ABSTRACT: Obsessive-compulsive disorder (OCD) is a psychiatric illness that is often underreported and underdiagnosed. Patients with OCD suffer from obsessions and compulsions that can be debilitating. Treatment guidelines recommend pharmacologic treatment primarily with selective serotonin reuptake inhibitors in addition to psychotherapy. Community pharmacists can support their OCD patients in achieving positive outcomes through enhanced clinical services such as patient counseling on medication dosing and side effects, medication therapy management, lifestyle coaching, and pharmacogenomics testing and guidance.

USPharm. 2020;45(5):20-24.

Obsessive-compulsive disorder (OCD) is a psychiatric disorder that is chronic, often debilitating, and characterized by obsessions and compulsions.1-4 Obsessions can be described as persistent and uncontrollable thoughts or urges that cause anxiety for the patient. Examples of commonly seen obsessions include fear of germs, the need for order, and fear of death or illness of oneself or loved ones. Compulsions are repetitive behaviors that a patient feels the need to do in response to an obsession. Examples of compulsions are excessive cleaning or handwashing or repetitive checking that doors are locked or the oven is turned off.3,4 Treatment normally consists of a combination of psychotherapy and pharmacologic management with various selective serotonin reuptake inhibitors (SSRIs).1-4 Pharmacists can improve the quality of life for their patients with OCD through counseling, medication therapy management (MTM), and pharmacogenomic testing to guide the selection of the best patient-specific SSRI for treatment.

The onset of OCD is bimodal, with characteristics of the disorder presenting predominantly in males in childhood, with a mean age of onset of 10 years.  Dominance switches to females in adolescence and young adulthood, with a mean age-range of onset of 19 to 21 years.3 The gender ratio in adulthood is approximately 1:1, and onset after the early 30s is atypical. The 12-month and lifetime prevalence of OCD are 1.2% and 2.3%, respectively.5 Although the cause of OCD is not fully understood, genetic factors and various environmental factors may play a role.1,3,4 Additionally, psychosocial (abuse, neglect, social isolation, and bullying) and developmental factors (perinatal complications) are also implicated in the development of the disorder.3,4,6,7 A majority of patients (up to 90%) who are diagnosed with OCD meet the criteria for at least one other psychiatric disorder, with anxiety disorders, mood disorders, and impulse-control disorders ranking highest in terms of comorbidities.3 For this reason, management of OCD in these patients is heavily influenced by comorbid disorders.

Treatment Guidelines

The American Psychiatric Association (APA), National Institute for Health and Care Excellence (NICE), and Canadian OCD guidelines all support the use of psychological treatment and/or pharmacologic treatment as effective first-line therapy.8-10 Selection of initial therapy is multifactorial. Aspects to consider include the patient’s severity of symptoms, additional disease states, availability of therapy, personal motivation, medication cost and side effects, and drug interactions; all ultimately impact patient adherence. Psychological therapy centers on cognitive behavioral therapy (CBT) that may or may not include exposure and response prevention (ERP) techniques. CBT plus ERP may be recommended as initial treatment in patients with mild functional impairments or in those who prefer not to take medications. In both instances, the patient must have the ability and motivation to engage in the comprehensive CBT-program recommendations. Pharmacologic therapy focuses on the use of SSRIs and clomipramine. These agents may be given alone in patients who have responded well in the past to the medication or who prefer to be treated only pharmacologically.8-10 

Combination therapy may be appropriate as well, and adding CBT to pharmacologic therapy may improve patient response and decrease relapse. It is important to note that CBT plus ERP has been shown to be equal or superior to pharmacotherapy, while combination therapy has been shown to be superior to pharmacotherapy alone, but not CBT alone.8-10

When an adequate response is not achieved, several strategies may be employed. These include, but are not limited to, combining pharmacologic and nonpharmacologic therapies, switching to a different SSRI, switching to or augmenting with clomipramine, or adding a second-generation (atypical) antipsychotic as adjunctive therapy.8-10

Pharmacologic Treatment

Acute treatment of OCD is targeted at decreasing symptom severity and improving the patient’s quality of life. SSRIs and clomipramine are used in the pharmacologic management of OCD. SSRIs have generally been noted to be equally efficacious, with no one SSRI providing better outcomes than the others.11 SSRIs are preferred over clomipramine due to better tolerability and fewer side effects.12

Treatment should be initiated with the lowest dose and titrated every 4 to 6 weeks of therapy depending on the patient response to the maximally tolerated dose.9 Patients should have an adequate trial of 8 to 12 weeks at maximally tolerated doses. Higher daily doses of SSRIs are needed in the treatment of OCD as compared with depression and anxiety.2,4,8,9,12 Higher doses are more effective than lower doses and produce higher response rates and greater symptom relief in OCD patients.8,12 Patients who are nonresponsive to initial pharmacologic therapy and resistant to treatment may benefit from the addition of a second-generation antipsychotic agent such as aripiprazole, risperidone, or quetiapine.13,14 TABLE 1 lists the commonly prescribed medications for OCD, doses, side effects, and black box warnings.

Nonpharmacologic Treatment

The 2007 APA Practice Guideline for the Treatment of Patients with OCD and the 2005 NICE clinical guidelines both recommend CBT in the treatment of OCD.8,9 CBT that focuses on ERP is most widely used and supported by OCD guidelines. A plethora of data supports the use of ERP as first-line treatment in patients with OCD who have no severe, depressive symptoms and who prefer nonpharmacologic treatment. ERP consists of repeated, prolonged exposure to the stimulus or situation that evokes the compulsion and gradually enhancing the level of severity of the threat.15 Patients are coached not to engage in the compulsive activity for the duration of the exposure in order to understand that given time, the fear/anxiety will naturally subside. CBT, with or without ERP, may be provided in individual, group, or family sessions and should occur at least once a week.8 Patients with milder OCD symptoms may see adequate benefit in a group setting, whereas patients with moderate-to-severe OCD may require individual sessions. The number, length, and overall duration of CBT sessions are not established; however, 13 to 20 weekly sessions lasting approximately 1 to 2 hours, followed by 3 to 6 months of booster sessions, have been recommended for most patients.8,9 Increasing the number of weekly sessions, increasing session duration, and using a more intensive setting (e.g., hospital, residential program) may be more suitable for patients with more severe symptoms or those who are at risk for suicide or who have comorbid conditions which require intensive treatment and monitoring.

Cognitive therapy, another form of CBT, requires that the patient keep a journal of their obsessions and how those obsessions are perceived.15 The patient is then taught to change their unrealistic perceptions of the feared situation during exposure to the fear-eliciting stimulus. This method uses Socratic questioning and challenges patients to restructure their thoughts by realizing the distortions in their cognitive patterns. Cognitive therapy may be conducted in individual, group, or family sessions and should be based on the treatment response of the patient.8

The FDA has approved deep brain stimulation (DBS) of the ventral capsule or ventral striatum to reduce symptoms of severe, refractory OCD in patients who have been nonresponsive to adequate trials of first-line therapies (serotonin reuptake inhibitors and CBT).3 The most common side effects associated with DBS are anxiety and hypomania; more serious adverse effects include postoperative confusion, intracerebral brain hemorrhage, and infection. The FDA has also approved transcranial magnetic stimulation (TMS) for the treatment of OCD symptoms, with common side effects including headache, facial pain, and muscle pain or spasms. Other procedures have reported effective reduction of OCD symptoms; however, the strength of clinical evidence is lacking. Neurosurgery is recommended by the NICE guidelines only if requested and if the patient has severe, treatment-resistant OCD.9

Pharmacogenomics

As pharmacogenomics (PGx) begins to emerge as a clinical service offered in community pharmacy, genetic testing of cytochrome P450 2D6 (CYP2D6) and cytochrome P450 2C19 (CYP2C19) may have implications in pharmacotherapeutic recommendations in OCD patients. SSRIs are largely metabolized by CYP2D6, CYP2C19, and to some extent by CYP3A4. CYP2D6 and CYP2C19 polymorphisms can influence the metabolism of SSRIs, and thus drug efficacy and safety. As such, the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines base recommendations on CYP2D6 and CYP2C19 genotypes.

When applying PGx testing, focus is placed on CYP2D6 polymorphisms in regard to fluoxetine, fluvoxamine, and paroxetine dosing and 2C19 for escitalopram and citalopram.16,17 There are varying levels of evidence that support this sampling of dosing recommendations. According to the CPIC guideline for paroxetine, strong evidence suggests that alternative medications not predominantly metabolized by CYP2D6 be selected for patients identified as CYP2D6 ultrarapid metabolizers because increased metabolism may increase the potential for treatment failure.17 Alternatively, when considering treatment with escitalopram or sertraline, patients identified as poor metabolizers of CYP2C19 may need a 50% reduction of the recommended starting dose or an alternative drug not metabolized by CYP2C19, as higher concentrations of these drugs may increase the risk for side effects; these recommendations are classified as moderate and optional respectively.

It is not recommended for patients to have PGx testing to guide initial clinical decision-making with SSRIs. Additionally, patients on a stable and effective dose of an SSRI most likely will not benefit from therapy modifications based on CYP2D6 or CYP2C19 results.16,17 However, if CYP2D6 and/or CYP2C19 PGx results exist, they may provide benefit in identifying patients at increased risk for experiencing adverse drug reactions and/or therapeutic failure. When caring for OCD patients, it would be prudent to observe that PGx testing provides just one data point in the decision-making process for treatment. For more information on PGx, including classification of recommendations, go to www.PharmGKB.org or www.CPICPGx.org.

Community Pharmacist Role

The typical clinical response to SSRIs and other OCD treatments does not occur rapidly or completely, and relapse is common in OCD patients.3,4 In addition, the delayed response and effect of antidepressants on the control of the patients’ OCD symptoms should be discussed and emphasized when counseling these patients. Adherence to treatment is paramount to a successful trial whether pharmacologic or nonpharmacologic. Community pharmacists are on the front lines, positioned to impact patient medication adherence through initial and follow-up medication counseling on dosing, side effects, drug interactions, and patient responses to therapy. Discussion of common side effects, such as those listed in TABLE 1, and how to mitigate these side effects are essential, along with discussion of other adherence barriers such as cost, transportation, and social stigma. MTM services should be offered to OCD patients for follow-up monitoring to their response to therapy, side effects, and medication adherence.

Due to the higher doses of SSRIs used in OCD patients, monthly monitoring for potential toxicities is in the patient’s best interest. Patients should be counseled on the signs of serotonin syndrome, such as mental status changes, tachycardia, sweating, tremors, nausea, vomiting, and diarrhea. Patients should also be counseled not to stop the medication abruptly due to discontinuation syndrome, characterized by problems with balance, sleep disorders, and gastrointestinal and flu-like symptoms.1,4,18 PGx testing can also be used if a patient is experiencing a poor clinical response or medication toxicities.  Pharmacists can provide solutions, discuss alternative treatment options, and provide external resources for OCD patients, such as those listed in TABLE 2.

Conclusion

Patients with OCD can greatly benefit by using clinical services offered in community pharmacies. Due to the nature of the disease and the potential waxing and waning of symptoms, OCD patients may have difficulty with medication adherence. Side effects, as well as intolerance of the pharmacologic agents used, also may result in negative patient outcomes. PGx services have the potential to identify patients at an increased risk for adverse effects and provide explanation for therapeutic failure. Through MTM services, frequent patient counseling opportunities, and providing patient resources, pharmacists can support patients in achieving better management of their OCD.

 

REFERENCES

1. Kirkwood CK, Melton SK, Wells BG. Posttraumatic stress disorder and obsessive-compulsive disorder. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: a Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017:1099-1109.
2. Obsessive-compulsive disorder. National Institute of Mental Health. Updated October 2019. www.nimh.nih.gov/health/topics/obsessive-compulsive-disorder-ocd/index.shtml. Accessed February 14, 2020.
3. Obsessive-compulsive disorder. In DynaMed [Database online]. EBSCO Information Services. Updated August 26, 2019. www.dynamed.com/condition/obsessive-compulsive-disorder-ocd. Accessed February 12, 2020.
4. Brock H, Hany M. Obsessive-compulsive disorder (OCD) [December 30, 2019]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; January 2020. www-ncbi-nlm-nih-gov.su.idm.oclc.org/books/NBK553162/?printable. Accessed February 12, 2020.
5. Ruscio AM, Stein DJ, Chiu WT, Kessler RC. The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication. Mol Psychiatry. 2010;15:53-63.
6. Grisham JR, Fullana MA, Mataix-Cols D, et al. Risk factors prospectively associated with adult obsessive-compulsive symptom dimensions and obsessive-compulsive disorder. Psychol Med. 2011;41:2495-2506.
7. Brander G, Rydell M, Kuja-Halkola R, et al. Association of perinatal risk factors with obsessive-compulsive disorder: a population-based birth cohort, sibling control study. JAMA Psychiatry. 2016; 73:1135-1144.
8. American Psychiatric Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. July 2007. www.psychiatry.org/psychiatrists/practice/clinical-practice-guidelines. Accessed January 20, 2020.
9. National Institute for Health and Care Excellence. Obsessive-compulsive disorder and body dysmorphic disorder: treatment. November 2005. www.nice.org.uk/Guidance/CG31. Accessed January 20, 2020.
10. Katzman MA, Bleau P, Blier P, et al; Canadian Anxiety Guidelines Initiative Group. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014;14(suppl 1):S1-S83.
11. Skapinakis P, Caldwell DM, Hollingworth W, et al. Pharmacological and psychotherapeutic interventions for management of obsessive-compulsive disorder in adults: a systematic review and network meta-analysis. Lancet Psychiatry. 2016;3(8):730-739.
12. Hirschtritt ME, Bloch MH, Mathews CA. Obsessive-compulsive disorder: advances in diagnosis and treatment. JAMA. 2017;317(13):1358-1367.
13. 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(5):403-439.
14. Komossa K, Depping AM, Meyer M, et al. Second generation antipsychotics for obsessive compulsive disorder. Cochrane Database of Systematic Reviews 2010;(12): CD008141.
15. Grant JE. Clinical practice: obsessive-compulsive disorder. N Engl J Med. 2014;371:646-653.
16. Nassan M, Nicholson WT, Elliott MA, et al. Pharmacokinetic pharmacogenetic prescribing guidelines for antidepressants: a template for psychiatric precision medicine. Mayo Clin Proc. 2016;91(7):897-907. P
17. Hicks JK, Bishop JR, Sangkuhl K, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther. 2015; 98(2):127-134.
18. Lexicomp Drug Information Handbook, 28th ed. Hudson, Ohio: Wolters Kluwer Clinical Drug Information, Inc; 2019.
19. Veale D, Miles S, Smallcombe N, et al. Atypical antipsychotic augmentation in SSRI treatment refractory obsessive-compulsive disorder: a systematic review and meta-analysis. BMC Psychiatry. 2014;14:317.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

To comment on this article, contact rdavidson@uspharmacist.com.