# Pediatric Psychopharmacology Principles

## Introduction

Prescribing psychotropic medications to children and adolescents requires an understanding of developmental pharmacology, the limited evidence base for many off-label uses, and the particular importance of combining pharmacotherapy with psychosocial interventions. This lecture reviews core principles, FDA-approved indications, and safety considerations unique to pediatric psychopharmacology.

## General Principles

### Developmental Pharmacokinetics

Children have **higher hepatic metabolic rates** relative to body weight than adults, often requiring weight-adjusted doses that are proportionally higher. Renal clearance is increased in children, affecting drug elimination. Phase I metabolism (CYP enzymes) matures at different rates; CYP3A4 and CYP2D6 reach adult activity by ages 1-2 years. **Body composition changes** during puberty alter volume of distribution for lipophilic drugs. Adolescents may have unpredictable pharmacokinetics during rapid growth.

### Prescribing Philosophy

Use medication only when the severity of the condition warrants it and when psychosocial interventions alone are insufficient. **Start low, go slow** but treat to target. Monotherapy is preferred; polypharmacy should be minimized. Set clear, measurable treatment goals before initiating medication. Engage both the child and the parent/caregiver in shared decision-making.

![Decision framework for initiating psychotropic medication in pediatric patients](images/pediatric-prescribing-framework.png)

## FDA-Approved Medications by Indication

| Indication | FDA-Approved Agent(s) | Minimum Age | Key Trial Evidence |
|------------|----------------------|-------------|-------------------|
| ADHD | Methylphenidate, amphetamine salts, lisdexamfetamine | 3-6+ | MTA Study |
| ADHD (non-stimulant) | Atomoxetine, guanfacine XR, clonidine XR, viloxazine | 6+ | Multiple RCTs |
| MDD | Fluoxetine | 8+ | TADS trial |
| MDD | Escitalopram | 12+ | Wagner et al. 2006 |
| GAD | Duloxetine | 7+ | Strawn et al. |
| OCD | Fluvoxamine, fluoxetine, sertraline, clomipramine | 6-10+ | POTS trial |
| Bipolar mania | Lithium, aripiprazole, quetiapine, risperidone, olanzapine | 7-13+ | Multiple RCTs |
| Irritability in ASD | Risperidone, aripiprazole | 5-6+ | RUPP Autism Network |
| Schizophrenia | Several SGAs (aripiprazole, quetiapine, others) | 13+ | Multiple RCTs |

### ADHD

**Stimulants**: methylphenidate (age 6+), mixed amphetamine salts (age 3+), lisdexamfetamine (age 6+) **Non-stimulants**: atomoxetine (age 6+), guanfacine XR (age 6+), clonidine XR (age 6+), viloxazine (age 6+)

### Depression

**Fluoxetine**: FDA-approved for MDD in children age 8+. **Escitalopram**: approved for MDD in adolescents age 12+. Other SSRIs are frequently used off-label.

### Anxiety Disorders

**Duloxetine**: approved for generalized anxiety disorder in children age 7+. SSRIs (sertraline, fluoxetine, fluvoxamine) have strong evidence from the CAMS and RUPP studies but limited FDA approvals for pediatric anxiety.

### OCD

**Fluvoxamine** (age 8+), **fluoxetine** (age 7+), **sertraline** (age 6+), **clomipramine** (age 10+)

### Bipolar Disorder

**Lithium** (age 7+ for acute mania), **aripiprazole** (age 10+), **quetiapine** (age 10+), **olanzapine** (age 13+), **risperidone** (age 10+)

### Irritability in ASD

**Risperidone** (age 5+) and **aripiprazole** (age 6+)

### Psychosis

Several second-generation antipsychotics are approved for schizophrenia in adolescents aged 13+.

## Safety Monitoring

### Antidepressants

FDA **black box warning** for suicidality in youth under 25. Close follow-up: weekly for 4 weeks, biweekly for 4 weeks, then monthly. Monitor for behavioral activation, agitation, and emergent manic symptoms.

### Stimulants

Monitor **height, weight, appetite, blood pressure, and heart rate** at each visit. Assess for tics, mood changes, and sleep disruption. Growth velocity may be reduced by 1-2 cm/year; consider drug holidays if growth concerns arise. Obtain cardiac history; ECG if family history of sudden death or structural heart disease.

### Antipsychotics

**Metabolic monitoring**: fasting glucose, lipid panel, weight/BMI, waist circumference at baseline, 3 months, then annually. Monitor for **extrapyramidal symptoms (EPS)** and tardive dyskinesia using the AIMS scale. Prolactin elevation is particularly common with risperidone; monitor for gynecomastia and menstrual irregularities. Children and adolescents are **more susceptible to weight gain** from antipsychotics than adults.

### Mood Stabilizers

**Lithium**: monitor renal function, thyroid function, and serum levels; ensure adequate hydration. **Valproate**: monitor LFTs, CBC, and valproate levels; contraindicated in females of reproductive potential without effective contraception (teratogenicity)

![Metabolic monitoring schedule for pediatric patients on antipsychotic medications](images/pediatric-antipsychotic-monitoring.png)

## Off-Label Prescribing

The majority of psychotropic prescribing in children is **off-label**. Off-label does not mean unsupported; many off-label uses have robust clinical trial evidence. Document the rationale for off-label use, the evidence base, and informed consent discussions. Stay current with emerging evidence and practice guidelines.

## Polypharmacy Concerns

Rates of psychotropic polypharmacy in youth have increased significantly. Combinations of two or more antipsychotics or three or more psychotropics warrant careful review. Each medication should have a clear target symptom and documented efficacy. Periodically attempt dose reduction or discontinuation to reassess necessity.

![Algorithm for reviewing and rationalizing polypharmacy in pediatric psychiatric patients](images/pediatric-polypharmacy-review.png)

## Key Clinical Pearls

Pharmacotherapy should almost never be the sole intervention in pediatric psychiatry; combine with evidence-based psychotherapy. The placebo response rate in pediatric psychopharmacology trials is high (30-50%), which complicates interpretation of drug efficacy. Always consider the developmental stage when assessing side effects: a sedating medication may impair learning during critical academic years. Obtain assent from the child in addition to consent from the parent whenever possible. Document treatment rationale, target symptoms, monitoring plans, and informed consent conversations meticulously.

## References

1. Walkup JT, Albano AM, Piacentini J, et al. Cognitive behavioral therapy, sertraline, or a combination in childhood anxiety. *N Engl J Med*. 2008;359(26):2753-2766.
2. Correll CU, Manu P, Olshanskiy V, et al. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. *JAMA*. 2009;302(16):1765-1773.
3. Greenhill LL, Pliszka S, Dulcan MK, et al. Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults. *J Am Acad Child Adolesc Psychiatry*. 2002;41(2 Suppl):26S-49S.
4. Safer DJ, Zito JM. Treatment-emergent adverse events from selective serotonin reuptake inhibitors by age group. *J Child Adolesc Psychopharmacol*. 2006;16(1-2):159-169.