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Osler Institute Child & Adolescent Psychiatry Review







Drug interactions are ubiquitous

• Only rarely an absolute contraindication

Drug-drug interactions in • Only one of many factors involved in

prescribing decisions

psychopharmacology

• More critical examples include: lithium,

Shauna P. Reinblatt, MD nortriptyline, monoamine oxidase

Johns Hopkins University inhibitors, pimozide, carbamazepine,

ketoconazole









Examples of particular

Other relevant factors

relevance

• Age • Unexplained mental status changes

• Gender • Clinical deterioration

• Hepatic or renal disease

• Refractoriness to standard treatment

• Smoking

• Extreme or erratic drug plasma levels

• Alcohol use

• Diet and nutritional status • Issues with drug absorption, serum protein

• Compliance

binding, altered elimination

• Genetic polymorphisms









Useful drug interactions Categories of drug interactions

• Naloxone (Narcan) for opiate overdose • Idiosyncratic – rare, unpredictable,

• Flumazenil (Romazicon) for unexpected from pharmacokinetic and

benzodiazepine overdose pharmacodynamic properties

• Bethanechol (Urecholine) for • Pharmacodynamic

anticholinergic side effects (urinary

retention) • Pharmacokinetic

• Anticholinergics for antipsychotic induced

extrapyramidal symptoms









Reinblatt_Clinical Psychopharmocolgy 1

Osler Institute Child & Adolescent Psychiatry Review







Pharmacodynamic Pharmacodynamic examples

• Known direct effects at biologically active • CNS depression from alcohol,

receptor sites that do not involve an benzodiazepines and/or barbiturates

alteration in drug plasma levels • Cardiac conduction delays from quinidine-

• May be additive, synergistic, or like effects ie low potency antipsychotics

antagonistic and tricyclic antidepressants

• Anticholinergic toxicity from drugs sharing

antimuscarinic properties









Pharmacodynamic examples Pharmacokinetic interactions

• Hypotension with alpha-1-adrenergic • Involve a change in the plasma level

blockade and/or tissue distribution of drugs, rather

– Antidepressants – trazodone, imipramine than their pharmacological activity.

– Low potency and atypical antipsychotics – • Mediated by effects on

clozapine, olanzapine – Absorption

– Interference with dopamine agonist or – Distribution

precursor for Parkinson’s disease or – Metabolism

hyperprolactinemia by an antipsychotic – Excretion









Children compared with adults Absorption issues

• Greater hepatic capacity • Accelerated gastric emptying

• More glomerular filtration – Metaclopramide (Reglan)

• Less fatty tissue • Diminished gastrointestinal motility

• Therefore more rapid elimination of – TCA’s, morphine, canabis

stimulants, antipsychotics, TCAs, lithium • Binding to other drugs

• Shorter half-life of meds in children – Cholestyramine (Questran), charcoal, kaolin-

pectin, non-absorbable fats

• Higher mg/kg dosing is usually required









Reinblatt_Clinical Psychopharmocolgy 2

Osler Institute Child & Adolescent Psychiatry Review







Absorption issues Distribution issues

• Altered gastric pH • Regional blood flow

– Aluminum hydroxide, magnesium hydroxide, • Lipophilicity

sodium bicarbonate, potentially altering the

non-polar, un-ionized fraction of drug • Amount of drug bound to tissue and

available for absoption plasma proteins

• inhibition of gastric or intestinal enzymes • Adipose to lean body mass ratio

resulting in elevated concentration of

substrate

– Monoamine oxidase – tyramine









Competition for protein-binding

Minimal protein binding

sites

• Most psychotropic drugs are highly • Lithium

protein-bound at 80% to 90% to albumin, • Gabapentin

alpha-1-acid glycoproteins, or lipoproteins • Topiramate

• Effects usually have no practical • Oxcarbazine

significance because of offset by rapid

redistribution to sites of metabolism • venlafaxine









Effects on transport to tissue Interference with metabolism

• Amino acids competing with l-dopa for • Phase I

protein carrier across blood-brain barrier – Oxidation, reduction, hydrolysis





• Phase II

– Glucuronidation and acetylation resulting in

highly polar, water-soluble metabolites

suitable for renal excretion









Reinblatt_Clinical Psychopharmocolgy 3

Osler Institute Child & Adolescent Psychiatry Review







Exceptions Metabolic enzymes

• Benzodiazepines (lorazepam, oxazepam, • Cytochrome P450 isoenzymes

temazepam, and clonazepam undergo – Inducing agents produce gradual decline of

only Phase II substrate level

– Inhibitors produce abrupt elevations over

• Lithium, gabapentin, and amantadine are hours to days of blood levels and levels fall

excreted by the kidneys without hepatic rapidly upon discontinuation

biotransformation • Flavin-containing monoxygenases

(FMOs), N-acetyltransferase,

glucuronyltransferases,

methyltransferases, and sufotransferases









Renal excretion Cytochrome P450 isoenzymes

• Lithium interactions • Over 30

• Emergency management • Located in the endoplasmic reticulum of

– Enhanced excretion of weak bases such as hepatocytes and GI tract and brain

PCP and amphetamines by acidification of • 1A2

urine with ammonium chloride

• 2C

– Enhanced excretion of weak acids such as

tricyclic antidepressants and barbiturates with • 2D6

acetazolamide • 2A3/4









2D6 polymorphisms 1A2 substrates

• 2D6 • Acetaminophen, aminophylline, caffeine,

– 7-10%Caucasians are poor clozapine, haloperidol, olanzapine,

metabolizers phenacetin, procarcinogens, ropinirole,

– 1-3% A-A or Asian tertiary tricyclic antidepressants,

theophylline

– Have higher baseline concentrations of

substrate, lower concentration of

metabolites, and little effect from

inhibitors or inducers









Reinblatt_Clinical Psychopharmocolgy 4

Osler Institute Child & Adolescent Psychiatry Review







1A2 2C

• Inhibitors • Substrates

– Fluoroquinolones (Cipro), fluvoxamine, – Barbiturates, diazepam, NSAIDS, propranolol,

grapefruit juice tertiary TCA’s, THC, tolbutamide, warfarin

• Inducers • Inhibitors

– Fluoxetine, fluvoxamine, ketoconazole,

– Cigarette smoking, omeprazole (Prilosec), omeprazole, oxcarbazepine, sertraline

charbroiled meats

• Inducers

– rifampin









2D6 Substrates 2D6 Inhibitors

• Amoxetine (Strattera), beta-blockers • Antimalarials, bupropion, duloxetine,

(lipophilic), codeine, donepezil (Aricept), fluoxetine, methadone, moclobemide,

dextromethorphan, encainide, flecainide, paroxetine, phenothiazines, protease

haloperidol, hydroxycodone, inhibitors (ritonavir), quinidine, sertraline,

phenothiazines, risperidone, aripiprazole, TCAs, yohimbine

SSRIs, TCAs, tramadol (Ultram)

• Inducers ?









3A3/4 Substrates 3A3/4

• Alprazolam, amiodarone, aripiprazole, • Inhibitors

buspirone, calcium channel blockers, – Ketoconazole, verapamil, cimetidine,

carbamazepine, clozapine, cyclosporine, fluvoxamine, grapefruit juice, erythromycin,

diazepam, disopyramide, estradiol, nefazodone

lidocaine, lovastatin, loratadine,

• Inducers

methadone, midazolam, quetiapine,

sildenafil, simvastatin, tertiary TCAs, – Carbamazepine, oxcarbazepine,

triazolam, warfarin, zaleplon (Sonata), phenobarbital, phenytoin, rifampin, St. John’s

ziprasodone, zolpidem (Ambien) wort









Reinblatt_Clinical Psychopharmocolgy 5

Osler Institute Child & Adolescent Psychiatry Review





PSYCHOTROPIC SIDE

Developmental Considerations

EFFECTS

• Developmental Issues • Increased renal clearance

• Medications • Hormonal changes during puberty

• Contraindications • Increased hepatic metabolism

• Interactions

• Side effects

• Important notes









Stimulants: Stimulants

• ADHD in children and adolescents • Contraindications:

• ADHD in adults (Adderall) – Hypersensitivity

• Narcolepsy – Cardiac abnormalities

– Active psychosis

– MAOI treatment

Others off label…

– glaucoma









Side Effects

• Irritability, dysphoria, GI distubance, • Concerns re: clonidine and

insomnia, increased heart rate, decreased methylphenidate? …

appetite, ?tics

• Sudden death risk (Adderall)-Risks when

personal or family history of cardiac

problems esp long QTc.









Reinblatt_Clinical Psychopharmocolgy 6

Osler Institute Child & Adolescent Psychiatry Review







Atomoxetine

• Rebound • Indicated kids 6 years and over for ADHD

• Headache • Contraindication: Narrow Angle Glaucoma

• Irritability • Somnolence, fatigue, decreased appetite,

• Tics weight loss

• Warnings: hepatic injury and suicidality









Tricyclic antidepressants

• Indications: ADHD, OCD, Enuresis • Sudden cardiac death in children with

• Contraindication: MAOI desipramine- 7 cases. (Ref; Varley,

• Relative: Pregnancy, cardiac problems, CK(2001) Pediatric Drugs 3(8) 613.

thyroid conditions Several of the children had family history

of cardiac problems









Alpha Adrenergic Agents –

TCAs and Cardiac Monitoring

Clonidine and Guanfacine

• Baseline EKG and blood pressure, pulse • ADHD, Tourettes, tics (all off label)

and repeat with increased dose and every • Contraindication: cardiac problems, renal

three months. or liver disease

• Side effects: Sedation, hypotension,

dizziness, abdominal pain









Reinblatt_Clinical Psychopharmocolgy 7

Osler Institute Child & Adolescent Psychiatry Review







Mood stabilizers Lithium

• Lithium • Indication: Acute mania nad prophylaxis

• Valproate over 12 yrs

• Carbamazepine • Side effects: weight gain, psoriasis,

• Lamotrigine enuresis, polyuria, polydipsia,

hypothyroidism.

• Gabapentin

• Narrow therapeutic window.

• Topiramate

• Ebstein’s abnormality in pregnancy

• Toxicity symptoms…coarse tremor









Lithium Lithium

• Increased lithium level • Increased antithyroid effect

– Thiazide diuretics, ACE inhibitors, NSAIDS • Check calcium (PTH)

(except sulindac, aspirin), metronidazole, • Neurotoxicity (rare)

spectinomycin, tetracycline – Antipsychotics, calcium channel blockers,

carbamazepine, methyldopa

• Decreased lithium level

• Prolonged neuromuscular blockade

– Aminophylline, theophylline, acetazolamide,

– Succinylcholine, pancuronium

sodium bicarbonate, sodium chloride, osmotic

diuretics (mannitol, urea) • Serotonin syndrome (rare)

– SSRIs, serotonergic TCAs, tramadol, venlafaxine









Valproate

• Informed consent re: medication • Indications in adults: migraines, partial

interactions, ex. No NSAIDs, careful seizures, mania or mixed episodes

hydration, inform of new medications. • Side Effects: nausea, sedation, inc.

appetite, hair loss, black box warnings for

hepatotoxity and pancreatitis

• Polycystic ovary disease









Reinblatt_Clinical Psychopharmocolgy 8

Osler Institute Child & Adolescent Psychiatry Review







Valproate Valproate

• Increased valproate levels • Inhibited metabolism of co-administered

– Aspirin (increased unbound levels), agents

cimetidine, erythromycin, ibuprofen, – Lorazepam, oxazepam, tempazepam,

phenothiazines diazepam, LAMOTRIGINE, carbamazepine,

phenobarbital, tolbutamide, warfarin, AZT

• Decreased valproate levels

– Carbamazepine, phenobarbital, phenytoin,

rifampin









Carbamazepine Carbamazepine

• No indication in children, in adults • Increased carbamazepine levels

indicated for acute manic and mixed – Valproate (active CBZ-E metabolite), P450

episodes 3A4 inhibitors, antifungals, macrolide

antibiotics, calcium channel blockers,

• Cytochrome P450 interactions and

fluvoxamine, grapefruit juice, isoniazid,

autoinduction nefazodone, protease inhibitors

• Hyponatremia

• Black box agranulocytosis









Carbamazepine

• Decreased carbamazepine levels • Carbamazepine– autoinduction after

– Carbamazepine (autoinduction), several weeks

phenobarbital, phenytoin, primidone

– Hyponatremia

• Induced metabolism of co-administered

agents

– Anticonvulsants (phenytoin, lamotrigine,

valproate), antidepressants, antipsychotics,

benzodiazepines, cyclosporine,

glucocorticoids, methadone, oral

contraceptives, warfarin









Reinblatt_Clinical Psychopharmocolgy 9

Osler Institute Child & Adolescent Psychiatry Review







Effects of P450 inhibition Effects of P450 inhibition

• Antihistamines (astemizole, loratidine) 3A4 • Codeine

• Antipsychotics – Metabolized by 2D6 into active (morphine)

– 1A2 clozapine, olanzapine, haloperidol metabolite

– 2D6 risperidone, phenothiazines • Secondary TCAs

– 3A4 quetiapine – Metabolized by 2D6

• Benzodiazepines • Tertiary TCAs

– 2C diazepam

– Metabolized by 1A2, 2C, 2D6, 3A4

– 3A4 triazolam









2D6 Serotonin syndrome

• Most inhibition • Myoclonus

– Fluoxetine, paroxetine, duloxetine • Hyperreflexia

• Moderate inhibition • Nausea

– Sertraline • Hyperthermia

• Autonomic instability

• Negligible inhibition

• Agitation

– Citalopram, escitalopram

• Delirium

• Coma









Serotonin Syndrome TCA interactions

• Monoamine oxidase inhibitors • Increased TCA levels

– Methylphenidate, SSRIs

– Remember Demerol

• Decreased TCA levels

• Lithium – Carbamazepine, phenobarbital, phenytoin

• Serotonergic agents • Prolonged cardiac conduction

– Type I antiarrhythmics, low potency antipsychotics,

CCBs

• Hypotension

– Antihypertensives, antipsychotics, trazodone









Reinblatt_Clinical Psychopharmocolgy 10

Osler Institute Child & Adolescent Psychiatry Review







Antipsychotic interactions Antipsychotic interactions

• Increased antipsychotic levels • Decreased absorption - antacids

– Inhibitors of 1A2, 2D6, 3A4 including • Prolonged cardiac conduction

fluoxetine, paroxetine, fluvoxamine, – CCBs, TCAs, P450 inhibitors

nefazodone, bupropion, duloxetine, • Hypotension – TCAs, trazodone

fluoroquinolones, macrolides, antifungals • Anticholinergic toxicity

• Decreased antipsychotic levels • Interference with dopaminergic effects

– Lipophilic betablockers, carbamazepine, • Additive risk of myelosuppression

phenobarbital, phenytoin – Carbamazepine, AZT with clozapine









Antipsychotic interactions Antipsychotic interactions

• Pimozide (Orap) 3A4 • Quetiapine and ziprasidone are 3A4

– Dangerous arrhythmia potential substrates

• Clozapine, olanzapine, haloperidol 1A2 – Concentration increased by erythromycin

– Inhibited by Luvox, Cipro – Concentration decreased by carbamazepine

– Induced by omeprazole, cigarette smoking • Aripiprazole substrate of 3A4 and 2D6

• Phenothiazines are both substrates and – Increased by fluoxetine

inhibitors of 2D6 – Decreased by carbamazepine









Neuroleptic Malignant Concerns with Atypical

Syndrome Antipsychotics

• CPK elevation • Metabolic syndrome

• Neuroleptics • EPS

• Autonomic instability • Tardive dyskinesia

• Delirium • Hyperprolactinemia

• Febrile • Cardiac

• Dantrolene









Reinblatt_Clinical Psychopharmocolgy 11

Osler Institute Child & Adolescent Psychiatry Review







Cardiac Anxiolytic pharmacodynamics

• Montior baseline and when raise • Additive CNS depressant effects

mediation. – Barbiturates

• Caution with QTC> =450! – Antihistamines

– TCAs

or high HR – Antipsychotics

Or elevated PR or QRS – Antiepileptic drugs

– Hypnotics – zolpidem, zaleplon, Lunesta

Monitor – alcohol









Anxiolytic pharmacokinetics Anxiolytic pharmacokinetics

• Antacids may delay absorption • 3A3/4 inhibitors – macrolides, antifungals,

• Phase I inducers (CBZ, PHB) may lower nefazodone, fluvoxamine, grapefruit juice

blood levels except lorazepam, oxazepam, may increase levels of alprazolam,

and temazepam triazolam and midalozam

• Valproate inhibits glucuronide conjugation • 2C inhibitors – omeprazole, ketoconazole,

increasing levels of lorazepam, oxazepam, fluoxetine, fluvoxamine, sertraline, may

and temazepam increase levels of diazepam









St. John’s wort induces 3A4 Methylphenidate

• Cyclosporine • Inhibits metabolism of

• Antiretrovirals

• Anticoagulants – SSRIs

• Theophyllinge

• Digoxin – TCAs

• Oral contraceptives

– anticonvulsants









Reinblatt_Clinical Psychopharmocolgy 12

Osler Institute Child & Adolescent Psychiatry Review







Modafinil (Provigil) Atomoxetine (Strattera)

• Induces 3A4 • Substrate of 2D6

• May lower level and effectiveness of oral • Metabolism is inhibited by fluoxetine,

contraceptives paroxetine, bupropion









Cholinesterase inhibitors Codeine

• Rivastigmine (Exelon) has no P450 aspect • Substrate of 2D6 which converts it into its

active form (morphine). Diminished

• Galantamine (Rasadyne) and donepezil analgesic effect if co-administered with

(Aricept) are substrates for 2D6 and 3A4 2D6 inhibitor

but do not induce or inhibit P450









Disulfiram (Antabuse) SSRIs

• Inhibits any array of enzymes interfering • Indications:

with the metabolism of a variety of drugs – MDD- Fluoxetine

– OCD: Clomipramine, Fluoxetine, Flv,

sertraline

– SIDE EFFECTS: include GI, headache, and

behavioral activation

– Suicidality black box warning- extended til mid

20’s re: increased risk of suicidality 4X vs. 2X

in placebo in pooled data









Reinblatt_Clinical Psychopharmocolgy 13

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Osler Institute Child & Adolescent Psychiatry Review





Adjustment Disorder def.

• An adjustment disorder is a psychological response to

an identifiable stressor or stressors that results in the

development of clinically significant emotional or

behavioral symptoms.

ADJUSTMENT DISORDERS • The symptoms must develop within 3 months after the

onset of the stressor(s).

• Clinical significance of the reaction is determined by

either marked distress in excess of what would be

Shauna P. Reinblatt, MD expected given the nature of the stressor or by

significant impairment in social, occupational, or

academic functioning.

• A normal or expectable reaction to a stressor can

qualify as an adjustment disorder if the reaction is

sufficiently severe to cause significant impairment.









• The stressor may be single or multiple, recurrent or • The DSM-IV also recognizes that the patient’s

continuous, minor or severe, common or unique – in vulnerability is as important to symptom

short, the stressor need only be a psychosocial event

that precedes the symptoms and that the patient and/or

production as is the exact stressor

therapist views as stressful and responsible for the • The disturbance must be something other than

symptoms. “one instance of a pattern of overreaction to

• The maladaptive reaction must be severe enough to stress” or an exacerbation of another mental

impair school (or work) performance, hinder social illness.

activities or interpersonal relationships, and/or be in

“excess of a normal and expectable reaction to the • Adjustment disorder = age independent, defined

stressor(s).” primarily by its symptom picture rather than by

age









Classification Classification

• Adjustment disorder is a specific diagnosis, not a • DSM-III (1980) renamed this category

nebulous category. adjustment disorder and required that specific

objective criteria be met to make the

• The current DSM-IV diagnosis is a refinement of a diagnosis. The DSM-III also defined 8

number of similar diagnoses developed over the years

and called reactive, transient, situational, and adjustment subtypes based upon symptom patterns,

disorders. excluded very minor symptom pictures as

well as psychotic reactions (reclassified as

• The Group for the Advancement of Psychiatry brief psychotic reactions), and removed the

Committee on Child Psychiatry (GAP) in 1966 used developmental stage (age) requirement.

reactive disorder to describe a generally (but not With minor variations, this is the classification

exclusively) transient disorder caused by an emotionally

traumatic event that reflected a conscious conflict in place today in DSM-IV.

between the child and his or her environment. The

DSM-II (1968) described a set of “transient situational

disturbances” .







Schwartz_Reinblatt_Adjustment

Disorders 1

Osler Institute Child & Adolescent Psychiatry Review





DSM-IV diagnostic criteria for

Caveats

adjustment disorders

• One of the most telling problems lies not with the • 1. The development of emotional or behavioral symptoms in

severity of the stressor but with its chronicity. response to an identifiable stressor(s) occurring within 3

months of the onset of the stressor(s).

• If a stressor is continuously present or frequently • 2. Symptoms are clinically significant as evidenced by the

recurrent, does the disturbance become something other following:

than an adjustment disorder after 6 months? • • Marked distress that is in excess of what would be

• Those patients with chronic symptoms due to ongoing expected from exposure to the stressor

stress who also do not meet criteria for another • • Significant impairment in social or occupational

diagnosis fit poorly within this nosology. (academic) functioning

• In addition, sometimes it is exceptionally difficult in the • 3. The stress-related disturbance does not meet the criteria

clinical situation to differentiate between a parent-child for another specific Axis I disorder and is not merely an

problem or uncomplicated bereavement and an exacerbation of a preexisting Axis I or Axis II disorder.

adjustment disorder. -- the severity of both stressors • 4. The symptoms do not represent bereavement.

and symptoms is continuous rather than discrete. • 5. Once the stressor (or its consequences) has terminated,

the symptoms do not persist for more than an additional 6

months









Types

• Adjustment disorders are coded based on the subtype,

• • Acute: if the disturbance last fewer than which is selected according to the predominant

6 months symptoms. The specific stressors(s) can be specified

on Axis IV.

• • 309.0 With depressed mood

• • 309.24 With anxiety

• • Chronic: if the disturbance lasts for 6 • • 309.28 With mixed anxiety and depressed mood

months or longer • • 309.3 With disturbance of conduct

• • 309.4 With mixed disturbance of emotions and

conduct

• • 309.9 Unspecified









With depressed mood -

• Differential diagnosis includes major • This diagnosis requires a predominance of

symptoms of depressed mood, tearfulness, and

depression, dysthymia, bipolar disorder feelings of hopelessness.

(depressed), uncomplicated bereavement, • The differential diagnosis is broad in that it

mood disorder 2e GMC. includes not only key mood disorders but also

• Considered by some to be the most uncomplicated bereavement, which can be

viewed as a variant of adjustment disorder –

common subtype among adults, serious depressive symptoms in response to the

• also common among children loss of a loved one that, however, are an

expected reaction to such a severe stress.









Schwartz_Reinblatt_Adjustment

Disorders 2

Osler Institute Child & Adolescent Psychiatry Review





With anxiety-

• Axis II disorders of the borderline and • differential diagnosis=

histrionic types, particularly in adolescents, – generalized anxiety disorder,

are likely to present with depressive – panic disorder,

symptoms and develop in an individual – post traumatic stress disorder

from a turbulent environment. – anxiety disorder 2e GMC









With disturbance of conduct

• Sx= nervousness, worry, and jitteriness. • Differential diagnosis includes conduct disorder,

oppositional-defiant disorder; child or adolescent

• Subsyndromal levels of anxiety are common antisocial behavior (V-code).

among children and certainly compose a major • This subtype requires the violation of the rights of others

portion of the differential diagnosis. Differential (eg, vandalism and fighting), and conduct-disordered

behavior such as truancy, reckless driving, and

of this subtype includes generalized anxiety defaulting on legal responsibilities.

disorder, panic disorder, PTSD, ASD, and • It is particularly common in adolescents but can also

anxiety disorder 2e GMC. occur in children. The primary differential, of course, is

with conduct disorder and oppositional defiant disorder

• With mixed anxiety and depressed but needs also to include the lesser degree of

mood - differential diagnosis includes mood and misbehavior found in the V Code category of childhood

anxiety disorders. or adolescent antisocial behavior. Limited evidence

suggests a poor prognosis in children who react to stress

with this behavior pattern.









With mixed disturbance of Prevalence

• . Between 2% and 8% in community samples of children and

emotions and conduct adolescents and the elderly.

• Differential diagnosis includes disruptive behavioral • It has been diagnosed in up to 12% of general hospital inpatients

disorders. The most likely differential is with the who are referred for a mental health consultation, in 10%-30% of

those in mental health outpatient settings, and in as many as 50%

combination of a conduct disorder and a full emotional in special populations that have experienced a specific stressor

disorder of some type. (eg, following cardiac surgery).

• Includes emotional and conduct manifestations. It is • Individuals from disadvantaged life circumstances experience a

presumably uncommon in adults but will find occasional high rate of stressors and may be at increased risk for the

use with children and adolescents. The most common disorder. (DSM-IV-TR, pg.681) The New York Longitudinal Study

pattern seems to be disordered behavior with a of Temperament notes that adjustment disorder was the primary

depressed mood, although other combinations are diagnosis in 40 of the 45 children in their study who developed a

possible. Few data are available about this condition. mental illness prior to 13 years of age. The majority of cases

occurred in the 3-5 age group, and mild cases predominated.

Although the number of afflicted children was small, the findings

• Unspecified - "wastebasket." This may include such are particularly significant since their sample flowed from a healthy

things as massive denial of illness, markedly regressed population that during the course of the study developed illness,

behavior, or a preoccupation with fantasies rather than from a self-selected population of psychiatric patients.

Thus their figure compares the relative frequency of children in the

general population who develop an adjustment disorder to those

who develop other mental illness.







Schwartz_Reinblatt_Adjustment

Disorders 3

Osler Institute Child & Adolescent Psychiatry Review





Etiology Course

• By definition, the disorder begins within 3 months of

• Vulnerability of the child is the most onset of a stressor and lasts no longer than 6 months

important factor in the development of an after the stressor has ceased.

• If the stressor is an acute event, the disturbance is

adjustment disorder. usually immediate and the duration relatively brief.

• • Type of stressor • If the stressor persists, the disorder may also persist.

The persistence of adjustment disorder or progression to

other, more severe mental disorders (eg, major

depressive disorder) may be more likely in children and

adolescents than in adults. This increased risk may be

attributable to the presence of co-morbid conditions (eg,

attention-deficit/hyperactivity disorder) or to the

possibility that the adjustment disorder actually

represented a subclinical prodrome manifestation of the

more severe mental disorder.









Three DSM-IV Disorders in

• Thirty percent of children with a significant new medical

diagnosis have one form of adjustment reaction Response to Stressors

• Adjustment disorders are likely most common childhood • Adjustment disorder

psychiatric diagnosis after conduct disorders. • 1. Described as the development of clinically significant,

• It is one of the most common psychiatric diagnoses for emotional or behavioral symptoms in response to an

patients hospitalized for medical or surgical problems, with as identifiable psychosocial stressor, (personal misfortune)

much as 30 %... within three months of the onset of the stress.

• • This condition is most frequently diagnosed in

adolescence but occurs at any age. • a. The stressor may be of any degree of intensity and

the degree of dysfunction does not appear to be related

• • Older studies suggest that 30% of children who suffer a directly to what the stressor is.

chronic medical illness develop psychological symptoms.

Thirty-three percent of children newly diagnosed with insulin- • b. The symptoms must, by definition, resolve within six

dependent diabetes are noted to develop an adjustment months of termination of the stressor.

disorder within the first three months. (Kovacs 1985) • g. Chronic stressors which may lead to chronic

• In community disasters over one-third of individuals display adjustment disorders include medical conditions that are

symptoms of adjustment disorders. ongoing and chronically disabling or a stressor of

enduring consequences, such as financial or emotional

difficulties resulting from their parent’s divorce.









Differential

• B. Post-traumatic stress disorders • Adjustment disorder with depressed mood

• 1. The differential diagnosis is between major

• • Require an extreme stressor for the depression, dysthymia or bipolar disorder,

diagnosis to be made, with fear of death depressed phase, or uncomplicated

etc. bereavement.

• C. Acute stress disorders • • Vegetative signs are not as prominent in

children and adolescents, specifically motor

• • Like the post-traumatic stress disorder retardation or weight loss or change.

requires an extreme stressor: extreme = • • Guilt is more typical in depressive disorders

fear of death etc. than in adjustment reaction.









Schwartz_Reinblatt_Adjustment

Disorders 4

Osler Institute Child & Adolescent Psychiatry Review





Bereavement Bipolar disorder

• Viewed by some as a variant of adjustment disorder, • There is often a familial loading [might also be present in

although the diagnosis of adjustment disorder is not to major depression].

be made in this circumstance.

• The children tend not to be normal between cycles.

Bereavement is generally diagnosed when the reaction

is an expectable response to the death of a loved one. • Pre-pubertal children may have school phobia and

The diagnosis of adjustment disorder, on the other hand, evidence of impaired concentration

may be made when the reaction is in excess of, or more • Adolescents appear irritable, aggressive, have increased

prolonged than, that normally expected. activity, loud speech, and suicidality; Unreasonable or

• Serious depressive symptoms as an expected reaction unpredictable explosive behavior In children, the loss of

to loss do not qualify for adjustment disorder. self-esteem and the presence of guilt is probably the

most helpful distinctions.









Other adjustment disorder

characteristics



• 1. In making the differential, assess whether symptoms • Some events which may lead to adjustment disorder:

reflect a consistent pattern of behavior over time, the Almost any event can lead to an adjustment disorder.

quality of the family relationships, and the presence of a Some of those that are notable include:

precipitating condition.

• • Foster placements

• 2. The differential diagnosis of adjustment disorders

also includes certain personality disorders, specifically • • Divorce of parents or break-up of family

borderline and hysterical personality. • • Menarche in female, onset of spermarch in male

• Look for specific ego deficits such as poor reality testing, • • Rejection in an interpersonal relationship

and inadequate development of age-appropriate defense

mechanisms. [These should be chronic and without the • • Parental problems and arguments within the

evidence of a specific stressor.] family

• • Birth of a new sibling









Miscellaneous Information Re:

Pharmacotherapy

Adjustment Disorders

• Drugs may be useful in treating the specific • Children tend to develop guilt for a personal illness. This

is most likely in children who have had no previous

symptoms; brief periods. All drug categories are experience with a serious illness or with younger children

applicable but particularly the antianxiety and who are likely to assume that the illness is a punishment.

Providing a child with explanations for the cause of an

antidepressant medications. Antipsychotic illness lessens the chance of this occurring.

medications may be useful for severe anxiety • The birth of a child with congenital defects presents the

and decompensation, and psychostimulant family with a crisis similar to a premature birth. Conflicts

may develop around the appearance of the baby and

medication may work for withdrawn or inhibited related social stigma.

states or children with comorbid ADHD. • Families experiencing early death of an infant would

benefit from interventions such as support groups, visual

and physical contact with the infant, ongoing

psychosocial follow-ups, and routine autopsy.









Schwartz_Reinblatt_Adjustment

Disorders 5

Osler Institute Child & Adolescent Psychiatry Review





• Even though some cases remit without intervention,

• Adolescents experience a greater amount of anxiety adjustment disorder is not a minor condition requiring no

compared to younger children related to medical treatment. It is painful for the patient and the patient’s

procedures and chemotherapy. A lack of protest family, likely to worsen if the illness and its underlying

regarding a procedure is not always synonymous with causes are not addressed, and often responsive to

the lack of distress. In children, the thing that helps most vigorous and appropriate treatment.

in coping with pain experience is the presence of a

parent. • Treatment begins with a thorough evaluation, including a

search for physical causes for any physical symptoms

• • Hospitalizations occurring from the 12th to 48th present. Because adjustment disorder can mimic so

month age are associated with later difficulty in adaptive many different psychiatric disorders, such other

functioning. conditions must be sought in the hope of finding a

• • Factors associated with increased risk for specific treatment for the child’s difficulties.

psychological morbidity in children following the death of • The next step is to remove the stressor, if possible.

a sibling include (a) loss that occurred when a child was

under 5 years of age or during early adolescence; (b) • The core of treatment typically centers around both

unanticipated death or deaths from suicide or homicide; working with the child individually to address his or her

and (c) lack of adequate family or community support. concerns and working with the family about many of the

same issues. The conceptual approach and techniques

• Increased risk of morbidity also include the loss of a used, of course, depend in part on the age of the child

mother for girls fewer than 11 years of age and loss of a and the therapist’s assessment

father for adolescent boys.









• Treatment generally should be brief and focused, with an

emphasis on the child’s adjustments to the difficulties he

or she has experienced. The stressor must not be

ignored, particularly if chronic; rather, the child should be

allowed (or encouraged) to express fear, dismay,

resentment, and anger.

• Avoid, except temporarily and for very well-determined

reasons, fostering regression or the hope of a magical

recovery. A supportive, problem-solving approach often

works well and individual therapy becomes

indispensable when the family is destructive or has few

resources upon which to draw.

• Because the family is bound up in so many of the

stressors faced by these children, family therapy is an

equally essential mode of intervention. The family should

be involved in any efforts at behavioral management and

environmental manipulation, if they can participate

constructively.

• Limited research in this area; treatment relies on clinical

judgment.









Schwartz_Reinblatt_Adjustment

Disorders 6

This page was intentionally left blank.

Osler Institute Child & Adolescent Psychiatry Review







Psychotherapy

Individual Psychotherapy in

• Individual

Children and Adolescents

• Group

• Family



Shauna Pencer Reinblatt, MD

Johns Hopkins University









Goals of Psychotherapy Focus of Treatment

• Reduction in Psychiatric symptoms • Cognitive functions: Thought disorders

• Treatment of underlying cause of • Affective functions: Emotional /Mood

symptoms problems

• Behavior functions: Compulsions









Psychodynamic psychotherapy Play therapy

• Unconscious conflict • Drawings

• Unbalanced id/ ego/superego • Toys

• Defense mechanisms • Psychodynamic, short term

• Transference/ countertransference









Reinblatt_Individual Psychotherapy 1

Osler Institute Child & Adolescent Psychiatry Review







Psychic Determinism Psychoanalytic treatment

• Individuals are unaware of unconscious • Role of unconscious factors affecting

factors that determine their emotions, current relationships and behavior

moods and behavior • Helps the individual to deal better with the

• We are all unconsciously controlled realities of adult life

Transference

• Patient unconsciously reenacts the past

significant relationship









Interpretation of Transference Countertransference

• Feelings, Emotions, Thoughts are • Psychiatrist develops Counter transference

encouraged in Therapy • Patient reminds the psychiatrist about someone

from his past

• Transference: Unconscious

• Countertransference is monitored internally by

• Interpretation makes it conscious for the the psychiatrist

patient and leads to recovery • Awareness of Countertransference prevents

Psychiatrist’s anti-therapeutic behavior/

response









Resistance Methodology: Psychoanalysis

• Patient’s attempt to oppose gaining insight • Typically, the patient comes four or five

and change times a week

• Represents a compromise between forces • Lies on a couch

of recovery and pathology • Not suitable for children and Adolescents

• Late for appointment • Fantasies, dreams, and fears reveal

• Silent in Sessions clinical data

• Non compliance









Reinblatt_Individual Psychotherapy 2

Osler Institute Child & Adolescent Psychiatry Review







Window to Unconscious “Defenses”:

Uncomfortable Unconscious material or Opposing forces prevent expression of

drives come out in indirect way: “Wishes”

Slip of tongue Denial

Fantasies Projection

Dreams.









Tripartite Structural Model of

Id

Freud

Id • Unconscious

Ego • Discharges tension

Superego • Aggressive drive

• Libidinal or sexual drive









Ego Superego

• Unconscious + Conscious • Policeman of psyche

• Unconscious contains Defenses • Moral Conscience: internalization of

• Conscious integrates information, parental or societal values

executes action and makes decision • Ego ideal: role model









Reinblatt_Individual Psychotherapy 3

Osler Institute Child & Adolescent Psychiatry Review







Ego Psychology Defenses

• Id has sexual and aggressive drives which • Part of Ego

want expression, but ego and superego • Defenses protect ego from sexual and

opposes their expression aggressive drives from id.

• Conflict produces anxiety

• Anxiety produces a defense

• Defenses lead to formation of psychiatric

symptoms









Defense: Repression Defense: Displacement

• Freud • Feelings, emotions are redirected to

• Expels unacceptable drives, wishes or another target

fantasies from conscious awareness • Angry at boss hits a dog on the street

• It produces distress “Conflict model”

• Explains Neurotic symptoms i.e. anxiety,

depression and Hysterical Neurosis (Loss

of strength in one arm)









Object Relations Theory Rapprochement

• Previous relationships leave mental • Between 16 to 24 months of age

representations of self and others • Realizes more separateness from the

• Drives emerge in context of a relationship mother

• Infant-mother relationship • Increased sense of vulnerability to

• Interpersonal relationships are internalized separations from mother

as self-object representations of

relationships • Checks back frequently with the mother









Reinblatt_Individual Psychotherapy 4



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