Table 3.

Review of Select Alternative Pharmacotherapy with Evidence for Management of Self-Injurious Behaviors in Children with Neurodevelopmental Disorders^ab

Alternative Agent	Mechanism of action	Rationale for Use in Self- Injurious Behaviors	Available Data	Specific Neurodevelop mental Disorders Studied	Behaviors Targeted	Ages Studied	Suggested Dosing	Clinical Notes
Allopurinol88	Xanthine oxidase inhibitor; leads to decrease in uric acid	Inborn error of purine metabolism in Lesch-Nyhan syndrome leads to hyperuricemia, which has been associated with SIBc	Case reports, case series (adults)	Lesch-Nyhan syndrome	– SIB – Aggression	54-80 years	Initial dose: 5-10 mg/kg/day Maintenance dose: 200-300 mg/day	Specific to Lesch-Nyhan syndrome
Baclofen89	Gamma-aminobutyric acid analogue; crosses the blood-brain barrier and reduces excitatory stimulus in the cortex and basal ganglia	Some children with NDDsd might be deficient in GABAe	Double-blind, cross-over trial	Nonspecific	– SIB – Aggression	9-37 years	Initial: 10 mg 3 times a day (2.5 mg once daily for young, small, or fragile patients) Titration: Every 3 days to weekly Maintenance: 20-80 mg/day in divided doses (higher doses have been used with prolonged duration)	Patients may develop tolerance
Ecopipam90	Selective D1-dopamine receptor antagonist	Abnormal function of basal ganglia dopamine pathways has been proposed as mechanism of SIB in Lesch-Nyhan syndrome	Phase 1b, nonrandomized, dose-escalation safety study	Lesch-Nyhan syndrome	– SIB	9-52 years	Initial: 12.5 mg/day Titration: Double the dose every 2 days, as tolerated Maintenance: 200 mg/day	Experimental therapy90 Specific to Lesch-Nyhan syndrome
Fluphenazine91	First-generation antipsychotic; D1-receptor antagonist	SIBs in Lesch-Nyhan syndrome may be caused by supersensitivity to dopamine91	Case report of two patients	Lesch-Nyhan syndrome	– SIB	20 months; 15-year-old	Initial: 0.25 mg once daily Titration: Increase by 0.25 mg each week Maintenance: 5 mg divided 1 to 2 times daily
Loxapine92	Medium potency, dibenzoxazepine antipsychotic; D1, D2, D4 antagonist	Proposed to induce changes in cerebral subcortical inhibitory areas of the brain leading to suppression of aggression	Prospective, open-label trial	ASDf	– Irritability	13-65 years	5-15 mg/day (low-dose)	Studied as add-on therapy to various baseline medications Acts like a second-generation antipsychotic at low doses
Pioglitazone93	Potent, selective agonist of peroxisome proliferator-activated receptor-gamma	Crosses the blood brain barrier and may decrease inflammation in the cortex of patients with ASD	Randomized, double-blind, placebo-controlled trial (combination therapy only)	ASD	– Irritability	4-12 years	15 mg twice a day	Substrate of CYPg2C8 (major); CYP3A4 (minor) Pharmacodynamic interactions with hypoglycemic medications
Vitamin B1294	Co-factor of antioxidants; stimulates regeneration of methionine	Physiologic abnormalities such as oxidative stress and inflammation have been associate with symptoms of ASD	Small, pilot, randomized controlled trial; large, randomized controlled trial	ASD	– Nonspecific	3-8 years	64.5 μg/kg subcutaneously every three days	Conflicting outcomes Assess behavioral symptoms in general; primary outcome was overall improvement based on CGI
5-hydroxytryptophan10,95	Precursor for the synthesis of serotonin	Hypoxanthine-guanine phosphoribosyltransferase enzyme deficiency in Lesch-Nyhan syndrome leads to dysfunction of cholinergic and serotonergic systems; increase in 5-hydroxytryptophan synthesis has been proposed to stimulate receptors	Open-label trial; double-blind clinical trial of one patient	Lesch-Nyhan syndrome	– SIB	1-12 years	8 mg/kg	Specific to Lesch-Nyhan syndrome Conflicting outcomes

^aAlternative pharmacologic agents are presented in alphabetical order.

^bData in this table have been compiled and extrapolated from studies discussed in this review as well as the LexiComp and Micromedex databases. Although these dosing recommendations are meant to provide guidance on the usual dosing ranges for these understudied agents, prescribing clinicians should always consult drug information resources and/or consult with a clinical pharmacist for the most up-to-date and patient-specific dosing recommendations when initiating therapy. Clinicians are urged to prescribe the most conservative initial dose, with titration to the lowest effective dose.

^cSelf-Injurious Behaviors

^dNeurodevelopmental Disorders

^eGamma-Aminobutyric Acid

^fAutism Spectrum Disorders

^gCytochrome P450