Psychiatric Annals


Obsessive-Compulsive Disorder: Overview and Standard Treatment Strategies

Phillip J. Seibell, MD; Rebecca J. Hamblin, PhD; Eric Hollander, MD


Obsessive-compulsive disorder (OCD) is a common psychiatric illness defined by the presence of distressing intrusive thoughts, impulses, or images (obsessions) and behaviors aimed at neutralizing those thoughts (compulsions). OCD is often chronic and highly debilitating to those who suffer from it, yet appropriate diagnosis and treatment are often not received for many years due to shame, stigma, and misunderstanding. First-line treatments include cognitive-behavioral therapy in the form of exposure and response prevention (ERP), selective serotonin reuptake inhibitors (SSRIs), or a combination of ERP and an SSRI. For treatment-resistant cases of OCD, a number of pharmacological agents have been explored as possible augmentation strategies. This article reviews the epidemiology, pathophysiology, and assessment and treatment approaches for OCD, including a number of exploratory augmentation strategies for refractory cases. [Psychiatr Ann. 2015;45(6):297–302.]


Obsessive-compulsive disorder (OCD) is a common psychiatric illness defined by the presence of distressing intrusive thoughts, impulses, or images (obsessions) and behaviors aimed at neutralizing those thoughts (compulsions). OCD is often chronic and highly debilitating to those who suffer from it, yet appropriate diagnosis and treatment are often not received for many years due to shame, stigma, and misunderstanding. First-line treatments include cognitive-behavioral therapy in the form of exposure and response prevention (ERP), selective serotonin reuptake inhibitors (SSRIs), or a combination of ERP and an SSRI. For treatment-resistant cases of OCD, a number of pharmacological agents have been explored as possible augmentation strategies. This article reviews the epidemiology, pathophysiology, and assessment and treatment approaches for OCD, including a number of exploratory augmentation strategies for refractory cases. [Psychiatr Ann. 2015;45(6):297–302.]

Obsessive-compulsive disorder (OCD) is a common psychiatric illness that is characterized by obsessions and compulsions. Obsessions refer to repetitive thoughts or images that are experienced as foreign, intrusive, and unwanted. Obsessions cause marked anxiety and distress and lead to compulsions, repetitive behaviors or mental rituals that are performed in an attempt to reduce anxiety and to prevent a dreaded outcome.1 Alternatively, some compulsions are performed in an effort to obtain a “just right” feeling. Reduction in anxiety resulting from a compulsion is temporary and leads to intensification of obsessions over time by way of reinforcement, resulting in a cycle in which more compulsive behavior is needed to reduce anxiety. OCD is the fourth most common mental illness,2 affecting 2% to 3% of the population. Similar prevalence rates and symptom presentations are seen across cultures.3 Mean age of onset is 19.5 years and onset after age 35 years is rare.4 Women tend to have a later age of onset than men; thus, OCD is more prevalent among boys and men for younger age groups, but gender differences disappear in adulthood.5 Symptoms tend to have gradual onset and intensify over time. Although symptoms may wax and wane, remission without treatment is uncommon.6,7

There is great suffering, disability, and impairment of quality of life in OCD, and it has been estimated that OCD is among the top 20 causes of illness-related disability worldwide for individuals between ages 15 and 44 years.8 Those who suffer from OCD tend to hide their symptoms due to shame, and the condition is often not recognized, properly diagnosed, or properly treated in clinical practice. Sufferers seek treatment from an average of 3 to 4 doctors and spend an average of 9 years in treatment before receiving a correct diagnosis. In total, an average of 17 years goes by after onset of symptoms before proper treatment is obtained.9 These numbers speak to the need for more intensive education regarding OCD across disciplines in medicine and mental health.


Perhaps the most widely recognized symptom domain in OCD is contamination, in which obsessions regarding dirt or germs result in cleaning, washing, and avoidance compulsions. An individual with contamination symptoms may experience anxiety when in contact with a doorknob, for example. The anxiety and distress may lead the individual to wash his or her hands repetitively in an attempt to eliminate the thoughts and feelings of contamination that resulted from touching these items. The person may also use barrier devices (ie, tissues, sleeves, paper towels) in public in an attempt to avoid contact with potential contaminants. Each time the individual with OCD washes, the central pathophysiology of the disorder is reinforced, leading to progressive worsening of symptoms. Other common symptom categories in OCD include symmetry, ordering/counting, forbidden thoughts/images/scrupulosity, and harm.10 As described by Seibell and Hollander,10 symptoms in the symmetry domain include a need for alignment of objects, often in an attempt to reduce anxiety and obtain the “just right” feeling. Some patients engage in ordering or counting behaviors in an attempt to prevent a dreaded outcome. Patients may experience forbidden thoughts or images and attempt to neutralize them with compulsions. Symptoms in the scrupulosity domain refer to obsessions and compulsions that are religious in nature and clearly outside the typical boundaries of a particular religion. Patients with symptoms in the harm domain experience obsessions directly related to harm coming to self or others. Checking compulsions are common in this category (for example, to prevent a house robbery, a person may repeatedly check to see whether or not the front door is locked). The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)11 has placed OCD within the new category of Obsessive-Compulsive and Related Disorders. Note that the DSM-5 now includes additional insight specifiers that are clinically useful. Hoarding is now categorized as its own disorder (hoarding disorder) and the reader may consult a separate review for more information.12


OCD results from multiple variables.1,10 Genetic studies have indicated that monozygotic twins are more likely to exhibit symptoms than dizygotic twins.13 Studies of first-degree relatives have also suggested that transmission within families occurs by way of an autosomal dominant inheritance pattern.14–17 Serotonin is thought to play a clear role in pathophysiology as the mainstay of pharmacological treatment is serotonin-reuptake inhibiting medications.1 Other neurotransmitter systems thought to play a role include dopamine and glutamate, as evidenced by attempts to augment treatment using antipsychotics and glutamate-modulating agents.18 Functional neuroimaging studies have revealed that certain areas are hyperactive in OCD: the orbitofrontal cortex, anterior cingulate gyrus, thalamus, and striatum.19 Evidence suggests that these areas are also dysfunctional in children.20 Of note, it has been shown that after administration of selective serotonin reuptake inhibitors (SSRIs) or cognitive-behavioral therapy (CBT), the hyperactivity in the aforementioned areas/circuit decreases.21,22 One study of 59 women with OCD found that 39% described onset of symptoms during pregnancy, suggesting that pregnancy may play a role in the development of the disorder in some women.23 Onset after head trauma or striatal lesions has also been described.8,10 Also of note is that some patients experience onset or exacerbation of symptoms following beta-hemolytic streptococcal infection.10 This phenomenon is referred to as “PANDAS” (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection).24

Diagnosis/Gold Standard Rating Scale

OCD is typically diagnosed using DSM-5 criteria as a guide.11 The gold standard measure of symptoms in OCD is the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS).10 It has demonstrated validity, both adult and child versions exist, and it can be used as a self-report or clinician-administered scale.25 The two components of the Y-BOCS are the symptom checklist and the severity rating scale. The symptom checklist is clinically useful as it provides data on specific symptom domains that require further clinical attention. The severity scale has 10 questions—5 about obsessions and 5 about compulsions, and the overall score gives an indication of OCD severity. We recommend that anyone treating OCD become familiar with this scale and administer it to patients both at the outset of treatment and then periodically thereafter.10 The Y-BOCS sometimes helps delineate functional improvement that may be difficult to assess using standard clinical interviewing techniques. Such an objective measure of improvement can help provide motivation to patients during the course of treatment, as participation in treatment for OCD is often continuously challenging.


The treatment of OCD includes CBT in the form of exposure and response prevention (ERP) and medication management, with first-line pharmacology consisting of SSRIs (because clomipramine may have more adverse effects than SSRIs, the American Psychological Association [APA] Practice Guideline recommends using SSRIs rather than SRIs as first-line treatments for OCD).1 Mild-to-moderate severity of illness is indicated by a Y-BOCS score of 8 to 23 (maximum score is 40), and treatment can include either ERP or administration of an SRI alone.1 It is important to note that most medication trials used a 25% to 35% reduction in total Y-BOCS score to classify responders to treatment. In one study, when ERP and drug treatment alone were compared, ERP was found to be more effective26; however, practice guidelines from the United States (APA Practice Guideline) and the United Kingdom (British Medical Journal Best Practice Guideline/NICE Practice Guideline) suggest that SSRIs, ERP, and SSRIs in combination with ERP are all first-line treatments for OCD.1 For more severe symptoms, medication management in combination with ERP is recommended and some patients will have difficulty engaging in ERP if they are not already exhibiting a medication response.10

Exposure and Response Prevention

Although specific treatment outcomes with ERP are covered in this issue by Wheaton and colleagues, it is useful for the practicing psychiatrist to learn about the general ERP treatment approach, as it has been shown to be the most effective single treatment for OCD. When administered by a skilled therapist, ERP can help the individual with OCD make significant real-life gains in overall level of functioning and quality of life. As described by Seibell and Hollander,10 the first step includes providing psychoeducation about the illness and ERP process. Patients then often complete a 24-hour obsession and compulsion symptom log after the Y-BOCS is administered. These data are then used in the construction of a hierarchy of symptom triggers. The hierarchy is created by listing symptom triggers in order of most (higher on hierarchy) to least triggering (lower on hierarchy). For example, a public doorknob may be less triggering than a public toilet seat for a patient working on contamination OCD. Patients then work on completing exposure tasks, using less triggering items first. The patient may, for example, hold onto a public doorknob until his/her anxiety reduces substantially. Exposures are repeated until they trigger little to no anxiety, and higher-level exposures are then targeted in a stepwise fashion. It is important that patients with OCD complete exposure exercises during in-office CBT/ERP sessions and that they leave sessions with well-defined homework assignments. The more time that is spent on ERP, the greater the likelihood that there will be a successful outcome. We recommend at least 1 hour per day. A point that should be emphasized in sessions is that it is important to work on both planned exposures for ERP homework and to confront avoidance behaviors/resist engaging in compulsive behaviors when encountering unplanned triggers as well.

Reassurance-Seeking Behavior in OCD

A common symptom of OCD includes asking for reassurance regarding certain themes as part of an endless quest for feelings of certainty. As part of any ERP protocol and during treatment of any individual with OCD, psychoeducation regarding reassurance-seeking questions should be provided. A basic example of a reassurance-seeking question is: “Do you think I’ll get sick if I don’t wash my hands?” Reassurance-seeking attempts targeting family members, friends, or the individual’s psychiatrist should be considered compulsions. Each time the sufferer is provided with reassurance, such as “No, I don’t think you will get sick,” the OCD gains strength. Therefore, a plan for tapering the provision of reassurance is often a useful component of treatment—a plan that enlists both family members and clinicians.

First-Line Psychopharmacology in OCD

SSRIs are considered first-line pharmacologic treatment choices in OCD.10 Those that have US Food and Drug Administration (FDA) approval include fluoxetine, fluvoxamine, paroxetine, and sertraline. The tricyclic antidepressant clomipramine is also FDA-approved for the treatment of OCD but is not considered first-line due to the potential for a greater side-effect burden.1 The SSRIs are considered similar in efficacy and it can be difficult to predict who may respond better to one agent versus another.27 Factors to consider when choosing an SSRI include comorbid medical conditions and potential drug-drug interactions, individual side-effect profiles, prior treatment response, family history of treatment response, and patient age.28 To make a judgment regarding response to a particular SSRI, the dose must be at least in the moderate range and treatment must be continued for 12 weeks.1 Usual target doses in OCD that have been suggested by the APA Treatment Guideline28 include fluoxetine 40–60 mg/day, fluvoxamine 200 mg/day, paroxetine 40–60 mg/day, and sertraline 200 mg/day. Usual maximum doses include fluoxetine 80 mg/day, fluvoxamine 300 mg/day, paroxetine 60 mg/day, and sertraline 200 mg/day. Occasionally, it may be helpful to push the dose past the usual maximum dose and per the APA guideline,28 occasionally prescribed maximum doses include fluoxetine 120 mg/day, fluvoxamine 450 mg/day, paroxetine 100 mg/day, and sertraline 400 mg/day. Strict attention to potential side-effect issues and drug-drug interactions/comorbid medical conditions is especially important when prescribing above the usual maximum doses. Because there has been increasing concern regarding QTc prolongation with citalopram and escitalopram, especially at higher doses, we no longer recommend them as first-line options for OCD.


Although clomipramine is not considered first-line treatment in OCD due to potential for side effects, patients who have not responded to one or more SSRI trials (with lack of response defined as a less than 25% reduction in Y-BOCS score)1 may benefit from a clomipramine trial as a meta-analysis suggested that it is more effective than the SSRIs.29 Side effects include sedation, weight gain, and anticholinergic side effects. The suggested usual target dose range is 100–250 mg/day and the usual maximum dose is 250 mg/day. Clomipramine has the potential to cause cardiac toxicity; electrocardiograms (ECGs) are useful in monitoring heart rate, rhythm, and QTc interval. Blood levels of clomipramine and its active metabolite, desmethylclomipramine, should be regularly monitored as well to avoid cardiac and central nervous system toxicity (which can result in seizures). Levels suggested during treatment include 225–350 ng/mL for clomirapmine and combined clomipramine and desmethylclomipramine levels ≤500 ng/mL.30 An interesting pharmacologic pearl in OCD relates to the fact that clomipramine inhibits the reuptake of serotonin and desmethylclomipramine inhibits the reuptake of norepinephrine. As CYP1A2 converts clomipramine to desmethylclomipramine, adding 25 mg of fluvoxamine, which inhibits CYP1A2, can result in an increased clomipramine/desmethylclomipramine ratio.10 This strategy can help some OCD patients who are struggling on standard clomipramine treatment. Particular attention to monitoring of ECGs and blood levels is required when attempting this approach.10 Also note that those with low CYP1A2 activity require lower-than-typical doses of clomipramine.

Antipsychotic Augmentation

Haloperidol, risperidone, quetiapine, olanzapine, and aripiprazole have been studied as SRI augmentation agents in OCD.31,32 A recent meta-analysis found that antipsychotics as a group have a small effect size over placebo when used as augmentation agents,32 and individual medications appear to differ in potential efficacy.32,33 Although overall effect size has been small,32 risperidone augmentation appears to benefit some individuals with OCD.32–35 Meta-analyses have consistently failed to provide evidence for quetiapine or olanzapine as augmentation strategies,32,33 although one randomized, open-label pilot study found that quetiapine augmentation of SSRIs led to significant reductions in Y-BOCS scores, whereas clomipramine augmentation of SSRIs did not.36 Aripiprazole has some data to suggest efficacy as an augmentation agent in the short-term.32,37,38 Overall, it has been suggested that approximately one-third of patients with OCD will benefit from antipsychotic augmentation33; therefore, if a patient does not appear to be exhibiting a response, the antipsychotic should be discontinued.

Several points are worth mentioning regarding this strategy. A meta-analysis39 suggested that over 25% more patients will respond if given a full 12 weeks on their initial SRI trial when compared to augmenting with antipsychotics before the 12-week mark. This same meta-analysis39 suggested that patients with comorbid tics may respond better to antipsychotic augmentation than OCD patients without comorbid tics. In addition, we now have evidence that augmentation of SRIs with ERP is more effective than augmentation with risperidone, and in fact, risperidone augmentation did not separate from placebo in the recent study by Simpson et al.40 Given the potential side-effect burden of antipsychotic drugs, this strategy should be considered carefully before implementation, and if ERP is available, evidence suggests that it should be used as a treatment augmentation strategy before antipsychotics for patients who have not had an adequate response to SRI treatment alone.10

Other Augmentation Strategies

There is interest in agents that modulate glutamate as augmentation strategies in OCD; please see Pittenger’s article in this issue for a review. In addition, there is interest in using 5-HT3 antagonists such as ondansetron and granisetron to augment SRIs in OCD.41–44 In one ondansetron augmentation trial, 14 patients received 12 weeks of single-blind ondansetron augmentation, which was initiated at 0.25 mg twice daily for 6 weeks and increased to 0.5 mg twice daily for an additional 6 weeks. Nine patients were classified as responders (≥25% reduction in Y-BOCS score and Clinical Global Impression [CGI] score of 1 or 2) at 12 weeks.41 In another single-blind ondansetron augmentation trial, patients received 0.25 mg of ondansetron twice daily for 2 weeks, followed by 0.5 mg twice daily for an additional 10 weeks.44 Response was defined as a ≥25% reduction in Y-BOCS score, an end of treatment score of ≤24, and a CGI score of ≤2. Twelve of 21 patients were classified as responders; patients were observed for an additional 4 weeks after discontinuation of ondansetron. During the discontinuation phase, Y-BOCS scores worsened by 15.5% in all patients and by 38.3% in responders. These results suggest that ondansetron augmentation could be an effective strategy for some patients with OCD and that it is a strategy that warrants further study. Caffeine and d-amphetamine have also been studied in OCD. A randomized, double-blind trial comparing augmentation of SSRI or serotonin norepinephrine reuptake inhibitor treatment with either caffeine or d-amphetamine suggested that augmentation with either of these agents might benefit some patients with OCD, and further investigation of both as potential augmentation strategies is warranted.45


OCD can be chronic and debilitating if left without appropriate treatment. CBT in the form of ERP, SRIs, and ERP and SRI combination treatment are the gold standard treatments for OCD, although pharmacologic treatment is often needed for more severe cases. The first-line pharmacologic agents are the SSRIs, and although evidence suggests that clomipramine is more effective than the SSRIs, it is not considered first-line treatment due to its side-effect burden. Several augmentation strategies have been explored, including antipsychotics, glutamate-modulating agents, ondansetron, granisetron, caffeine, and d-amphetamine. Potential risks and benefits of pharmacologic augmentation strategies should be weighed carefully and considered only after allowing ample time for first-line treatments to provide full clinical benefits. Moreover, if an individual is not engaged in an adequate trial of ERP, evidence suggests that if available, it should be offered as augmentation prior to offering augmentation with antipsychotics for those who have not adequately responded to initial treatment with an SRI alone.


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Phillip J. Seibell, MD, is a Psychiatrist in the partial hospitalization and intensive outpatient programs for obsessive-compulsive and related disorders, anxiety disorders, and eating disorders, Rogers Behavioral Health/Tampa Bay; and is an Affiliate Assistant Professor, Department of Psychiatry, Morsani College of Medicine, University of South Florida. Rebecca J. Hamblin, PhD, is a Postdoctoral Fellow, Rogers Behavioral Health/Tampa Bay; and a Postdoctoral Fellow, Rothman Center for Pediatric Neuropsychiatry, Department of Pediatrics, Morsani College of Medicine, University of South Florida. Eric Hollander, MD, is the Director of the Autism and Obsessive Compulsive Spectrum Program, and Anxiety and Depression Program, and a Clinical Professor of Psychiatry and Behavioral Sciences, Department of Psychiatry, Albert Einstein College of Medicine/Montefiore Medical Center; and the Director, Spectrum Neuroscience and Treatment Institute.

Address correspondence to Phillip J. Seibell, MD, Rogers Behavioral Health-Tampa Bay, 2002 N. Lois Avenue, Suite 400, Tampa, FL 33607; email:

Disclosure: Phillip J. Seibell discloses fees received for non-CME services from Sunovion Pharmaceuticals-Speakers Bureau and honoraria received from the British Medical Group and the Nevada Psychiatric Association. Eric Hollander discloses contracted research for Brainsway. The remaining author has no relevant financial relationships to disclose.


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