Why do psychiatrists start lorazepam at 0.75 mg every six hours (total 3 mg per day) for a 14‑year‑old with 22q11.2 deletion syndrome and mild‑to‑moderate intellectual disability presenting with catatonia, and when should the dose be increased?

Why Psychiatrists Start at 3 mg/day Lorazepam (0.75 mg QID) and When to Escalate

Psychiatrists initiate lorazepam at 0.75 mg every 6 hours (3 mg/day total) in this 14-year-old with 22q11.2 deletion syndrome and catatonia because this population requires a "start low, go slow" approach due to heightened medication sensitivity, and the dose should be increased within 24–48 hours if catatonia symptoms persist, targeting a therapeutic range of 6–8 mg/day for adequate catatonia treatment. 1, 2

Initial Dosing Rationale in 22q11.2 Deletion Syndrome

• Patients with 22q11.2DS exhibit increased drug sensitivity and are more prone to side effects, necessitating conservative initial dosing across all psychotropic medications. 1

• The "start low, go slow" principle is explicitly recommended for this genetic syndrome to minimize adverse effects while establishing tolerability. 1, 2

• Intellectual disability (present in this patient) further supports cautious dosing, as children with ID/IDD may be more sensitive to medication side effects, though this reflects dose-response shifts rather than altered drug mechanisms. 1

• The standard FDA-approved dosing for lorazepam suggests 2–3 mg/day in divided doses for anxiety, with a range of 1–10 mg/day, making 3 mg/day a reasonable conservative starting point. 3

When and How to Increase the Dose

Rapid Escalation Protocol (24–48 Hours)

• If catatonia symptoms do not substantially improve within the first 24–48 hours, the lorazepam dose should be increased aggressively, as catatonia is a medical emergency with significant morbidity and mortality risk. 2, 4, 5

• Target therapeutic doses for catatonia are 6–8 mg/day or higher, substantially above the initial 3 mg/day starting dose. 2, 5, 6

• The response to lorazepam in catatonia is typically rapid (10 minutes to 2 hours), so lack of improvement after 24 hours indicates inadequate dosing rather than treatment failure. 4, 5

Specific Escalation Strategy

• Increase the dose by 50–100% every 24–48 hours until catatonia symptoms resolve or side effects (excessive sedation, respiratory depression) emerge. 2, 5

• The evening dose should be increased before daytime doses to minimize daytime sedation while maximizing therapeutic effect. 3

• Monitor closely for response using objective measures: ability to speak (if previously mute), voluntary movement (if previously akinetic), willingness to eat/drink (if previously negativistic). 4, 5

Critical Decision Point: When to Pursue ECT

• If there is no meaningful improvement after 4–6 weeks of adequate-dose lorazepam (≥6 mg/day), electroconvulsive therapy should be pursued as it is highly effective for catatonia. 2

• ECT should be considered earlier (within days) if life-threatening complications develop, including severe rigidity, autonomic instability, refusal of nutrition, or malignant catatonia features. 2, 6

• Intellectual disability is not a contraindication to ECT in this population, and ECT can be safely administered to adolescents. 2

Critical Metabolic Considerations in 22q11.2DS

Hypocalcemia Must Be Ruled Out Immediately

• Approximately 80% of adults with 22q11.2DS have hypocalcemia, which can manifest with rigidity, irritability, and altered mental status that mimic or worsen catatonia. 2

• Obtain ionized calcium, magnesium, phosphorus, PTH, and a 12-lead ECG before attributing all symptoms to catatonia, as hypocalcemia-induced seizures can coexist with or be mistaken for catatonic features. 2

• Hypocalcemic seizures typically resolve after calcium repletion, and treating the metabolic derangement may dramatically improve the clinical picture independent of lorazepam effects. 2

• All patients with 22q11.2DS should receive routine calcium and vitamin D supplementation regardless of current serum levels. 2

Additional Metabolic Screening

• Check TSH immediately, as hypothyroidism affects >25% of adults with 22q11.2DS and can aggravate neuropsychiatric symptoms. 2

• Hypomagnesemia frequently co-occurs with hypocalcemia and should be corrected when identified. 2

Monitoring During Dose Escalation

• Assess daily for sedation, respiratory depression, and paradoxical agitation as lorazepam is titrated upward. 2

• The four-fold increased risk of epilepsy in 22q11.2DS means seizures may be precipitated by hypocalcemia, medications, or physiological stress during the acute catatonic episode. 2

• Subtle seizure presentations (brief behavioral arrest, confusion, transient memory loss) can be mistaken for psychiatric phenomena and require careful observation. 2

Common Pitfalls to Avoid

Underdosing Due to Excessive Caution

• The most common error is maintaining subtherapeutic doses for too long out of concern for side effects in a vulnerable population, when catatonia itself carries substantial mortality risk. 2, 5

• Research demonstrates 85–100% response rates to benzodiazepines in catatonia when adequate doses are used, making treatment failure at low doses a dosing problem, not a medication failure. 4, 7

Premature Introduction of Antipsychotics

• Avoid initiating antipsychotics while catatonia is active, as they can exacerbate catatonic features and increase the risk of neuroleptic malignant syndrome. 2

• If antipsychotics become necessary after catatonia resolves (for underlying psychosis, which affects 10% of adolescents with 22q11.2DS), use the "start low, go slow" approach with heightened vigilance. 2

• If clozapine is eventually required for treatment-resistant psychosis, prophylactic anticonvulsants should be co-prescribed due to the lowered seizure threshold in 22q11.2DS. 2, 8

Failure to Obtain Collateral Information

• Individuals with intellectual disability may have limited ability to self-report symptoms, making family and caregiver input vital for assessing baseline functioning and treatment response. 1, 2

• Relatively good verbal skills may camouflage deficits in receptive language and comprehension, leading to overestimation of the patient's understanding and ability to report symptoms accurately. 1

Alternative Benzodiazepine Strategy

• If lorazepam fails at adequate doses (rare), diazepam infused IV (10 mg in 500 mL normal saline every 8 hours) can be attempted before proceeding to ECT, with 100% response rates reported in combined lorazepam-diazepam protocols. 4, 7

• This escalation to IV diazepam should occur within 24–48 hours of inadequate lorazepam response, not after prolonged trials at subtherapeutic doses. 4, 7