 2

• Thyroid-stimulating hormone (TSH) – hypothyroidism affects >25% of individuals with 22q11.2DS and can aggravate neuropsychiatric symptoms 2

• 12-lead ECG if hypocalcemia is detected, to assess for QT-interval prolongation 2

• Comprehensive neuropsychological testing to establish baseline cognitive and adaptive functioning, as certain psychotherapeutic/cognitive-behavioral modalities may not be effective in those with weak verbal/cognitive skills 1

First-Line Pharmacologic Treatment

For anxiety disorders in this adolescent, selective serotonin reuptake inhibitors (SSRIs) represent the standard first-line pharmacologic approach. 1

SSRI Selection and Dosing Strategy

• Start with sertraline or citalopram at the lowest available dose – these agents have established efficacy for anxiety disorders in adolescents 3, 4

• Use a "start low, go slow" titration approach because patients with 22q11.2DS exhibit heightened drug sensitivity 2

• For sertraline: begin at 25 mg daily in adolescents, then titrate in weekly 25-50 mg increments based on clinical response, with a maximum dose of 200 mg/day 4

• For citalopram: the maximum recommended dose is 20 mg/day for patients >60 years, but standard adolescent dosing (starting at 10-20 mg daily) applies to this 14-year-old 3

Critical Monitoring During SSRI Treatment

• Monitor for behavioral activation, increased anxiety, or emergence of suicidal ideation – SSRIs carry a black box warning for increased suicidal thinking in children and adolescents 3, 4

• Assess for serotonin syndrome symptoms (agitation, confusion, tremor, hyperreflexia, autonomic instability) 3, 4

• Regular weight and growth monitoring – decreased appetite and weight loss have been observed with SSRIs in pediatric patients 3, 4

Mood Disorder Considerations

For mood symptoms:

• If depressive symptoms predominate, the same SSRI approach applies, though the evidence base for SSRIs in pediatric depression with 22q11.2DS is limited 3, 4

• If bipolar features are present (elevated mood, decreased need for sleep, grandiosity), SSRIs may precipitate manic episodes and mood stabilizers should be considered instead 5

• Approximately 14% of individuals with 22q11.2DS meet criteria for a mood disorder, with bipolar disorder risk increasing in adolescence 1, 6

Critical Pitfalls to Avoid

Do not initiate antipsychotics for anxiety or mood symptoms alone – antipsychotics should be reserved for psychotic symptoms, as they can cause significant metabolic and neurologic side effects 2

Avoid benzodiazepines as first-line treatment – while they may provide rapid symptom relief, they carry risks of sedation, respiratory depression, paradoxical agitation, and dependence 2

Never overlook substance use screening – cannabis and other psychoactive substances markedly increase psychosis risk in 22q11.2DS and should be strictly avoided 1, 2

Correct hypomagnesemia before attempting calcium correction – calcium replacement will be futile in the presence of severe hypomagnesemia 7

Psychosocial Interventions

Medication should be combined with:

• Stress-reduction strategies – individuals with 22q11.2DS experience greater perceived stress and reduced resilience 2

• Environmental modifications to reduce academic and social demands that exceed the patient's cognitive capacities 1

• Safety planning addressing vulnerability to bullying, exploitation, and poor social judgment 1, 2

• Monitoring of screen time and social media contacts to reduce cyberbullying risk 1

Ongoing Surveillance

Schedule neuropsychiatric reassessment every 3 years – approximately 10% of individuals with 22q11.2DS develop psychotic disorders by late adolescence, with risk increasing to 25-40% over the lifespan 1, 2, 5

Maintain vigilance for prodromal psychotic symptoms (attenuated positive symptoms, social withdrawal, cognitive decline) – 21% of individuals with 22q11.2DS meet criteria for attenuated positive symptom syndrome 8

Continue routine monitoring of calcium, thyroid function, and growth parameters even in the absence of overt complaints 2