Psychopharmacologic Medication:

What Teachers, Clinicians, and Parents

Need to Know

Four major classes of medications are commonly used to treat children

with learning or behavioral disorders: stimulant medications,

antidepressants or mood stabilizers, antipsychotics, and

anticonvulsants. In addition, anxiolytics (e.g., Valium) and

adrenergic agents (e.g., clonidine) are occasionally used to treat some

disorders.

• Research estimates suggest that between 2% and 3% of all school children may be on one of these medications at any time.

• It has been further estimated that between 15% and 20% of children in special education may be receiving one or more of these drugs.

• The use of psychopharmacology in treating children and adolescents with a variety of problems and psychiatric diagnoses has increased significantly in the 1990s (Campbell & Cueva, 1995).

• This increase is attributed in particular to the expansion of the definition of attention-deficit disorder in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV; 1994) to include individuals without impulsivity or hyperactivity.

PSYCHOSTIMULANTS• The psychostimulants methylphenidate (Ritalin),

dextroamphetamine sulfate (Dexedrine), and magnesium pemoline (Cylert) are among the most commonly prescribed and most controversial medications in child psychiatry.

• Nearly 2% of the school-age population receives stimulant medication for attention-deficit/hyperactivity disorder (ADHD) symptoms despite concerns about abuse and addiction.

• A decrease in classroom performance among children treated with psychostimulants for ADHD and disruptive classroom behavior, questioned whether the resultant decrease in behavior problems or relative gains in attention are worth the greater loss of learning performance in some children. However, Forness and Kavale (1988) and Forness et al. (1992) have also noted the potential efficacy of these drugs across a wide range of classroom functioning for many children.

PSYCHOSTIMULANTS (cont’d)

• The only uses approved by the Food and Drug Administration (FDA) for these drugs in children and adolescents are for ADHD and narcolepsy. However, current prescription studies indicate that psychostimulants are also being prescribed to treat ADHD symptoms co-existing with mental retardation, Fragile X syndrome, pervasive developmental disorders (PDD), or autism, organic brain disease, and Tourette's syndrome. All stimulant treatment for such disorders should nonetheless be considered experimental and be closely monitored by the prescribing physician relying on behavioral observations from parents and teachers.

Table 1. Time of Onset and Half-Life for

Psychostimulants

Generic name(Brand name)

Onset of actionPlasma half-life (Peak duration)

Methylphenidate (Ritalin)

30-60 minutes (up to 3 hours for sustained release tablets)

1-2 hours

Dextroamphetamine sulfate (Dexedrine)

30-60 minutes (1-2 hours for spansule)

6-8 hours

Magnesium pemoline (Cylert)

2-4 hours 8-12 hours

Table 2. Psychostimulant Characteristics

Indications Contraindications Known side effects

FDA-approved indicationsADHD in children and adolescents Narcolepsy Exogenous obesity Possible indicationsADHD in preschool childrenUndifferentiated attention-deficit disorderADHD in intellectually subaverage children and adolescents

ADHD symptoms in children and adolescents with Fragile X syndrome ADHD symptoms in children and adolescents with PDD (autism) ADHD symptoms in children and adolescents with head trauma ADHD symptoms in children and adolescents with tic disorders (e.g., Tourette's syndrome)

AbsoluteImpaired liver functioning (Cylert) RelativePregnancyHistory of substance abuse in patient and/or familyTic disorders (e.g., Tourette's syndrome) in child and/or familyHistory of adverse reaction to stimulants Height/growth retardation Cardiac/blood pressure anomalies Patient being treated with MAOI

CommonDecreased appetiteInsomniaGastrointestinal painIrritabilityIncreased heart rate (clinically insignificant)Paradoxical worsening ofsymptomsUncommonPsychosisSadness/isolation Major depressive episodesCognitive impairment Growth retardationTic disorders (e.g., Tourette's syndrome) Increased heart rate (clinically significant)Impaired liver function (Cylert) Increased blood pressureDizziness, lethargy, fatigue Nausea, constipation Rash/hives Acute sense of hearingSkin sensation, sensitivityto touch

Note. ADHD = attention-deficit/hyperactivity disorder; PDD = pervasive developmental disorder;MAOI = monoamine oxidase inhibitor.

ANTI DEPRESSANTS/ MOOD STABILIZERS

• Antidepressants or mood stabilizers are quickly becoming the second most often prescribed psychotropic drugs for children and adolescents.

• . Antidepressants are not only used to treat depression but also ADHD, obsessive- compulsive disorder (OCD), and school phobia (Werkman, 1993). Four different types of mood stabilizers will be discussed: tricyclic antidepressants (TCAs), novel (atypical) antidepressants, lithium, and monoamine oxidase inhibitors (MA0Is).

Tricyclic Antidepressants • TCAs have been found effective for treating major depressive disorders, anxiety

disorders, and panic disorders in adults.

• Most are relatively safe, effective, and easy to administer.

• Within children and adolescents, however, they have not proven as effective

• TCAs are metabolized more rapidly in children and adolescents than in adults.

• The only FDA-approved indications for the use of TCAs with children and adolescents is for the treatment of enuresis. However, current research and practice suggests that TCAs may also be indicated for generalized depression, school phobia, and OCD in both children and adolescents.

• The administration of TCAs alone or in combination needs to be closely monitored and supervised. In particular, a few case reports have documented sudden unexplained deaths among children taking desipramine, although these events are extremely rare and factors other than the medication itself may be at issue.

• No set guidelines exist for dosing patterns or duration of treatment in children and adolescents.

Table 3. Characteristics of Tricyclic

Antidepressant (TCAs)

Indications Contraindications Known side effects

FDA-approved indicationsEnuresis Established indicationsEnuresisADHD in children and adolescentsProbable indicationsADHD in adultsSchool phobiaOCDDepression

AbsolutePregnancy Prior hypersensitivity reaction Currently on MAOIRelativeEpilepsyPsychosisCardiac abnormalitiesThyroid abnormalitiesDiabetes

Cardiac complicationsImpulsivityPsychosisManiaSeizuresHigh blood pressureConfusionInsomnia/nightmaresRashTicsTremorUncoordinationAnxietySexual dysfunctionAbnormal skin sensitivity to sunlight

Note. ADHD = attention-deficit/hyperactivity disorder; MAOI = monoamine oxidase inhibitors; OCD = obsessive-compulsive disorder.

Novel Antidepressants

• The novel or atypical antidepressants include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil), also known as selective serotonin reuptake inhibitors (SSRIs). This category also includes bupropion (Welbutrin) and trazadone (Desyrel).

• Bupropion and trazadone, although not chemically related to TCAs or SSRIs, have proven effective in the treatment of depression in adults.

• Of these, Prozac has become the drug of choice in treating adults because of its relative lack of side effects and withdrawal symptoms.

• In general, all the SSRIs have fewer side effects than the TCAs

– are more selective in their chemical action– thereby reducing possible negative side effects.

• All three of the SSRIs approved for use in the United States begin to work within 2 to 4 weeks, with Prozac having the longest half-life.

• There are no currently established indications for the use of SSRIs in the treatment of children and adolescents

Table 4. Most Commonly Prescribed TCAs

Drug Available forms

ImipramineGenericTofranilImipramine pamoate

Desipramine NorpraminPertofrane

AmitriptylineGenericElavilEndep

Nortriptyline Pamelor

MaprotileneGenericLudiomil

Note. TCA = tricyclic antidepressant.

• When used in combination with TCAs, SSRIs appeared effective, with few side effects in the treatment of childhood anxiety disorders.

– Tierney, Joshi, Llinas, Rosenberg, and Riddle (1995) reported that

although some children with major depressive disorders (MDD) responded well to sertraline, adverse behavioral effects were common.

• Among the other atypical antidepressants approved for use in the United States, it should be noted that trazadone is usually not recommended for routine use with children and adolescents.

• Bupropion, on the other hand, has been used to treat ADHD and is being used experimentally in the treatment of MDD in children and adolescents, either alone or in combination with other medications (Barrickman et al., 1995; Campbell & Cueva, 1995; Jensen, 1993).

• Bupropion is not FDA approved for use with patients under the age of 18, but it has been used in youngsters with ADHD or MDD who have not responded to treatment with SSRIs or TCAs.

Table 5.

Time of Onset and Half-Life for Novel (Atypical) Antidepressants (SSRIs)

Generic name (Brand name)

Onset of action Plasma half-life

Fluoxetine (Prozac) 2-4 weeks 2-3 days

Sertraline (Zoloft) 2-3 weeks 26 hours

Paroxetine (Paxil) 2-3 weeks 14 hours

Note. SSRI = selective serotonin reuptake inhibitor.

Table 6. Characteristics of Novel (Atypical) Antidepressants (SSRIs)

Indications Contraindications Known side effects

FDA-established indicationsNoneProbable indicationsNone Possible indicationsMDD/dysthymiaADHDOCDTrichotillomaniaCompulsive impulse control disordersPanic disorderAnorexia nervosaBulimia nervosaPrader-Willi syndromeSelf-injurious behaviorBorderline personality disorderPTSDDrug craving

AbsoluteKnown hypersensitivity reactionOn MAOI or fluoxetine within past 5 weeksOn sertraline within past 2 weeks Pregnancy Liver disease RelativeEpilepsyPsychosis Cardiac problemsThyroid disordersDiabetes

CommonGastrointestinal (Nausea, diarrhea, dyspepsia)Decreased appetite Weight loss (fluoxetine)NervousnessInsomniaExcess sweatingSedationDream intensificationMotor restlessnessDry mouthSexual dysfunction OccasionalSubjective sensation of excitationHypomania/maniaRash/allergic reactionsSeizureHair loss

Note. SSRI = selective serotonin reuptake inhibitor; MDD = major depressive disorder; ADHD = attention-deficit/hyperactivity disorder; PTSD = posttraumatic stress disorder; MA0I = monoamine

oxidase inhibitor; OCD = obsessive-compulsive disorder.

Table 7. Characteristics of Other Atypical Antidepressants

Drug Indications ContraindicationsKnown side effects

Trazadone Not recommended for routine use in children and adolescents Used for depression in adults with accompanying sleep disturbances

History of liver or kidney disorders SedationLow blood pressure when standingDizzinessHeadacheNausea/vomiting

Bupropion Established indicationsNonePossible indicationsADHDMDD

AbsoluteKnown hypersensitivity Pregnancy On MAOI History of eating disorders Seizure disorder Organic brain diseaseHistory of head traumaCentral nervous system tumorElectroencephalogramabnormalitiesRecent withdrawal from alcoholRelativeConcomitant administration of psychotropics known tolower seizure thresholdHepatic diseaseRenal disease

AgitationWeight lossHeadacheNauseaUpper respiratory complaintsSeizures

Given the extensive list of absolute and relative contraindications for bupropion, it is suggested that it be used in children and adolescents only in relatively controlled settings.

Note. ADHD = attention-deficit/hyperactivity disorder; MDD = major depressive disorder; MA0I = monoamine oxidase inhibitor.

Lithium• Lithium is also being used to treat some psychiatric disorders of

children and adolescents.

• Although its only established indication is for the treatment of bipolar disorders in patients over the age of 12, lithium has also been used in combination with other antidepressants for depression that seems resistant to standard treatment.

• Campbell et al. (1995) found lithium to be effective in the treatment of severely aggressive children with conduct disorders.

• Alessi, Naylor, Ghaziuddin, and Zubieta (1994) noted that lithium also proved effective in treating childhood aggression and behavior disorders associated with mental retardation and other developmental disorders such as autism.

• Although GI problems are the most common side effects of lithium treatment:

– eye irritation– cardiovascular problems – thyroid problems– diabetes– hair loss– and growth and development delays have also been reported.

• Like the other classes of medication reviewed here, dosing levels and intervals for lithium have not been established when used to treat children and adolescents.

• Thus, best practice again suggests that treatment with lithium needs to be closely supervised, with blood levels monitored regularly to determine the most effective dosage.

Monoamine Oxidase Inhibitors• As one of the first types of antidepressants developed,

MAOls have been researched for 50 years.

• Currently, no MAOI is approved for psychiatric use in children less than 16 years old.

• Over the years, they have fallen into disuse because side effects such as liver failure and hypertensive crisis have been associated with their use and as newer antidepressants have been developed.

• Patients on these medications also have to follow a restricted diet because foods such as cheese or yeast may cause severe or life-threatening drug interactions.

ANTI PSYCHOTIC/ NEUROLEPTIC AGENTS

• The antipsychotic agents, also called neuroleptics or major tranquilizers.

• Are a primary mode of treatment in adults with psychotic symptoms.

• However, because of concerns over possible severe neurological and developmental aftereffects with long-term use and the possibility of short-term side effects that may hamper socialization and learning, only seven agents have FDA approval for use with children younger than 12 years of age (Baldessarini & Teicher, 1995; Forness et al., 1992; McClellan & Werry, 1994).

• These medications are increasingly being used to replace more costly behavioral interventions as a way of controlling a wide range of disruptive or aggressive disorders and self-injurious behavior in school settings (Campbell & Cueva, 1995; Wilens et al., 1995).

• In addition to the established indications, neuroleptics are also used experimentally in the treatment of PDD and some autistic behavior. Trials with such populations have yielded mixed results, and the efficacy of treatment has not been clearly established.

• In research focusing specifically on childhood-onset schizophrenia, several new atypical neuroleptics such as clozapine and risperidone have shown promising results, with relatively few side effects reported when treating children and adolescents (Frazier et al., 1994; Quintana & Keshavan, 1995).

• These medications seem to relieve not only the positive or active symptoms of schizophrenia such as agitation, delusions, or hallucinations.

– Also the so-called "negative" symptoms, such as withdrawal, flat affect, and cognitive

dulling, that do not respond as well when treated by more traditional neuroleptics.

– Many of the side effects associated with traditional neuroleptics are also minimized with these newer drugs.

• Initially, clozapine was restricted to use in patients over 16 years of age and was only indicated when the patient had failed to respond to other traditional neuroleptics.

• Another atypical neuroleptic, olanzapine, has proven promising in reducing both positive and negative symptoms with few side effects.

• More recent studies have found these atypical neuroleptics effective in treating' aggression, self-injury, explosivity, and overactivity in older adolescents diagnosed with autism, such that they are rapidly becoming the treatment of choice for psychiatric conditions that have failed to respond to first-line neuroleptics, such as Mellaril or Haldol.

Table 8.

Characteristics of Lithium

Indications Contraindications Known side effects

ApprovedBipolar disorder with acute maniaProphylaxis for bipolar disorderPossibleBipolar disorder with acute depressionUnipolar depressionCyclothymia PsychosisAggression and violent behaviorADHD Alcohol abuse/dependence Bulimia Personality disorder Functional encopresis

Allergic drug reaction Pregnancy Renal disease Cardiovascular disease Thyroid diseaseSevere dehydration/sodium depletion

CommonGastrointestinal complications: (nausea/vomiting, diarrhea)TremorDecrease in white blood cellsMalaiseUncommonRenal problemsOcular irritationHypothyroidismDermatologicCardiovascularWeight gain/fluid retentionDiabetes Hair lossGrowth and development delays

Note. Lithium is not FDA approved for children less than 12 years of age. ADHD = attention-deficit/hyperactivity disorder.

Table 9.

Characteristics of Monoamine Oxidase Inhibitors (MAOIs)

Drug Indications Contraindications Known side effects

NonselectiveIponiazid (Marsalid) Isocarboxazid (Marplan)Phenelzine (Nardil) Tranylcypromine (Parnate) Selective MAO-A Clorgyline Moclobermide Selective MAO-B 1-deprenyl (Selegiline) Pargyline (Eutonyl) Uncharacterized Furazolidone (Furoxone)Procarbazine(Matulane)

ApprovedAntidepressantRefractory depressionAtypical depressionMajor depression w/o melancholiaProbable Major depressionPanic disorder Social phobia Borderline personality disorder with depressionExperimentalADHDChildhood depressionAnorexia and bulimiaBorderline personality disorderSeparation anxiety disorder/school phobia

Inability to maintain dietary restrictionsConcurrent use of other MAOIsConcurrent use of SSRIs HypertensionLiver disease Impending surgeryAsthma

SedationLow blood pressure when standingDizzinessHeadacheNausea/vomitingLiver failure

Note. No MAOI compound is currently FDA approved for psychiatric use in children under 16 years of age. Brand names are provided in parentheses. ADHD = attention-deficit/hyperactivity disorder; SSRI = selective

serotonin reuptake inhibitor; MAOI = monoamine oxidase inhibitor.

ANTICONVULSANTS

• The fourth class of medication are the anticonvulsants, which are primarily used in the treatment of epileptic disorders.

• Recent research has indicated that anticonvulsants are also useful in the treatment of some behavioral disorders (Rosenberg et al., 1994).

• Although anticonvulsants have been used experimentally to treat mood disorders, aggression, and impulse control disorders, the anticonvulsants of choice have changed over the years.

• Current best practice employs Tegretol or Depakene when treating behavioral disorders with anticonvulsants.

Table 10.

Characteristics of Antipsychotic (Neuroleptic) Agents

Drug Indications ContraindicationsKnown side effects

PhenothiazinesThorazineMellarilSerentilStelazineProlixinTrilafonCompazineThioxanthenes Taractan Navana Indolic compounds MobanDiphenylbutylipiperdinesOrapButyrophenonesHaldolDibenzoxapinesLoxitaneClozaril

Other RisperdalOlanzapine

ApprovedPsychosis Aggressive behaviorADHDManiaNonpsychotic anxietyTourette's syndrome Other uses Nausea/vomiting Intractable hiccupsPreoperative restlessnessAllergic reactionMotion sickness Sedation and sleep

Hypersensitivity to neuroleptics AgranulocytosisConcurrent central nervous system depressantsSubcortical temperature Pregnancy

Acute irregular muscle movementsCardiac arrhythmiaMotor restlessnesSedationAffective bluntingCognitive dullingSocial withdrawalTardive dyskinesiaLiver toxicityNeuroleptic malignant syndromeSudden death

Note. Neuroleptic drugs are only rarely indicated for children less than 12 years of age. ADHD = attention-deficit/hyperactivity disorder.

Table 11.

Characteristics of AnticonvulsantsDrug Indications Contraindications Known side effects

Carbamazepine (Tegretol)

PsychiatricBipolar disorder in adultsAlcohol withdrawalChronic pain associated with nerve injury PossibleBipolar disorder in children and adolescents Major depressionADHD Conduct disorderPsychotic disorderss Functional enuresisSleep terror disorder

Absolute

Known hypersensitivity History of bone marrow depression On MAOIPregnancyRelativeLiver diseaseKidney disease

CommonDouble visionDrowsinessUncoordinationRapid eye movementNauseaLow white blood cellsSkin rashesUncommonLiver toxicityNeurotoxicityManiaIncrease in behavior problemsElectrolyte abnormalities

Valporic acid (Depakene)

AbsoluteKnown hypersensitivityHistory of bone marrow depressionPregnancy

RelativeLiver disease Kidney disease

CommonGastrointestinal upsetIncreased appetiteSedationTremorUncommonLiver toxicityPancreas inflammationHyperglycemiaMenstrual problems

Phenytoin (Dilantin)

 

AbsoluteKnown hypersensitivity PregnancyRelativeLiver diseaseKidney diseaseAlcohol use/dependence Diabetes Cardiac disorders

CommonHair growthGum enlargement & sensitivityFolic acid deficiencyPsychomotor delaysUncommon

Degenerative brain diseaseAltered vitamin D, calcium metabolismBiotin deficiencyVitamin E deficiencyLiver toxicityNeurotoxicityHyperglycemia

Note. Brand names are given in parentheses. ADHD = attention-deficit/hyperactivity disorder; MA0I = monoamine oxidase inhibitor.

• Anticonvulsants are currently being used in the treatment of bipolar disorders, major depression, and aggressive behavior in children and adolescents.

• The efficacy of treating these problems in this population is still under study.

• The use of anticonvulsants alone or in combination with other psychoactive drugs for the treatment of nonepileptic disorders needs to be closely controlled and monitored.

ANXIOLYTIC/SEDATIVE AGENTS• Originally developed for the treatment of anxiety disorders.

• Anxiolytic (antianxiety) and sedative agents are among the most frequently prescribed drugs.

• In children and adolescents, antidepressants are the long-term treatment of choice for most anxiety disorders.

• Likewise, antipsychotics and adrenergic agents (clonidine) are often prescribed to children and adolescents for their sedative and antianxiety properties.

• Thirty years ago this category of drugs included barbiturates, benzodiazepines, and sedating antihistamines.

• Today the term anxiolytic is nearly synonymous with the benzodiazepines, even though antihistamines continue to be used as hypnotics.

• A new category of nonsedating, nonaddictive anxiolytic (a• zapirones) has recently been introduced, including buspirone. • Despite having no FDA approved indications for use with persons younger than 18 years of age,

the use of buspirone with children and adolescents is of great interest to child psychiatrists because of its minimal sedation and low potential for abuse (Keltner & Folks, 1993; Rosenberg et al., 1994). I

Benzodiazepines• Since chlordiazepoxide (Librium) and diazepam (Valium) were first introduced in the

1960s, the benzodiazepines.(BZPs) have become the most widely prescribed psychoactive agents in the world.

• The BZPs are easy to use, have relatively low toxicity, and are highly effective in reducing anxiety.

• However, these same qualities have caused the BZPs to become one of the most widely abused prescription drugs, prompting some states to require mandatory triplicate prescription regulations.

• Some of the BZPs have been approved for pediatric use, but controlled studies of their efficacy in children and adolescents are scarce.

• The BZPs most often used to treat adolescents with anxiety disorders include Xanax, Klonopin, and Ativan.

• Because the relationship between BZPs and birth defects has not been clearly established, appropriate contraception should be ensured in adolescent girls of childbearing age.

Antihistamines• Antihistamines are primarily used to treat insomnia due to their mild, rapid sedating

effect.

• There is no evidence supporting this use to treat anxiety disorders in children, although some evidence suggests that they may be useful as brief treatments for situational or anticipatory anxiety.

• Because antihistamines may increase the effects of alcohol and other prescription or illicit drugs, they should be prescribed for adolescents with caution.

• All of the anxiolytics are used infrequently with children and adolescents because the tricyclic and novel antidepressants have demonstrated better efficacy with fewer side effects in the treatment of anxiety.

• Anxiolytics continue to be used to treat specific psychiatric disorders, including certain sleep disorders and panic disorders. All such uses should be considered short-term interventions, however, because tolerance to the sedative properties develops quickly and all of the anxiolytics may predispose patients to drug abuse.

ADRENERGIC AGENTS• The two adrenergic agents to be considered here are the

antihypertensive clonidine and the beta-blocker propranolol.

• Adrenergic, agents influence the secretion or absorption of adrenaline and noradrenaline. – When adrenaline or noradrenaline levels are determined to be low,

adrenergic agents are used to increase the secretion of these substances.

– When the levels of adrenaline or noradrenaline are determined to be adequate but are not being absorbed at receptor sites, adrenergic agents are used to increase absorption.

– Adrenaline or noradrenaline are central nervous system neurotransmitters that are involved in blood pressure regulation, cardiac output, and arousal.

– Neither of the adrenergic agents considered here are approved by the FDA for treatment of psychiatric disorders but are often routinely prescribed for treatment of several disorders that fail to respond to other forms of medication or to reduce side effects of other medications.

Clonidine• Clonidine (Catapres) is an antihypertensive with no established FDA

recommendations for use in child and adolescent psychiatry.

• Clonidine has been investigated most often as a treatment for Tourette's syndrome, although there is a recent trend toward treating this disorder more often with certain novel antidepressants.

• It has also been used to treat ADHD in children and adolescents, especially when conventional stimulant medications are not effective.

• Further, clonidine has been used in clinical trials for the treatment of anxiety and panic disorders, bipolar disorders in children and adolescents, psychosis, agitation, ADHD in adults, borderline personality disorder, social phobia, conduct disorders, mania, autism, and posttraumatic stress disorder.

– These trials have suggested that clonidine is more effective in reducing hyperarousal and motor activity and less effective in decreasing distractibility and improving attention span (Hunt, Capper, & O'Connell, 1990).

• Clonidine is sometimes used in combination therapy with Ritalin in the treatment of ADHD.

Table 12. Anxiolytic Characteristics

Indications Contraindications Known side effects

Indications for adultsAnxiety disorders: panic disorder, OCD, PTSDInsomnia AggressionDepression Bipolar affective disorder Possible indications in childrenSeparation anxiety disorder (school phobia)Overanxious disorder Avoidant disorder

AbsoluteKnown hypersensitivity to the drugNarrow-angled glaucoma MAOIs (buspirone) Gastrointestinal or urinary obstructions (antihistamines) Relative

History of disinhibitory reactionsBZP dependence or abuse History of substance or alcohol abuseLiver dysfunction (for agents metabolized for the liver) Debilitated patients AIDS Sleep apnea Liver or kidney dysfunction (buspirone)

CommonBenzodiazepines (BZPs)SedationCognitive impairment Psychomotor impairmentParadoxical worsening of symptomsSocial disinhibitionBuspironeDizzinessInsomniaGastrointestinal upsetHeadacheFatigueAnxietyIrritabilityAntihistaminesDry mouthConstipationUrinary retentionBlurred visionConfusionUncommonBZPsWithdrawal seizuresHallucinationsRecurrent psychosisManiaLeukopeniaThrombocytopeniaAgranulocytosisBuspironeSocial disinhibitionAntihistaminesLowered seizure thresholdLow blood pressureBlood diseasesGastrointestinal disturbances 

Note. OCD = obsessive-compulsive disorder; PTSD = posttraumatic stress disorder; MAOI = monoamine oxidase inhibitor.

Table 13. Available Benzodiazepines, Their Age Range, and Plasma Half-Life

in Adults

Generic name (Brand name) Age rangePlasma half-life in adults

Oxazepam (Serax) > 6 years 12 hours

Clorazepate (Tranxene) > 9 years 30-200 hours

Chordiazepoxide (Librium) > 12 years 24-48 hours

Prazepam (Centrax) > 18 years 6-11 hours

Lorazepam. (Ativan) > 12 years 30-200 hours

Diazepam (Valium) > 6 months 2 0-100 hours

Alprazolam (Xanax) > 18 years 6-2 7 hours

Temazepam (Restoril) > 18 years 9-12 hours

Midazolam (Versed) > 18 years 1-12 hours

Flurazepam (Dalmane) > 15 years 40-100 hours

Quazepam (Doral) > 18 years 40-100 hours

Triazolam (Halcion) > 18 years 2-6 hours

Estazolam (Prosom) > 18 years 10-24 hours

Table 14.

Available Antihistamine Agents

Generic name (Brand name) Onset of action Plasma half-life in adults

Diphenhydramine (Benadryl)

1-3 hours 3-14 hours

Hydroxyzine (Atarax, Vistaril)

15-30 minutes 3-29 hours

Cypoheptadine (Periactin)

1-3 hours < 5 hours

Promethazine(Phenergan)

1-3 hours for tablets, liquid or suppository

1-5 minutes forinjection

< 5 hours

Propranolol• Propranolol (Inderal) is a nonselective beta-adrenergic blocking agent with many established

uses for treatment of cardiovascular disorders but no FDA-established indications for use in psychiatric disorders.

• Investigative studies have suggested that propranolol may be effective in reducing aggression in patients with brain damage and in the treatment of posttraumatic stress disorders, anxiety and panic disorders, and motor restlessness (Rosenberg et al., 1994).

• Propranolol is also used to treat behavior disorders in some children with mental retardation when other first-line agents have failed.

• Because the efficacy and safety of propranolol have not been established in children and adolescents with psychiatric disorders, its use should be considered investigative when prescribed to these populations.

• Propranolol is metabolized by the liver, and in adults exerts its peak effect 1 to 1 1/2 hours after oral administration. It has a serum half-life in adults of between 3 and 6 hours, so it must be given more than once per day.

• Due to the potential life-threatening side effects of propranolol (e.g., asthma and congestive heart failure), a complete medical history and physical examination should be completed before beginning treatment.

• None of the other beta-blockers (e.g., atenolol, nadolol, or metoprolol) are currently indicated for use with children or adolescents.

Table 15.

Clonidine Characteristics

Indications Contraindications Known side effects

FDA-approved indicationsNoneLikely indications Tourette's disorderADHD symptoms in children and adolescents Opiate withdrawal Nicotine withdrawal Possible indicationsAnxiety and panic disordersBipolar disorder in children and adolescents Psychosis Agitation ADHD in adults Borderline personality disorderSocial phobiaPTSD

AbsoluteNoneRelative Depression (in patient or family history)Cardiovascular disordersRenal disease Skin disease/irritation (patch) Use with caution in children and adolescents with:Hypertension/hypotensionCerebrovascular diseaseDiabetesDepressionBeta-blockade (propranolol)

CommonSedationHypotensionCardiovascularHeadache and dizzinessStomachache/nausea/vomitingUncommonDepressionCardiac arrhythmiaRebound hypertensionRetinal degenerationSkin irritation with patchCentral nervous system impulse obstructionVivid dreams/nightmaresAppetite increase or decreaseSexual dysfunctionFluid retentionAnxietyIncreased blood sugarRaynaud's phenomenon

Note. ADHD = attention-deficit/hyperactivity disorder; PTSD = posttraumatic stress disorder.

Table 16.

Propranolol Characteristics

Indications Contraindications Known side effects

FDA-approved indications NonePossible indications

Aggression (secondary to central nervous system damage) Lithium tremor Motor restlessness Performance anxietyGeneralized anxiety disorderPanic disorderHyperventilation attacksAlcohol withdrawalPosttraumatic stress disorderNot indicatedSchizophrenia Tardive dyskinesia Extrapyramidal side effects of neuroleptics

AbsoluteBronchospastic disease (asthma) Diabetes/hypoglycernia Allergic reaction Medicated with MAOI HyperthyroidismCardiovascular conditionsDepressionPregnancy 

CommonDecreased heart rateRaynaud's phenomenonLethargyImpotenceUncommon

Bronchoconstriction Congestive heart failureDepressionHallucinationsRareHypoglycemiaHypotension/dizzinessNausea/diarrheaVivid dreams and nightmares

Note. MAOI = m onoamine oxidase inhibitor.

 

ETHICAL AND LEGAL CONCERNS

• Despite substantial advances over the past several years, the field of pediatric psychopharmacology is faced with several ethical, methodological, and regulatory issues that remain unresolved (Biederman, 1996). Glantz (1996) pointed out that several ethical issues surround the use of psychotropics with children and adolescents in the absence of sufficient data to support their use, including the inability to obtain informed consent from minor or incapacitated subjects and the risk of using placebo in patients with a known illness.

• Until recently, no large-scale studies had investigated the efficacy of psychotropic medications in the treatment of psychiatric illnesses in children and adolescents (Greenhill et al., 1996). This lack of research has contributed to the absence of FDA approval for the use of many psychotropic agents with children and adolescents, which requires that the safety and effectiveness of each medication be adequately demonstrated within each age group for each condition indicated (Laughren, 1996).

• Issues to be considered in such clinical trials include drug effects on growth and development and onset of potentially dangerous side effects.

– Current FDA regulations do not require pharmaceutical companies to conduct research in pediatric populations prior to bringing a new drug to market; therefore., little funding is available for such studies.

– Some professionals are becoming more concerned that this increased reliance on psychopharmacology represents a trend in which quality programming for children and adolescents with emotional or behavioral disorders is being replaced by attempts to find a quick cure to behavior problems through the use of medication (Forness, Sweeney, & Toy, 1996). However, Gadow (1992) noted that advances in pharmacology have provided better information about dosing levels, concentration of the drug at the effector site, and the end response.

– As a result, many drugs may be used selectively to treat psychiatric symptoms or behaviors not previously thought to respond to these medications. For example, antidepressants and neuroleptics are sometimes used to treat certain disruptive behavior disorders (Rosenberg et al., 1994).