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4. Galanter M, Gleaton T, Marcus CE, McMillen J: Self-help groups for parents of young drug and alcohol abusers. Am J Psychiatry 141:889-891, 1984. 5. Henggler SW, Borduin CM: Family Therapy and Beyond: A MultisystemicApproach to Treating the Behavior Problems of Children and Adolescents. Pacific Grove, CA, Brooks/Cole, 1990. 6 . Kaminer Y: Adolescent Substance Abuse: A Comprehensive Guide to Theory and Practice. New York, Plenum, 1994. 7. Kandel DB, Chen K, Warner LA, Kessler RC, Grant B: Prevalence and demographic correlates of symptoms of last year dependence on alcohol, nicotine, marijuana and cocaine in the US population. Drug Alcohol Depend 44:ll-29, 1997. 8. Kandel DB, Johnson JG, Bird HR, et al: Psychiatric disorders associated with substance use among children and adolescents: findings from the Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. J Abnonn Child Psycho1 25:121-132, 1997. 9. Riggs DD: Depression in substance-dependent delinquents. J Am Acad Child Adolesc Psychiatry 34:764771, 1995. 10. Weissman MM, Warner V, Wickramaratne PJ, Kandel DB: Mental smoking during pregnancy and psychopathology in offspring followed to adulthood. J Am Acad Child Adolesc Psychiatry 38392-899, 1999. 1 1. Zoccolillo M, Vitaro F, Tremblay RE: Problem drug and alcohol use in a community sample of adolescents. J Am Acad Child Adolesc Psychiatry 38:900-907, 1999.

6 1. PRINCIPLES OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY

Frederick B. HeGert, M.D.

1. Why are physicians concerned about child and adolescent medications?

Practitioners sometimes avoid giving medications to children and adolescents because they are concerned about unusual responses or dosage requirements. However, except for the lack of a euphoric response to stimulants in children, there are few qualitative differences between children and adults in their response to medication. Childrens younger organs frequently clear medications more quickly, whereas adolescents generally need adult doses.

2. What are major issues for the family practitioner?

Families sometimes focus all difficulties on unlikely medical causes or past injuries and expect that medications either will not work at all or will work miracles. Medications may allow a seriously ill child to be treated as an outpatient; this is an important point, but hardly a miracle. Medications are part of a total treatment plan. Parents and practitioners need to be supportive, never using medications as a punishment. Children and adolescents need to remember that medications do not excuse them from the need to work on their problems. Below are specific principles for treatment of attention deficit-hyperactivity disorder, depression, psychosis, conduct disorders, and anxiety disorders.

ATTENTION DEFICIT-HYPERACTIVITY DISORDER

3. Why is so much attention paid to attention deficit-hyperactivity disorder (ADHD)?
ADHD is a common and well-researched childhood disorder. The central notion of a short attention span and hyperactivity has been around since a German poet wrote about Fidgety Phil a hundred years ago. In the ensuing years, over 10,000 articles have been published in the scientific literature. Although stimulant medications have been used for over 50 years, from time to time splinter groups have raised questions about their use. From the standpoint of the scientific community, stimulants remain one of the safest and most effective of all psychotropic medications. The increase in use of stimulants is probably the result of an increased recognition that 15% of patients with

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ADHD continue to show signs and symptoms in adolescence. Girls suffer from ADHD only onefourth as often as boys. In the differential diagnosis, mood disorders are most difficult to rule out. A positive family history of mood disorder and lack of learning disability are more likely in bipolar patients. Thirty to 50% of the mental health referrals for children are for ADHD.

4. Are stimulant medications still the mainstay of the medication treatment for ADHD? Absolutely. Stimulants remain the best medications for ADHD. Recent concern over the short duration of action of methylphenidate (Ritalin) and the small dose size of dexedrine tablets has led to the development of mixed salts of a single-entity amphetamine product, marketed as Adderal. Adderal showed greater efficacy than methylphenidate at mid-day and days end across several behavioral measures. Side effects were similar to other stimulants: anorexia, insomnia, stomach pain, headache, irritability, and weight loss. Adderal often is titrated up to 0.75 mgkg, or 75% of the dose of methylphenidate. In addition, bupropion, marketed as an antidepressant, has been shown to be equal to methylphenidate in at least one study of ADHD when it was given at doses of about 3 m a g body weight. The larger tablet sizes available in Adderal(10, 20, 30 mg, scored) and Wellbutrin (75, 100, 100 SR, 150 mg SR, unscored) permit dosing in heavier adolescents and young adults but may pose a problem in children. Risk of seizure with bupropion also is a consideration (especially with a history of head injury or seizure disorder). 5. What can we tell parents about ADHD? The physician must take a careful history and have parents and teachers fill out checklists, because only 20% of children show signs of ADHD in the office. Historical factors in ADHD known to be associated with the mothers pregnancy include heavy metal exposure, chronic drug abuse, moderate alcohol use, or smoking more than 4 cigarettedday. Once the diagnosis is made and before medication is started, an explanation to the parents is helpful. Compare the brain to a machine, and tell parents that the medication lubricates the system and makes it run more smoothly; it does not offer a cure. Physician and parents can tell the child that the medication is like a baseball glove; if the child takes the medication, it will help him or her, but the child must still try to play the game.

6. What is the role of clonidine in the treatment of child and adolescent behavior disorders?
Clonidine is useful in treating patients with ADHD and oppositional defiant disorders who have not responded to more conservative treatment with stimulants and behavioral therapy. It is a centrally acting drug that inhibits release of norepinephrine and acts centrally to reduce brain arousal; its effects on attention are indirect. Its antihypertensive effects are not clinically evident in children and adolescents, despite a 10% decrease in measured blood pressure. Clonidine reduces arousal and irritability, improving frustration tolerance. Parents have noted improvement in doing chores, and teachers have seen a reduction in classroom aggression. Clonidine is rapidly absorbed, peaking in 60-90 minutes. If inactive, such as sitting on a school bus, patients may fall asleep for up to 30 minutes afterwards. When active, patients are alert and not sedated. The clinical effects last only 3-4 hours because of rapid metabolism by both liver and kidneys. The dose ranges from 4-6 pg/kg/day. A typical starting dose is one-half of a 0. I-mg tablet at bedtime for 3 days. Another half tablet is added in the afternoon or morning, increasing gradually to a dose of 2-4 tablets given 2-3 timedday. Clonidine has been used as a test for growth hormone release, but it is not clear whether it actually increases growth. It increases appetite, however, and this effect is helpful in reducing weight loss when clonidine is combined with methylphenidate hydrochloride (Ritalin). Clonidine also reduces energy and stamina, and these effects, along with lowered blood pressure, should be monitored. Clonidine is available in the form of a skin patch (Catapres TTS) in doses of 1, 2, and 3 mg; the patch lasts for about 5 days. Young patients adapt easily and wear the patch on their back. The patch tolerates brief exposure to water (as in the shower), but if submerged or pulled at, it loosens. An overlay patch, which comes with each medication patch, may be used. A new area of the back should be chosen each week. About 25-50% of patients react with local irritation, itching, and erythema. The reaction is more commonly to the gum in the patch than to the medication itself. Older children

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and adolescents frequently want to demonstrate their own control by improving or removing the patch. Some adolescents explain its presence as a way of staying off nicotine, although clonidine was not effective for this indication in adult trials.

7. Can clonidine be combined with methylphenidatehydrochloride? For patients with both oppositional or conduct disorders and ADHD, clonidine may be combined with methylphenidate hydrochloride. Such children often are highly distractible and explosively aggressive; combined medication helps to avoid institutional placement. Often patients take high (> 1 mg/kg) doses of methylphenidate hydrochloride in the morning and at noon and are difficult to control in the afternoon and evening. The addition of clonidine allows an afternoon nap for younger children and more controlled bedtime behavior. In the evening, clonidine should be given at bedtime; otherwise, some patients awaken later in the evening and cannot return to sleep. Frequently, the dose of methylphenidate hydrochloride can be reduced by one-third or more. Side effects such as anorexia and insomnia are relieved whether clonidine is given concurrently or separately later in the day. Clonidine also has been combined clinically with tricyclic antidepressants (TCAs) and neuroleptics. In one case report a patient with only a 1-day wash-out from propranolol had a serious drop in heart rate when clonidine was started. Heart rate rebounded when clonidine was discontinued. Propranolol and clonidine should not be given simultaneously.

8. Can Tourettes disorder (TD) in children be treated with clonidine? It is important to establish the correct diagnosis. Many children have motor tics, but the diagnosis of TD requires additional vocalizations (grunts, yelps, explosive sounds, or words). TD in adults
most often is treated with haloperidol, but child psychiatrists often start with clonidine. Clonidine has a slower onset of action and lower response rate than haloperidol or pimozide, but a lower incidence of side effects and no risk for tardive dyskinesia.

DEPRESSION
9. Do children become depressed like adults?
Depression is now recognized in children, although it may not be the same disorder as in adults. Because larger numbers of children respond to placebo, it is difficult to tell whether medications are effective. Symptoms of depression in children include self-deprecation, inhibition, sleep disturbance, morning tiredness, decreased activity, difficulty in concentrating, and poor school perfornot mance. But they also may exhibit aggression, enuresis, and hypochondriasis-symptoms predicted from the adult model. TCA doses have ranged from 1-5 mg/kg, usually of imipramine, after an initial EKG. Blood levels and serial EKGs are performed weekly when patients take doses > 4 mgkg to monitor the quinidine-like effect of imipramine. Responders had higher plasma levels (about 150 nglml) than nonresponders, with optimal response at blood levels of about 200 ng/ml of imipramine and its metabolites. Higher levels were associated with decreased efficacy and delirium on some occasions.

10. Is monitoring of blood levels necessary in every child? It is important to measure TCA blood levels routinely in children, because clinical response is related to blood level, not dosage, and a 40-fold difference may exist in the plasma concentration of different patients receiving the same dose. Because children differ from adults in body fat, percent of total body water, and protein-binding characteristics, and have more active enzyme systems, they may create and accumulate more metabolites than adults. Available studies indicate that both beneficial and serious side effects of TCAs are related to plasma concentration and that the therapeutic range is relatively narrow; thus monitoring of plasma levels is necessary in the treatment of childhood depression. A I-week baseline period should be obtained in all children before treatment, as about 20% will no longer be depressed after this interval. There is no benefit in monitoring blood levels of other antidepressants, as blood levels are not well correlated with clinical response.

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11. What about adolescent depression? Although scientific evidence is lacking, most clinicians agree that adolescents whose depression resembles adult endogenous depressions respond to TCAs. Adolescent major depressions are characterized by gradual onset, anorexia, weight loss, middle- and late-night insomnia, psychomotor disturbance, and family history of serious depression. Early morning wakening is so strikingly different from the usual stay-up late and sleep-in style of adolescents that it should raise the clinicians suspicion. Many adolescents also no longer appear depressed after a short hospital stay without medication. There are no reliable laboratory studies for diagnosing depression (e.g., dexamethasone suppression test). As in adults, diagnosis is based upon history and presentation. Be alert to family histories of mood disorder.

12. What controversies exist in the treatment of adolescent mood disorders?

The problems stem from diagnostic issues. Most adolescents dont present with depressions that look like adult depressions. When they do have symptoms of adult depression (e.g., weight loss, decreased sleep and energy) they also may have auditory hallucinations. Some evidence suggests that these adolescents may be at risk for bipolar disorder. Therefore, adolescent patients with hallucinations may be helped by putting them on mood stabilizers before, or in addition to, antidepressants or antipsychotics. Another diagnostic issue occurs when adolescents present with aggression and irritability, but no grandiosity or hallucinations. The diagnostic manual, DSM IV, allows the diagnosis of manic disorder without euphoria or hallucinations. However, the combination of irritability and aggression most often presents in adolescents who suffer from conduct disorder, and this is the diagnosis typically given by child psychiatrists. Adult or general psychiatrists are likely to make the diagnosis of bipolar disorder and commence treatment with a mood stabilizer (e.g., valproic acid). This places the patient at some risk because valproate has known side effects for adolescents; while hair loss is only a temporary problem, polycystic ovaries, a life-long concern, have been reported in adolescent girls. It is the opinion of many child psychiatrists that bipolar disorder should not be diagnosed in the absence of psychosis or euphoria, even if irritability is present. Epidemiological studies show that conduct disorder is many times more frequent than bipolar. Giving a sedating medication like valproate to every irritable adolescent does not prove the diagnosis of bipolar disorder, but may create a patient who appears improved largely because he or she is sedated.

13. Are adolescents at risk for overdosing on medications?

The adolescents ability for rapid behavior change necessitates caution. Adolescents attempt suicide more than other age groups, many by drug overdose. This fact emphasizes the need for careful assessment of suicide risk and follow-up of adolescents taking medications with a high potential for lethal overdose (e.g., TCAs, lithium).

14. What about outpatient follow-up for adolescent depression?

When the adolescent is followed as an outpatient, only small amounts of antidepressants are prescribed at one time; thus the patient must be seen frequently or a responsible adult must be in control of dispensing. In follow-up visits, the patient is asked routinely about sleep disturbance. If middle or late insomnia recurs, the patient should resume therapeutic doses and may be on maintenance treatment for 1 year. Such long-term therapeutic regimens are extrapolations of prescribing patterns for adults; there are no comparable adolescent studies. To date, drug studies in adolescents do not demonstrate the superiority of antidepressant over placebo in the treatment of depression, but practitioners continue to see clinical improvement after careful diagnostic screening for major depression.

15. Are newer medications safer? Yes. Many of the newer antidepressants (e.g.. fluoxetine and sertraline) have been used with adolescents and are less toxic in overdosage than TCAs; hence they are safer to use. Fluoxetine is the selective serotonin reuptake inhibitor (SSRI) that has been used most often with adolescents who are depressed, as an extrapolation of its wide use in adults. Trazodone also has been successfully used in

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doses up to 400 mg/day. Because trazodone is initially quite sedating and may cause light-headedness, it was originally given in divided doses after meals. Now it is most often used as an adjunct to fluoxetine to help the patient sleep. It is given at bedtime after a snack. Anticholinergic and cardiac effects are unlikely, but priapism shortly after initiating treatment has been reported; this side effect is a relative contraindication for adolescent boys. Like all currently known antidepressants, trazodone is excreted in breast milk and should not be given to nursing mothers; it is considered a category C drug because of increased fetal absorption in rats. Overall, these medications are much safer than older tricyclics, are at least as effective, and often are better tolerated.

16. Do all classes of depression in adolescents look like depression in adults? Although major depressions respond to regular antidepressants, many depressed adolescents do not meet criteria for major depression, Atypical depressions present with dysphoric mood, but patients maintain mood reactivity while depressed; that is, they respond to comments by the interviewer with a change of mood. In addition, patients may have a history of sensitivity to rejection. Instead of weight loss and inability to sleep, they may show increased appetite or weight gain and sleep over 10 hourdday. Any sleep disturbance in adolescents needs to be distinguished from the common habit of staying up late and sleeping in with overall adequate sleep time. Patients also may complain of severe fatigue, sometimes manifested by complaints of leaden weights in arms or legs.
17. What medications are useful in atypical depression? Earlier studies demonstrated that for atypical depression in young adults, monoamine oxidase inhibitors (MAOIs) were better than TCAs. Of adolescents unresponsive to TCAs, 75% responded to phenelzine in one study. Side effects were numerous, but dietary compliance was a problem for less than one-third. Most patients had no significant side effects, even with dietary indiscretion. Later studies concluded that atypical depression may reflect primarily the age of the patient. A more recent study found that adolescents who fail to respond to treatment with TCAs often improve when lithium carbonate is added. At therapeutic doses of lithium, adolescents took up to 2 weeks to respond, but improvement persisted. Atypical depressions may also represent depression in individuals with bipolar disorder; hence treatment may need to be modified. Atypical depressions may also respond to SSRIs and venlafaxine.

18. Can newer medication be used for atypical depression? Concern over lethal overdose led to a search for treatments of adolescent depression of all types with agents that are less likely to be harmful. Fluoxetine has gained wide use in adults, but few studies are available in adolescents. Bupropion, which is unrelated to both TCAs and SSRIs, has been effective in atypical depression in adults. It has shown stimulant effects and was withheld from introduction because of seizures in bulimic patients who took the drug. Overall risk is low if the dose is below 400 mg per day and any single dose is less than 150 mg. The usual adult dose is 150 mg SR, two timedday; a typical dose in adolescents is 250 mg/day or less. Menstrual irregularities were seen infrequently with bupropion. Both medications are safer in overdose than TCAs, MAOIs, or lithium carbonate.

PSYCHOSIS
19. What kinds of psychoses are seen in children and adolescents? Psychosis in children and adolescents may be reflective of primary psychiatric illness or secondary to medical problems (e.g., toxicity). Delirium is usually the result of drug ingestion, either accidental in children or recreational in adolescents. In either case, treatment is directed to the underlying cause, but delirium-induced agitation may need separate treatment.

20. How is delirium treated in children and adolescents? Treatment usually takes the form of a structured and locked setting, including the use of a seclusion room or restraints if necessary. Delirium-induced agitation also may require judicious medication. A child who is thrashing about may need to be sedated for brain scan, EEG, or radiograph.

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Adolescents who have taken hallucinogens usually can be talked down. Patients who have taken phencyclidine (PCP) may become agitated if a therapeutic encounter is attempted. Such patients may seriously harm themselves and others because the anesthetic properties of PCP keep them from knowing that they have painful injuries. Agitated and delirious patients can be sedated with haloperidol, 0.1-0.3 mglkg, over 1 hour; dystonia is the only likely acute side effect. This side effect frequently is more frightening to the patient and family than the original delirium. Any child or adolescent given haloperidol should be observed closely for 24 hours so that dystonic reactions can be treated. Benadryl (diphenhydramine), 25-50 mg orally or intramuscularly, and reassurance once the dystonia subsides usually are the only treatments needed for dystonias.

21. What about chronic psychotic disorders that accompany autism and head injuries?
More recently, medications have been used to treat the obsessive-repetitive behaviors in autistic children. Clomipramine and fluoxetine have reduced stereotypic behaviors. Patients with chronic psychoses due to head injury, autism, or pervasive developmental disorders may respond to low doses of haloperidol, which reduce stereotyped and aggressive behavior.

22. Can short-term use of antipsychotic medications cause serious side effects?
A major concern is the potential for movement disorders, especially tardive dyskinesia (TD). Acute use of antipsychotic medications is unlikely to cause TD. However, children and adolescents may develop a time-limited form of TD after taking antipsychotics only 6 months. Symptoms appear in the extremities as choreiform movements or as ataxia and usually disappear 2 weeks after the medication is discontinued, but movements may persist from 3-12 months. Many chronically ill children and adolescents may need to be on neuroleptics for years and, like adults, are at risk for long-term oral-buccal tardive dyskinesia. One of the newer atypical neuroleptics, resperidone, has also caused dyskinesias. Olanzapine has led to large weight gain and akathisia. Quetiapine has been associated with cataracts in dogs.

23. What primary psychiatric illnesses can present as psychosis? Mania, schizophrenia, and depression can all present as psychosis. Psychotically depressed children and adolescents have more auditory hallucinations than adults; these can be treated by adding neuroleptics to the antidepressants. Hallucinations usually remit in less than 1 month, and the neuroleptics can be discontinued. Adolescents and children with psychotic depressions are at risk for bipolar disorder. Although mania is quite uncommon in children, 20% of all bipolar disorders have their onset before the age of 20, most often presenting initially as major depression.

24. How is mania treated?

Mania in children and adolescents presents more commonly with irritability than euphoria and also has a high incidence of hallucinations, making differentiation from schizophrenia difficult. Clinicians should err in favor of the least disabling diagnosis; thus the diagnosis frequently is mania, even if not all hallucinations are related to mood. Agitation and hallucinations respond to neuroleptics, but the grandiosity usually requires lithium carbonate. Baseline kidney and thyroid function studies are done to confirm the patients ability to clear lithium and euthyroid status. Lithium carbonate is begun at up to 30 mglkg in divided doses. Lithium carbonate, 300 mg in sustained-release form, avoids the gastric upset and dizziness associated with regular lithium. Within 5 days the patient should be in range of 0.8-1.2 mEq/L. Children and many adolescents need to reach levels of 1.5 mEqL for a good serum level. Doses which maintain a serum range of 0.8-1.2 mEqL are also appropriate for maintenance. The serum level is followed at gradually greater intervals. Thyroid studies should be repeated at 6-month intervals, because a few patients become hypothyroid. If a good response ensues, with tolerable side effects, chronic maintenance is recommended as bipolar illness tends to get worse over repeated episodes. Preventing recurrence is extremely important to the long-term prognosis.

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25. What are the alternative medications for mania?

Carbamazepine and valproic acid have been used as alternatives because 3 0 4 0 % of adult manic patients do not respond to or cannot tolerate lithium carbonate. The use of carbamazepine is less common in children than in adults. Sodium divalproex is used for dysphoric mania, rapid cycling, and patients whose presentation includes psychotic symptoms or substance abuse in addition to mania. Many adolescents present with psychotic symptoms, and sodium divalproex often is added to lithium carbonate, but also may be used alone. After baseline liver and platelet studies, sodium divalproex is given in divided doses of 20 m g k g . It is rapidly absorbed with a peak action at 4-6 hours. The dose is gradually increased until levels of SO-120 mg/ml are reached. Patients frequently respond in 5-10 days. The most common side effects are GI upset, mild tremor, and initial lethargy. A decrease in platelets and an increase in liver enzymes may occur. An increase of liver function values to 300% of baseline is acceptable, and thrombocytopenia usually is not seen until blood levels exceed 100 mg/ml of valproate. Hair thinning is transient and dose-related but may be particularly disturbing to adolescents. Sodium divalproex also is available in pull-apart capsules as a sprinkle that can be used in soft foods with younger children or patients who cannot take capsules by mouth. Unlike lithium, sodium divalproex is 80-95% protein-bound and thus competes with other protein-bound medications, such as carbamazepine or fluoxetine. As a result of the interaction, the less tightly bound drug is displaced and its side effects are increased. Although sodium divalproex and carbamazepine have been used in combination in adults, their interaction is complex. Little experience is available in adolescents; it is safer to use one or the other by itself. Sodium divalproex is a recent addition to the child psychiatry armamentarium and, if polypharmacy is avoided in younger children, a safe alternative to lithium. However, use of valproate in girls poses a risk of polycystic ovary; hence it should be used only when other options have failed or are contraindicated.

26. How is schizophrenia treated? Schizophrenia frequently begins in adolescence. A gradual decline in functioning with the onset of suspiciousness and auditory hallucinations that comment on ones behavior are ominous signs. A baseline CT scan is done to check ventricular size. Atrophy is associated with poor prognosis. This also screens for lesions that could cause psychosis. Treatment with neuroleptics requires a minimal dose of 300 mg of chlorpromazine or 5 mg of haloperidol. Chlorpromazine and thioridazine cause problems with sexual side effects (retrograde ejaculation or galactorrhea) and general inhibition of movement (akinesia). The potent neuroleptics tend to induce dystonia, particularly if large doses are given early in treatment. The newer, atypical antipsychotic medications are rapidly becoming the first-line treatments because of more tolerable side effects and greater efficacy. Akathesia, which may appear later with any neuroleptic, requires a reduction in dose or the addition of propranolol, 40-120 mg/day. If the patients agitation or perplexity persists, the dose of neuroleptic is gradually increased, and the patient is observed for approximately a week before increasing the dose again. Over a period of approximately 6 weeks the patients hallucinations and psychosis gradually come under control. A significant portion of psychoses in adolescents seems to result from severe external stresses and remit without further recurrence. Mania and schizophrenia, on the other hand, are considered life-time illnesses.

BEHAVIOR OR CONDUCT DISORDERS

27. Is there a practical way of classifying behavior disorders? Behavior disorders can be divided into good kid and bad kid styles. The good kid has discrete episodes of anger, usually with little or no precipitant. Good kid adolescents trash their rooms, throw things, or hit whoever happens to be close. Once over this episode, they are contrite and apologetic. An EEG may be helpful, because some patients have an epileptic focus, usually in the temporal lobe. However, up to 40% of EEGs are false negatives, and nasal pharyngeal leads are not well tolerated.

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Sometimes diagnosed as having explosive disorders, such patients do better on carbamazepine. A baseline CBC with reticulocyte count is necessary, because carbamazepine usually reduces the WBC initially. If carbamazepine is started at a low dose of 200 mg/day and increased by 200 mg each week with weekly blood counts for the first month, there are few problems. If the dose is increased too quickly, the patient often complains of upset stomach. In almost all cases, the reticulocyte count decreases, with a later decrease in overall white cell count. A petechial rash rarely appears. Therapeutic carbamazepine levels of 0.8-1.2 pg/ml are associated with a reduction in outbursts after 1 month with adequate drug serum levels. If the white cell count drops below 4000, the clinician may consider the trial a failure. Patients who respond need regular white counts with gradually decreasing frequency. As in adults, blood levels may drop over time because of enzyme induction. Clinically, some adolescents show increased imtability on carbamazepine, particularly those with an associated affect disorder.

28. Are the bad kids more commonly diagnosed? The bad kids are classified as conduct disorders. DSM-IV lists 15 symptoms of conduct disorder, requiring at least three for the diagnosis: Often bullies, threatens, or intimidates others Often initiates physical fights Used a weapon that can cause serious physical harm to others Has been physically cruel to people Has been physically cruel to animals Has stolen, with confrontation of the victim Forced sexual activity on someone Deliberately engaged in fire setting with intention of serious damage Deliberately destroyed others property Has broken into someone elses property Often lies, to obtain favors or avoid obligations (cons) Has stolen without confrontation of victim more than once Stays out at night, with onset before age 13 Has run away from home overnight at least twice Often truant from school, with onset before age 13 The diagnosis of conduct disorder is much more common than explosive disorder (good kid), because only three symptoms from the list above are required.
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29. What other diagnoses should be considered? Even when the patient meets the criteria for diagnosis of conduct disorder, a careful review of the possibility of ADHD and affective disorders should be performed. ADHD is commonly associated with conduct disorder and worsens the overall prognosis. It is worthwhile to consider a trial of clonidine if the aggression is mostly verbal and ADHD is prominent; clonidine seems to reduce irrtability in patients with ADHD. Of delinquent populations, 23-30% meet the criteria for major depression and deserve treatment. In one study of depressed conduct-disordered male adolescents, behavior improved as the depression lifted after treatment with imipramine. Bipolar disorder also should be ruled out, with particular attention to family history. Clinicians have increasing awareness of bipolar disorder in adolescents with the understanding that the offspring of bipolar parents also are at risk for mania. Mania in adolescents frequently presents as imtability, and underlying irritability frequently accompanies conduct disorder behavior; thus, lithium was tried in the treatment of conduct disorder. One study comparing lithium with haloperidol found both to be equally effective, but lithium caused fewer side effects, including no detrimental effect on learning. Although responsiveness to lithium does not prove a bipolar diagnosis, it is reasonable to give a conduct-disordered adolescent a trial of lithium if other treatable disorders are unlikely. Only one controlled study has shown that youth with affective symptoms are more responsive to lithium. 30. What are the general principles of treating conduct disorder with medication? Treatment for conduct disorder with lithium follows the regimen for bipolar disorder with kidney and thyroid studies and with gradual increase in the lithium level to the range of 1.O-1.5

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mEq/L. An EEG should be obtained before lithium is started, because lithium in the system creates EEG artifacts. Hand tremor and gastric distress are common but mild. Sustained-release lithium may be used to reduce gastric distress, and beta blockers may reduce tremors. Medications frequently are necessaryfor conduct disorder, hut never sufficient. Structure and control during inpatient care and follow-up are always necessary. Many, if not all, patients with conduct disorders need remedial education for reading and learning disabilities.

GENERAL ANXIETY AND OBSESSIVE-COMPULSIVE DISORDER

31. Why were childhood anxiety disorders not treated in the past? Child psychiatrists traditionally have not treated anxiety disorders with medications because of a belief that anxiety was part of the developmental process and a concern that medication may interfere with the process. Until recently, medications used to treat anxiety also carried some potential for addiction or at least psychological dependence among adults. The introduction of buspirone allows the treatment of anxiety disorders with a medication that has no addiction liability and does not produce sedation. There are few reports of its use in children or adolescents. Case reports have found it useful in treating anxiety in adolescents. Additional reports have shown it to be a useful adjunct in reducing aggression in autistic adolescents. Currently the indications are clinical; its efticacy has not been established for general use. 32. Does increasing evidence suggest that obsessive-compulsive disorder (OCD) is an organic medical problem? One specific type of anxiety associated with obsessions and compulsions has responded to agents that increase serotonin in the CNS. Such agents markedly reduce behaviors associated with this particular anxiety. Although the cause is unknown, recent biologic, clinical, radiologic, and physiologic evidence strongly implicates problems in the caudate or connections from caudate to the prefrontal area of the brain. Patients with Sydenhams chorea and postencephalitic patients have OCD more often than the general population, and both disorders have obvious organic causes. OCD is much more common than previously thought. As much as 2-3% of the U.S. population is estimated to be affected-more than 4 million people. Clues in children include erased school papers (sometimes so repeatedly that holes are worn through the paper) and/or retraced letters. Clues in adolescents include bleeding gums from overbrushing and extreme religiosity.
33. What treatments have been used for OCD? Many treatments have been tried. Psychotherapy is ineffective. Behavior therapies have been variably effective. Stimulus exposure with response prevention is effective, but 25% of patients drop out, and many do not follow through on exposure-response prevention. Antianxiety agents, neuroleptics, and antidepressants have been tried without much success. Infrequently, children respond to imipramine and, rarely, clonidine. Clomipramine is a strong serotonin reuptake blocker often used for OCD in children. Clomipramine has a typical tricyclic side-effect profile of dry mouth, constipation, tremor, dizziness, somnolence, headache, and fatigue, but such effects are seen less often in children. As much as 200 mg/day or as little as 3 mg/kg may be used for children or adolescents. Fluvoxamine is now also indicated in the pediatric age group (8-17) for the treatment of OCD. Doses start with 25 mg at bedtime, titrated up to 200 mg per day in divided doses, with the largest dose given at bedtime. Behavior therapy with parental assistance helps.
BIBLIOGRAPHY
1, Campbell M, et al: Lithium in hospitalized children with conduct disorder: A double-blind and placebo-con-

trolled study. J Am Acad Child Adolesc Psychiatry 34:445-453, 1995. 2. Conners CK: Rating scales in attention-deficit disorder: Use in assessment and treatment monitoring. J Clin Psychiatry 59:24-30, 1998. 3. Cowart VS: The Ritalin controversy: Whats made this drugs opponents hyperactive? JAMA 259:25212523. 1988.

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