Chapter 96 

- Drug-Induced Movement

Introduction and Overview

 The problem of pediatric drug-induced movement disorders (DIMDs) has received

increased attention as the number of children treated with psychotropic medications
has increased.
 Clinical trials and systematic reviews such as those from the Cochrane
Collaboration have analyzed recent pediatric data.
 Naturalistic studies of polypharmacy and epidemiologic studies, particularly those
involving children with autism, 3-5can provide additional insights.\
 Following most texts and reviews, this chapter is organized by drug class rather
than by movement disorder phenomenology.
 The reason for this is that the history, particularly with electronic patient records, of
drug exposures is often readily obtained.
 Of course, there are exceptions to this. Ingestions, exposures to illicit drugs, and
poor adherence to complex medical regimens can make the drug exposure less
clear.
 As is the case for adults, agents that modulate dopamine are the most common
causes of DIMDs in children.
 Because dopamine receptor blocking agents, also termed antipsychotics or
neuroleptics, can cause tardive dyskinesia and are widely used in children, these
agents require comprehensive discussion.
 In recent years, the U.S. Food and Drug Administration (FDA) has approved
antipsychotics for several pediatric indications.
 These include psychiatric symptoms that can be difficult to consistently define,
recognize, and diagnose: irritability in autism, schizophrenia in adolescents, manic
or mixed episodes of bipolar disorder.
 It is important to understand that although the newer agents, sometimes referred to
as the atypicals, were designed to confer lower risks of dopaminergic side effects,
this does not indicate the absence of risk.
 For example, risperidone has high potency for D2 receptors and can have an
adverse effect profile6 similar to the typical antipsychotic haloperid01 7 or the
antiemetic metoclopramide Iatrogenic conditions are a sensitive topic for
physicians.
 To place this in a central nervous system context, much pediatric prescribing of
medications by neurologists, psychiatrists, and developmental pediatricians is,
necessarily, "off label" (done outside the realm of FDAapproved indications).
Further, it remains difficult to design high-quality, statistically robust clinical trials of
neurologic and psychiatric medications in the pediatric population.
 There are special challenges to feasibility, validity, and generalizability given the
stress and disruption of these diseases to family life, the reliance of diagnoses on
poorly defined symptom clusters, statistical requirements for clinical trials, and
regulations for trials in vulnerable populations.
 Finally, even with better knowledge of iatrogenic risks than we have now, the
substantial burden of neurologic and psychiatric illnesses means that the
benefit/risk ratio often still would favor treatment.
 Fortunately, in the short term, it appears that most DIMDs are reversible in children.
It is important to be vigilant for these, however, and to recognize them early.

Definition of Drug-Induced Movement Disorders

 Iatrogenic movement disorders, or drug-induced movement disorders (DIMDs), are

conditions in which the abnormal movements are related to the use of medication.
 Several time courses may occur, as detailed in Table 96-1.

TABLE 96-1 Temporal Classification of Drug-Induced Movement Disorders

Clinical Characteristics—Phenomenology of DrugInduced Movement Disorders in

Children

 The phenomenologies of DIMDs span the spectrum of movement disorders:

tremor, hypokinetic/rigid syndrome (parkinsonism), ballism, athetosis, chorea,
dystonia, ataxia, tics, stereotypies, and poorly specified dyskinesias.
 Tremor is one of the most common DIMDs.
 The case report literature supports clinical experience in that almost any movement
disorder may be linked to almost any medication.
 However, there are certain patterns.
 Table 96-2 is not exhaustive but presents the more common types of movement
disorders seen with the five broad classes of medications emphasized in this
chapter.
 Akathisia may be included in discussions of DIMDs because of the motor
phenomenology of restlessness.
 Akathisia primarily involves uncomfortable sensations of inner restlessness, with
compulsion to move secondarily

TABLE 96-2 Common Drug-Induced Movement Disorders and Classes of

Medications

Drug-Induced Movement Disorders

 In general, for each drug class, epidemiology, clinical features, pathophysiology,

diagnostic approach, treatment, and outcome are discussed.

Drug-Induced Movement Disorders Associated with Dopamine Receptor

Blockade: Typical Antipsychotics, Atypical Anti psychotics

Epidemiology
 For decades, conventional low- and high-potency neuroleptics have been
prescribed in children as antiemetics and for behavioral indications, particularly in
children with intellectual impairment and autism.
 High-potency dopamine receptor blockers, effective for tic suppression in Tourette
syndrome, 14 are known to have both high risks of side effects and high
discontinuation rates.
 In addition, the dopamine receptor blockers, such as metoclopramide, have been
used in children as antiemetics and for migraine-associated nausea for many
years, despite descriptions of DIMDs.

 Pharmaco-epidemiologic studies show dramatic increases in the use of

antipsychotics for behavior problems in children of all ages.
 Conventional neuroleptics are still prescribed because of their effectiveness,
relatively lower cost, and concerns about metabolic consequences of the atypical
antipsychotics, including weight gain and increased risk of type 2 diabetes
 However, most of the increase in prescribing in children involves atypical
antipsychotics for mood stabilization, aggression, and autistic spectrum disorder
(ASD) behaviors rather than for their original indications for psychotic disorders.
 It is important for neurologists to be aware of situations and groups of patients at
risk for DIMDs.
 Table 96-3 @ is meant to aid in this process. Because dopamine receptor blocking
agents have many short- and long-term uses outside of neurology and psychiatry,
Table 963 @ shows the FDA-labeled and non-FDA-labeled indications and
specifically pediatric indications.
 It is important to note that there are other uses in addition to those listed. Further,
although pediatric indications (underlined in Table 96-3 @) form only a subset of
the total uses, it is common for pediatric use to follow adult approval.
 This occurs routinely in the absence of specific pediatric approval or dosing
recommendations.
 Although potential side effects involve many organ systems, for the purpose of this
chapter the discussion is limited to the neurologic system.
 Outside of the nervous system, these medications pose risks of weight gain,
gynecomastia, and other signs of metabolic syndrome.
 It is important to consult an updated reference when prescribing any of these
medications and particularly to adhere to recommendations regarding
electrocardiogram (ECG) monitoring.
 Dizziness and chest pain are common, and a possible serious side effect of many
neuroleptics is a prolonged QT interval. Prescribers must be aware of the range of
complications of these medications.

TABLE 96-3 Selected Dopamine Receptor Blocking Agents: Indications,

Approvals, and Risks

 With regard to the prevalence of DIMDs, three recent systematic studies with
different methods have generated estimates worth considering.
 The rates reported in two of the studies are remarkably close.
 Taking the estimates in the context of the study methodologies is informative.

Study 1 : Systematic review of clinical trials A recent systematic review identified and
analyzed 10 open-label and controlled studies of atypical antipsychotics with
duration of 12 months or more, involving 783 children and adolescents.

 Demographics were 80% Caucasian. The authors reported an overall prevalence of

DIMDs of 16%.
 In this study, tardive dyskinesia was reported in three patients, two prescribed
risperidone and one prescribed olanzapine.
 This represents 0.4% of the children in the study. 24
 Study limitations noted by the authors are pertinent when applying this to clinical
practice.
 In general, given the selection process for study enrollment, one would expect that
risk factors (polypharmacy, unusual clinical phenotypes, preexisting movement
disorders) would be screened out and the overall prevalence estimates would thus
be lower those for the general population.
 Finally, as in many branches of clinical medicine, there is a lack of standardization.
 Thus different raters, different side-effect rating methods, and failure to
systematically assess and rate adverse events likely influenced the outcome of this
study.

Study 2: Large, single-site cohort In a more naturalistic manner, researchers at the

Maryland Psychiatric Research Center studied a cohort of 424 pediatric psychiatry
patients over a 3 -year period.

 They reported that 9.3% of children ages 5 to 18 treated for 6 or more months with
typical or atypical antipsychotics developed tardive dyskinesia.
 Although this was an observational study with no direct placebo group, several
features of this study make it a model for future research.
 The results may be more generalizable than a study pooling clinical trial data.
 Here are some key points:

• The cohort was ethnically diverse.

• The study had a 90% capture rate of the children in the psychiatric facilities
involved. Polypharmacy, including exposure to multiple antipsychotics, and
multiple concurrent diagnoses were common, as is true in the clinical setting of
psychiatry patients referred to child neurologists.
• Although there was no placebo control, the authors did identify two comparator
groups: (1) 80 neuroleptic-naive, age- and gender-matched youths with
psychiatric disorders and (2) 35 healthy children with no psychiatric disorders.
• The authors used a structured and validated assessment, the Involuntary
Movement Scale.25 This scale is similar to the Abnormal Involuntary Movement
Scale (AIMS) 26 and is highly correlated with it.
 • The authors trained raters to a high interrater reliability (intraclass correlation
coefficient) level of 0.80.
• Raters were blinded to treatment group and diagnosis.
•   The positive diagnostic threshold was set based specifically on the pediatric
examination, to avoid classifying age-appropriate tics or hyperkinesis as being
DIMDs.

 Key findings from this study should inform clinical practice. First, the cohort did not
have psychosis.
 Rather, 80% of the prescriptions of antipsychotics were for youths with mood and
other problems, not psychosis.
 Second, attention deficit hyperactivity disorder (ADHD) was highly comorbid.
 Third, a total of 9.3% (11 of 118) of the children treated for greater than 6 months
with antipsychotics showed tardive DIMDs.
 This is compared with none in the antipsychotic-naWe group.
 This tardive dyskinesia risk is much higher than the 0.4% risk estimate from the
systematic review of clinical trials24 and higher than the 0% incidence reported in a
48-week, open-label extension of risperidone. 11
 Finally, the tardive dyskinesia appeared to be reversible, not permanent.
 However, long-term follow up of cohorts like this are still needed.
 The size of this study allowed for statistical exploration of potential risk factors.
 Several factors appeared to affect the risk of tardive DIMDs.
 These included longer duration, ranging from 3% at 6 to 12 months to 14% at
greater than 2 years.
 Also, race was important, with higher risks in black than white children. Risks
differed also by medication class, with the tardive DIMD prevalence at 6% (5 of 81)
for atypicals only, versus 2 7% (11 of 3 7) for combined atypical and typical
antipsychotics.
 The effects of other nondopamine blocking medications were more difficult to
analyze.
 This is because, as expected, polypharmacy use was higher. Over half of the
antipsychotic-exposed patients were treated with mood stabilizers (75%),
antidepressants (75%), and psychostimulants (68%). The rates of concurrent
medications in the antipsychoticnaive group were lower.

Study 3: Systematic review ofpublished literature The methodology of the third study
involved counting patients in the medical literature from 1953 to 2009 to estimate
risks for tardive syndromes in children. After removing the case reports and the
Maryland study (so as not to double count), this analysis was able to identify 50
affected children out of 540 exposed to neuroleptics, for a rate of 9.3% for tardive
dyskinesia. It is striking that this is essentially identical the rate identified in the group
treated for more than 6 months in the Maryland study.

 Despite differences in case mix, comorbidities, relative use of typical and atypical
antipsychotics and concurrent medications, and variability in raters and approaches
 to the clinical diagnosis of movement disorders, the estimates from the published
literature overa1127 and from the Maryland study are probably the best basis on
which clinicians can estimate risks.
 It cannot be forgotten that both estimates may be high as a result of positive
publication bias. Still, the vastly lower 0.4% rate of tardive dyskinesia in clinical
trials of atypical antipsychotics 24 may partly reflect clinical trial selection criteria,
lower treatment doses, and less polypharmacy—features less common in patients
referred to child neurology.
 Taken together, these studies should promote clinical caution and vigilance,
whether atypical or typicals are prescribed.

Clinical Features of Drug-Induced Movement Disorders Induced by

Dopamine Receptor Blocking Agents

 Dopamine receptor blocking agents are known to induce parkinsonism, dystonia,

tics, tremor, oculogyric movements, orolingual and other dyskinesias, and
akathisia.Symptoms may occur at any time after treatment onset.
 Acute DIMDs, especially dystonia, oculogyric crises, and akathisia, are common
and present dramatically, often to the emergency room. Chronic DIMDs occur after
3 or more months of treatment and may take the form of more subtle dystonia,
tremor, and rigidity.
 Tardive DIMD phenomenologies include dyskinesias, stereotypies, tics, dystonia,
and oculogyric crises.
 These symptoms may also develop when dopamine receptor blocking agents are
withdrawn, tapered down rapidly, or discontinued because of carelessness or
neglect (nonadherence).
 When dyskinetic movements occur in this setting it is termed the withdrawal
emergent syndrome (WES). 27
 Development of a tardive orofacial lingual stereotypy has been described in an
infant treated with metoclopramide for gastroesophageal reflux.

Pathophysiology

 The pathophysiology of DIMDs associated with dopamine receptor blocker use may
involve effects on the striatal dopamine receptor blockade and imbalance in the
striatum of dopamine and acetylcholine levels.
 Much remains unknown, however, regarding an individual's vulnerability or
susceptibility to DIMDs, so this remains an area of active research.
 Clinical experience suggests that the susceptibility to DIMDs in childhood is not
completely random.
 It may relate in some basic way to the perturbed circuits underlying the
neurodevelopmental or psychiatric symptoms treated with these agents.
 It is intriguing that tardive DIMDs seem to be so much more common in neuroleptic-
treated schizophrenia than in, say, neuroleptic-treated Tourette syndrome. 23
 Yet tics, stereotypies, and other movement disorders are more common in children
with ASD,33-35 and clinically children with ASD seem to be particularly susceptible
to DIMDs.
 With regard to specific genetic risk factors, much research has been done, but few
findings have been replicated.
 On a cellular basis, mechanisms may include long-term effects of neuroleptics on
dopamine receptor density and function, or damage to striatal GABAergic or
cholinergic neurons.
 Genome-wide association studies may support previously unsuspected pathways
as well.
 Evidence related to dopamine receptor polymorphisms has been mixed.39—43
GABAergic pathway genes have also been implicated.
 Within serotonergic systems, polymorphisms in genes encoding receptors 2A or 2C
46 but not 3A47 may increase risk.
 Genetic variation in enzymes handling oxidative stress, such as glutathione-S-
transferase, glutathione peroxidase, catalase, and tumor necrosis factor alpha
polymorphisms, have not been linked to risk for DIMDs.

Diagnosis of Acute, Chronic, Tardive, and Withdrawal Emergent Syndromes

 The acute onset of an involuntary movement disorder in a toddler should raise the
diagnostic possibility of ingestion of a dopamine receptor blocking agent.
 Sources of possible exposure should be sought.
 Acute onset of dystonia, akathisia, parkinsonism, or other dyskinesias after
initiating or raising the dose of a dopamine blocker is also straightforward.
 Based on the time course of the prescription and the movement disorder, diagnosis
of a chronic or tardive DIMD in children should often be considered when a
movement disorder is unusual.
 For example, unilateral resting tremor, rigidity, and orolingual dyskinesias are all
uncommon as idiopathic or genetic presentations but common as drug-induced
presentations.
 Stereotypies and especially tics are less straightforward because they are common,
and a tendency to tics or risk for a tic disorder may have preceded drug treatment.
 Thus the emergence of these symptoms later in childhood may be unrelated to
medication.
 Unfortunately, often at the time of the first neurologic consultation, any pretreatment
neurologic examination by the primary physician or prescribing psychiatrist is not
well documented.
 When a new movement disorder occurs at the time of medication tapering or
discontinuation, a WES disorder should be considered as a possibility.
 This is often missed or not considered in the emergency department and even on
the inpatient psychiatry service.
 This phenomenology can also be severe choreic or ballistic movements, among the
most severe presentations within the realm of DIMDs.
 However, if dyskinetic symptoms that have emerged are mild, then the differential
diagnosis includes preexisting hyperkinetic movements, or a predisposition to those
not yet manifest at treatment onset.
 The emergence may then not be withdrawal induced directly but rather emergence
of now untreated symptoms after symptoms had been masked by treatment.
 The most common phenomenology where this is seen is tics.
Treatment of Drug-Induced Movement Disorders Related to Use of Dopamine
Receptor Blocking Agents

 Treatment recommendations are based primarily on clinical experience and expert

consensus.

Acute Drug-Induced Movement Disorders

 For acute DIMDs caused by dopamine receptor blockade, antihistamines and

anticholinergic agents, such as diphenhydramine and benztropine, remain the
mainstay of treatment.
 For akathisia, other options include the alpha-2 adrenergic agonist clonidine and
beta blockers such as propranolol.

Chronic Drug-Induced Movement Disorders

 For chronic DIMDs caused by dopamine receptor blockade, anticholinergics are

also used.
 In chronic and tardive DIMDs, when dyskinesias are mild, withdrawing the
offending agent may be sufficient.
 For functionally impairing tremor or rigidity in situations where withdrawing the
dopamine receptor blocking agent is not presently appropriate because of
aggression or severe mental illness, long-term anticholinergic treatment is
reasonable.
 Ongoing collaboration with the prescribing psychiatrist is advised.
 As an alternative for mood stabilization and aggression, withdrawal of these agents
(and of the counteracting anticholinergic) may be possible, with substitution of
anticonvulsants as mood stabilizers.

Tardive Movement Disorders

 Vigilance for emergence of DIMDs is critical because of the possibility of permanent

tardive dyskinesia.
 Although the risk is highest in adults with schizophrenia, the risk is nonzero in other
groups.
 No clinician wants a severe prolonged or permanent movement disorder in a child,
yet it must be noted that in some children with encephalopathies the aggression is
so severe that it is safer for the child and family for neuroleptics to be prescribed
than it is to avoid them.
 So although primary emphasis should be given to strict and appropriate selection
and management of patients by physicians with expertise in psychiatric diagnosis
and treatment, it is important not to give the impression that dopamine receptor
blockers should be avoided at all costs.
 Rather, when possible, the treatment duration and dose of these dopamine
receptor blocking agents should be limited and alternatives considered. In cases
where tardive dyskinesia is diagnosed or strongly suspected, removal of the
dopamine receptor blocking drug is recommended whenever possible, via slow
taper to reduce the risk of WES.
 For pharmacologic treatment of tardive dyskinesia or tardive dystonia, there are
several options.
 At various times these options are either very expensive or there has been limited
access.
 For example, use of alpha-methyl-para-tyrosine (AMPT), an inhibitor of tyrosine
hydroxylase, the rate-limiting enzyme in dopamine biosynthesis, has been
described.
 Reserpine, which depletes the synaptic pool of monoamines, may also be used.
 Tetrabenazine, a VMAT2 inhibitor/dopamine depletory that also blocks presynaptic
and postsynaptic D2 receptors, 59 has been recommended as well.
 Depression is sometimes noted as a side effect.60,61 Extensive studies of vitamin
E, based on the rationale that oxidative stress may be involved in the
pathophysiology of tardive dyskinesia, have yielded negative results.
 Calcium channel blockers are not currently considered effective.

Neuroleptic Malignant Syndrome

 Neuroleptic malignant syndrome (NMS) is rare in children.

 This most commonly occurs after initiation or dose increases, and mainly has been
described as occurring after taking antipsychotics (including the atypicals), but
NMS occasionally has been reported as occurring after the use of other psychiatric
medications.
 NMS can also occur as a withdrawal phenomenon after chronic dopaminergic
therapy.
 The main manifestations are autonomic (fever, tachycardia/tachypnea,
diaphoresis), motoric (rigidity/bradykinesia with elevated rhabdomyolysis and
creatine kinase), and cognitive (confusion).
 This is a life-threatening presentation.
 Treatment may include specific interventions such as withdrawing the offending
medication, administration of the dopamine agonist bromocriptine, and
administration of the skeletal muscle relaxant dantrolene, in addition to general
supportive care (hydration, fever reduction).
 The differential diagnosis includes several other serious reactions, including
malignant hyperthermia (hyperpyrexia, muscle contractions attributable to general
anesthesia) and anticholinergic or sympathomimetic poisoning.
 In addition, serotonin syndrome may occasionally be confused with NMS.
 In serotonin syndrome, hyperreflexia, clonus, tremor, myoclonus, and shivering
occur, but rigidity should be less severe.

Drug-Induced Movement Disorders Associated with

Treatment of Attention Deficit Disorder

Epidemiology of Psychostimulant Use in Children

 The prevalence of ADHD diagnosis and the use of pharmacologic treatment have
increased markedly in the last 20 years in the United States.
 This includes primarily stimulants in an ever-increasing variety of preparations, but
also includes atomoxetine, a selective norepinephrine reuptake inhibitor marketed
for ADHD treatment, 70 and the alpha-2 adrenergic agonists guanfacine 71 and
clonidine.

Clinical Features

 Stimulants have been prescribed for decades.

 When dosed at less than 1.0 mg/kg/day, they only rarely induce clinically significant
movement disorders.
 These medications and, to a less acute degree, the nonstimulants affect dopamine
and norepinephrine levels.
 Therefore the most common DIMDs are hyperkinetic disorders such as tics,
stereotypies, chorea, and other dyskinesias.
 The risk of DIMDs is higher in children who manifest clinical or subthreshold
diagnostic features of obsessive-compulsive disorder (OCD) or ASD.
 Such children may experience new or increased repetitive behaviors, including tics,
compulsions, or repetitive picking behaviors.
 They may also become hyper-focused or have personality changes parents
describe as a "zombie" or "robot" effect, in part resulting from increased attention to
internal stimuli or thoughts.
 A longstanding concern is the clinical observation that stimulants seem in some
cases to induce, unmask, or exacerbate tics.
 After case reports in the 1970s and 1980s, 76 the FDA mandated a labeling advisory
that stimulant medications are contraindicated in individuals with Tourette
syndrome or any family history of tics.
 It is critical to note that ADHD and tic disorders are commonly comorbid, and the
implication of this warning diverges from standard clinical practice by expert
clinicians and from recommendations of the U.S. Tourette Association Medical
Advisory Board.
 In fact, rigorous randomized controlled trials support that stimulants reduce ADHD
symptoms for most children, irrespective of the presence of a tic disorder, and that
should worsening of tics occur, it is usually transient, usually mild, and always
reversible.
 Prospective studies suggest that in most cases tics would have occurred
eventually, even in the absence of any exposure to stimulants.
 The most rigorous clinical assessment of the relationship between stimulants and
tics is the Treatment of ADHD in Children with Tics (TACT) study.
 In that study, children with comorbid tics and ADHD were randomized to treatment
with methylphenidate, clonidine, both, or double placebo.
 Tics improved by the study's end in all treated groups compared with the placebo.
 That is, even the group treated with methylphenidate alone had improved tics
compared with the placebo.
 Even in cases where tics consistently worsen on stimulant medication, some
individuals and families choose to continue stimulant medication if the benefits
warrant.
 Atomoxetine has been reported in a few cases to induce tics and dyskinesias in the
context of rapid dose change and polypharmacy.
 However, in a randomized, placebo-controlled trial of atomoxetine treatment for
ADHD in 148 children with tics, atomoxetine tended to reduce tic severity.

Pathophysiology

 The pathophysiology of this susceptibility is unknown. Induced stereotypies and

tics, as with idiopathic ones, may be more general markers of perturbed
neurodevelopment.
 A genetic influence on the risk of DIMDs has been suggested through genotyping
data from the Preschool ADHD Treatment Study (PATS).
 In that study, 183 preschoolers were treated with methylphenidate at several doses
or placebo.
 Several modestly statistically significant associations were identified, including
polymorphisms in synaptosomal-associated protein 25 (SNAP25) associated with
tics, buccal-lingual movements, and irritability and variants of dopamine receptor 4
(DRD4) associated with picking.

Diagnosis

 The diagnosis of a DIMD in a child treated for ADHD should be suspected if the
movements have the typical hyperkinetic phenomenology and the onset is within a
week or two of treatment onset or a dose increase.
 Stimulants are short acting and readily discontinued or restarted, allowing for a plan
of stopping and restarting medications to clarify cause and effect.

Treatment

 It is most often not necessary to discontinue stimulants when mild tics or tremor
emerge. If the stimulant dose exceeds 1 mg/kg/day, it is generally beneficial to
reduce the dose.
Drug-Induced Movement Disorders Associated with Other Medications

Serotonin Reuptake Inhibitors

 Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed in children

with mood disorders and OCD and tend to work better in combination with cognitive
behavioral therapy.
 The emergence of movement disorders related to use of SSRIs is well known.
 Phenomenology can include akathisia most commonly, with parkinsonism,
dystonia, acute dystonic reactions, and dyskinesias also described.
 The most serious complication, rare in childhood, is serotonin syndrome resulting
from excess SSRI exposure.
 This involves neuromuscular excitation (manifest by clonus, hyperreflexia,
myoclonus, tremor, shivering), autonomic stimulation (hyperthermia, diarrhea,
tachycardia, diaphoresis, tremor, flushing), and changed mental state (anxiety,
agitation, confusion).
 More commonly, treatment with an SSRI results in a mild degree of hyperreflexia
and tremor.
 The emergence of hyperreflexia in a child prescribed an SSRI is an indication that
toxicity is more likely if the dose is increased or if other psychiatric agents are
prescribed.
 Lack of awareness of SSRI-induced tremor and hyperreflexia may result in
unnecessary medical diagnostic tests such as brain magnetic resonance imaging
(MRI).
 Similarly, failure to observe and document SSRI-induced neurologic symptoms may
place patients at risk of developing more severe symptoms with future dose
increases. Myoclonus, in distinction to tics, is involuntary, not urge driven.
 The identification of SSRI-induced movement disorders in children83,84 supports
the importance of clinician and patient education.
 Treatment is dose reduction, elimination of the medication, or selection of
alternative interventions or cognitive behavioral therapies.

Antiseizure Medications

 Physicians prescn e antiseizure me rcaåons or iversem Ications, inc u ing

prevention o seizures and migraines, and sometimes stabilization of mood.
 Numerous case reports describe acute and chronic DIMDs in children caused by
antiseizure medications.
 The most common acute clinical presentations are acute ataxia and nystagmus.
 Phenytoin and carbamazepine are most commonly identified.
 These medications are also prone to cause problems resulting from
pharmacokinetics and drug—drug interactions.
 Less commonly, antiseizure drugs may produce other hyperkinetic movement
disorders.
 Phenytoin, carbamazepine, and even valproic acid have been reported to produce
acute chorea, orofacial dyskinesias, and Tourettism.
 Lamotrigine has been reported to induce tics. Tremor is also common.
 Generally, the treatment plan involves clinical watch and wait, weighing the
impairment related to the movement disorder against the benefits of the seizure
control, with thoughtful consideration of reduction of dose or changing of
medication or formation if the movement disorder causes much impairment.

Drug-Induced Movement Disorder Associated with Chemotherapeutic,

Immunomodulatory, and Antiinfectious Medications
 Neurology consult teams seeing oncology patients may encounter DIMDs.
Chemotherapeutic agents such as vincristine may cause sensory ataxia, along with
dysarthria and tremor.
 Seizures, stroke-like episodes, and ataxia can occur with intrathecal methotrexate.
 Acute neurologic symptoms such as headaches, confusion, and seizures, but also
associated with tremor, ataxia, dysarthria, and parkinsonism, may occur during
bone marrow transplantation.
 Seizures, tremor, and acute dystonic reactions have been observed after organ
transplantation, sometimes with a leukoencephalopathy syndrome involving
headache, confusion, and myoclonus.
 Metronidazole may rarely cause cerebellar dysfunction.

DIMDs Associated with Vitamin Administration

Treatment with B12 for deficiency can induce movement disorders.

Conclusion

 Neurologists should be aware of the wide spectrum of phenomenologies of drug-

induced movement disorders that may present acutely or chronically in childhood.
 Treatment strategies may involve specific antidotes, such as anticholinergics for
acute dystonic reactions, or longer term changes in medical regimens.