275Chapter 16


Psychopharmacological Interventions

As the efficacy of psychotropic medications has been demonstrated by research and their use destigmatized, their prescription to children and adolescents has become commonplace. For example, when adolescents in the United States were recently surveyed, more than 6% reported using a psychotropic medication in the past month (Jonas et al. 2013). This relatively widespread use of psychotropic medications means that caregivers have come to expect primary care practitioners, not just mental health specialists, to consider prescribing medication for a child or an adolescent with a mental illness.

When should a psychotropic medication be prescribed? Not every child with depression, anxiety, or attention-deficit/hyperactivity disorder (ADHD) needs to receive a medication, regardless of whether it fits an approved or research-supported indication. Because psychiatric medications can cause adverse effects, you must, at a minimum, believe that the potential benefit of psychotropic medication exceeds the potential risks your patient may experience. For instance, if a child has a relatively mild case of depression, psychotherapy alone is usually sufficient to help, and its use does not introduce the risk of medical adverse effects. If a child or an adolescent’s depression is more severe or persistent, use of a selective serotonin reuptake inhibitor (SSRI) combined with psychotherapy makes better clinical sense to achieve a more rapid recovery (e.g., Emslie et al. 2010).

As a rule of thumb, if a child or an adolescent has a moderate to severe range of symptoms and an evidence-based psychotropic medication is available, we usually prescribe the medication at the same time we initiate the appropriate psychosocial interventions. For a child or an adolescent with milder symptoms, we generally recommend starting treatment with psychotherapy or environmental interventions alone. Those with mild symptoms but persistent dysfunction 276become stronger candidates for a medication treatment when nonmedication strategies prove to be ineffective.

When approaching the decision about what to prescribe, we advise following evidence-based principles. Although we appreciate the wisdom of experienced practitioners and the insights reported in case series, these are small, unstandardized accounts. Whenever possible, we base our prescribing decisions on evidence generated from controlled trials conducted among children and adolescents. For practitioners who frequently prescribe psychotropic medications to children and adolescents, we recommend reading the evidence-based systematic reviews published by the Cochrane Database of Systematic Reviews, the Practice Parameters published by the American Academy of Child and Adolescent Psychiatry, or one of the available textbooks (e.g., McVoy and Findling 2013; Preston et al. 2015).

When such evidence is unavailable, we find that adult mental health medication research is informative but in need of translation before we can use the medication for children and adolescents. Children and adolescents are not “little adults” who will respond to “little doses” in the same way that adults do. For example, tricyclic antidepressants are effective in the treatment of depression in adults, but controlled trials found that tricyclic antidepressants are no better than placebo in the treatment of depression in children and are of marginal utility for treating depression in adolescents (Hazell and Mirzaie 2013). A result from the adult mental health literature therefore must be replicated in children and adolescents before it can be reliably followed.

However, appropriate evidence-based care does not mean limiting your prescriptions to only those medications approved for children and adolescents by a regulatory agency such as the U.S. Food and Drug Administration (FDA). Pediatric approvals exist for only about half of all the medications used with children, such that nearly three-fourths of all hospital-delivered medications (both medical and psychiatric) lack an age-matched pediatric regulatory approval (Murthy et al. 2013). This regulatory discrepancy occurs largely because the process of obtaining an FDA approval is a long and expensive endeavor that requires a vested party (the manufacturer). Rigorous research may support the use of medication without such an approval.

Some of the key questions we ask ourselves before prescribing any medication include the following:

277• Diagnosis—does the child have an evidence-based medication indication?

• Age—how does the child’s age change your risk-benefit analysis?

• Severity—how rapid of a treatment response is needed?

• History—what has already been tried, and how effective was it?

• Preferences—are there strong patient or caregiver opinions about the use of medication?

Practitioners may feel pressured to use medications well outside of evidence-based indications when patients and caregivers are struggling. We prefer to resist these demands and limit the prescription of psychotropic medications to the indications for which sound evidence exists. For instance, prescribing methylphenidate for a child whose poor school performance is not due to ADHD but rather is due to a learning disability, anxiety, social distractions, or depression may be ineffective and delay the use of more appropriate interventions. Similarly, antipsychotics may reduce the severity of nonspecific aggression, but they are unlikely to address the underlying causes of youth aggression and may unnecessarily introduce major adverse effects.

Tables 16–1 to 16–5 include only those psychotropic medications with a randomized controlled trial evidence base for use with young people. The age ranges of the listed FDA approvals do not necessarily reflect the age ranges for which these medications are clinically appropriate or effective.

Older antipsychotic medications with long-standing FDA approvals for use in young people include haloperidol (≥3 years old) for severe aggression and Tourette’s disorder, pimozide (≥12 years old) for Tourette’s disorder, chlorpromazine (≥1 year old) for severe aggression, and thioridazine (≥2 years old) for schizophrenia. However, concern about adverse effects, chiefly movement disorders, limits contemporary use of these medications in children and adolescents.

Psychopharmacological Monitoring for Adverse Effects


When we prescribe a medication to a child or an adolescent, we take responsibility for monitoring for the development of known adverse effects. The tables in the following subsections are drawn from the published literature (Hilt 2012) and from adverse effect labeling from medication manufacturers (U.S. Food and Drug Administration 2015).

278TABLE 16–1. Attention-deficit/hyperactivity disorder: short-acting evidence-based stimulant medications

Drug name

Stimulant class

Duration (hours)

Usual 6- to 10-year-old starting doses

Available doses (mg tablets)

FDA maximum daily dose (mg; approval ages)

Editorial comments

Methylphenidate (Ritalin, Methylin)

Methylphenidate

4–6

5 mg bid (2.5 mg if 3–5 years)

5, 10, 20

60 (≥6)

May have fewer side effects than dextroamphetamine; better evidence for very young children

279Dexmethylphenidate (Focalin)

Methylphenidate

4–6

2.5 mg bid (1.25 mg if 3–5 years)

2.5, 5, 10

20 (≥6)

Racemic isomer, so has twice the mg:mg potency of methylphenidate

Dextroamphetamine (Dexedrine, DextroStat)

Dextroamphetamine

4–6

2.5 mg bid (1.25 mg if 3–5 years)

2.5, 5, 7.5, 10, 20, 30

40 (≥3)

Tends to have longer duration than methylphenidate; slightly more side effects

280Amphetamine salt combination (Adderall)

Dextroamphetamine

4–6

2.5 mg bid (1.25 mg if 3–5 years)

5, 7.5, 10, 12.5, 15, 20, 30

40 (≥3)

Tends to have longer duration than methylphenidate; slightly more side effects

Note. bid=twice a day; FDA=U.S. Food and Drug Administration.

281TABLE 16–2. Attention-deficit/hyperactivity disorder: long-acting evidence-based stimulant medications

Drug name

Stimulant class

Duration (hours)

Usual 6-to 10-year-old starting doses (mg)

Available doses

FDA maximum daily dose (mg; approval ages)

Editorial comments

Methylphenidate ER/SR (Metadate ER)

Methylphenidate

4–8

10 qam

10, 20 mg tablets

60 (≥6)

Uses a wax matrix for delivery; variable duration of action

OROS methylphenidate (Concerta)

Methylphenidate

10–12

18 qam

18, 27, 36, 54 mg capsules

72 (≥6)

Osmotic release capsule; cannot be cut or crushed

Methylphenidate XR oral suspension (Quillivant XR)

Methylphenidate

Up to 8

20 qam

5 mg/mL liquid

60 (≥6)

Microsuspension yields an ER liquid

282Methylphenidate XR; 30% IR, 70% ER (Metadate CD)

Methylphenidate

~8

10 qam

10, 20, 30, 40, 50, 60 mg capsules

60(≥6)

Beads in capsule can be sprinkled on food

Methylphenidate XR; 50% IR, 50% ER (Ritalin LA)

Methylphenidate

~8

10 qam

10, 20, 30, 40 mg capsules

60 (≥6)

Beads in capsule can be sprinkled on food

Dexmethylphenidate XR (Focalin XR)

Methylphenidate

10–12

5 qam

5, 10, 15, 20 mg capsules

30 (≥6)

Beads in capsule are a racemic isomer of methylphenidate, so this medication has twice the mg potency

283Methlylphenidate patch (Daytrana)

Methylphenidate

Until 3–5 hours after patch removal

10 qam

10, 15, 20, 30 mg patch

30 (≥6)

Site rash problems; slow morning startup of effects; works until removed

Amphetamine salt combo-XR (Adderall XR)

Dextroamphetamine

8–12

5 qd

5, 10, 15, 20, 25, 30 mg capsules

30 (≥6)

Generic available; beads in capsule can be sprinkled on food

284Lisdexamfetamine (Vyvanse)

Dextroamphetamine

~10

30 qd

20, 30, 40, 50, 60, 70 mg capsules

70 (≥6)

Conversion ratio from dextroamphetamine not well established; gastrointestinal bioactivation

Dextroamphetamine ER (Dexedrine Spansule)

Dextroamphetamine

8–10

5 qam

5, 10, 15 mg capsules

40 (≥6)

Beads in capsule can be sprinkled on food

Note. bid=twice a day; ER=extended release; FDA=U.S. Food and Drug Administration; IR=immediate release; OROS=osmotic controlled-release oral delivery system; qam=every morning; qd=every day; SR=sustained release; XR= extended release.

TABLE 16–3. Attention-deficit/hyperactivity disorder (ADHD ): nonstimulant evidence-based medications

Drug name

Half-life (hours)

Medication type

Usual starting, doses

Available doses (mg)

FDA maximum daily dose (approval ages)

Editorial comments

285Atomoxetine (Strattera)

5

Norepinephrine reuptake inhibitor

0.5 mg/kg once a day then 1.2 mg/kg/day after 1 week

10, 18, 25, 40, 60, 80, 100 capsules

100 mg or 1.4 mg/kg/day, whichever is less (≥6)

Side effect risks same as with SSRIs (e.g., suicidality warning); cytochrome P450 2D6 metabolism; about 50% respond

Clonidine (Catapres)

12.5

Central-acting α2-agonist

0.05 mg bid

0.1, 0.2, 0.3, 0.4 tablets

0.4 mg

Dosing at bedtime may help manage sedation effects

286Clonidine XR (Kapvay)

12.5

Central-acting α2-agonist

0.1 mg qd

0.1, 0.2, 0.3, 0.4 tablets

0.4 mg (≥6)

Difference is a reduced peak blood level relative to IR form

Guanfacine (Tenex)

16

Central-acting α2-agonist

1 mg qd

1, 2, 3, 4 tablets

4 mg

Dosing at bedtime may help manage sedation effects

Guanfacine XR (Intuniv)

18

Central-acting α2-agonist

1 mg qd

0.1, 0.2, 0.3, 0.4 tablets

7 mg (≥6)

Difference is a reduced peak blood level relative to IR form

Note. bid=twice a day; FDA=U.S. Food and Drug Administration; IR=immediate release; qd=every day; SSRIs=selective serotonin reuptake inhibitors; XR=extended release. Unlike stimulants, these medications may take up to a month to generate their full efficacy in the treatment of ADHD in children and adolescents. Stimulants are considered the first-line treatment option.

TABLE 16–4. Depressive and anxiety disorders: evidence-based medications

Drug name

Half-life

Usual teenage starting dose (mg)

FDA maximum daily dose (approval ages)

Available doses

Conditions with RCT support

Editorial comments

287Fluoxetine (Prozac)

4–6 days

10 qam

60 mg (≥7 OCD, 1 ≥8 MDD)

10, 20, 40 mg capsules

OCD, MDD, GAD, SAD, SOC

First-line treatment for both depression and anxiety; long half-life reduces side effects from missed doses

Sertraline (Zoloft)

27 hours

50 qam

200 mg 2 (≥6 OCD)

25, 50, 100 mg tablets

OCD, MDD, GAD, SAD, SOC

First-line treatment for anxiety; easy to use small doses (i.e., half of a 25 mg tab)

Citalopram (Celexa)

35 hours

20 qam

40 mg in adults 1 (not child approved)

10, 20, 40 mg tablets

MDD, OCD

Very few drug-drug interactions

288Escitalopram (Lexapro)

29.5 hours

10 qam

20 mg (≥12 MDD)

5, 10, 20 mg tablets

MDD

Racemic isomer of citalopram; very few drug-drug interactions

Fluvoxamine (Luvox)

16 hours

25 qam

300 mg (≥8 OCD)

25, 50, 100 mg tablets

OCD, GAD, SOC, SAD

Often more side effects than other SSRIs; many drug-drug interactions; thus, not a first-line option

Paroxetine (Paxil)

18 hours

20 qam

40 mg in adults (not child approved)

10, 20, 30, 40 mg tablets

SOC

Mixed evidence; not preferred for child depression

289Clomipramine (Anafranil)

32 hours

25 mg

200 mg or 3 mg/kg/day (≥10 OCD)

25, 50, 75 mg ( capsules

OCD

Tricyclic, used for treatment-resistant OCD; not a first-line option because of greater adverse effects than with SSRIs

Duloxetine (Cymbalta)

12 hours

30 qd

120 mg (≥7 GAD)

20, 30, 60 mg ( capsules

GAD

Serotonin-norepinephrine reuptake inhibitor; has more adverse effects than SSRIs

Note. FDA=U.S. Food and Drug Administration; GAD=generalized anxiety disorder; MDD=major depressive disorder; OCD=obsessive-compulsive disorder; qam=every morning; qd=every day; RCT=randomized controlled trial; SAD=separation anxiety disorder; SOC=social phobia; SSRIs=selective serotonin reuptake inhibitors.

TABLE 16–5. Bipolar and psychotic disorders: evidence-based medications

Drug name

Half-life (hours)

Usual teenage starting dose (mg)

FDA maximum daily dose (approval ages)

Available doses (mg)

Conditions with RCT support

Editorial comments

290Risperidone (Risperdal)

17

0.5 qd

6 mg (≥13 schizophrenia, ≥10 bipolar mania, ≥5 autism irritability)

0.25, 0.5, 1, 2, 3, 4 tablets

Schizophrenia, bipolar mania, autism, Tourette’s disorder

Extensively studied in children; has relatively consistent and rapid effects; extra risk of prolactinemia

Aripiprazole (Zoloft)

75

2 qd

30 mg (≥13 schizophrenia, ≥10 bipolar mania, ≥6 autism irritability, ≥6 Tourette’s disorder)

2, 5, 10, 15, 20 tablets

Schizophrenia, bipolar mania, autism, Tourette’s disorder

Mixed agonist/antagonist at dopamine D2 receptor; may cause irritability; takes longer than others to see clinical changes

291Quetiapine (Seroquel)

7

25 bid

800 mg (≥13 schizophrenia, ≥10 bipolar mania)

25, 50, 100, 200, 300, 400 tablets

Schizophrenia, bipolar mania

Pills larger so might be harder to swallow; noted anxiolytic properties

Ziprasidone (Geodon)

7

10 qam

160 mg/day in adults (not child approved)

20, 40, 60, 80 capsules

Schizophrenia, bipolar mania

Greater risk of QT lengthening, so electrocardiogram monitoring is necessary; not a first-line option for children

292Olanzapine (Zyprexa)

30

25 qam

20 mg (≥13 schizophrenia, ≥13 bipolar mania, ≥10 bipolar depression, with fluoxetine)

2.5, 5, 7.5, 10, 15, 20 tablets

Schizophrenia, bipolar mania, bipolar depression

Has rapid benefits but greatest risk of weight gain and lipid changes in this group

Paliperidone (Invega)

23

3 qd

12 mg (≥12 schizophrenia)

1.5, 3, 6, 9 tablets

Schizophrenia

Major active metabolite of risperidone; similar risk of hyperprolactinemia

Note. bid=twice a day; FDA=U.S. Food and Drug Administration; qd=every day.

293Stimulants

Stimulants (i.e., methylphenidate, dextroamphetamine) are usually well tolerated, but they often cause decreased appetite and insomnia (Table 16–6). Dose and duration of action adjustments typically mitigate these problems. Tracking growth on a growth curve greatly helps with recognizing weight gain problems (Table 16–7). Sometimes stimulants cause irritability or dysphoria, which may resolve by switching to the other family of stimulant. Excessive doses can cause cognitive dulling. Stimulants often cause a very slight elevation in heart rate or blood pressure that is almost always clinically insignificant, but we screen for outlier responses via a vital signs check after initiation. A tic disorder is no longer considered a contraindication for stimulant use because tics are just as likely to increase or decrease temporarily during stimulant use (Pringsheim and Steeves 2011).

Selective Serotonin Reuptake Inhibitors

Common SSRI side effects include a change in appetite that can lead to weight gain or loss and a sleep change that may include dreams becoming more vivid (Table 16–8). Diminished sex drive is common, although this problem is less notable for adolescents than for adults. Because platelets use serotonin for aggregation signaling, easier bruising may occur. Very high SSRI doses or combining serotonin agents could result in serotonin syndrome, which includes agitation, ataxia, diarrhea, hyperreflexia, mental status changes, tremor, and hyperthermia. Manic symptoms occur rarely as an SSRI side effect; this occurrence is not proof that the child will develop bipolar disorder. SSRIs have a common risk of causing irritability or agitation, which, if added to significant anxiety or depression might be a reason why there is a reported twofold elevation of self harm thoughts early in treatment when youth use SSRIs versus a placebo. Prescribers need to discuss this black box suicidality warning with patients and caregivers when prescribing a SSRI, along with the need for early treatment monitoring. Safe SSRI use involves examining a patient for adverse effects at around 2 weeks and again at 4–6 weeks after initiation to screen for worsening mood or irritability (Table 16–9) (Bridge et al. 2007).

294TABLE 16–6. Highlights of stimulant adverse effects

Common

Decreased appetite

Nausea

Weight loss

Insomnia

Headaches

Stomachaches

Dry mouth

Less common

Irritability

Dysphoria

Cognitive dulling

Obsessiveness

Anxiety

Tics

Dizziness

Blood pressure and pulse rate elevation

Notable rare reactions

Seizure

Hallucinations

Mania

Loss of adult height potential


TABLE 16–7. Monitoring suggestions for stimulants

Record height and weight growth curve at baseline and at each follow-up, at least every 6 months.

Measure blood pressure and pulse rate at baseline and after initiation of medication.

Monitor refill dates to identify signs of drug diversion.

Repeat administration of attention-deficit/hyperactivity disorder symptom rating scale until remission is achieved.


295

TABLE 16–8. Highlights of selective serotonin reuptake inhibitor adverse effects

Common

Insomnia

Sedation

Appetite increase

Appetite decrease

Nausea

Dry mouth

Headache

Sexual dysfunction

Less common

Agitation

Restlessness

Impulsivity

Irritability

Silliness

Dizziness

Tremor

Constipation

Diarrhea

Notable rare reactions

Suicidal thoughts

Serotonin syndrome

Easy bleeding

Hyponatremia

Mania

Prolonged QT interval


296

TABLE 16–9. Monitoring suggestions for selective serotonin reuptake inhibitors

Record height and weight at baseline and at each follow-up, at least every 6 months.

Inquire about increased irritability or agitation at 2 weeks and at 4–6 weeks after initiation.

Inquire about new or worsened suicidal thoughts at 2 weeks and at 4–6 weeks after initiation.

Inquire about new bleeding or bruising at least once after initiation.

Repeat disorder-specific rating scale(s) until remission is achieved. Takes 4–6 weeks to see benefits from a given dose.


Newer-Generation Antipsychotics

Antipsychotics for children and adolescents are typically initiated by mental health specialists, but primary care practitioners often find themselves in the role of providing refills or monitoring. Patients can experience fairly significant adverse effects from these medications (Table 16–10). Weight gain is the most common problem, with patients in some trials gaining an average of more than 10 pounds in just 3 months of medication use (Correll et al. 2009). Weight gain seems to occur more frequently in children than in adults—for instance, aripiprazole and risperidone have been found to cause equal degrees of weight gain in children, a finding that contradicts the adult literature (Correll et al. 2009). Muscle stiffness or dystonia may occur, particularly during initial use, for which practitioners can warn a family to keep diphenhydramine around as an antidote. Sedation is common, but this might be managed through bedtime dosing. A metabolic syndrome of elevated levels of blood glucose, cholesterol, and triglycerides may occur for which regular blood tests are needed. A physical sense of restlessness (akathisia) or agitation may occur without parents realizing that this can be a side effect. The opposite could occur as well: medication-induced parkinsonism causes decreased movement. One of the most worrisome but rare reactions is neuroleptic malignant syndrome, which is a severe febrile, systemic allergic reaction that may occur typically in the first few months of use (Neuhut et al. 2009). Families also must be warned about a small, but cumulative and dose-related, risk of tardive dyskinesia, which is a potentially permanent repetitive involuntary movement disorder caused by antipsychotics. Although rare, this possibility needs to be part of the ongoing risk-benefit analysis around use of these medications. Tardive dyskinesia monitoring (Table 16–11) usually involves biannual examinations with the Abnormal Involuntary Movement Scale (AIMS) for any new-onset abnormal involuntary movements (McClellan and Stock 2013).

297TABLE 16–10. Highlights of newer-generation antipsychotic adverse effects

Common

Weight gain

Muscle rigidity

Parkinsonism

Constipation

Dry mouth

Dizziness

Somnolence/fatigue

Less common

Tremors

Nausea or abdominal pain

Akathisia (restlessness)

Headache

Agitation

Orthostasis

Elevated glucose level

Elevated levels of cholesterol and triglycerides

Notable rare reactions

Tardive dyskinesia

Neuroleptic malignant syndrome

Lowered blood cell counts

Elevated liver enzymes

Prolonged QT interval

Tachycardia


298

TABLE 16–11. Suggestions for monitoring of newer-generation antipsychotics

Record height and weight growth curve at baseline and at each follow-up, at least every 6 months.

Measure blood pressure and pulse rate at baseline and after initiation of medication.

Monitor levels of fasting blood glucose, triglycerides, and cholesterol every 6 months.

Obtain complete blood cell count with differential once after initiation.

Inform family about home monitoring for neuroleptic malignant syndrome and tardive dyskinesia.

Administer Abnormal Involuntary Movement Scale (AIMS) every 6 months.

Adjust medication until remission is achieved.

Repeat the risk-benefit analysis every 6 months to wean off the medication when appropriate.


Recording Adverse Medication Effects


If a child or an adolescent experiences an adverse effect of a medication prescribed for the treatment of a mental disorder, DSM-5 provides direction on how to record this information in the medical record (American Psychiatric Association 2013, pp. 709–714). We include Table 16–12 as a shorthand list so that you can record a movement disorder or other adverse medication effect that is a focus of clinical attention or that may otherwise affect the diagnosis, course, prognosis, or treatment of a patient’s mental disorder. A condition listed in the table may be coded if it is a reason for the current visit or helps to explain the need for a test, procedure, or treatment. Conditions and problems from this list also may be included in the medical record as useful information on circumstances that may affect the patient’s care, regardless of their relevance to the current visit.

299TABLE 16–12. ICD-10-CM codes for adverse medication effects

ICD-10-CM code

Disorder, condition, or problem

G21.11

Neuroleptic-induced parkinsonism

G21.19

Other medication-induced parkinsonism

G21.0

Neuroleptic malignant syndrome

G24.02

Medication-induced acute dystonia

G25.71

Medication-induced acute akathisia

G24.01

Tardive dyskinesia

G24.09

Tardive dystonia

G25.71

Tardive akathisia

G25.1

Medication-induced postural tremor

G25.79

Other medication-induced movement disorder

T43.205A

Antidepressant discontinuation syndrome: initial encounter

T43.205D

Antidepressant discontinuation syndrome: subsequent encounter

T43.205S

Antidepressant discontinuation syndrome: sequelae

T50.905A

Other adverse effect of medication: initial encounter

T50.905D

Other adverse effect of medication: subsequent encounter

T50.905S

Other adverse effect of medication: sequelae

Source. World Health Organization 1992.300