What is the optimal management for catatonia in a 14‑year‑old male with 22q11.2 deletion syndrome (22q11.2DS) and mild‑to‑moderate intellectual disability who has been treated with lorazepam 2 mg daily increased to 3 mg daily after 7 days with slow improvement, poor appetite, and normal laboratory studies, magnetic resonance imaging, and electroencephalogram?

Management of Catatonia in a 14-Year-Old with 22q11.2DS

Immediate Action: Continue and Escalate Lorazepam

Continue escalating lorazepam beyond 3 mg daily, as slow progress after 7 days is expected and does not indicate treatment failure—patients with chronic or severe catatonia may require higher doses (up to 6-8 mg daily or more) and longer treatment duration (weeks to months) to achieve full recovery. 1, 2

Rationale for Continued Benzodiazepine Therapy

• Lorazepam remains the first-line treatment for catatonia even in patients with intellectual disability and 22q11.2DS, with documented efficacy in both acute and chronic presentations 1, 2
• A case series of mentally retarded brothers with catatonia demonstrated that one patient with 5 years of chronic catatonia responded gradually over 5 months with higher lorazepam doses, eventually achieving full recovery and hospital discharge after 1 year of treatment 1
• Patients who do not respond immediately may require longer courses or higher doses rather than switching to alternative treatments 1
• The 13-case series of 22q11.2DS patients with catatonia supports benzodiazepine responsiveness in this specific population 2

Dosing Strategy

• Increase lorazepam by 1-2 mg every 3-7 days as tolerated, targeting 6-8 mg daily in divided doses 1
• Monitor closely for sedation, respiratory depression, and paradoxical agitation during titration 3
• Expect gradual improvement over weeks to months rather than immediate resolution 1

Critical Metabolic Workup (If Not Already Completed)

Immediately obtain pH-corrected ionized calcium, magnesium, parathyroid hormone, phosphorus, and creatinine levels, as hypocalcemia occurs in 80% of adults with 22q11.2DS and can present with neuropsychiatric symptoms including rigidity, irritability, and altered mental status that mimic or worsen catatonia. 4, 3

Hypocalcemia Management

• Hypocalcemia can trigger symptoms at any age in 22q11.2DS, even without prior history, due to underlying parathyroid dysfunction 4
• If ionized calcium is low, treat emergently with IV calcium gluconate 50-100 mg/kg over 10 minutes under continuous ECG monitoring 3
• Obtain 12-lead ECG to evaluate for QT prolongation, which increases risk of life-threatening arrhythmias 3
• Initiate daily calcium and vitamin D supplementation regardless of current calcium levels 4, 3

Additional Endocrine Evaluation

• Check thyroid function (TSH) immediately, as hypothyroidism affects >25% of adults with 22q11.2DS and can exacerbate psychiatric and neuropsychiatric symptoms 4, 3
• Check magnesium levels and supplement if low, as hypomagnesemia is associated with hypocalcemia in 22q11.2DS 4

Seizure Monitoring and Management

Maintain high vigilance for clinical or subclinical seizures, as 22q11.2DS patients have 4-fold increased epilepsy risk and seizures can be provoked by hypocalcemia, medications, or stress—the EEG finding of right temporal abnormalities, though reported as "clinically insignificant," warrants closer monitoring given this patient's syndrome. 4, 3

• Seizures in 22q11.2DS can present with subtle symptoms including behavioral arrest, confusion, or memory loss that may be misinterpreted as psychiatric symptoms 4
• Hypocalcemic seizures generally resolve with calcium supplementation but may require anticonvulsants if they persist after normalization of calcium 4
• Consider repeat EEG if clinical suspicion for seizures increases or if neuropsychiatric symptoms worsen 4

Addressing Poor Appetite and "Non-Life" Feelings

Nutritional Support

• Poor appetite may reflect catatonic features, underlying depression, or metabolic derangements (hypocalcemia, hypothyroidism) 3
• Ensure adequate caloric intake through high-calorie supplements or nasogastric feeding if oral intake becomes critically insufficient
• Monitor weight and hydration status closely

Psychiatric Assessment

• The description of feeling "non-life" suggests depersonalization, derealization, or negative symptoms that can occur in catatonia, emerging psychosis, or severe depression 2, 5
• Continue close psychiatric monitoring for evolution of psychotic symptoms, as 10% of 22q11.2DS patients develop psychosis by late adolescence and 25-40% develop it over their lifetime 3, 6, 2
• Differentiate catatonic symptoms from emerging psychosis through careful serial examinations and collateral history from caregivers 4, 2

When to Consider Electroconvulsive Therapy (ECT)

If there is no meaningful improvement after 4-6 weeks of adequate-dose lorazepam (≥6 mg daily) or if the patient develops life-threatening complications (refusal to eat/drink, severe rigidity, autonomic instability), proceed to ECT consultation, as ECT is highly effective for catatonia and can be safely administered in adolescents. 2

• ECT should not be delayed in malignant or life-threatening catatonia
• The presence of intellectual disability is not a contraindication to ECT

Antipsychotic Considerations

Avoid initiating antipsychotics while catatonia is active, as they can worsen catatonic symptoms and increase risk of neuroleptic malignant syndrome; if antipsychotics become necessary after catatonia resolves (for psychosis), use a "start low, go slow" approach with the lowest effective dose due to heightened drug sensitivity in 22q11.2DS. 4, 3, 6

• 22q11.2DS patients experience higher rates of medical comorbidities (cardiac arrhythmias, seizures, movement disorders) that complicate antipsychotic use 6
• Poor tolerability rather than poor clinical response drives antipsychotic switching in this population 6
• If clozapine is eventually needed for treatment-resistant psychosis, use prophylactic anticonvulsants given the lowered seizure threshold in 22q11.2DS 4

Ongoing Monitoring and Support

Multidisciplinary Coordination

• Ensure close collaboration between psychiatry, neurology, endocrinology, and primary care 4, 3
• Obtain collateral information from family and caregivers, as patients with intellectual disability may have difficulty articulating symptoms 4
• Conduct comprehensive neuropsychological assessment once catatonia resolves to establish baseline cognitive functioning and differentiate catatonic effects from underlying developmental issues 3

Environmental and Psychosocial Factors

• Individuals with 22q11.2DS may perceive more stress and have less resilience to change than others 4
• Implement stress-reduction strategies and avoid psychoactive substances (especially cannabis, which increases psychosis risk) 4, 3
• Address potential safety concerns including exploitation, bullying, and poor social judgment related to intellectual disability and concrete thinking 4

Sleep Evaluation

• Consider polysomnography if sleep disturbances are suspected, as sleep-disordered breathing is common in 22q11.2DS and can worsen neuropsychiatric symptoms 3

Common Pitfalls to Avoid

• Premature discontinuation of lorazepam: Do not abandon benzodiazepine therapy after only 7 days with "slow progress"—continue escalating dose and allow weeks to months for response 1
• Missing hypocalcemia: Always check ionized calcium in any 22q11.2DS patient with neuropsychiatric symptoms, as it can occur at any age and mimic psychiatric illness 4, 3
• Introducing antipsychotics too early: Antipsychotics can worsen active catatonia; reserve for post-resolution psychosis management 4, 6
• Overlooking seizures: Subtle seizures may present as confusion or behavioral changes rather than convulsions in 22q11.2DS 4
• Underestimating treatment duration: Chronic or severe catatonia may require months of lorazepam therapy for full recovery 1