Obsessive Compulsive Disorders.15

REVIEW ARTICLE

Obsessive-Compulsive
C O N T I N UU M A UD I O
I NT E R V I E W A V AI L A B L E
ONLINE
Disorders
By Carol Mathews, MD
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ABSTRACT
PURPOSE OF REVIEW: This article describes the phenomenology and clinical
presentation of obsessive-compulsive disorder (OCD), a common but
underdiagnosed psychiatric disorder. Guidance for effectively identifying
obsessive-compulsive symptoms is provided, and treatment options,
including psychotherapy, pharmacologic management, and
neuromodulation approaches for treatment-resistant OCD, are discussed.
RECENT FINDINGS: OCD affects 2% to 3% of adults worldwide and is associated

with substantial individual disability and societal costs. Lack of recognition
CITE AS: of common OCD symptom types, in addition to shame and fear of stigma on
CONTINUUM (MINNEAP MINN) the part of patients, has created an average delay in diagnosis by almost
2021;27(6, BEHAVIORAL NEUROLOGY
AND PSYCHIATRY):1764–1784.
10 years and a delay in effective treatment (ie, a treatment gap) of nearly
2 years. Cognitive-behavioral therapy (CBT), specifically a form of CBT that
Address correspondence to includes a type of behavioral intervention called exposure and response
Dr Carol Mathews, 100 S Newell
prevention, remains the most effective form of treatment for OCD. If CBT is
Dr, Gainesville Florida, 32610,
carolmathews@ufl.edu. not effective or not available, pharmacologic treatment with selective
serotonin reuptake inhibitors (SSRIs) or clomipramine, a nonselective
RELATIONSHIP DISCLOSURE:
Dr Mathews has received
serotonin reuptake inhibitor, can also be of benefit. Neuromodulation
research/grant support from the approaches such as deep brain stimulation and transcranial magnetic
National Institutes of Health stimulation are rapidly emerging as effective treatments for OCD,
(R01MH117114, R01NS105746,
R61AT009988, R01NS102371) and particularly for patients who have not experienced an adequate response
publishing royalties from W. W. to psychotherapy or pharmacologic management.
Norton & Company, Inc.
UNLABELED USE OF SUMMARY: OCD affects more than one in every 50 adults in the United States
PRODUCTS/INVESTIGATIONAL but is recognized and adequately treated in fewer than half of those affected.
USE DISCLOSURE:
Dr Mathews discusses the
Early intervention and appropriate treatment can substantially reduce OCD
unlabeled/investigational use of symptom severity, improve quality of life, and minimize the functional
aripiprazole, celecoxib, disability associated with this chronic and often debilitating illness.
citalopram, duloxetine,
escitalopram, haloperidol,
ketamine, lamotrigine,
memantine, N-acetylcysteine,
ondansetron, pindolol, riluzole, INTRODUCTION
O
risperidone, topiramate,
bsessive-compulsive disorder (OCD) is a chronic and, at times,
transcranial direct current
stimulation, transcranial debilitating neuropsychiatric illness that affects approximately
magnetic seizure therapy, vagus one in every 50 people (more than 8 million in the United States
nerve stimulation, and
venlafaxine for the treatment of
alone). It is one of the most common psychiatric illnesses in
obsessive-compulsive disorder. adults worldwide; only depression, substance abuse, hoarding
disorder, and social anxiety disorder have higher prevalence rates.1,2 OCD has a
© 2021 American Academy profound negative impact on functioning and quality of life for those who are
of Neurology. affected and levies substantial costs at the individual, familial, and societal
1764 DECEMBER 2021
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

levels.3,4 According to the World Health Organization and the Global Burden of KEY POINT
Disease Study, OCD is one of most impairing noncommunicable diseases
● Although obsessions and
globally, with the number of years of life lost to disability and all-cause mortality compulsions are the core
similar to that of schizophrenia and higher than many neurologic disorders, features of obsessive-
including epilepsy.5,6 In addition to the direct costs associated with treatment for compulsive disorder (OCD),
OCD and increased utilization of health care services because of comorbidities or avoidance of situations or
events that may trigger

other related health conditions, OCD is associated with substantial indirect costs
obsessions is also common.
to society and national economies, including reduced productivity (>30% of
individuals with OCD are underemployed or unemployed), reduced income, and
a high number of days off work.6 OCD is also associated with increased caregiver
burden and therefore decreased productivity, functioning, and quality of life,
particularly for parents and intimate partners of individuals with OCD.7
Although OCD is considered to be a chronic (and therefore, incurable) illness,
for most patients, effective treatments do exist, both pharmacologic and
psychotherapeutic; appropriate treatment can reduce symptomatology, improve
individual functioning, decrease disability, reduce caregiver stress, and lessen
the economic costs of this common disorder. Unfortunately, OCD is
underrecognized by the lay public and underdiagnosed by clinicians; as a result,
many people with OCD remain untreated or experience a delay in appropriate
diagnosis and treatment. The average time from onset of symptoms to diagnosis
and treatment is 8 to 10 years; this lag is caused by the failure of clinicians, both in
primary care and in specialty settings, to effectively screen for or recognize OCD
symptoms and is exacerbated by shame, stigma, and fear of OCD symptoms
being misunderstood as psychosis or worse on the part of patients.6,7 Clinicians,
particularly those who are not mental health experts, may be reluctant to ask
about OCD symptoms for fear of asking the wrong questions, not knowing how
to discriminate between obsessions and other psychiatric or behavioral
problems, or concern that they would not know what to do if they do find that a
patient has OCD. However, it is clear that assessing for OCD symptoms, even if
imperfectly, can not only effectively identify individuals who have the disorder
but also help to destigmatize the condition, prompting many to then seek out
appropriate treatment.
EVALUATION OF OBSESSIVE-COMPULSIVE DISORDER

The core features of OCD are the presence of obsessions (thoughts) and/or
compulsions (behaviors) that are time-consuming, are distressing, cause
functional impairment, or all three.2 Most patients with OCD will have both
obsessions and compulsions, but some may have one type of symptom and not
the other. Avoidance behaviors, which are not listed in the formal diagnostic
criteria according to the Diagnostic and Statistical Manual of Mental Disorders,
Fifth Edition (DSM-5), are nevertheless also often prominent features of OCD.
Obsessions are defined as recurrent, repetitive, intrusive, unwanted, and
uncomfortable thoughts, images, impulses, or urges that cause sufficient distress
or anxiety that the person experiencing them will attempt to ignore, suppress, or
neutralize them, for example, by performing a compulsion.2 Compulsions are
repetitive ritualized behaviors that the person recognizes as unreasonable,
unrealistic, or excessive but feels driven to perform to reduce anxiety, usually
(although not always) in response to an obsession.2 Compulsions are often
performed a specific number of times or according to rigid rules and must be
reperformed if not done exactly according to those rules the first time. In some
CONTINUUMJOURNAL.COM 1765

OBSESSIVE-COMPULSIVE DISORDERS
TABLE 12-1 DSM-5 Diagnostic Criteria for Obsessive-Compulsive Disordera
A Presence of obsessions, compulsions, or both:

Obsessions are defined by (1) and (2):
1 Recurrent and persistent thoughts, urges, or images that are experienced, at some time
during the disturbance, as intrusive and unwanted, and that in most individuals cause
marked anxiety or distress.
2 The individual attempts to ignore or suppress such thoughts, urges, or images, or to
neutralize them with some other thought or action (i.e., by performing a compulsion).
Compulsions are defined by (1) and (2):
1 Repetitive behaviors (e.g., hand washing, ordering, checking) or mental acts (e.g., praying,
counting, repeating words silently) that the individual feels driven to perform in response
to an obsession or according to rules that must be applied rigidly.
2 The behaviors or mental acts are aimed at preventing or reducing anxiety or distress, or
preventing some dreaded event or situation; however, these behaviors or mental acts are
not connected in a realistic way with what they are designed to neutralize or prevent, or are
clearly excessive.
Note: Young children may not be able to articulate the aims of these behaviors or mental
acts.
B The obsessions or compulsions are time-consuming (e.g., take more than 1 hour per day) or
cause clinically significant distress or impairment in social, occupational, or other
important areas of functioning.
C The obsessive-compulsive symptoms are not attributable to the physiological effects of a
substance (e.g., a drug of abuse, a medication) or another medical condition.
D The disturbance is not better explained by the symptoms of another mental disorder
(e.g., excessive worries, as in generalized anxiety disorder; preoccupation with appearance,
as in body dysmorphic disorder; difficulty discarding or parting with possessions, as in
hoarding disorder; hair pulling, as in trichotillomania [hair-pulling disorder]; skin picking,
as in excoriation [skin-picking] disorder; stereotypies, as in stereotypic movement
disorder; ritualized eating behavior, as in eating disorders; preoccupation with substances
or gambling, as in substance-related and addictive disorders; preoccupation with having
an illness, as in illness anxiety disorder; sexual urges or fantasies, as in paraphilic
disorders; impulses, as in disruptive, impulse-control, and conduct disorders; guilty
ruminations, as in major depressive disorder; thought insertion or delusional
preoccupations, as in schizophrenia spectrum and other psychotic disorders; or repetitive
patterns of behavior, as in autism spectrum disorder).
Specify if:
With good or fair insight: The individual recognizes that obsessive-compulsive disorder
beliefs are definitely or probably not true or that they may or may not be true.
With poor insight: The individual thinks obsessive-compulsive disorder beliefs are probably
true.
With absent insight/delusional beliefs: The individual is completely convinced that
obsessive-compulsive disorder beliefs are true.
Specify if:
Tic-related: The individual has a current or past history of a tic disorder.
DSM-5 = Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

a
Reprinted with permission from American Psychiatric Association.2 © 2013 American Psychiatric
Association.
1766 DECEMBER 2021

cases, compulsions are performed not according to a specific set of rules but KEY POINT
instead until they feel “just right” or “complete” in some unpredefined way. For
● Formal assessment of
the majority of patients with OCD, obsessions are experienced as ego-dystonic, OCD is typically conducted
or inconsistent with their underlying belief systems, personalities, and view of using standardized
reality; in other words, they are recognized as illogical and not grounded in assessments, but one or two
reality. Similarly, the performance of compulsions gives no pleasure to the questions can be effective
screening tools in a busy

individual experiencing them.8 Instead, obsessions cause anxiety, and the
clinical practice.
resulting compulsions or avoidance behaviors provide a sense of relief rather
than a sense of reward. TABLE 12-1 outlines the current DSM-5 diagnostic
criteria for OCD.

As with most psychiatric disorders, no formal diagnostic testing or laboratory
evaluations are particularly useful in making a diagnosis of OCD. However,
medical conditions such as brain injury or peripheral neuropathy; metabolic or
endocrine disorders such as hypothyroidism or diabetes; infections of the
central nervous system; autoimmune disorders (in particular autoimmune
encephalopathy); and neurologic disorders such as Parkinson disease, dementia,
or multiple sclerosis can be associated with obsessive-compulsive symptoms. If
other clinical signs or symptoms raise suspicion for one of these disorders, the
appropriate workup should be pursued before initiating treatment for OCD.
Formal assessment of OCD is often conducted using a standardized
questionnaire such as the Yale-Brown Obsessive Compulsive Scale (Y-BOCS),9
which asks about the presence or absence of specific types of obsessions and
compulsions and subsequently assesses the distress, amount of time consumed,
and functional impairment associated with OCD symptoms. Initial screening for
OCD in a clinical setting does not require administration of the Y-BOCS, which
can take up to an hour, but can instead be accomplished by asking two basic
questions that assess for the likely presence of obsessions and compulsions. If the
answer to both of the following questions is no, then the likelihood of OCD is
very low. If the answer to either of these questions is positive, further assessment
using the Y-BOCS or a similar instrument is warranted.
u To identify patients who may be experiencing obsessions, ask: “Have you ever been
bothered by repeated intrusive thoughts that did not make any sense to you and kept
coming back even when you tried not to have them or tried to suppress them?”
u To identify patients who may be experiencing compulsions, ask: “Do you have any rituals,
thoughts, or behaviors that you feel that you have to do or think over and over, cannot
resist doing, or have to do repeatedly until it is done exactly correctly or until it feels
just right?”
In a clinical setting, the proportion of patients who answer positively to either

or both of these questions (or to similar questions) is likely to be high; this does
not mean that everyone who has a positive screen will have OCD. Symptoms that
are superficially similar to obsessions and compulsions can also occur in many
other neuropsychiatric disorders (eg, ruminations in depression or generalized
anxiety disorder, tics in Tourette syndrome, or perseverations in autism
spectrum disorder). Obsessive-compulsive behaviors can also occur in conditions
other than OCD, such as autism spectrum disorder, dementia and other
neurodegenerative disorders, and schizophrenia. Because the prognosis and
treatment of each of these disorders differ, it is important that clinicians are able
to effectively differentiate OCD from other neuropsychiatric illnesses with
overlapping or similar presentations. The similarities and differences between

obsessions, compulsions, and other similar symptoms are outlined in TABLE 12-2
and TABLE 12-3.
Obsessions and compulsions can be subgrouped into thematic categories:
contamination and cleaning; taboo thoughts or fears; fear of harm; symmetry,
superstition, and perfectionism; somatic fears; and hoarding.10,11 Most people
with OCD will have many different types of obsessions and compulsions from
most, if not all, of these subtypes over the course of their lifetimes. Fear of
contamination and the resulting compulsions to clean excessively or ritualistically
are perhaps the most well-known type of OCD symptom. Contamination obsessions
take many forms and are not limited to fears of becoming sick. Individuals
with OCD may fear becoming contaminated from germs or sticky surfaces,
insects or animals, or food. They may also fear being contaminated by someone
else’s personality, sexuality, habits, or behaviors. Cleaning behaviors resulting
from contamination fears can involve oneself, others, or objects. Ritualized
handwashing or showering; excessive toilet or grooming routines; repeated or
ritualized washing of laundry, surfaces, or possessions; and excessive or
inappropriate use of cleaning agents are all examples of cleaning compulsions.
Taboo fears typically fall into three main types: sexual, religious, and
aggressive. Sexual obsessions can present as repeated fears that one has
inadvertently behaved in an inappropriate sexual manner, unwanted
uncomfortable sexual images or thoughts, or repetitive intrusive fears that one is
unknowingly of a different sexual orientation or gender. It is critical to remember
that these types of thoughts are OCD symptoms, and as such, they are
TABLE 12-2 Distinguishing Obsessions From Other Similar Thought Patterns
Obsessions Ruminations Delusions Overvalued ideas Perseveration
Ego-dystonic or Ego-dystonic Ego-syntonic Ego-syntonic Ego-syntonic Ego-syntonic

ego-syntonic
Pattern Content of specific Fluid reworking Typically Reasonable Excessive and

obsessions are of content over fixed conventional belief narrow focus on
fixed rather than and over to find content, can but oversubscribed a specific belief
fluid; can different/ generalize to by the individual or desire
generalize alternative
scenarios
Recognized Yes Yes No No No

as excessive
Examples Fear of contamination Repeated Belief that one Persistent belief Repeated thoughts
when touching a reworking of a past is being that one is regarding ways to
doorknob, unwanted social situation followed by overweight despite obtain a desired
urges to or thoughts (such as a romantic the Mafia or being of normal but inaccessible
that one might date) that did not being taken body weight, item or relationship,
inadvertently swerve go as expected in over by aliens insistence on overfocus and
car into traffic an attempt to proselytizing to a repeated thoughts/
identify possible specific belief discussion of a
different system in an perceived slight or
theoretical inappropriate injury out of
outcomes context proportion to the
event
1768 DECEMBER 2021

ego-dystonic, uncomfortable, and unwanted; they are not acted on, nor are they
realistic. Examples of common sexual obsessions include fearing that one is a
pedophile or has unknowingly or inadvertently inappropriately touched a child
(eg, when changing a diaper during babysitting), fearing that sitting next to
someone of the same sex in a movie theater or classroom will confer homosexuality
or trigger inappropriate sexual behavior in the person with OCD, and intrusive
unwanted sexual or explicit images of family members or friends or strangers.

Religious obsessions (which do not require a religious background or belief to
occur) include fears such as unintentionally or inadvertently offending God or
blaspheming, fears of religious objects or symbols, and superstitious fears of

symbols that have a religious history or meaning (eg, the fear that seeing the
number 666 will result in something bad happening or harm coming to someone).
Aggressive obsessions, which differ from fears of harm, include uncomfortable
ego-dystonic thoughts or urges to cause harm to oneself or others, including fears,
impulses, or urges to touch hot surfaces such as stoves or fires; fears of being around
knives or other sharp objects because of images of picking them up and cutting or
stabbing someone; urges to swerve a car or bicycle into oncoming traffic; and urges
or fears of blurting out something aggressive or offensive (eg, racial epithets).
Fears of harm, on the other hand, tend to be more passive in nature. These
obsessions include fears that one has inadvertently hit someone while driving,
with a concomitant urge to return to the scene and check for bodies or injured
people; fears that harm will come to another person because of something the
person with OCD either did or did not do; and fears that if an action or ritual is
not done in a particular way or a specific number of times, then someone will be
Distinguishing Compulsions From Other Similar Behaviors TABLE 12-3
Compulsions Habits Tics Stereotypies Perseverative behaviors
Involuntary versus Voluntary Both Involuntary Voluntary Voluntary

voluntary
Repetitive versus Ritualized Repetitive Repetitive Repetitive Repetitive

ritualized
Deliberate versus Deliberate Deliberate Nondeliberate Deliberate Nondeliberate

nondeliberate
Relief of anxiety or Relief Relief Relief Reward Reward

sensation or reward
Anxiety or discomfort Yes No Yes No No

generated when
attempting to stop
or suppress behavior
Examples Repeated ritualized Nail biting, Repetitive eye Hand flapping, Continued focus on
hand washing, hair twirling blinking, repeated body rocking a single topic of
checking multiple throat clearing conversation with
times to be sure inability to shift
stove is turned off topics, repeated
rereading of the
same comic book

harmed. Harm obsessions are often accompanied by checking behaviors,

including a frequent need to ask others for reassurance that the feared event did
not occur; checking to see that harm was not, in fact, done; and physically
checking oneself or others for injuries in the absence of a precipitating event that
could have caused injuries or harm. Superstitious obsessions (eg, worrying that
something bad will happen if a particular superstitious ritual is not followed) and
associated checking or avoidance behaviors also fall into this category.

Symmetry obsessions and compulsions include a perceived need for things to
be in a particular order or lined up in a certain way (eg, color coded), rewriting or
rereading over and over because of a perceived need for handwriting to look
“perfect” or a sentence to feel “just right,” evening up (such as doing the same
behavior with each arm to make it feel even or tying and retying shoelaces until
the pressure feels the same on both feet), or needing the television volume or
channel to be on an even or odd number. When symmetry symptoms are the
predominant or only type of OCD symptom, the clinician should spend some
time assessing for the underlying presence of a current or past tic disorder, as
these symptoms are much more common in individuals with Tourette syndrome
or other chronic tic disorders. Perfectionism obsessions and behaviors also fall
into the symmetry category. In addition to the symptom of needing things to look
or feel perfect as described above, perfectionism symptoms can also be expressed
as needing homework or other work or school assignments to be done perfectly
to the point that assignments will go unfinished because the patient can never
achieve perfection. Avoidance is also commonly seen when perfectionism is
present because of the feeling that if perfectionism cannot be achieved, then it is
futile to begin an assignment or a project at all.
Somatic fears tend to fall into two primary types: unreasonable excessive fears
that the person with OCD has contracted an illness (including noncommunicable
illnesses such as cancer) and fears that something (often something indefinable)
is wrong with a body part or feature. These symptoms can be difficult to
distinguish from symptoms of other related psychiatric illnesses, such as illness
anxiety disorder and body dysmorphic disorder. These disorders should be
carefully assessed for if somatic symptoms are identified. Somatic symptoms can
also occur in the context of contamination fears; for example, someone who
obsessively worries about contracting or transmitting herpes simplex (often in
the absence of any evidence of an actual infection) may compulsively check to
make sure they have no lesions on their lips or mouth. As with other OCD
symptoms, somatic obsessions are ego-dystonic. In contrast, when such somatic
preoccupations are the primary focus in body dysmorphic disorder or illness
anxiety disorder, the individuals experiencing these disorders are less likely to
have insight into the irrational or excessive nature of their fears.
The final category of OCD symptom types is hoarding behaviors.
Understanding and assessing for this category of symptoms is complicated by the
fact that hoarding disorder is a distinct neuropsychiatric illness, albeit one that
was once thought to be a subtype of OCD. The hoarding symptoms that occur in
hoarding disorder and those that occur in OCD differ in both content and intent.
Individuals with hoarding disorder tend to save everyday items such as papers,
containers, clothes, household items, tools, and sentimental objects, usually
because of the thought that the item might be needed or wanted again, either
for a concrete purpose or to preserve a memory or important piece of
information. In OCD, hoarding behaviors are explicitly due to obsessional fears
1770 DECEMBER 2021

(eg, contamination fears or fears of harm), and the items hoarded are more likely KEY POINTS
to be unusual or bizarre (eg, saving fingernail clippings for fear that someone
● The content of
could harvest DNA from them and cause harm to a person). Up to 30% of people obsessions and compulsions
who present with OCD will also have co-occurring hoarding disorder, however, can be grouped into several
as these two disorders are related. thematic categories (eg,
When evaluating someone for OCD, it is important to ask about symptoms in all contamination and cleaning
or taboo thoughts).
of the categories as well as asking about the person’s own understanding of their
symptoms. Most people with OCD will know that their fears and behaviors do not ● Obsessions and
make sense (ie, are irrational or excessive) (CASE 12-1). Some will suspect that they compulsions regarding
have OCD based on their knowledge of the illness from the media or their own symmetry are more
research, especially if they experience some of the better-known OCD symptoms common in individuals with
co-occurring chronic tic
such as contamination fears, cleaning obsessions, or repeated checking. Others, disorders.
however, particularly those who have taboo symptoms or some of the other lesser-
known symptom types, will fear that their symptoms indicate that something is ● Somatic and hoarding
fundamentally wrong with them as a person or that something is seriously wrong symptoms can occur either
in OCD or as a part of other
with their mental function (ie, that they are “crazy”). For this reason, patients with related disorders, such as
OCD may be reluctant to disclose their symptoms without specific prompting. body dysmorphic disorder,
illness anxiety disorder, or
EPIDEMIOLOGY OF OBSESSIVE-COMPULSIVE DISORDER hoarding disorder.
OCD is equally common in males and females (the male to female ratio is
● OCD affects
between 1:1 and 1:1.5), although the age of symptom onset differs somewhat approximately 2%
between the sexes. The lifetime prevalence of OCD is between 2% and 3%, and to 3% of adults.
the prevalence of subclinical OCD symptoms is estimated to be as high as 25% in
the adult population.6 For the vast majority of patients, symptoms begin in ● The presence of one or
more psychiatric disorders
adolescence or early adulthood; the age of onset is thought to be bimodal, with a co-occurring with OCD is the
first peak in childhood (75% of those affected, mean age of onset 11 years) and a rule rather than the
second peak in early adulthood (mean age of onset 23 years).6 Boys tend to have exception.
an earlier age of onset than do girls, with a substantial proportion experiencing
their first symptoms before age 10.6,9 Although most girls will also have symptom
onset in early adolescence, for some women, reproductive events such as
pregnancy or childbirth and even, in rare cases, menopause can trigger OCD
symptoms.9 Males with OCD, especially those whose symptoms begin early in
childhood, are more likely to have a co-occurring tic disorder; females with early
onset of symptoms, particularly those with prominent symmetry or “just right”
symptoms (the need to repeat a simple activity over and over again until it feels
“just right” or complete), may also be at higher risk for tic disorders. Girls (and,
increasingly, boys) who have somatic or body-related symptoms may also be at
risk for developing body dysmorphic disorder or an eating disorder.12
The majority of adults presenting for clinical care of OCD will meet lifetime
criteria for another psychiatric disorder, most commonly depression (up to 65%)
or an anxiety disorder (60% to 90%).1,9 Tic disorders occur in up to 30% of
individuals with OCD,2 and attention deficit hyperactivity disorder in up to
20%.9 These co-occurring disorders contribute to poorer quality of life and
worsened functioning when present, and, if not addressed, they can also
adversely impact effective treatment of OCD.9
ETIOLOGY AND PATHOPHYSIOLOGY OF OBSESSIVE-COMPULSIVE

DISORDER
The etiology of OCD is complex and multifactorial. Although genetic factors
clearly contribute to OCD susceptibility, heritability estimates are between 30%

and 65%, with symptom onset in childhood having a higher heritability than
symptom onset in adulthood. The moderate heritability estimates indicate that
environmental factors as yet unknown also contribute to the development of
OCD. Prenatal and perinatal complications, stress, traumatic brain injuries such
as mild concussion, and inflammatory responses to bacterial or viral infections
have all been postulated to contribute to the development of OCD symptoms,
although none of these has been consistently or reliably associated with OCD13
and thus no formal assessment of such potential contributors is recommended.
OCD is a disorder of neural circuitry. Although multiple brain regions are
associated with OCD pathogenesis, those involved in the cortico-striato-thalamo-

cortical circuits are the most strongly implicated.9,14 These parallel circuits
mediate emotional/affective, sensorimotor, cognitive, and motivational
processes, all of which are important in OCD pathophysiology. Roughly
speaking, the affective circuitry (ventromedial prefrontal cortex, anterior
cingulate cortex, nucleus accumbens, and thalamus) and cognitive circuitry
(dorsal: dorsolateral prefrontal cortex, caudate, and thalamus; and ventral:
anterolateral orbitofrontal cortex, putamen, and thalamus) are involved in
obsessive symptomatology (anxiety, uncertainty with regard to goal-directed
behaviors, and response inhibition). The sensorimotor circuitry (premotor
cortex, putamen, and thalamus) and the frontoparietal network (parietal lobe,
CASE 12-1 A 19-year-old man presented with fears of contamination and excessive
cleaning symptoms. His girlfriend, who suggested the appointment, was
concerned because he was spending up to 2 hours a day “cleaning” the
air in their apartment with air fresheners and felt compelled to shower
every time he left the home and returned, even when just going
downstairs to the lobby to get the mail from the mailbox. He reluctantly
agreed to come to the appointment because his behaviors were
beginning to cause problems in his relationship with his girlfriend, who
was worried about the potential adverse health effects of his excessive
use of air freshener and cleaning agents. Although he admitted to
spraying air freshener in the house over and over and to showering every
time he returned from leaving the house, he denied any fears of germs or
illness. He admitted to a variety of additional cleaning behaviors,
including needing to wash his clothing daily and to change his clothes
multiple times a day, as well as too frequent hand washing. He
recognized these behaviors as excessive and admitted that they were not
logical. When asked specifically about taboo symptoms, he admitted that
when he came into contact with, or was in the vicinity of, another person,
especially someone unknown to him, he was afraid that he would
somehow become contaminated by that person’s essence and take on
their characteristics, becoming less like himself and more like the other
person. He also feared that if the other person had a belief system that
differed from his, or expressed an idea that he did not agree with, he
would take on that belief or idea also just by being in their proximity. He
did not feel this way around family members. He fully recognized that his
fears were irrational but noted that he could not control them and felt
1772 DECEMBER 2021

sensorimotor area, inferior frontal gyrus, and ventrolateral prefrontal cortex) are
thought to be involved in the development of compulsive (habit-based)
behaviors.9,14
Although many neurotransmitters are likely to be relevant in the development
or maintenance of psychiatric symptoms, evidence from clinical and preclinical
studies indicates that serotonin, dopamine, and glutamate may be of particular
relevance for OCD. These neurotransmitter systems are active within the
cortico-striato-thalamo-cortical circuits, and pharmacologic agents that affect
the serotonergic and dopaminergic systems have proven to be effective
treatments for OCD. The evidence for the role of serotonin comes primarily from
the observation that clomipramine and the SSRIs effectively treat OCD
symptoms; less is known about its putative mechanism of action, although
serotonergic neurons project to key regions within the cortico-striato-thalamo-
cortical circuitry from the raphe nucleus. Dopamine has been implicated in OCD
symptomatology both from observations drawn from treatment studies using
neuroleptics and, more importantly, from the fact that dopamine plays a
significant role in the development of automatic grooming and other habit-based
behaviors in animals. The potential role of glutamate comes primarily from
knowledge of its key role in the cortico-striato-thalamo-cortical circuitry;
glutamatergic neurons project bidirectionally between the cortex and regions in
compelled to clean everything on his person and in his apartment,

including the air he breathed, to avoid being contaminated in the way that
he feared. The patient had tried to resist the thoughts and related
behaviors, which had been present since he was 16, without success. He
had recently also been experiencing depressive symptoms, including
social isolation, sadness and hopelessness, and excessive sleeping. He
was relieved to know that his symptoms had a name and a treatment and
was interested in both pharmacologic management and behavioral
therapy to treat them.
This man has contamination obsessions. Fear of being contaminated by COMMENT

another person’s personality, aura, or essence, although less common than
germ fears, are still quite common and are less likely to be disclosed unless
patients are directly asked about them because of fear of being ridiculed
or thought to be psychotic. Effective treatment for this type of symptom
involves exposure and response prevention approaches to reduce and
eventually eliminate the compulsive behaviors and to reduce the intensity
of the fears. Pharmacologic management with selective serotonin reuptake
inhibitors (SSRIs) can also be of benefit, not only for the obsessive-
compulsive disorder symptoms but also for the depression symptoms that
he has recently developed. Although each of these forms of treatment can
be effective on its own, combining exposure and response prevention and
pharmacologic treatment with an SSRI increases the likelihood of response
and often produces an additional reduction in symptoms over and above
either treatment alone.

FIGURE 12-1
Suggested treatment algorithm for obsessive-compulsive disorder (OCD) in adults.
CBT = cognitive-behavioral therapy; DBS = deep brain stimulation; ERP = exposure response prevention; rTMS = repetitive transcranial magnetic
stimulation; SSRI = selective serotonin reuptake inhibitor.
a
Severity of OCD as determined by Obsessive-Compulsive Inventory, Short Version (OCI-R) scores: mild (scores of 15-19), moderate (20-34), and
severe (≥35). If OCD is suspected according to OCI-R score or clinical history, the Yale-Brown Obsessive Compulsive Scale may be administered
for further assessment of obsessive-compulsive and associated symptoms.
b
There is insufficient evidence to support the superiority of one particular SSRI over any other; all appear to have similar efficacies.
Reprinted with permission from Hirschtritt ME, et al, JAMA.7 © 2017 American Medical Association.
1774 DECEMBER 2021

the striatum and are responsible for excitation of the cortex.9 Some early KEY POINTS
evidence also indicates a role of glutamatergic genes in the development of OCD.
● Early intervention is
Glutamatergic agents have been studied for the treatment of OCD, but, to date, critical for improving quality
none have been consistently demonstrated to be of benefit.7,9 of life in OCD and the
likelihood of functional
TREATMENT OF OBSESSIVE-COMPULSIVE DISORDER remission.
Although OCD is a chronic disorder, early intervention can be effective in

● Obsessive-compulsive
reducing symptom severity and improving quality of life and functioning.6,7,9 symptoms are often missed
For some patients, perhaps as many as 50%, functional remission (eg, minimal or misdiagnosed by
residual symptoms that are not perceived to be functionally impairing to the clinicians, in part because
patient) can be achieved with early and appropriate treatment.6,15-17 the symptoms are confused
with other similar
Unfortunately, the current treatment gap for OCD (the time between seeking symptoms.
help for a medical problem and receiving appropriate care) is approximately
2 years.18,19 This delay puts patients at higher risk for a more chronic and ● The most effective form
intractable course of illness and suggests that many providers, including mental of treatment for OCD is a
form of cognitive-behavioral
health professionals, do not effectively identify and treat OCD when patients do therapy called exposure and
present for care. Three contributors to this treatment gap have been identified: response prevention.
(1) misidentification of OCD symptoms (particularly sexual, religious, or
aggressive symptoms) as something else; (2) referral to non–evidence-based
forms of treatment, such as psychodynamic or supportive psychotherapy; and
(3) use of ineffective pharmacologic agents or use of effective pharmacologic
agents at subtherapeutic doses or for suboptimal lengths of time.20
Three primary types of effective treatment are available for OCD: (1)
cognitive-behavioral therapy (CBT), (2) pharmacologic management, and (3)
neuromodulation.9 For most people with OCD, the most effective forms of
treatment continue to be those that have been in place for decades.8 Despite
clinical trials examining other forms of treatment, the evidence base continues to
be the strongest for CBT and pharmacologic management or a combination of
the two.21-24 FIGURE 12-1 shows a suggested treatment algorithm.
For most providers, especially those who are not OCD specialists, the choice of
treatment is often driven by knowledge of, comfort with, and local availability of
the three primary treatment types. Although pharmacotherapy is the most
widely used, the most effective form of treatment for OCD is actually CBT, either
alone or in combination with medication; this form of treatment also has the
highest long-term response rates.7,25 Pharmacologic management primarily
consists of the use of high-dose SSRIs, with the use of additional agents as
augmentation as needed.7-9 Neuromodulation is a newer option and has shown
some benefit for patients who show inadequate response to more standard forms
of treatment, although it is still limited in availability and scope. Other important
interventions that are relevant and should be addressed regardless of the chosen
treatment modality include psychoeducation and the assessment and reduction
of family accommodation of symptoms.6,9,26,27 These interventions are not
considered to be actual treatments, but they can help to increase patient
engagement in treatment and facilitate treatment response.9
Cognitive-Behavioral Therapy for Obsessive-Compulsive Disorder

When it is available, the best treatment for OCD is CBT, particularly a form of
CBT that includes exposure and response prevention.7,21,22,28 Both the cognitive
and the behavioral components of CBT have some efficacy in treating OCD,
although somewhat stronger evidence exists for the efficacy of behavioral

interventions.29-32 The cognitive component of CBT consists primarily of cognitive

appraisal and cognitive restructuring.30,33 In the cognitive appraisal component,
patients are first asked to identify cognitive distortions, erroneous thought patterns,
and maladaptive beliefs associated with their OCD symptoms. Then, in the
cognitive restructuring component, they are asked to identify possible alternative
thought patterns or expected outcomes to distinguish what they fear will happen
from what they believe is the most likely logical outcome and to modify their
automatic and fear-driven interpretation or expectation to be more in line with
their own perception of reality. Acceptance of the thoughts or fears and tolerance of
the distress arising from them is also an important part of cognitive therapy.
The behavioral component of CBT, and exposure and response prevention
specifically, is the most common form of evidence-based psychotherapy for
OCD.7,34,35 In this treatment modality, the focus is on systematically reducing
and eventually eliminating the compulsive or avoidance behaviors that occur in
response to an obsession. Patients and therapists work together to identify and
rank the obsessions and associated compulsions according to the level of distress
they engender, creating a fear hierarchy. Potential behavioral exposures are then
identified for each fear listed, typically beginning with a fear that ranks
somewhat lower (ie, less distressing) on the fear hierarchy. As differences in
environment and situation may lead to different levels of fear or distress for the
same behavior (eg, eating at a possibly dirty table in one’s own home may be less
distressing than eating at a possibly dirty table in a restaurant for someone with
food contamination fears), the fear hierarchy typically includes behaviors
(including avoidance) in a variety of situations to create as rich a list of potential
exposures as possible.
A key element of exposure and response prevention is that exposure to the
feared situation or object occurs without the performance of the compensatory
compulsion; this is the response prevention piece of exposure and response
prevention. There are three forms of exposures: imaginal, in vivo, and
interoceptive.28 The first two are most commonly used in the treatment of OCD;
the third is more common in the treatment of panic and generalized anxiety
disorder.36 Imaginal exposures, which are usually fairly low on the fear hierarchy
and thus easier for a patient to complete, involve imagining the feared situation
and facing the anxiety associated with it without engaging in a compulsion or
avoidance behavior. In vivo exposures involve actual exposure to the feared
situation. A modified form of in vivo exposure that also sits lower on a typical
fear hierarchy is watching someone else in a feared situation, for example, in a
movie or other video clip. The next step in an in vivo exposure might be
watching, but not participating in, the feared situation in person (eg, watching a
therapist or family member eat a jellybean off a dirty surface), and the final step
might be having the patient perform the exposure along with the therapist.
Interoceptive exposures involve the same principles of exposure and response
prevention but are applied to the unpleasant physical sensations of anxiety, such
as hyperventilation or shortness of breath, rather than to a compulsion or other
behavior.36 In a clinical setting, these physical symptoms are typically induced by
standard exposure techniques, for example, by imagining or viewing a feared
object or experience (eg, seeing a picture of a spider if one is afraid of spiders).
Exposure and response prevention can be administered in multiple contexts
and multiple levels of intensity. Treatment sessions are typically an hour in
length and can be administered weekly or multiple times weekly in a standard
1776 DECEMBER 2021

outpatient setting or daily for several hours a day in intensive outpatient, partial KEY POINT
hospitalization, or residential treatment settings.9 Similarly, exposure and response
● The average number of
prevention can be administered in the context of individual or group treatment exposure and response
and is available via the internet and as a self-administration module.7,28,34,37,38 In all prevention sessions needed
forms, patients who are undergoing exposure and response prevention for OCD to attain a desired response
are typically asked to complete exposure and response prevention homework is 16 to 20.
between treatment sessions; usually, the homework is to be completed daily,

either for a prescribed period of time (eg, waiting for 15 minutes to wash one’s
hands) or for a prescribed number of repetitions (eg, driving by a particularly
feared intersection 2 times a day without going back to check whether an accident
had happened there). The assignment and completion of exposure and response
prevention homework is an integral part of effective treatment for OCD.
Multiple studies have examined the characteristics of CBT for OCD that are
the strongest predictors of treatment response, including the inclusion of a
cognitive component, the inclusion of a behavioral component (eg, exposure and
response prevention), the number and/or frequency of sessions, and treatment
adherence.9,28,31,34,39,40 Taken together, these studies indicate that number of
sessions matters (the minimum number of needed sessions for patients to show
an adequate response appears to be approximately 16 to 20) and that adherence
to both sessions and to assigned CBT homework are the strongest predictors of
treatment response.8,9,28,31,34,39-41 The modality (eg, group or individual) and
type of CBT (eg, cognitive therapy or exposure and response prevention) are not
clearly predictive of differential treatment response for patients with OCD,42
although some studies indicate increased benefit of exposure and response
prevention over purely cognitive approaches.31,32 The intensity or frequency of
treatment (eg, once or twice weekly, daily, or for multiple hours per day) does
not appear to predict treatment outcome in the long term, although some
evidence indicates that more intense treatment formats can lead to earlier
response.8,43 Predictors of lack of response that have been identified in some
studies but not others include severity of baseline symptoms, presence of
significant depressive symptoms, and level of insight into illness.28 It is important
to note that CBT for OCD can be effective in a variety of clinical settings and
under less-than-ideal conditions.34
Pharmacologic Treatment of Obsessive-Compulsive Disorder

Because patients with OCD may not have access to a therapist but will likely have
the ability to see a physician, most commonly a primary care provider,
pharmacologic management is often the first or most easily accessed treatment
option. Pharmacotherapy for OCD, as is the case for many psychiatric disorders,
began with a serendipitous discovery; clomipramine, a tricyclic antidepressant
that was used in the mid-1960s as a treatment for depression, was also associated
with an improvement in obsessional thoughts.8 This observation led to the use of
multiple tricyclic antidepressants for the treatment of OCD and the subsequent
finding that of all the medications in this class, only clomipramine was effective.8
The reason for this is likely because of an important difference in the chemical
structure of clomipramine compared to the other tricyclic antidepressants.
Although all tricyclic antidepressants act as inhibitors of norepinephrine
reuptake, as a tertiary amine, clomipramine acts as a more potent inhibitor of
serotonin reuptake than do the other tricyclics (eg, imipramine, desipramine, or
nortriptyline), which have little to no effect on serotonin reuptake.

Somewhat astonishingly, to date, medications that block serotonin reuptake

are the only class of drugs to have primary efficacy for the treatment of OCD; no
other class of medications, if used on its own, has been shown to be of benefit.
Today, although clomipramine remains an important treatment option, it is no
longer considered to be a first-line treatment, not because of lack of efficacy but
because of its substantial side effect burden at therapeutic doses. Instead, the
class of antidepressants called SSRIs has replaced clomipramine as the primary

treatment of choice for pharmacologic management of OCD.8 Although only
clomipramine and four SSRIs (fluoxetine, fluvoxamine, paroxetine, and
sertraline) have been approved by the US Food and Drug Administration (FDA)
for the treatment of OCD, evidence exists that all of the SSRIs (which, in the
United States, also include citalopram and escitalopram) are similarly
efficacious.44 Dual serotonin norepinephrine reuptake inhibitors (SNRIs) such as
duloxetine and venlafaxine have shown some efficacy but generally do not work
as well as SSRIs because the degree of serotonin reuptake blockade is lower.7,8
Current dosing recommendations for OCD treatment with SSRIs differ
substantially from those for depression treatment. OCD treatment guidelines
call for doses that are 2 to 3 times higher than are typically needed for
depression.7,9,44-46 In addition, for OCD, the SSRI dose should be titrated to the
highest expected effective dose at the beginning of treatment and maintained
throughout treatment. In contrast, treatment recommendations for depression
usually suggest titrating to the lowest expected effective dose and, once response
TABLE 12-4 Recommended Primary Pharmacologic Treatment Options for

Obsessive-Compulsive Disorder
Standard Recommended as FDA approved for treatment

Standard obsessive-compulsive first- or second-line of obsessive-compulsive
Medication depression dosesa disorder dosesa treatment disorder
Fluoxetine 40 mg 80 mg First Yes

b
Citalopram 40 mg 40 mg Second No
Clomipraminec 125 mg 250 mg Second Yes

d d
Duloxetine 60 mg 120 mg Second No
Escitalopram 20 mg 40 mg First No
Fluvoxamine 150 mg 300 mg First Yes
Paroxetine 40 mg 60 mg First Yes
Sertraline 100 mg 200 mg First Yes
Venlafaxine 150 mg 300 mg Second No
FDA = US Food and Drug Administration.

a
Doses are presented as dose equivalents using fluoxetine 40 mg as a reference and were derived from studies by Furukawa and colleagues46 and
Hayasaka and colleagues59 and are rounded to nearest available tablet/capsule.
b
Doses greater than 40 mg of citalopram are not recommended because of an FDA boxed warning regarding the potential for QT prolongation.
c
Despite evidence of primary efficacy in obsessive-compulsive disorder, clomipramine is recommended typically as a second-line agent because
of its high side effect burden.
d
Data on dose equivalents are not available; doses are based on FDA-recommended dosing for major depression.
1778 DECEMBER 2021

or remission is achieved, further titrating the dose down to a lower maintenance KEY POINTS
dose.46,47 TABLE 12-4 details the primary and secondary pharmacotherapeutic
● Only one class of
options for OCD, with associated doses. medications, the serotonin
Pharmacologic treatment for OCD should continue for 10 to 12 weeks to reuptake inhibitors, which
ensure adequate response before switching SSRIs or augmenting with another includes clomipramine and
agent.7,9,44 Results from two recent meta-analyses suggest that the highest the selective serotonin
reuptake inhibitors (SSRIs),

incremental gain from SSRI treatment occurs within 2 weeks of achieving an
is effective as a primary
adequate dose, but these studies also show that symptom improvement treatment for OCD; high
continues up through week 12.44,48 As most treatment studies do not follow doses and long treatment
participants past 12 weeks, little is known about whether continued treatment times are needed for
maximum benefit.
response occurs past that point. However, the slope of the curves in the primary
treatment studies and data from studies examining the role of augmentation of ● Adequate pharmacologic
SSRIs in treatment-resistant OCD indicate that continued response to an SSRI is response to treatment
seen as far out as 6 months in 10% to 30% of individuals (as indicated by the cannot be determined until a
response rate for the placebo arms of these augmentation studies).49,50 patient has been on a
selective serotonin reuptake
One possible way to integrate these findings clinically is to think of early inhibitor at an appropriate
robust response to treatment with an SSRI as a potential indicator of a good dose for at least 12 weeks.
prognostic outcome. Thus, patients who have an early response may not need
augmentation of their primary medication. In contrast, those who have a more ● Adjunctive medications
such as neuroleptics or the
delayed or less substantial response in the first few weeks of treatment may
addition of cognitive-
ultimately have insufficient benefit from an SSRI alone, and thus, the treating behavioral therapy to
clinician may consider augmenting the SSRI earlier in the course of treatment. As pharmacologic treatment
the first 2 to 4 weeks of treatment are typically dedicated to dose titration, leads to continued
improvement in up to 30%
noticeable treatment response is not necessarily expected to be apparent until
of patients with OCD.
weeks 4 to 6, that is, 1 to 2 weeks after reaching therapeutic doses.
So, what should be done for those who do not respond to an initial course of
SSRIs at the recommended higher doses? No answer to this question is
universally accepted, but the current literature suggests several possible courses
of action. The first is to add CBT to SSRI treatment; this approach has
consistently shown the most benefit for individuals who do not respond or who
have an inadequate response to an initial trial of medications.8,34,50 For those who
cannot or will not participate in psychotherapy, psychopharmacologic options
are also available. These include augmenting the SSRI with an additional agent,
switching the primary agent to another with known efficacy in OCD, switching
to a second-line agent, or using IV clomipramine. Of these, the first option is the
best studied and has the strongest evidence base.
Of the many drugs that have been examined as adjunctive medications in
OCD, the addition of a second-generation neuroleptic (in particular, either
aripiprazole or risperidone) has the strongest scientific support.8,49-51 Evidence
also supports the use of haloperidol, a first-generation neuroleptic.50,51 As many
as 30% of patients with an inadequate response to an SSRI will show benefit from
the addition of a neuroleptic medication. Other medications that have some
(albeit weak) evidence for potential benefit as an augmenting agent include
topiramate, pindolol, lamotrigine, memantine, and N-acetylcysteine.50 These
medications may be considered as augmenting agents in clinical practice only if
other choices have failed or are not an option and if the potential benefit is
thought to be higher than the potential risk, given that the current level of
evidence for their utility is low.
Another alternative is to switch primary agents, and some evidence also exists
for this approach.50 The preferred choice would be to switch to another SSRI

with an indication for OCD (TABLE 12-4); the second would be to switch to a
second-line agent such as clomipramine, venlafaxine, or duloxetine. If an
inadequate treatment response is seen with the second medication trial,
augmentation with a neuroleptic would again be suggested, particularly if adding
CBT is not an option, is not tolerated, or is ineffective. The final option before
moving to neuromodulation would be to try IV clomipramine.50 The evidence for
this strategy is limited to a few open-label trials and two randomized controlled
trials and indicates that for some patients, IV clomipramine may be effective,
although the appropriate doses and approach to maintenance are not determined.
For patients for whom these interventions have failed, neuromodulation

(specifically deep brain stimulation or transcranial magnetic stimulation) may be
an option.
Neuromodulation
Neuromodulation approaches such as deep brain stimulation and transcranial
magnetic stimulation are the most recent additions to the OCD treatment
armamentarium; in contrast to the psychotherapeutic and psychopharmacologic
approaches, which have remained stable for decades, neuromodulation
approaches are rapidly expanding as an area of scientific and clinical interest.
Although currently limited to patients with treatment-resistant OCD, if evidence
of their efficacy is confirmed, noninvasive approaches may also become widely
available to patients with less severe illness. Although neuromodulation can be
very effective, these interventions are rarely, if ever, appropriate for use as the
only form of treatment. Instead, they can best be thought of as increasing
neuroplasticity and thus as adjunctive treatments. Medication management
and/or cognitive behavioral therapy are still required in many, if not all, cases.
Deep brain stimulation is the most well-developed of the neuromodulation
approaches and is based on a fairly extensive literature demonstrating the
effectiveness of stereotactic ablative surgery for OCD combined with data on the
use and utility of deep brain stimulation for Parkinson disease and other neurologic
disorders with psychiatric symptomatology.52 Although surgical ablation targeting
specific brain regions (in particular, the anterior limb of the internal capsule in
capsulotomy and the cingulate bundle in cingulotomy) are effective in reducing
OCD symptom severity for many patients with treatment-refractory OCD, this
approach is not reversible and therefore is not acceptable to many patients and
clinicians.8 In contrast, deep brain stimulation, which uses microelectrodes
implanted in specific brain regions or white matter tracts to deliver electrical
stimulation in a controlled fashion, is not only reversible but the parameters and
specific targets can be modified to provide more individualized treatment.8,52
Deep brain stimulation is approved by the FDA for the treatment of refractory
OCD, which is defined as failure to achieve an adequate response to an
appropriate course of CBT in addition to three or more first-line pharmacologic
treatments. The anatomic sites most widely used in deep brain stimulation for
OCD are the ventral capsule/ventral striatum, the anterior limb of the internal
capsule, the nucleus accumbens, the subthalamic nucleus, and the bed nucleus of
the stria terminalis.8,52,53 In OCD, treatment response is defined as a 35%
improvement in obsessive-compulsive symptoms; remission is rarely achieved
and is not the expected outcome of any treatment modality to date.
By this metric, deep brain stimulation is remarkably effective in treating OCD.
More than half of patients treated with deep brain stimulation are classified as
1780 DECEMBER 2021

treatment responders.52 Across studies, symptoms are reduced by an average of KEY POINTS
nearly 40%, and response does not appear to differ substantially by choice of
● Deep brain stimulation in
anatomic target.52 Interestingly, examination of the fiber tracts that project from brain regions that activate a
each of the most common brain regions used in deep brain stimulation for OCD white matter fiber tract
demonstrates that stimulation in a single tract that connects the medial prefrontal connecting the medial
cortex to the subthalamic nucleus is the likely common mechanism of action for prefrontal cortex to the
subthalamic nucleus can

all deep-brain stimulation targets. The degree of stimulation of this fiber tract
lead to substantial symptom
strongly predicts OCD treatment response independent of the targeted brain improvement in patients
region and has been replicated in multiple independent cohorts.53 with treatment-refractory
Other forms of neuromodulation have been much less studied, but because OCD.
they are noninvasive (ie, do not require surgery), they have the potential to
● Transcranial magnetic
become additional primary treatment options for OCD, along with CBT and stimulation targeting the
pharmacotherapy. The modality that currently has the strongest evidence base is anterior cingulate cortex
deep transcranial magnetic stimulation (TMS).8 TMS involves stimulating and the dorsal medial
cortical structures using a magnetic coil placed next to the head with either low or prefrontal cortex is
emerging as a noninvasive
high frequency daily for several weeks. In OCD treatment, high-frequency form of neuromodulation
stimulation that can penetrate to the deeper cortical structures thought to be that may also be effective in
involved in OCD pathophysiology, specifically the anterior cingulate cortex and treating OCD.
the dorsal medial prefrontal cortex, is administered, paired with a personalized
OCD symptom provocation protocol designed to activate the target cortical
regions. Although still fairly sparse, the current evidence indicates that TMS (and
in particular, deep TMS) is effective for the treatment of OCD, with a response
rate of approximately 30% (compared to approximately 5% for sham treatment)
and sustained effects up to 4 weeks posttreatment.54,55 Individuals who have not
had an adequate response to either CBT or three or more medication trials appear
to benefit from deep TMS at similar rates to those who have not had prior CBT or
who have had fewer medication trials.56 As currently structured, deep TMS
requires someone with clinical expertise in OCD to devise the symptom
provocation protocols, thus potentially limiting the availability and utility of this
treatment. Studies examining the efficacy of deep TMS without symptom
provocation are thus needed.
Other forms of neuromodulation, including transcranial direct current
stimulation, transcranial magnetic seizure therapy, and vagus nerve stimulation,
have also been studied as potential treatments for OCD. Some early evidence
indicates that transcranial direct current stimulation may have some benefit;
however, so far, symptom improvements do not seem to persist for more than a
few hours or days posttreatment.57 To date, sufficient evidence is not available for
the efficacy of any of these newer approaches, including transcranial direct
current stimulation, to warrant their use for the treatment of OCD outside of a
clinical trial.57,58 However, as noted, the use of neuromodulatory approaches is a
fast-growing area of investigation and one that shows promise for improving the
lives of people with OCD. As noninvasive interventions continue to be developed
and tested, these neurostimulation approaches may soon come to be a realistic
alternative to psychotherapy and pharmacology for the management of OCD.
CONCLUSION
OCD is a chronic complex neuropsychiatric disorder that is frequently
underdiagnosed or misdiagnosed by clinicians. Appropriate treatment for OCD is
effective in reducing symptoms and improving quality of life, particularly when

begun early in the course of illness. Although treatment with a form of CBT
specifically designed for OCD has the best therapeutic outcomes, pharmacologic
management is more readily available and more suited for use by a nonspecialist.
Neurostimulation approaches, many of which are familiar to practicing
neurologists, are also rapidly becoming a part of the OCD treatment
armamentarium.
USEFUL WEBSITE
YALE-BROWN OBSESSIVE COMPULSIVE SCALE

This site provides the instructions, questions, and
checklist needed to obtain a patient’s score on the
Y-BOCS.
iocdf.org/wp-content/uploads/2014/08/
Assessment-Tools.pdf
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REVIEW ARTICLE

RECENT FINDINGS: OCD affects 2% to 3% of adults worldwide and is associated

1764 DECEMBER 2021

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events that may trigger

EVALUATION OF OBSESSIVE-COMPULSIVE DISORDER

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TABLE 12-1 DSM-5 Diagnostic Criteria for Obsessive-Compulsive Disordera

A Presence of obsessions, compulsions, or both:

DSM-5 = Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

1766 DECEMBER 2021

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screening tools in a busy

criteria for OCD.

In a clinical setting, the proportion of patients who answer positively to either

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TABLE 12-2 Distinguishing Obsessions From Other Similar Thought Patterns

Obsessions Ruminations Delusions Overvalued ideas Perseveration

Ego-dystonic or Ego-dystonic Ego-syntonic Ego-syntonic Ego-syntonic Ego-syntonic

Pattern Content of specific Fluid reworking Typically Reasonable Excessive and

Recognized Yes Yes No No No

1768 DECEMBER 2021

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unwanted sexual or explicit images of family members or friends or strangers.

blaspheming, fears of religious objects or symbols, and superstitious fears of

Distinguishing Compulsions From Other Similar Behaviors TABLE 12-3

Compulsions Habits Tics Stereotypies Perseverative behaviors

Involuntary versus Voluntary Both Involuntary Voluntary Voluntary

Repetitive versus Ritualized Repetitive Repetitive Repetitive Repetitive

Deliberate versus Deliberate Deliberate Nondeliberate Deliberate Nondeliberate

Relief of anxiety or Relief Relief Relief Reward Reward

Anxiety or discomfort Yes No Yes No No

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harmed. Harm obsessions are often accompanied by checking behaviors,

associated checking or avoidance behaviors also fall into this category.

1770 DECEMBER 2021

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ETIOLOGY AND PATHOPHYSIOLOGY OF OBSESSIVE-COMPULSIVE

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associated with OCD pathogenesis, those involved in the cortico-striato-thalamo-

1772 DECEMBER 2021

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compelled to clean everything on his person and in his apartment,

This man has contamination obsessions. Fear of being contaminated by COMMENT

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1774 DECEMBER 2021

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Although OCD is a chronic disorder, early intervention can be effective in

Cognitive-Behavioral Therapy for Obsessive-Compulsive Disorder

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interventions.29-32 The cognitive component of CBT consists primarily of cognitive

1776 DECEMBER 2021

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between treatment sessions; usually, the homework is to be completed daily,

Pharmacologic Treatment of Obsessive-Compulsive Disorder

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Somewhat astonishingly, to date, medications that block serotonin reuptake

class of antidepressants called SSRIs has replaced clomipramine as the primary

TABLE 12-4 Recommended Primary Pharmacologic Treatment Options for

Standard Recommended as FDA approved for treatment

Fluoxetine 40 mg 80 mg First Yes

Clomipraminec 125 mg 250 mg Second Yes

Fluvoxamine 150 mg 300 mg First Yes