Download OBSESSIVE–COMPULSIVE DISORDER

81-1
OBSESSIVE–COMPULSIVE
DISORDER
Five Is the Magic Number. . . . . . . . . . . . . . . . . . . . . . . . Level I
Sarah T. Melton, PharmD, BCPP, BCACP, CGP, FASCP
CASE SUMMARY
A 30-year-old-woman presents to her family physician accompanied by her mother after threatening to overdose on diphenhydramine. She complains of feeling anxious and uneasy about
intrusive thoughts of harming her child. She also has reassuranceseeking rituals of checking and counting. She has developed
significant impairment from her anxiety, including dysfunctional
mother–child behavior. Her past medical history is significant for
obesity. After a complete history and physical examination, she
is diagnosed with obsessive–compulsive disorder (OCD) and is
inappropriately prescribed paroxetine. Nonpharmacologic therapy
such as cognitive-behavioral therapy (CBT) should be initiated
concurrently with appropriate pharmacotherapy. Pharmacologic
treatment options include selective serotonin reuptake inhibitors
(SSRIs) (other than paroxetine in this case) and venlafaxine which
have a lower risk of weight gain than paroxetine and clomipramine.
The major goal of pharmacotherapy is reduction of obsessions and
compulsions and improved quality of life (QOL). Efficacy of the
chosen therapy is determined by evaluating specific target symptoms and the use of a standardized rating scale such as the Yale–
Brown Obsessive–Compulsive Scale (Y-BOCS).
QUESTIONS
Problem Identification
1.a. Create a list of the patient’s drug therapy problems.
• Possible OCD, presently untreated with first-line therapy
• Suicidal threat made prior to visit
• Suboptimal pharmacotherapy paroxetine selected by prescriber
(relative contraindication is based on patient’s comorbid
obesity, BMI = 30.4 kg/m2)
1.b. What information (signs, symptoms, and laboratory values)
indicates the presence or severity of OCD?
• The diagnosis of OCD is made after evaluation of the patient’s
history and presenting symptoms. The diagnostic criteria for
OCD are detailed in the Diagnostic and Statistical Manual of
Mental Disorders, Fifth Edition (DSM-5). Please refer to the
textbook chapter related to OCD for a more detailed discussion
of this disease state.
Symptoms consistent with OCD:
• She has obsessions as defined by recurrent and persistent intrusive thoughts. Her obsessions include a severe fear of harming
her child.
• To overcome the anxiety that accompanies the obsessions,
Sonya performs several compulsions and rituals. These include
repeatedly checking appliances, checking her baby, checking
• The obsessions and compulsions cause marked distress; they
are time-consuming (take more than 1 hour a day) and significantly interfere with her normal routine, functioning, and
relationships.
Signs of OCD:
• On physical examination, she shows evidence of redness and
swelling from compulsively rubbing her arm.
• Score of 30 on Y-BOCS.1 The results of a Y-BOCS can range
from 0 to 40. A score of 0–7 indicates subclinical symptoms;
8–15, mild symptoms; 16–23, moderate symptoms; 24–31,
severe symptoms; and 32–40, extreme symptoms. A score of
>18 is generally considered to be significant anxiety.
Laboratory values:
• OCD is a clinical diagnosis that cannot be made on the basis
of laboratory data.
Desired Outcome
2.What are the goals of pharmacotherapy for OCD in this case?
• Decrease the frequency of obsessive thoughts and her overall
level of anxiety. Complete elimination and remission of obsessive and compulsive symptoms are rarely achieved.
• Reduce the time Sonya spends performing compulsive behaviors and rituals (eg, counting rituals, checking appliances, and
rubbing her arm in sets of five).
• Prevent suicide. OCD is associated with an increased risk of
suicide—27% of patients report a previous history of suicide
attempt. It is important to ensure the safety of the patient.
Sonya does not have a history of attempting suicide but she
stated a plan and the family was concerned enough to bring
her in for evaluation. Appropriate management of the OCD
through pharmacotherapy and CBT, as well as close monitoring by healthcare professionals would be expected to reduce
suicidal risk.
• Clinical response is defined as a 25–45% decrease in Y-BOCS
score.2
• Minimize adverse drug effects, both short-term (eg, agitation,
insomnia, and nausea) and long-term (eg, sexual dysfunction,
weight gain). The antidepressant dosages used in OCD tend to
be higher than those used for depression, and patients are at
risk of developing dose-related adverse effects.2,3
• Long-term goals include a return to functional status, improved
QOL, better mother–child relationship, and prevention of
relapse of OCD symptoms.
Therapeutic Alternatives
3.a. What are the most appropriate nonpharmacologic therapies
for this patient?
• Patient education beginning at the time of diagnosis helps
patients to understand their obsessions and compulsions and
the availability of effective treatments for OCD. Information
about the symptoms and long-term course of OCD, treatment options, what to expect during therapy, and the length
of treatment are important factors to discuss with the patient.
Education about OCD is also essential for the patient’s family. Relatives can learn specific ways to encourage the person
with OCD by supporting the chosen modality of treatment.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Obsessive–Compulsive Disorder
Cynthia K. Kirkwood, PharmD, BCPP
• She recognizes that the obsessions and compulsions are excessive and unreasonable.
CHAPTER 81
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the toddler’s car safety seat, and compulsively rubbing her arm
in multiples of five.
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SECTION 7
Support groups for patients diagnosed with OCD and their
families can also be beneficial. People with OCD are often
ashamed and embarrassed by their condition and may find it
very difficult to discuss their symptoms with healthcare professionals, friends, and family. Healthcare professionals should
help patients and their families where appropriate, to understand the involuntary nature of the symptoms by providing
accurate information in an appropriate format.2
Psychiatric Disorders
• The patient can be referred to the National Institute of Mental Health website, www.nimh.nih.gov, which is a valuable
source of information and includes publications such as
“When Unwanted Thoughts Take Over: Obsessive Compulsive Disorder” (http://www.nimh.nih.gov/health/publications
/obsessive-compulsive-disorder-when-unwanted-thoughts-take
-over/index.shtml). If a patient is interested in participating
in a clinical trial, information on trials involving anxiety
medications can be found at https://clinicaltrials.gov/ct2/resu
lts?term=obsessive+compulsive+disorder&Search=Search. The
International OCD Foundation website (https://iocdf.org) has
a 24-page patient brochure in an easy-to-read format (https://
iocdf.org/wp-content/uploads/2014/10/What-You-Need-To
-Know-About-OCD.pdf).
• CBT is the gold standard for nonpharmacologic treatment
of OCD. Exposure and response prevention are the primary
forms of CBT used in OCD.2,3
✓Exposure involves repeated contact with provocative stimuli
that evoke anxiety. Over time, the patient’s anxiety is
decreased through habituation.
✓Response prevention involves teaching the patient to resist
performing a compulsive behavior. Over a long period of
time, there is less need to perform the compulsive behavior
and less accompanying anxiety.
✓The number of exposure sessions varies, but often between
13 and 20 sessions are required for meaningful relief of
symptoms.2
✓ Current guidelines recommend that CBT begins with weekly
sessions, with homework assignments or therapist-assisted,
out-of-office therapy.2,3
✓ In severely ill patients, it is recommended that medication be
initiated first, before the addition of CBT.2,3
✓ For optimal response, patients generally must receive CBT in
combination with pharmacotherapy.2,3
✓ The patient should be referred to national organizations such
as the International OCD Foundation (https://iocdf.org) for
help with finding therapists experienced in the treatment of
OCD.
3.b. What pharmacotherapeutic alternatives are available for the
treatment of OCD?
• SSRIs are considered first-line pharmacotherapy for the treatment of OCD. Approximately 50% of patients respond to
an SSRI.4 The SSRIs have similar efficacy, and fluoxetine,
fluvoxamine, paroxetine, and sertraline are FDA-approved for
the treatment of OCD. Citalopram and escitalopram are also
effective in patients with OCD.3 Paroxetine is not optimal for
this patient because its use is associated with weight gain when
used long term.2,3
• Clomipramine is not optimal in this patient because of her
obesity. Clomipramine inhibits histamine, which is associated
with weight gain.2 It also carries a higher risk of seizures than
other antidepressants. Clomipramine is not a first-line agent in
patients with OCD.2 Clomipramine is a tricyclic antidepressant
(TCA) with a less-tolerated adverse effect profile compared
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
with the SSRIs. Antihistaminic, anticholinergic, and antiadrenergic effects limit use of clomipramine. It can also cause
cardiac conduction delays and is toxic in overdoses. The risk
of seizures with clomipramine is related to both higher doses
and the duration of use. For this reason, the maximum dose in
adults is 250 mg/day.
Optimal Plan
4.a. What drug, dosage form, dose, schedule, and duration of
therapy are best for this patient?
• The selection of an individual SSRI depends on adverse effect
profiles, drug costs or insurance coverage, and concurrent
medications. The SSRIs have several potential drug–drug
interactions. For example, fluoxetine and paroxetine can alter
drug levels of TCAs. Fluvoxamine can increase levels of TCAs,
warfarin, clozapine, and other drugs. In this patient, potential
drug interactions are not an issue at the present time. An
adequate trial of medication requires at least 10–12 weeks,
and the optimal doses of SSRIs typically exceed those used for
depression.2–4 Any of the following SSRI regimens would be
appropriate for this patient:
✓Fluoxetine: The initial dose is 20 mg/day, with dosage
increases every other week. Fluoxetine is usually given in
one dose in the morning. When the daily dose is divided,
the split doses are usually given in the morning and at noon
to reduce the occurrence of insomnia. The usual therapeutic
dosage of fluoxetine in OCD is 20–80 mg/day. Fluoxetine is
available in a generic formulation. Fluoxetine causes insomnia, and this would have to be monitored in this patient who
uses diphenhydramine as needed for insomnia.
✓Fluvoxamine: The initial dose is 50 mg/day given at bedtime,
with dosage increases of 50 mg/week every week until the
target dose is reached. If doses are 100 mg/day or greater,
they are usually divided into two doses with the larger dose
given at bedtime. The initial dose of extended-release fluvoxamine is 100 mg once daily at bedtime, with increases
of 50 mg at weekly intervals. The usual therapeutic dosage
of fluvoxamine in OCD is 100–300 mg/day. Fluvoxamine
and fluvoxamine extended-release are available as generic
formulations.
✓Sertraline: The initial dose is 50 mg/day, with dosage
increases of 25–50 mg/day weekly until the target dose is
reached. The usual therapeutic dosage of sertraline in OCD
is 50–200 mg/day.
✓Citalopram or escitalopram: Although not FDA-approved
for the treatment of OCD, either citalopram or escitalopram
can be used first-line. The starting dose of citalopram is
20 mg/day, and the dose may be increased by 10 mg/day
each week to a target dose of 40 mg/day. Of note, the FDA
has issued a warning that daily doses of citalopram exceeding 40 mg increase the risk of QT interval prolongation.3 The
starting dose of escitalopram is 10 mg/day, and the dose can
be increased by 10 mg/day each week until clinical response
is obtained. The target daily dose for escitalopram in the
treatment of OCD is unknown.
• Expert consensus guidelines recommend monthly follow-up
visits for at least 3–6 months. Booster CBT sessions may reduce
the risk of relapse when medication is withdrawn.
• Consensus guidelines recommend continuing effective pharmacotherapy for at least 1 year before considering a medication
taper.5 If medication is discontinued after this time, the dosage
should be gradually tapered. The dose should be decreased by
25% and may be further decreased thereafter every 2 months.
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4.b. What pharmacotherapeutic alternatives would be appropriate if the optimal plan fails?
• CBT used concomitantly with pharmacotherapy can increase
the response rate.
• If the patient fails an adequate trial with an SSRI, she should be
given an adequate trial of another SSRI.
• If the patient fails two adequate trials of SSRIs, another SSRI
should be tried.
4.c. When is a patient considered to be “treatment-refractory?”
What other pharmacologic alternatives are available if
this patient is determined to be refractory to standard
pharmacotherapy?
• Nonresponse to treatment in OCD is common; 20–40% of
patients do not respond to pharmacotherapy.
• A patient is considered refractory to standard therapy if he or
she fails to respond to well-delivered sequential trials of SSRI
therapy combined with expert CBT.2
• Experts recommend adding an augmenting medication to
SSRI therapy. There are few evidenced-based data regarding
augmentation therapy, but case studies and open trials support
the use of clomipramine, clonazepam, and second-generation
antipsychotics.2,3 Clomipramine should not be used in this
patient because of her obesity. Low dose risperidone or aripiprazole may be effective when added to SSRI therapy although
weight gain can occur with use of these agents.4–6 A response
rate of approximately 30–50% can be expected.
• Other recommendations include trying a new CBT setting or
technique. In patients with extremely severe or unremitting
OCD, ondansetron, immunoglobulins and plasmapheresis,
intravenous clomipramine, neurosurgery, transcranial magnetic stimulation, deep brain stimulation, or electroconvulsive
therapy may sometimes be considered.2,3,5
Outcome Evaluation
5.Which clinical and laboratory parameters are necessary to
evaluate the therapy for achievement of the desired therapeutic
outcomes and to detect or prevent adverse effects?
Efficacy:
• Initially, monitor patients weekly to every other week for a
reduction in the frequency, duration, and severity of obsessions
and compulsions and improvement in occupational, social, and
interpersonal functioning.
• Question the patient at each clinical encounter about response
to treatment by asking about specific target symptoms of OCD
(eg, obsessions regarding harming the child, compulsions of
checking, counting, rubbing her arm).
• After achieving an optimal drug dosage, evaluate the patient
monthly until remission, then every 2–3 months until the drug
is discontinued.
• Use of an objective measurement of anxiety symptoms, such as
the clinician-rated Y-BOCS is helpful in evaluating the clinical
response to medication.1
Adverse effects:
• SSRIs (eg, sertraline): GI distress (eg, nausea, constipation, diarrhea, and vomiting), sexual dysfunction (eg, ejaculatory disturbances, anorgasmia), diaphoresis, asthenia, and insomnia.
Patient Education
6.What information should be provided to the patient to
enhance adherence, ensure successful therapy, and minimize
adverse effects?
General information on OCD:
• OCD is a real illness. OCD can be treated with medicine and
therapy. Patients with OCD have repeated, upsetting thoughts
(ie, obsessions). They may do the same thing over and over
again to make the thoughts go away. They feel that they cannot
control these thoughts or actions. Examples include a fear of
germs, a fear of being hurt or hurting others, and disturbing
religious or sexual thoughts. The actions patients perform over
and over again to make the thoughts go away are called “compulsions.” Examples of these repeated actions include counting,
cleaning, and checking.
Sertraline (Example SSRI):
• You have been prescribed sertraline. You will take the 50-mg
tablet orally once daily for 1 week and then will increase your
dosage to 100 mg/day. The dose that we would like to reach
over the next few weeks is 200 mg once a day. This medication
should be taken at the same time each day and can be taken
with food if it upsets your stomach.
• It will take several weeks before you see a noticeable change
in your anxiety symptoms. It may take 10–12 weeks to achieve
maximum benefit. It is very important that you take the medication as prescribed each day and that you not stop taking the
medication during the time you are increasing the dose.
• It is important to understand that OCD is a difficult disease
to treat. Treatment with medication works best in combination with psychotherapy. Many patients notice a significant
improvement in their symptoms over time with continued
therapy. However, it is important to realize that only about one
in five patients experiences complete disappearance of all OCD
symptoms.
• Take this medication only as directed by your physician. Do
not take more of it or take it more often than your physician
has ordered.
• Avoid drinking alcohol while taking this medication. You may
experience more side effects such as sedation when antidepressants are used in combination with alcohol. Alcohol can
increase the chances of depression and anxiety by preventing
your medication from working as well.
• Consult your prescriber or pharmacist whenever you are using
other medications, especially over-the-counter medications,
because there may be interactions.
• Avoid the use of herbal products such as valerian, kava kava,
St. John’s wort, SAMe, or tryptophan while taking sertraline.
Using them together can cause a severe reaction called serotonin syndrome or make you feel excessively sedated.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Obsessive–Compulsive Disorder
• Before initial pharmacotherapy is considered to have failed,
the dosage should be optimized (eg, 200 mg/day sertraline) with an adequate time to assess response of at least
10–12 weeks (with a minimum of 4–6 weeks at the maximum
tolerated dose).2,3,5
• Have the patient keep a written account or diary of her anxiety,
obsessions, and compulsions. Knowing the amount of time
the patient spends performing compulsions is helpful to assess
response to therapy. Review this with her at each clinical
encounter, and assess for specific areas that continue to cause
frequent anxiety symptoms.
CHAPTER 81
• Patients who present with comorbid disorders are at highest risk for relapse and some patients may need to be treated
indefinitely.
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SECTION 7
• You will continue on this medication for approximately 1 year
after you have responded. When your physician decides to
discontinue the sertraline, it will be slowly tapered. Do not
abruptly stop taking this medication.
• Sertraline is safe to take on a long-term basis. Some people
wish to continue taking it for their lifetime. It is not addicting
or habit-forming.
Psychiatric Disorders
• Adverse effects you may experience include GI symptoms
(nausea, vomiting, and diarrhea), nervousness, somnolence,
dizziness, and insomnia. These adverse events are usually
mild and dissipate with continued use of the medication. A
possible long-term side effect is sexual dysfunction that may
include decreased libido (sexual desire) or inability to experience orgasm. If this occurs, please discuss it with your prescriber.
There are other medication options available to help this adverse
effect. These options include the addition of another medication
or switching to another antidepressant agent.
• Contact your physician immediately if you start to notice an
increase in your anxiety symptoms or feel you are relapsing.
The dosage of your medicine may need to be adjusted.
• Contact your physician if you plan to become pregnant or discover that you are pregnant.
• If you have difficulty affording your medication, some pharmacies offer some antianxiety medications (eg, citalopram,
fluoxetine, and paroxetine) at a discounted rate, and many of
the pharmaceutical companies have special programs that provide medication for free if you meet financial criteria. You can
visit the website for the Partnership for Prescription Assistance
(www.pparx.org) to help find a patient assistance program that
meets your needs, including discounted generic prescriptions
at various pharmacies. You or your physician can also call
the companies directly for assistance with non-discounted
medications:
✓Escitalopram (Lexapro): Forest Pharmaceuticals Patient
Assistance Program: (800) 851-0758
✓Sertraline (Zoloft): Pfizer RxPathways: (866) 706-2400
■■ FOLLOW-UP QUESTIONS
1.When is a decrease in the Y-BOCS score considered clinically
significant?
• In clinical drug trials, a decrease of 25–35% from baseline on
the Y-BOCS is considered to be partial response to treatment.
Full response to pharmacotherapy in clinical trials is often
defined as a 50% or greater decrease in the score from baseline.
2.If this patient had presented to the physician desiring to
become pregnant after 6 months of pharmacotherapy, what
would your recommendations be regarding pharmacotherapy?
• The safest option during pregnancy is CBT.2 For women who
also need pharmacotherapy, data suggest that the fluoxetine,
fluvoxamine, paroxetine, and sertraline were not associated
with increased rates of intrauterine death.7
• There was no increase in the association of major malformations reported between periconceptional use of citalopram,
escitalopram, or sertraline.8 Several birth defects were associated with the use of fluoxetine (eg, craniosynostosis) or
paroxetine (eg, anencephaly, atrial septal defects) early in
pregnancy.9 Some data support the development of persistent
pulmonary hypertension with third trimester use of SSRIs.8
• First trimester exposure to paroxetine can increase risk of
congenital malformation (especially cardiac), and this drug
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
is Pregnancy Category D. (Note: As of June 30, 2015, FDA
published the Pregnancy and Lactation Labeling Rule which
removed the pregnancy categories and instead required manufacturers to provide the drug’s Risk Summary, Clinical Considerations, and Data related to teratogenicity in the prescribing
information. Prescription drugs and biologic products submitted after June 30, 2015, will use the new format immediately
while labeling for prescription drugs approved on or before
June 30, 2001, will be phased in gradually.)
• If Sonya desires to breastfeed her infant and needs pharmacotherapy, an SSRI with a short half-life is recommended.
Paroxetine and sertraline are the most commonly used SSRIs
in breastfeeding mothers. The infant should be monitored for
any unusual behavioral or physical effects.
• All psychotropic medications are secreted into breast milk to
some degree. Studies performed with sertraline or paroxetine
found undetectable plasma levels in infants exposed to these
agents through breastfeeding.10 Sertraline would be preferred
for Sonya because of obesity.
• There are a few reports of adverse reactions after exposure to
fluoxetine. Because of the significantly longer half-life of fluoxetine, it is more likely to accumulate in the infant.
• Refer Sonya to an online resource to assist her in making her
decision (eg, MotherToBaby California at http://mothertobaby
.org sponsored by the Organization of Teratology Information
Specialists).
REFERENCES
1. Goodman WK, Price LH, Rasmussen SA, et al. The Yale–Brown Obsessive Compulsive Scale I. Development, use, and reliability. Arch Gen
Psychiatry 1989;46:1006–1011.
2. American Psychiatric Association. Practice Guideline for the Treatment
of Patients with Obsessive–Compulsive Disorder. Arlington, VA, American Psychiatric Association, 2007. Available at: http://psychiatryonline
.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/ocd.pdf.
Accessed March 30, 2016.
3. Koran LM, Simpson HB. Guideline watch (March 2013): Practice
guideline for the treatment of patients with obsessive-compulsive disorder. Available at: http://psychiatryonline.org/pb/assets/raw/sitewide
/practice_guidelines/guidelines/ocd-watch.pdf. Accessed March 30, 2016.
4.Fineberg NA, Reghunandanan S, Simpson HB, et al. Obsessivecompulsive disorder (OCD): practical strategies for pharmacological
and somatic treatment in adults. Psychiatry Res 2015;227:114–125.
5. Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder,
and obsessive–compulsive disorder: a revision of the 2005 guidelines
from the British Association for Psychopharmacology. J Psychopharmacol 2014;28:403–439.
6. Matsunaga H, Nagata T, Hayashida K, Ohya K, Kiriike N, Stein DJ. A
long-term trial of the effectiveness and safety of atypical antipsychotic
agents in augmenting SSRI-refractory obsessive–compulsive disorder.
J Clin Psychiatry 2009;70:863–868.
7. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists number 92, April 2008 (replaces practice bulletin
number 87, November 2007). Use of psychiatric medications during
pregnancy and lactation. Obstet Gynecol 2008;111:1001–1020.
8. Alwan S, Friedman JM, Chambers C. Safety of selective serotonin
reuptake inhibitors in pregnancy: review of current evidence. CNS
Drugs 2016;30:499–515. doi:10.1007/s40263-016-0338-3.
9. Reefhuis J, Devine O, Friedman JM, Louik C, Honein MA. Specific SSRIs and birth defects: Bayesian analysis to interpret new
data in the context of previous reports. BMJ 2015;351:h3190.
doi:10.1136/bmj.h3190.
10. Berle JO, Spigset O. Antidepressant use during breastfeeding. Curr
Womens Health Rev 2011;7:28–34.