In a 14‑year‑old male with 22q11.2 deletion syndrome and mild‑to‑moderate intellectual disability who has catatonia partially improved on lorazepam 0.75 mg every six hours, but remains zoned out, laughing, irritable, with normal laboratory studies, nonspecific electroencephalogram findings, unremarkable magnetic resonance imaging, and essentially normal cerebrospinal fluid, what are the recommended next management steps to return him to baseline?

Next Steps for Partial Catatonia Response in 22q11.2DS

Immediately check pH-corrected ionized calcium, magnesium, parathyroid hormone, and thyroid-stimulating hormone, because hypocalcemia affects 80% of adults with 22q11.2DS and can directly cause the persistent rigidity, irritability, and altered mental status you are observing, even when catatonia is partially treated. 1

Urgent Metabolic Workup

Your patient's incomplete response to lorazepam 3 mg/day—with persistent zoning out, inappropriate laughter, and irritability despite improved motor function—strongly suggests an unaddressed metabolic component rather than inadequate benzodiazepine dosing.

• Obtain pH-corrected ionized calcium immediately, as hypocalcemia mimics and worsens catatonia with rigidity and irritability, and parathyroid dysfunction can manifest at any age in 22q11.2DS regardless of prior endocrine history. 1
• Check magnesium concurrently, because hypomagnesemia frequently co-occurs with hypocalcemia in this population and must be corrected first or calcium replacement will fail. 1, 2
• Measure TSH promptly, since hypothyroidism affects more than 25% of individuals with 22q11.2DS and aggravates neuropsychiatric symptoms. 1
• Obtain a 12-lead ECG when hypocalcemia is detected to assess for QT-interval prolongation, which raises the risk of life-threatening arrhythmias. 1, 3

The 3 white blood cells in CSF and nonspecific EEG findings do not exclude metabolic seizures—hypocalcemia directly lowers the seizure threshold and can cause subtle seizure presentations (behavioral arrest, confusion, transient memory loss) that are easily mistaken for psychiatric phenomena. 1, 2

Calcium and Vitamin D Supplementation

• Start daily calcium and vitamin D supplementation immediately in all patients with 22q11.2DS, regardless of current serum calcium levels, as routine prophylaxis is recommended. 1
• If symptomatic hypocalcemia is confirmed, administer IV calcium gluconate 50–100 mg/kg over 10 minutes under continuous ECG monitoring. 1, 2
• Correct magnesium deficiency before attempting calcium correction, as calcium replacement is futile in severe hypomagnesemia. 2

Benzodiazepine Optimization

Your current lorazepam dose of 3 mg/day is below the threshold for adequate catatonia treatment.

• Increase lorazepam to at least 6 mg/day (1.5 mg four times daily or 2 mg three times daily), as meaningful improvement requires ≥6 mg/day for 4–6 weeks before considering ECT. 1
• Monitor daily for sedation, respiratory depression, and paradoxical agitation while titrating. 1
• The partial motor improvement you observe (skating, reduced rigidity) indicates benzodiazepine responsiveness, but persistent negative symptoms (zoning out, disengagement) and irritability suggest either inadequate dosing or unaddressed metabolic factors.

Seizure Surveillance

• Repeat EEG if clinical suspicion for seizures rises or if neuropsychiatric status deteriorates, because individuals with 22q11.2DS have a four-fold increased risk of epilepsy and subtle seizure presentations can be mistaken for psychiatric phenomena. 1
• Hypocalcemic seizures typically resolve after calcium repletion, but persistent seizures after normalization may necessitate anticonvulsant therapy. 1

Psychiatric Monitoring Without Antipsychotics

• Do not initiate antipsychotics while catatonia is active, as they can exacerbate catatonic features and increase the risk of neuroleptic malignant syndrome. 1
• The inappropriate laughter and zoning out may represent residual catatonic symptoms, emerging psychotic features (10% risk by late adolescence in 22q11.2DS), or metabolic encephalopathy—distinguish these by correcting metabolic abnormalities and optimizing lorazepam first. 1
• Avoid cannabis and other psychoactive substances, as they markedly increase psychosis risk in this genetic condition. 1

Electroconvulsive Therapy Threshold

• Pursue ECT if there is no meaningful improvement after 4–6 weeks of lorazepam ≥6 mg/day or if life-threatening complications arise (severe rigidity, autonomic instability, refusal of nutrition). 1
• Intellectual disability is not a contraindication to ECT in 22q11.2DS, and ECT is highly effective for catatonia in adolescents. 1

Multidisciplinary Coordination

• Designate one clinician to coordinate care among psychiatry, neurology, endocrinology, and primary care to address the complex medical and neuropsychiatric needs. 4, 1
• Incorporate family and caregiver input, as individuals with intellectual disability may have limited ability to self-report symptoms. 1
• Assess sleep quality with polysomnography if not already done, because poor sleep affects overall functioning, behavior, and learning capacities in 22q11.2DS. 4, 1

Common Pitfalls to Avoid

• Do not assume seizures are idiopathic epilepsy without checking calcium levels, especially in new-onset or subtle seizures in adolescents with 22q11.2DS—delayed diagnosis leads to ineffective treatment and preventable morbidity. 2
• Do not rely solely on caregiver report or solely on patient report without directly assessing the child, as discrepancies in functioning between cognitive, adaptive, and emotional domains are common. 4
• Do not overlook anatomical variants or assume normal endocrinological functions in the absence of complaints—routine monitoring of calcium, growth, and thyroid is essential. 4