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David L. Ginsberg, MD

Primary Psychiatry. 2006;13(8):25-30

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Diagnosis and Treatment of Obsessive-Compulsive Disorder

Andrea Allen, PhD, and Eric Hollander, MD

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Abstract

Obsessive-compulsive disorder (OCD), a relatively common disorder, is underdiagnosed and undertreated despite the existence of effective treatments. OCD can be differentiated from other disorders with obsessive or compulsive features based on the content of the obsessions or the characteristics of the compulsions. Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral therapy are proven treatments for OCD; they bring clinically significant reduction in symptoms, although complete remission is not common in clinical trials. The efficacy and safety of SRI treatment of OCD has been demonstrated by numerous double-blind, randomized, controlled trials. These trials suggest that it usually takes longer for response to begin and higher doses are required than for depressive disorders. Research also supports a trial of another SRI for patients who have failed a trial of one SRI. For refractory cases, augmentation with atypical antipsychotics such as risperidone or quetiapine is recommended.  

Introduction

Obsessive-compulsive disorder (OCD) is the fourth most common mental disorder in the United States, with an estimated lifetime prevalence of 2.3%.1,2 The disorder is often chronic and disabling. Although effective treatments exist, OCD is underdiagnosed and undertreated. More than half of OCD patients (54.9%) in the US receive no treatment at all; worldwide the figure is 59.5%.3 Due to important advances in pharmacologic treatment, many patients with OCD can be treated in primary care settings.

At this time the two first-line treatments for OCD are selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy (CBT). Many believe that a combination of these is ideal. This article reviews the diagnosis and treatment of OCD.

Diagnosing Obsessive-Compulsive Disorder

Characteristics and Course

OCD is characterized by obsessions and compulsions. However, it is not the only disorder with these symptoms. Obsessions are recurring thoughts, urges or images; in OCD these are experienced as alien, intrusive and distressing. Compulsions are repetitive behaviors (rituals) that patients feel compelled to perform.

Obsessions and compulsions can take many forms. In recent years, public awareness of OCD has been raised by movies and television shows featuring characters with OCD contamination obsessions and typical cleaning and hand-washing compulsions. Another familiar set of symptoms is an obsessive fear accompanied by a compulsion to check (eg, fearing burglars and repeatedly checking that doors and windows are locked shut). However, not all obsessions and compulsions come in neat, sensible pairings.

Typical obsessions are listed in Table 1; these include preoccupation with contamination, unacceptable violent or sexual thoughts, doubting, concern about asymmetry or imperfections, and thoughts that something will go wrong.

Typical rituals are listed in Table 2; these include washing, cleaning, checking, counting, repeating, and arranging. Although some patients may have obsessions without any compulsions, often the compulsive behaviors are simply not recognized as they can be mental acts or very subtle behaviors. An OCD patient might need to have specific thoughts or mental images in order to counter an obsession (eg, the image of a loved one being harmed might be countered by picturing something good happening to the person). Patients who have fearful thoughts may hold their breath until the thought passes, shake their head, or blink. Patients generally perform rituals to reduce anxiety created by thoughts of fearful consequences. However, some patients perform rituals simply because of a general sense of foreboding or because it feels wrong if they do not.

OCD patients usually have good insight. They recognize that their fears are unrealistic,4 yet, their distress compels them to perform rituals. In their worst moments, insight may waver and fears may seem not only realistic but inevitable unless the ritual is performed. Although in severe cases of OCD insight may be lost, it must have been present at some time to meet diagnostic criteria.5 It is normal to have occasional unwanted thoughts or perform repetitive or superstitious behaviors accompanied by transient anxiety, but an OCD diagnosis requires that symptoms cause marked distress, be time consuming (≥1 hour/day), or significantly interfere with functioning.5

OCD onset is often in late adolescence or young adulthood, though it can begin at any age. Childhood onset is not rare. Onset is earlier in males than in females. The course is chronic and waxes and wanes in severity, often in response to stress.

Differential Diagnosis

Thoughts and behaviors that might be confused with the obsessions and compulsions of OCD may occur during the course of several disorders. Different terms may more commonly be used to describe these persistent thoughts and urges, and the irresistible, repetitive behaviors of these other disorders. If the symptoms are entirely accounted for by another disorder, the OCD diagnosis is not given.

Several disorders may be characterized by both obsessive thoughts and recurrent, compulsive behaviors, but with a specific focus: body dysmorphic disorder, eating disorders, hypochondriasis, and some impulse-control disorders, including pathological gambling, kleptomania, and pyromania.

Several disorders have compulsive behaviors but not obsessive thoughts. These include the pathological grooming disorders (eg, trichotillomania, compulsive skin picking, nail biting), Tourette’s syndrome, and tics. Complex tics can be similar to OCD compulsive rituals but are done to release physical discomfort as opposed to being compelled by an obsession.

Other disorders have obsessive thoughts that may be similar to those found in OCD, but lack compulsive behaviors that are typical of OCD. Major depressive disorder is often accompanied by obsessive thoughts, but these are either guilty regrets about real past events or somewhat realistic, albeit exaggerated, fears of possible events (eg, depression will lead to being fired, being divorced by their spouse, and then ending up homeless). In contrast, OCD patients will obsess and feel guilt about things that did not happen, and they will fear things in the future that are unrealistic (eg, that they will run over someone while driving and not know it). The thoughts and urges to harm an infant that may accompany postpartum depression also differ from OCD. A new mother with OCD may fear she will harm her infant, but these thoughts are ego dystonic; the woman will avoid the feared circumstances (eg, throw out or hide all knives), and will not necessarily be depressed. The thoughts of harming an infant that arise from postpartum depression are not necessarily ego dystonic, and symptoms of depression will be prominent. OCD sexual obsessions differ from paraphilias. OCD thoughts are ego dystonic, distressing, and not accompanied by sexual arousal. In addition, OCD patients do not engage in the behaviors they obsess about. Rather, they fear that they will engage in such behaviors, despite not having the desire to do so.

A small proportion of OCD patients who lose insight and become convinced that their obsessions are realistic concerns may appear to have a psychotic disorder. Often OCD patients can acknowledge that their fear may be exaggerated; this is less likely with a psychotic patient. Additionally, OCD patients believe their thoughts are coming from their own minds, whereas psychotic patients may believe the thoughts are being inserted into their minds.

Patients with phobias fear and avoid specific objects or situations, such as animals, insects, blood, heights, or airplanes. Patients with OCD also avoid feared objects or situations, but have compulsive rituals that are not always related in a realistic way to their fear.

Approximately 6% of OCD patients have obsessive-compulsive personality disorder (OCPD).6 Although they have some similarities, most cases can be distinguished. Patients with OCPD may be preoccupied with details and orderliness, perfectionistic, overly devoted to work and productivity, overly conscientious, inflexible about moral and ethical matters, unable to discard worthless objects, or may need to have things done their own way. Patients with OCD may have some of these characteristics, but usually in a less global manner. Unlike in OCPD, patients with OCD have intrusive obsessive thoughts and ritualized compulsive behaviors.

Assessment

In addition to the diagnostic points already detailed, when assessing whether a patient has OCD, consideration should also be given to medical conditions that can cause OCD-like symptoms. A thorough medical history should be taken. A physical should be conducted if necessary, checking thyroid function and ruling out, in rare cases, conditions such as temporal lobe epilepsy, traumatic brain injury, vascular problems, and complications of encephalitis.

In addition, some medical conditions may lead to or exacerbate OCD. For example, there is evidence that in some children OCD may be associated with streptococcus type A infection. In this OCD-related condition, known as PANDAS (Pediatric Autoimmune Disorders Associated with Streptococcus Type A), the symptoms may be caused or exacerbated by autoimmune mechanisms.7 Some women suffer from OCD only during pregnancy, or pregnancy may exacerbate it.4 Women may also experience premenstrual worsening of OCD.4

Likewise, some physical symptoms can be caused or exacerbated by OCD, such as chapped and bleeding hands in hand washers, or problems related to excessive vomiting or urination in those with somatic OCD.

When assessing OCD, it can be valuable to administer the Yale Brown- Obsessive-Compulsive Scale (YBOCS) and its Symptom Checklist.8,9 The scale measures the severity of obsessions and compulsions separately, focusing on the time spent, interference with functioning, distress, effort to resist the obsessions and compulsions, and success in resisting them. The checklist includes most of the obsessions and compulsions found in OCD, thus allowing the clinician to get a detailed overview of the patient’s specific concerns and behaviors. The YBOCs can also be used to measure response to treatment.

Neurological comorbidities should be assessed in OCD patients since they can influence treatment decisions. Neurological soft signs should be assessed if subtle neurological dysfunction is suspected, as should the presence of tics. The latter can be assessed by using a scale such as the Yale Global Tic Severity Scale.10

Serotonin Reuptake Inhibitors

Serotonin reuptake inhibitors (SRIs), including the seven SSRIs and some serotonin norepinephrine reuptake inhibitors (SNRIs), are effective pharmacologic treatments for OCD (Table 3). Their efficacy in OCD is unique; other antidepressants are ineffective in OCD, and there are no other effective monotherapies. In addition, compared to SRI treatment of other disorders, SRI treatment of OCD usually takes longer for response to begin. Higher doses are also required.

To date, five SRIs have been approved by the Food and Drug Administration for the treatment of adult OCD. They are the SNRI clomipramine, and the SSRIs fluvoxamine, fluoxetine, sertraline, and paroxetine. Four of these, clomipramine, fluoxetine, fluvoxamine, and sertraline, have also been approved for treatment of pediatric OCD. Citalopram, escitalopram, and the SNRI venlafaxine are also used in OCD.

Evidence supporting the efficacy of SRIs in OCD is substantial. A single SRI trial will provide clinically meaningful relief for 40% to 60% of OCD patients.11 However, medications rarely bring about remission. Response in OCD research is generally defined as a reduction of 25% to 35% in OCD symptoms, and the average reduction found is usually in this range. No SRI has been proven to be more effective than others in OCD. However, individual patients may respond more favorably to one than to another. It is impossible to predict which SRI will be most effective for a given patient. Therefore, differences in side-effect profile, half-life, available formulations, and cost can guide the selection. Clomipramine, citalopram, fluoxetine, fluvoxamine, and paroxetine are currently available in generic forms and are therefore considerably less expensive than other SRIs or their newer weekly or extended-release formulations. Other SRIs will be losing their patent protection in the near future. As the specific cost of these medications can also depend on what is approved by a particular health plan, specific cost comparisons cannot be made in this article.

Published consensus guidelines consider an adequate SRI trial in OCD to consist of 10–12 weeks with at least 4–6 at the maximum tolerated dose.12 As noted, if a patient does not respond after one trial, a trial of another SRI is indicated. There is evidence that higher doses are required to treat OCD. Therefore, many clinicians prefer to raise the dose weekly up to a high dose, and even to the maximum dose as long as the drug is being well tolerated, rather than stay with a lower dose for weeks waiting to see if the patient will respond before increasing the dose.

Common SRI side effects include gastrointestinal distress (eg, nausea, diarrhea, dyspepsia), initial agitation, headache, and disturbances in sexual desire or functioning. These effects are a result of serotonergic reuptake blockade, their primary mechanism of action.

Some of these side effects, such as increased anxiety and nausea, are most likely to occur during the first few weeks of treatment and often subside. Nausea can often be ameliorated by taking the medication with meals. Drowsiness can be managed by taking all or most of the dose at night. Sexual problems are important to monitor because they are a common reason for noncompliance. Additionally, patients who continue to take the medication may manage the side effects by skipping doses. This can be a problem with SRIs with shorter half-lives. There are pharmacologic treatments that may help restore libido, such as bupropion.13 Other treatments may help with erectile dysfunction, such as sildenafil, cyproheptadine, and mirtazapine.14

In addition to the strategies outlined above, if side effects are a problem then the dose can be lowered or the patient can be switched to another SRI. Some patients may need to start at very low doses. Some SRIs are available in extended-release formulations that may cause fewer side effects. Fluoxetine is available in a weekly formulation.

To avoid discontinuation effects, SRIs should be tapered slowly rather than stopped abruptly. Discontinuation is rarely an issue with fluoxetine due to its long half-life.

Clomipramine

Clomipramine is a tricyclic antidepressant (TCA) and an SNRI. It was the first drug found to be effective in OCD. Its efficacy has been firmly established in adults since the first finding more than 35 years ago. In 1989, clomipramine became the first drug to be approved by the FDA for OCD. Randomized, controlled trials have shown clomipramine to be superior to placebo.15-18 In active comparison studies19-22 and meta-analyses of randomized controlled medication trials,23-26 no medication has shown to be more effective in treating OCD. SSRIs have greater tolerability, but clomipramine may be more effective in OCD. This has been the finding in several meta-analyses, but not in head-to-head comparisons. All these studies have methodological or other limitations that could explain the findings. Because of this possible superiority, a trial of clomipramine should be considered if a patient has failed several SSRI trials.

Clomipramine is more likely than the SSRIs to have adverse effects. Like other TCAs, it has side effects related to anticholinergic and a-adrenergic effects, and not simply to serotonergic effects. The most common effects are dry mouth, constipation, blurred vision, orthostatic hypotension, drowsiness, and nausea. Clomipramine may increase sensitivity to sunlight. Some of the less common side effects, such as confusion and memory impairment, can be particularly problematic in elderly patients. Uncommon but potentially serious side effects are tachycardia, skin rashes, and seizures. Additionally, the drug may cause elevated aminotransferase levels. Notably, despite the side effects, patients in clinical trials were not likely to withdraw from the studies due to adverse events, and most studies show no greater withdrawal due to side effects for clomipramine than for placebo or SSRI comparison groups.

Adults can be started at 25 mg/day and titrated upward to 150–250 mg/day over 2–3 weeks to minimize side effects.

Clomipramine is toxic in overdose and potentially fatal, with death resulting from cardiac arrhythmia, hypotension, or intractable seizures.

Fluvoxamine

Fluvoxamine was one of the first SSRIs to be tested in the treatment of OCD. Since that research began in the late 1980s, its efficacy in OCD has been firmly established by both placebo-controlled27-31 and active-comparison studies.19,20,22,32 Of the SSRIs, fluvoxamine has the largest supporting database in the treatment of OCD.

Most studies of fluvoxamine in OCD showed a response at ≥6 weeks, and most showed continuing improvement and more responders over time. However, response has been reported as early as 2 weeks, as in a study of the controlled-release formulation that started at a dose of 100 mg/day.31

Fluvoxamine is well tolerated. Among the SSRIs, fluvoxamine is one of the weakest inhibitors of norepinephrine and dopamine reuptake.33 Thus, as demonstrated by studies in animals and humans, it has relatively few and mild cardiovascular and anticholinergic effects.33,34 The most frequently reported side effects with fluvoxamine are nausea, drowsiness, asthenia, headache, dry mouth, and insomnia.35

The usual dose of fluvoxamine for the treatment of OCD in adults is 150–300 mg/day. Starting at 25–50 mg/day and increasing by 50 mg/day weekly may help to minimize early side effects. The mean maximum dose used in most studies was 250–300 mg/day.

Fluoxetine

Fluoxetine is an SSRI with a notably long half-life (84 hours). Its efficacy in OCD has been established by several double-blind, placebo-controlled trials.36-39 Fluoxetine has been extensively studied in OCD at three fixed doses (20 mg/day, 40 mg/day, and 60 mg/day) and is clearly effective at 40 and 60 mg/day. Efficacy at 20 mg/day is also shown in some studies.37 Higher doses, especially 80 mg/day, are used frequently in clinical practice, and there are a few studies at 80 mg/day which were also successful in terms of efficacy and tolerability. Both obsessions and compulsions were found to respond to fluoxetine treatment independently of any antidepressant effect.

Fluoxetine is generally well tolerated, and the dropout rate due to adverse effects in clinical trials has been low. Common side effects are anxiety, insomnia, decreased appetite, headache, drowsiness, gastrointestinal symptoms (eg, nausea, diarrhea, dyspepsia), and sexual dysfunction.

Treatment is generally started at 20 mg/day, but it can be started at 10 mg/day to minimize side effects. As noted, the therapeutic range is thought to begin at 40 mg/day and the maximum recommended dose is 80 mg/day for adults.

Paroxetine

Several large, randomized placebo-controlled trials have demonstrated the efficacy of paroxetine in OCD.21,40,41 One, a study of paroxetine in three fixed doses, found that 40 and 60 mg/day were more effective than placebo, but 20 mg/day was not.40

Paroxetine has a different side-effect profile than other SSRIs. It is somewhat more likely to have anticholinergic side effects such as dry mouth, constipation, and dizziness.21 It also can cause nausea and sexual dysfunction and may be more prone to cause weight gain.42 Paroxetine should be used cautiously in patients with renal impairment as well as hepatic impairment.

In OCD, paroxetine can be started at 20 mg/day and can be increased weekly with the target range being 40–60 mg/day. The highest approved dose is 60 mg/day.

Sertraline

The efficacy of sertraline in OCD has been demonstrated in large, randomized, placebo-controlled trials.43,44

Its most common side effects of sertraline include nausea, diarrhea, dry mouth, sleepiness or insomnia, and sexual side effects. Sertraline has notably low levels of nervousness or agitation as side effects.

The typical starting dose for adults is 50 mg/day with increases of 50 mg/day weekly to reach a target dose (150–200 mg). Patients can be started at ≤25 mg/day and titrated up more slowly if side effects are a concern. The maximum recommended dose is 200 mg/day.

Citalopram

Citalopram appears to be effective in OCD based on the research available to date, which includes one large, randomized, placebo-controlled trial.45 This trial found that citalopram was more effective than placebo at all doses tested (20, 40, and 60 mg/day). The efficacy of citalopram is also supported by open-label trials.46,47

Citalopram has a favorable side-effect profile. The most common side effects in short-term trials are nausea, dry mouth, and somnolence. Some common SSRI side effects occurred at the same rate with citalopram as with placebo; these include insomnia, fatigue, anxiety, agitation, nervousness, and gastrointestinal side effects other than nausea.

Dosing is usually started at 10 mg/day and increased to 40–60 mg/day in treating OCD.

Escitalopram

Escitalopram is the newest of the SSRIs. There are currently no published studies on its efficacy in OCD. Since it is the active isomer of citalopram, it is generally expected that escitalopram’s efficacy will equal that of citalopram. It has been shown to have the least secondary binding properties of the SRIs48 as well as the least drug-drug interaction.49 In its pre-release clinical trials, only nausea was reported by >10% of the patients (15% versus 7% for placebo).

The starting dose of escitalopram is 10 mg/day and can be increased to 20 mg/day.

Cognitive-Behavioral Therapy

CBT, including behavioral therapy, is an established treatment for OCD, which has been shown to be equal to or perhaps superior to pharmacotherapy.18 CBT is an appropriate first-line treatment for OCD and can be used either instead of or in addition to an SSRI, depending on the willingness of the patient to participate in therapy or to take medication, and the presence of comorbid diagnoses. For example, if a patient has significant depression, an SSRI would be a good first-choice treatment, but even more so if the depression would make participation in CBT difficult. If a patient begins a medication but has an inadequate response, CBT should be attempted. Likewise, if a patient tries CBT but is unable to complete assignments, an SSRI trial is indicated. CBT is also valuable for patients who wish to discontinue medication, since there is evidence that it helps to prevent relapse.50-52 Additional studies are needed regarding the use of CBT as an augmentation strategy in patients who are SSRI resistant.

In CBT, patients face a feared object or activity without performing their compulsive ritual. For example, a patient with a fear of germs will touch a contaminated object but not wash his or her hands. The key element in this therapy is the exposure and prevention of the response or ritual. The exposure can be to actual feared objects or situations, or to imagery or descriptions of these. If a patient has obsessions without typical compulsions, exposure is still an effective and essential component.53,54 Cognitive aspects of the treatment focus on correcting errors of assessing danger and their feelings of responsibility. Cognitive elements to therapy can be important and are often used to motivate patients to attempt exposures or to be able to tolerate them without having to perform their usual rituals. There is little evidence that cognitive therapy is effective if it does not include exposure to what is feared. Therapy which emphasizes the cognitive component seems to be successful if it also includes “behavioral experiments” to collect evidence to assess the alternate appraisals of danger.55

Although individual CBT is most common, there is also evidence that group therapy is effective.11,56 CBT sessions should be weekly or more frequently until significant symptom reduction has been achieved, at which point session frequency can be reduced. It is important for relapse prevention to be part of CBT. After a course of CBT is completed, patients can return for booster sessions if symptoms return.

Medication Treatment Decision Guidelines

After a patient is diagnosed with OCD and comorbid diagnoses are determined, a patient should begin CBT and/or medication. Decision guidelines for the management of medication and other somatic treatments are outlined below and in the Figure provided.

Certain comorbid psychiatric diagnoses require a change in medication strategy. Such diagnoses include Tourette’s  syndrome and tics, attention-deficit/hyperactivity disorder (ADHD), bipolar spectrum disorders, and impulse control disorders. The SRIs are effective without major modifications for other conditions that are frequently comorbid with OCD (eg, depression, anxiety, eating disorders, and obsessive-compulsive spectrum disorders not mentioned above). While there is evidence that the SRIs are effective in many patients with other obsessive-compulsive spectrum disorders, the efficacy in some of these disorders is less clear than for OCD. This lack of clarity may be due to comorbidities (ADHD, bipolar spectrum disorders) or additional symptom domains (affective instability, inattention). These treatment guidelines take such comorbidities and symptoms into account, but the SRIs are included wherever possible because the goal is to treat the OCD rather than to treat only

the comorbid disorder. If a patient does not have OCD, the optimal treatment strategy might well differ from these guidelines.

An SSRI is the first-choice medication treatment for most OCD patients, and venlafaxine may be the first choice for patients with ADHD. SSRIs are preferred for an initial trial due to more favorable side-effect profiles and fewer potentially serious side effects than clomipramine. A mood stabilizer is the recommended first medication treatment for OCD patients with bipolar spectrum disorders, but if affective instability is well controlled and OCD symptoms persist, then addition of an SSRI may be indicated. However, close monitoring must insure that roughening of the bipolar disorder does not occur.

Of note, if a patient with Tourette’s syndrome or tics does not respond, augmentation with an atypical antipsychotic or haloperidol should be considered. Although haloperidol would be less costly, the risk of tardive dyskinesia with long-term use must be considered. For patients with comorbid impulse-control disorders, augmentation with a mood stabilizer, an opiate antagonist, or an atypical antipsychotic is an option if there is no response to an SRI or if the response is lost.

If patients do not respond to an adequate trial of the first SSRI, another SSRI or an SNRI should be tried, as studies of patients who have failed one or more SRI trials have shown response rates in trials of new SRIs ranging from 11%57 to 56%.58 For nonresponders, one or two SSRI trials and one SNRI trial are recommended.

If a patient has a partial response to his or her first treatment, an increased dose or augmentation with an atypical antipsychotic should be considered. The two augmentation strategies with the strongest research support are augmentation of the SRI with the atypical antipsychotics risperidone or quetiapine. In OCD patients with comorbid tic disorders, augmentation with haloperidol has been helpful. This augmentation was not effective in patients without tics.59 Evidence shows that low doses (<3 mg/day risperidone equivalents) of atypical antipsychotics are effective in a broader range of OCD patients, not just those with comorbid tics. There is support from small, double-blind, controlled trials for the efficacy of risperidone60,61 and quetiapine.62 The findings for olanzapine are mixed, with one positive63 and one negative64 randomized, controlled trial.

If a patient does not have an adequate response after two to three SRI trials, including at least one SNRI trial and augmentation with an atypical antipsychotic, several other possible strategies are suggested. An SRI can be augmented with a stimulant or an anticonvulsant, or an SSRI can be augmented with clomipramine. The patient may also be switched to a trial of intravenous clomipramine or citalopram, or to an opiate.

For the most refractory patients, there are other somatic therapies that can be considered. These include deep brain stimulation,65 transcranial magnetic stimulation,66 electroconvulsive therapy, vagal nerve stimulation, and neurosurgery (ie, cingulotomy).

Long-Term Treatment

Since OCD is often chronic, it often requires long-term treatment. Those SRIs that have been studied in long-term trials have been shown effective beyond the acute treatment time period.40,67 Published Expert Consensus Guidelines12 highly recommend that OCD treatment be continued for 1–2 years to prevent relapse, and usually longer treatment is needed. After this prolonged treatment, patients can have their dose slowly titrated down to see if their symptoms remain under good control. Discontinuation of the medication may not be possible in many cases and, if a patient has serious relapses two or more times, lifelong medication treatment may be necessary.

The medication treatment guidelines provided in the discussion of acute treatment are applicable throughout the course of treatment. That is, wherever patients are in the guideline diagram, they can remain on their medication so long as their symptoms remain in remission. If a medication treatment becomes less effective or ineffective over the long term, the options to be considered are the same as if the treatment was ineffective earlier. If patients receive long-term augmentation with an atypical antipsychotic, it is important to monitor them for metabolic syndrome.

When treatments are discontinued, studies seem to show lower relapse rates for CBT than are found for medication treatment.68 This is especially true when the CBT includes consideration of relapse prevention.69 However, to date adequate head-to-head trials are not available. Likewise, there is some evidence that CBT in combination with SRIs may help prevent relapse. Definitive research is needed,70 yet, it seems reasonable to recommend CBT for patients in need of long-term medication treatment.

Conclusion

Treatment for patients with OCD has improved dramatically in recent years. Primary care physicians may be the first healthcare professionals consulted by these patients, and they can provide appropriate pharmacologic treatment and therapeutic guidance. Psychiatric consultations may be needed for refractory cases or those complicated by comorbid psychiatric conditions. PP

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28. Jenike MA, Hyman S, Baer L, et al. A controlled trial of fluvoxamine in obsessive-compulsive disorder: implications for a serotonergic theory. Am J Psychiatry. 1990;147(9):1209-1215.

29. Greist JH, Jenike MA, Robinson D, et al. Efficacy of fluvoxamine in obsessive-compulsive disorder: results of a multicentre, double-blind, placebo controlled trial. Eur J Clin Res. 1995;7:195-204.

30. Goodman WK, Kozak MJ, Liebowitz M, White KL. Treatment of obsessive-compulsive disorder with fluvoxamine: a multicentre, double-blind, placebo-controlled trial. Int Clin Psychopharmacol. 1996;11(1):21-29.

31. Hollander E, Koran LM, Goodman WK, et al. A double-blind, placebo controlled, study of the efficacy and safety of controlled-release fluvoxamine in patients with obsessive-compulsive disorder. J Clin Psychiatry. 2003;64(6):640-647.

32. Goodman WK, Price LH, Delgado PL, et al. Specificity of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder. Comparison of fluvoxamine and desipramine. Arch Gen Psychiatry. 1990;47(6):577-585.

33. Palmer KJ, Benfield P. Fluvoxamine: an overview of its pharmacological properties and review of its therapeutic potential in non-depressive disorders. CNS Drugs. 1994;1:57-87.

34. Stahl SM. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 2nd ed. Cambridge, UK: Cambridge University Press; 2000.

35. Wagner W, Zaborny BA, Gray TE. Fluvoxamine. a review of its safety profile in world-wide studies. Int J Psychopharmacol. 1994;9(4):223-227.

36. Montgomery SA, McIntyre A, Osterheider M, et al. A double-blind, placebo-controlled study of fluoxetine in patients with DSM-III-R obsessive-compulsive disorder. The Lilly European OCD Study Group. Eur Neuropsychopharmacol. 1993;3(2):143-152.

37. Tollefson GD, Rampey AH, Potvin JH, et al. A multicenter investigation of fixed-dose fluoxetine in the treatment of obsessive-compulsive disorder. Arch Gen Psychiatry. 1994;51(7):559-567.

38. Jenike MA, Baer L, Minichiello WE, Rauch SL, Buttolph ML. Placebo-controlled trial of fluoxetine and phenelzine for obsessive-compulsive disorder. Am J Psychiatry. 1997;154(9):1261-1264.

39. Romano S, Goodman W, Tamura R, Gonzales J. Long-term treatment of obsessive-compulsive disorder after an acute response: a comparison of fluoxetine versus placebo. J Clin Psychopharmacol. 2001;21(1):46-52.

40. Hollander E, Allen A, Steiner M, et al. Acute and long term treatment and prevention of relapse of obsessive-compulsive disorder with paroxetine. J Clin Psychiatry.  2003;64(9):1113-1121.

41. Kamijima K, Murasaki M, Asai M, et al. Paroxetine in the treatment of obsessive-compulsive disorder: randomized, double-blind, placebo-controlled study in Japanese patients. Psychiatry Clin Neurosci. 2004;58(4):427-433.

42. Maina G, Albert U, Salvi V, Bogetto F. Weight gain during long-term treatment of obsessive-compulsive disorder: a prospective comparison between serotonin reuptake inhibitors. J Clin Psychiatry. 2004;65(10):1365-1371.

43. Greist J, Chouinard G, Duboff E, et al. Double-blind parallel comparison of three dosages of sertraline and placebo in outpatients with obsessive-compulsive disorder. Arch Gen Psychiatry. 1995;52(4):289-295.

44. Kronig MH, Apter J, Asnis G, et al. Placebo-controlled, multicenter study of sertraline treatment for obsessive-compulsive disorder. J Clin Psychopharmacol. 1999;19(2):172-176.

45. Montgomery SA, Kasper S, Stein DJ, Bang Hedegaard K, Lemming OM. Citalopram 20 mg, 40 mg and 60 mg are all effective and well tolerated compared with placebo in obsessive-compulsive disorder. Int Clin Psychopharmacol. 2001;16(2):75-86.

46. Koponen H, Lepola U, Leinonen E, Jokinen R, Penttinen J, Turtonen J. Citalopram in the treatment of obsessive-compulsive disorder: an open pilot study. Acta Psychiatr Scand. 1997;96(5):343-346.

47. Marazziti D, Dell’Osso L, Gemignani A, et al. Citalopram in refractory obsessive-compulsive disorder: an open study. Int Clin Psychopharmacol. 2001;16(4):215-219.

48. Owens MJ, Knight DL, Nemeroff CB. Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. Biol Psychiatry. 2001;50(5):345-350.

49. von Moltke LL, Greenblatt DJ, Giancarlo GM, Granda BW, Harmatz JS, Shader RI. Escitalopram (S-citalopram) and its metabolites in vitro: cytochromes mediating biotransformation, inhibitory effects, and comparison to R-citalopram. Drug Metab Dispos. 2001;29(8):1102-1109.

50. Hembree EA, Riggs DS, Kozak MJ, Franklin ME, Foa EB. Long-term efficacy of exposure and ritual prevention therapy and serotonergic medications for obsessive-compulsive disorder. CNS Spectr. 2003;8(5):363-371,381.

51. Simpson HB, Liebowitz MR, Foa EB, et al. Post-treatment effects of exposure therapy and clomipramine in obsessive-compulsive disorder. Depress Anxiety. 2004;19(4):225-233.

52. Biondi M, Picardi A. Increased maintenance of obsessive-compulsive disorder remission after integrated serotonergic treatment and cognitive psychotherapy compared with medication alone. Psychother Psychosom. 2005;74(2):123-128.

53. Freeston MH, Ladouceur R. What do patients do with their obsessive thoughts? Behav Res Ther. 1997;35(4):335-348.

54. Freeston MH, Ladouceur R, Gagnon F, et al. Cognitive-behavioral treatment of obsessive thoughts: a controlled study. J Consult Clin Psychol. 1997;65(3):405-413.

55. Whittal ML, Thordarson DS, McLean PD. Treatment of obsessive-compulsive disorder: Cognitive behavior therapy vs. exposure and response prevention. Behav Res Ther. 2005;43(12):1559-1576.

56. Fals-Stewart W, Marks AP, Schafer J. A comparison of behavioral group therapy 30 and individual behavior therapy in treating obsessive-compulsive disorder. J Nerv Ment Dis. 1993;181(3):189-193.

57. Albert U, Aguglia E, Maina G, Bogetto F. Venlafaxine versus clomipramine in the treatment of obsessive-compulsive disorder: a preliminary single-blind, 12-week, controlled study. J Clin Psychiatry. 2002;63(11):1004-1009.

58. Denys D, van Megen HJ, van der Wee N, Westenberg HG. A double-blind switch study of paroxetine and venlafaxine in obsessive-compulsive disorder. J Clin Psychiatry. 2004;65(1):37-43.

59. McDougle DJ, Goodman WK, Leckman JF, Lee NC, Heninger GR, Price LH. Haloperidol addition in fluvoxamine-refractory obsessive-compulsive disorder. A double-blind, placebo-controlled study in patients with and without tics. Arch Gen Psychiatry. 1994;51(4):302-308.

60. McDougle CJ, Epperson CN, Pelton GH, Wasylink S, Price LH. A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder. Arch Gen Psychiatry. 2000;57(8):794-801.

61. Hollander E, Baldini Rossi N, Sood E, Pallanti S. Risperidone augmentation in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo-controlled study. Int J Neuropsychopharmacol. 2003;6(4):397-401.

62. Denys D, de Geus F, van Megen HJ, Westenberg HG. A double-blind, randomized, placebo-controlled trial of quetiapine addition in patients with obsessive-compulsive disorder refractory to serotonin reuptake inhibitors. J Clin Psychiatry. 2004;65(8):1040-1048.

63. Bystritsky A, Ackerman DL, Rosen RM, et al. Augmentation of serotonin reuptake inhibitors in refractory obsessive-compulsive disorder using adjunctive olanzapine: a placebo-controlled trial. J Clin Psychiatry. 2004;65(4):565-568.

64. Shapira NA, Ward HE, Mandoki M, et al. A double-blind, placebo-controlled trial of olanzapine addition in fluoxetine-refractory obsessive-compulsive disorder. Biol Psychiatry. 2004;55(5):553-555.

65. Kopell BH, Greenberg B, Rezai AR. Deep brain stimulation for psychiatric disorders. J Clin Neurophysiol. 2004;21(1):51-67.

66. Alonso P, Pujol J, Cardoner N, et al. Right prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a double-blind, placebo-controlled study. Am J Psychiatry. 2001;158(7):1143-1145.

67.    Greist JH, Bandelow B, Hollander E, et al. WCA recommendations for the long-term treatment of obsessive-compulsive disorder in adults. CNS Spectr. 2003;8(8 suppl 1):7-16.

68. Foa EB, Kozak MJ. Psychological treatment for obsessive-compulsive disorder. In: Mavissakalian MR, Prien RF, eds. Long-Term Treatments of Anxiety Disorders. Washington, DC: American Psychiatric Association; 1996:285-309.

69. Hiss H, Foa EB, Kozak MJ. Relapse prevention program for treatment of obsessive-compulsive disorder. J Consult Clin Psychol. 1994;62(4):801-808.

70. Simpson HB, Liebowitz MR, Foa EB, et al. Post-treatment effects of exposure therapy and clomipramine in obsessive-compulsive disorder. Depress Anxiety. 2004;19(4):225-233.

Dr. Allen is assistant professor of psychiatry in the Department of Psychiatry at Mount Sinai School of Medicine in New York City. Dr. Hollander is professor of psychiatry in the Department of Psychiatry and director of the Compulsive, Impulsive and Anxiety Disorders Program at Mount Sinai School of Medicine.


Disclosure: Dr. Allen has received research/grant support from the National Institute of Mental Health (NIMH). Dr. Hollander has received research/grant support from Abbott, Eli Lilly, the Food and Drug Administration, GlaxoSmithKline, NIMH, the National Institute of Neurological Disorders and Stroke, the National Institute on Drug Abuse, Pfizer, and Solvay.

Please direct all correspondence to: Andrea Allen, PhD, Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029; Tel: 212-241-3176; Fax: 212-987-4031; E-mail: andrea.allen@mssm.edu.


 

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Andrea Allen, PhD, and Eric Hollander, MD

Abstract

Obsessive-compulsive disorder (OCD), a relatively common disorder, is underdiagnosed and undertreated despite the existence of effective treatments. OCD can be differentiated from other disorders with obsessive or compulsive features based on the content of the obsessions or the characteristics of the compulsions. Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral therapy are proven treatments for OCD; they bring clinically significant reduction in symptoms, although complete remission is not common in clinical trials. The efficacy and safety of SRI treatment of OCD has been demonstrated by numerous double-blind, randomized, controlled trials. These trials suggest that it usually takes longer for response to begin and higher doses are required than for depressive disorders. Research also supports a trial of another SRI for patients who have failed a trial of one SRI. For refractory cases, augmentation with atypical antipsychotics such as risperidone or quetiapine is recommended.  

Introduction

Obsessive-compulsive disorder (OCD) is the fourth most common mental disorder in the United States, with an estimated lifetime prevalence of 2.3%.1,2 The disorder is often chronic and disabling. Although effective treatments exist, OCD is underdiagnosed and undertreated. More than half of OCD patients (54.9%) in the US receive no treatment at all; worldwide the figure is 59.5%.3 Due to important advances in pharmacologic treatment, many patients with OCD can be treated in primary care settings.

At this time the two first-line treatments for OCD are selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy (CBT). Many believe that a combination of these is ideal. This article reviews the diagnosis and treatment of OCD.

Diagnosing Obsessive-Compulsive Disorder

Characteristics and Course

OCD is characterized by obsessions and compulsions. However, it is not the only disorder with these symptoms. Obsessions are recurring thoughts, urges or images; in OCD these are experienced as alien, intrusive and distressing. Compulsions are repetitive behaviors (rituals) that patients feel compelled to perform.

Obsessions and compulsions can take many forms. In recent years, public awareness of OCD has been raised by movies and television shows featuring characters with OCD contamination obsessions and typical cleaning and hand-washing compulsions. Another familiar set of symptoms is an obsessive fear accompanied by a compulsion to check (eg, fearing burglars and repeatedly checking that doors and windows are locked shut). However, not all obsessions and compulsions come in neat, sensible pairings.

Typical obsessions are listed in Table 1; these include preoccupation with contamination, unacceptable violent or sexual thoughts, doubting, concern about asymmetry or imperfections, and thoughts that something will go wrong.

Typical rituals are listed in Table 2; these include washing, cleaning, checking, counting, repeating, and arranging. Although some patients may have obsessions without any compulsions, often the compulsive behaviors are simply not recognized as they can be mental acts or very subtle behaviors. An OCD patient might need to have specific thoughts or mental images in order to counter an obsession (eg, the image of a loved one being harmed might be countered by picturing something good happening to the person). Patients who have fearful thoughts may hold their breath until the thought passes, shake their head, or blink. Patients generally perform rituals to reduce anxiety created by thoughts of fearful consequences. However, some patients perform rituals simply because of a general sense of foreboding or because it feels wrong if they do not.

OCD patients usually have good insight. They recognize that their fears are unrealistic,4 yet, their distress compels them to perform rituals. In their worst moments, insight may waver and fears may seem not only realistic but inevitable unless the ritual is performed. Although in severe cases of OCD insight may be lost, it must have been present at some time to meet diagnostic criteria.5 It is normal to have occasional unwanted thoughts or perform repetitive or superstitious behaviors accompanied by transient anxiety, but an OCD diagnosis requires that symptoms cause marked distress, be time consuming (≥1 hour/day), or significantly interfere with functioning.5

OCD onset is often in late adolescence or young adulthood, though it can begin at any age. Childhood onset is not rare. Onset is earlier in males than in females. The course is chronic and waxes and wanes in severity, often in response to stress.

Differential Diagnosis

Thoughts and behaviors that might be confused with the obsessions and compulsions of OCD may occur during the course of several disorders. Different terms may more commonly be used to describe these persistent thoughts and urges, and the irresistible, repetitive behaviors of these other disorders. If the symptoms are entirely accounted for by another disorder, the OCD diagnosis is not given.

Several disorders may be characterized by both obsessive thoughts and recurrent, compulsive behaviors, but with a specific focus: body dysmorphic disorder, eating disorders, hypochondriasis, and some impulse-control disorders, including pathological gambling, kleptomania, and pyromania.

Several disorders have compulsive behaviors but not obsessive thoughts. These include the pathological grooming disorders (eg, trichotillomania, compulsive skin picking, nail biting), Tourette’s syndrome, and tics. Complex tics can be similar to OCD compulsive rituals but are done to release physical discomfort as opposed to being compelled by an obsession.

Other disorders have obsessive thoughts that may be similar to those found in OCD, but lack compulsive behaviors that are typical of OCD. Major depressive disorder is often accompanied by obsessive thoughts, but these are either guilty regrets about real past events or somewhat realistic, albeit exaggerated, fears of possible events (eg, depression will lead to being fired, being divorced by their spouse, and then ending up homeless). In contrast, OCD patients will obsess and feel guilt about things that did not happen, and they will fear things in the future that are unrealistic (eg, that they will run over someone while driving and not know it). The thoughts and urges to harm an infant that may accompany postpartum depression also differ from OCD. A new mother with OCD may fear she will harm her infant, but these thoughts are ego dystonic; the woman will avoid the feared circumstances (eg, throw out or hide all knives), and will not necessarily be depressed. The thoughts of harming an infant that arise from postpartum depression are not necessarily ego dystonic, and symptoms of depression will be prominent. OCD sexual obsessions differ from paraphilias. OCD thoughts are ego dystonic, distressing, and not accompanied by sexual arousal. In addition, OCD patients do not engage in the behaviors they obsess about. Rather, they fear that they will engage in such behaviors, despite not having the desire to do so.

A small proportion of OCD patients who lose insight and become convinced that their obsessions are realistic concerns may appear to have a psychotic disorder. Often OCD patients can acknowledge that their fear may be exaggerated; this is less likely with a psychotic patient. Additionally, OCD patients believe their thoughts are coming from their own minds, whereas psychotic patients may believe the thoughts are being inserted into their minds.

Patients with phobias fear and avoid specific objects or situations, such as animals, insects, blood, heights, or airplanes. Patients with OCD also avoid feared objects or situations, but have compulsive rituals that are not always related in a realistic way to their fear.

Approximately 6% of OCD patients have obsessive-compulsive personality disorder (OCPD).6 Although they have some similarities, most cases can be distinguished. Patients with OCPD may be preoccupied with details and orderliness, perfectionistic, overly devoted to work and productivity, overly conscientious, inflexible about moral and ethical matters, unable to discard worthless objects, or may need to have things done their own way. Patients with OCD may have some of these characteristics, but usually in a less global manner. Unlike in OCPD, patients with OCD have intrusive obsessive thoughts and ritualized compulsive behaviors.

Assessment

In addition to the diagnostic points already detailed, when assessing whether a patient has OCD, consideration should also be given to medical conditions that can cause OCD-like symptoms. A thorough medical history should be taken. A physical should be conducted if necessary, checking thyroid function and ruling out, in rare cases, conditions such as temporal lobe epilepsy, traumatic brain injury, vascular problems, and complications of encephalitis.

In addition, some medical conditions may lead to or exacerbate OCD. For example, there is evidence that in some children OCD may be associated with streptococcus type A infection. In this OCD-related condition, known as PANDAS (Pediatric Autoimmune Disorders Associated with Streptococcus Type A), the symptoms may be caused or exacerbated by autoimmune mechanisms.7 Some women suffer from OCD only during pregnancy, or pregnancy may exacerbate it.4 Women may also experience premenstrual worsening of OCD.4

Likewise, some physical symptoms can be caused or exacerbated by OCD, such as chapped and bleeding hands in hand washers, or problems related to excessive vomiting or urination in those with somatic OCD.

When assessing OCD, it can be valuable to administer the Yale Brown- Obsessive-Compulsive Scale (YBOCS) and its Symptom Checklist.8,9 The scale measures the severity of obsessions and compulsions separately, focusing on the time spent, interference with functioning, distress, effort to resist the obsessions and compulsions, and success in resisting them. The checklist includes most of the obsessions and compulsions found in OCD, thus allowing the clinician to get a detailed overview of the patient’s specific concerns and behaviors. The YBOCs can also be used to measure response to treatment.

Neurological comorbidities should be assessed in OCD patients since they can influence treatment decisions. Neurological soft signs should be assessed if subtle neurological dysfunction is suspected, as should the presence of tics. The latter can be assessed by using a scale such as the Yale Global Tic Severity Scale.10

Serotonin Reuptake Inhibitors

Serotonin reuptake inhibitors (SRIs), including the seven SSRIs and some serotonin norepinephrine reuptake inhibitors (SNRIs), are effective pharmacologic treatments for OCD (Table 3). Their efficacy in OCD is unique; other antidepressants are ineffective in OCD, and there are no other effective monotherapies. In addition, compared to SRI treatment of other disorders, SRI treatment of OCD usually takes longer for response to begin. Higher doses are also required.

To date, five SRIs have been approved by the Food and Drug Administration for the treatment of adult OCD. They are the SNRI clomipramine, and the SSRIs fluvoxamine, fluoxetine, sertraline, and paroxetine. Four of these, clomipramine, fluoxetine, fluvoxamine, and sertraline, have also been approved for treatment of pediatric OCD. Citalopram, escitalopram, and the SNRI venlafaxine are also used in OCD.

Evidence supporting the efficacy of SRIs in OCD is substantial. A single SRI trial will provide clinically meaningful relief for 40% to 60% of OCD patients.11 However, medications rarely bring about remission. Response in OCD research is generally defined as a reduction of 25% to 35% in OCD symptoms, and the average reduction found is usually in this range. No SRI has been proven to be more effective than others in OCD. However, individual patients may respond more favorably to one than to another. It is impossible to predict which SRI will be most effective for a given patient. Therefore, differences in side-effect profile, half-life, available formulations, and cost can guide the selection. Clomipramine, citalopram, fluoxetine, fluvoxamine, and paroxetine are currently available in generic forms and are therefore considerably less expensive than other SRIs or their newer weekly or extended-release formulations. Other SRIs will be losing their patent protection in the near future. As the specific cost of these medications can also depend on what is approved by a particular health plan, specific cost comparisons cannot be made in this article.

Published consensus guidelines consider an adequate SRI trial in OCD to consist of 10–12 weeks with at least 4–6 at the maximum tolerated dose.12 As noted, if a patient does not respond after one trial, a trial of another SRI is indicated. There is evidence that higher doses are required to treat OCD. Therefore, many clinicians prefer to raise the dose weekly up to a high dose, and even to the maximum dose as long as the drug is being well tolerated, rather than stay with a lower dose for weeks waiting to see if the patient will respond before increasing the dose.

Common SRI side effects include gastrointestinal distress (eg, nausea, diarrhea, dyspepsia), initial agitation, headache, and disturbances in sexual desire or functioning. These effects are a result of serotonergic reuptake blockade, their primary mechanism of action.

Some of these side effects, such as increased anxiety and nausea, are most likely to occur during the first few weeks of treatment and often subside. Nausea can often be ameliorated by taking the medication with meals. Drowsiness can be managed by taking all or most of the dose at night. Sexual problems are important to monitor because they are a common reason for noncompliance. Additionally, patients who continue to take the medication may manage the side effects by skipping doses. This can be a problem with SRIs with shorter half-lives. There are pharmacologic treatments that may help restore libido, such as bupropion.13 Other treatments may help with erectile dysfunction, such as sildenafil, cyproheptadine, and mirtazapine.14

In addition to the strategies outlined above, if side effects are a problem then the dose can be lowered or the patient can be switched to another SRI. Some patients may need to start at very low doses. Some SRIs are available in extended-release formulations that may cause fewer side effects. Fluoxetine is available in a weekly formulation.

To avoid discontinuation effects, SRIs should be tapered slowly rather than stopped abruptly. Discontinuation is rarely an issue with fluoxetine due to its long half-life.

Clomipramine

Clomipramine is a tricyclic antidepressant (TCA) and an SNRI. It was the first drug found to be effective in OCD. Its efficacy has been firmly established in adults since the first finding more than 35 years ago. In 1989, clomipramine became the first drug to be approved by the FDA for OCD. Randomized, controlled trials have shown clomipramine to be superior to placebo.15-18 In active comparison studies19-22 and meta-analyses of randomized controlled medication trials,23-26 no medication has shown to be more effective in treating OCD. SSRIs have greater tolerability, but clomipramine may be more effective in OCD. This has been the finding in several meta-analyses, but not in head-to-head comparisons. All these studies have methodological or other limitations that could explain the findings. Because of this possible superiority, a trial of clomipramine should be considered if a patient has failed several SSRI trials.

Clomipramine is more likely than the SSRIs to have adverse effects. Like other TCAs, it has side effects related to anticholinergic and a-adrenergic effects, and not simply to serotonergic effects. The most common effects are dry mouth, constipation, blurred vision, orthostatic hypotension, drowsiness, and nausea. Clomipramine may increase sensitivity to sunlight. Some of the less common side effects, such as confusion and memory impairment, can be particularly problematic in elderly patients. Uncommon but potentially serious side effects are tachycardia, skin rashes, and seizures. Additionally, the drug may cause elevated aminotransferase levels. Notably, despite the side effects, patients in clinical trials were not likely to withdraw from the studies due to adverse events, and most studies show no greater withdrawal due to side effects for clomipramine than for placebo or SSRI comparison groups.

Adults can be started at 25 mg/day and titrated upward to 150–250 mg/day over 2–3 weeks to minimize side effects.

Clomipramine is toxic in overdose and potentially fatal, with death resulting from cardiac arrhythmia, hypotension, or intractable seizures.

Fluvoxamine

Fluvoxamine was one of the first SSRIs to be tested in the treatment of OCD. Since that research began in the late 1980s, its efficacy in OCD has been firmly established by both placebo-controlled27-31 and active-comparison studies.19,20,22,32 Of the SSRIs, fluvoxamine has the largest supporting database in the treatment of OCD.

Most studies of fluvoxamine in OCD showed a response at ≥6 weeks, and most showed continuing improvement and more responders over time. However, response has been reported as early as 2 weeks, as in a study of the controlled-release formulation that started at a dose of 100 mg/day.31

Fluvoxamine is well tolerated. Among the SSRIs, fluvoxamine is one of the weakest inhibitors of norepinephrine and dopamine reuptake.33 Thus, as demonstrated by studies in animals and humans, it has relatively few and mild cardiovascular and anticholinergic effects.33,34 The most frequently reported side effects with fluvoxamine are nausea, drowsiness, asthenia, headache, dry mouth, and insomnia.35

The usual dose of fluvoxamine for the treatment of OCD in adults is 150–300 mg/day. Starting at 25–50 mg/day and increasing by 50 mg/day weekly may help to minimize early side effects. The mean maximum dose used in most studies was 250–300 mg/day.

Fluoxetine

Fluoxetine is an SSRI with a notably long half-life (84 hours). Its efficacy in OCD has been established by several double-blind, placebo-controlled trials.36-39 Fluoxetine has been extensively studied in OCD at three fixed doses (20 mg/day, 40 mg/day, and 60 mg/day) and is clearly effective at 40 and 60 mg/day. Efficacy at 20 mg/day is also shown in some studies.37 Higher doses, especially 80 mg/day, are used frequently in clinical practice, and there are a few studies at 80 mg/day which were also successful in terms of efficacy and tolerability. Both obsessions and compulsions were found to respond to fluoxetine treatment independently of any antidepressant effect.

Fluoxetine is generally well tolerated, and the dropout rate due to adverse effects in clinical trials has been low. Common side effects are anxiety, insomnia, decreased appetite, headache, drowsiness, gastrointestinal symptoms (eg, nausea, diarrhea, dyspepsia), and sexual dysfunction.

Treatment is generally started at 20 mg/day, but it can be started at 10 mg/day to minimize side effects. As noted, the therapeutic range is thought to begin at 40 mg/day and the maximum recommended dose is 80 mg/day for adults.

Paroxetine

Several large, randomized placebo-controlled trials have demonstrated the efficacy of paroxetine in OCD.21,40,41 One, a study of paroxetine in three fixed doses, found that 40 and 60 mg/day were more effective than placebo, but 20 mg/day was not.40

Paroxetine has a different side-effect profile than other SSRIs. It is somewhat more likely to have anticholinergic side effects such as dry mouth, constipation, and dizziness.21 It also can cause nausea and sexual dysfunction and may be more prone to cause weight gain.42 Paroxetine should be used cautiously in patients with renal impairment as well as hepatic impairment.

In OCD, paroxetine can be started at 20 mg/day and can be increased weekly with the target range being 40–60 mg/day. The highest approved dose is 60 mg/day.

Sertraline

The efficacy of sertraline in OCD has been demonstrated in large, randomized, placebo-controlled trials.43,44

Its most common side effects of sertraline include nausea, diarrhea, dry mouth, sleepiness or insomnia, and sexual side effects. Sertraline has notably low levels of nervousness or agitation as side effects.

The typical starting dose for adults is 50 mg/day with increases of 50 mg/day weekly to reach a target dose (150–200 mg). Patients can be started at ≤25 mg/day and titrated up more slowly if side effects are a concern. The maximum recommended dose is 200 mg/day.

Citalopram

Citalopram appears to be effective in OCD based on the research available to date, which includes one large, randomized, placebo-controlled trial.45 This trial found that citalopram was more effective than placebo at all doses tested (20, 40, and 60 mg/day). The efficacy of citalopram is also supported by open-label trials.46,47

Citalopram has a favorable side-effect profile. The most common side effects in short-term trials are nausea, dry mouth, and somnolence. Some common SSRI side effects occurred at the same rate with citalopram as with placebo; these include insomnia, fatigue, anxiety, agitation, nervousness, and gastrointestinal side effects other than nausea.

Dosing is usually started at 10 mg/day and increased to 40–60 mg/day in treating OCD.

Escitalopram

Escitalopram is the newest of the SSRIs. There are currently no published studies on its efficacy in OCD. Since it is the active isomer of citalopram, it is generally expected that escitalopram’s efficacy will equal that of citalopram. It has been shown to have the least secondary binding properties of the SRIs48 as well as the least drug-drug interaction.49 In its pre-release clinical trials, only nausea was reported by >10% of the patients (15% versus 7% for placebo).

The starting dose of escitalopram is 10 mg/day and can be increased to 20 mg/day.

Cognitive-Behavioral Therapy

CBT, including behavioral therapy, is an established treatment for OCD, which has been shown to be equal to or perhaps superior to pharmacotherapy.18 CBT is an appropriate first-line treatment for OCD and can be used either instead of or in addition to an SSRI, depending on the willingness of the patient to participate in therapy or to take medication, and the presence of comorbid diagnoses. For example, if a patient has significant depression, an SSRI would be a good first-choice treatment, but even more so if the depression would make participation in CBT difficult. If a patient begins a medication but has an inadequate response, CBT should be attempted. Likewise, if a patient tries CBT but is unable to complete assignments, an SSRI trial is indicated. CBT is also valuable for patients who wish to discontinue medication, since there is evidence that it helps to prevent relapse.50-52 Additional studies are needed regarding the use of CBT as an augmentation strategy in patients who are SSRI resistant.

In CBT, patients face a feared object or activity without performing their compulsive ritual. For example, a patient with a fear of germs will touch a contaminated object but not wash his or her hands. The key element in this therapy is the exposure and prevention of the response or ritual. The exposure can be to actual feared objects or situations, or to imagery or descriptions of these. If a patient has obsessions without typical compulsions, exposure is still an effective and essential component.53,54 Cognitive aspects of the treatment focus on correcting errors of assessing danger and their feelings of responsibility. Cognitive elements to therapy can be important and are often used to motivate patients to attempt exposures or to be able to tolerate them without having to perform their usual rituals. There is little evidence that cognitive therapy is effective if it does not include exposure to what is feared. Therapy which emphasizes the cognitive component seems to be successful if it also includes “behavioral experiments” to collect evidence to assess the alternate appraisals of danger.55

Although individual CBT is most common, there is also evidence that group therapy is effective.11,56 CBT sessions should be weekly or more frequently until significant symptom reduction has been achieved, at which point session frequency can be reduced. It is important for relapse prevention to be part of CBT. After a course of CBT is completed, patients can return for booster sessions if symptoms return.

Medication Treatment Decision Guidelines

After a patient is diagnosed with OCD and comorbid diagnoses are determined, a patient should begin CBT and/or medication. Decision guidelines for the management of medication and other somatic treatments are outlined below and in the Figure provided.

Certain comorbid psychiatric diagnoses require a change in medication strategy. Such diagnoses include Tourette’s  syndrome and tics, attention-deficit/hyperactivity disorder (ADHD), bipolar spectrum disorders, and impulse control disorders. The SRIs are effective without major modifications for other conditions that are frequently comorbid with OCD (eg, depression, anxiety, eating disorders, and obsessive-compulsive spectrum disorders not mentioned above). While there is evidence that the SRIs are effective in many patients with other obsessive-compulsive spectrum disorders, the efficacy in some of these disorders is less clear than for OCD. This lack of clarity may be due to comorbidities (ADHD, bipolar spectrum disorders) or additional symptom domains (affective instability, inattention). These treatment guidelines take such comorbidities and symptoms into account, but the SRIs are included wherever possible because the goal is to treat the OCD rather than to treat only

the comorbid disorder. If a patient does not have OCD, the optimal treatment strategy might well differ from these guidelines.

An SSRI is the first-choice medication treatment for most OCD patients, and venlafaxine may be the first choice for patients with ADHD. SSRIs are preferred for an initial trial due to more favorable side-effect profiles and fewer potentially serious side effects than clomipramine. A mood stabilizer is the recommended first medication treatment for OCD patients with bipolar spectrum disorders, but if affective instability is well controlled and OCD symptoms persist, then addition of an SSRI may be indicated. However, close monitoring must insure that roughening of the bipolar disorder does not occur.

Of note, if a patient with Tourette’s syndrome or tics does not respond, augmentation with an atypical antipsychotic or haloperidol should be considered. Although haloperidol would be less costly, the risk of tardive dyskinesia with long-term use must be considered. For patients with comorbid impulse-control disorders, augmentation with a mood stabilizer, an opiate antagonist, or an atypical antipsychotic is an option if there is no response to an SRI or if the response is lost.

If patients do not respond to an adequate trial of the first SSRI, another SSRI or an SNRI should be tried, as studies of patients who have failed one or more SRI trials have shown response rates in trials of new SRIs ranging from 11%57 to 56%.58 For nonresponders, one or two SSRI trials and one SNRI trial are recommended.

If a patient has a partial response to his or her first treatment, an increased dose or augmentation with an atypical antipsychotic should be considered. The two augmentation strategies with the strongest research support are augmentation of the SRI with the atypical antipsychotics risperidone or quetiapine. In OCD patients with comorbid tic disorders, augmentation with haloperidol has been helpful. This augmentation was not effective in patients without tics.59 Evidence shows that low doses (<3 mg/day risperidone equivalents) of atypical antipsychotics are effective in a broader range of OCD patients, not just those with comorbid tics. There is support from small, double-blind, controlled trials for the efficacy of risperidone60,61 and quetiapine.62 The findings for olanzapine are mixed, with one positive63 and one negative64 randomized, controlled trial.

If a patient does not have an adequate response after two to three SRI trials, including at least one SNRI trial and augmentation with an atypical antipsychotic, several other possible strategies are suggested. An SRI can be augmented with a stimulant or an anticonvulsant, or an SSRI can be augmented with clomipramine. The patient may also be switched to a trial of intravenous clomipramine or citalopram, or to an opiate.

For the most refractory patients, there are other somatic therapies that can be considered. These include deep brain stimulation,65 transcranial magnetic stimulation,66 electroconvulsive therapy, vagal nerve stimulation, and neurosurgery (ie, cingulotomy).

Long-Term Treatment

Since OCD is often chronic, it often requires long-term treatment. Those SRIs that have been studied in long-term trials have been shown effective beyond the acute treatment time period.40,67 Published Expert Consensus Guidelines12 highly recommend that OCD treatment be continued for 1–2 years to prevent relapse, and usually longer treatment is needed. After this prolonged treatment, patients can have their dose slowly titrated down to see if their symptoms remain under good control. Discontinuation of the medication may not be possible in many cases and, if a patient has serious relapses two or more times, lifelong medication treatment may be necessary.

The medication treatment guidelines provided in the discussion of acute treatment are applicable throughout the course of treatment. That is, wherever patients are in the guideline diagram, they can remain on their medication so long as their symptoms remain in remission. If a medication treatment becomes less effective or ineffective over the long term, the options to be considered are the same as if the treatment was ineffective earlier. If patients receive long-term augmentation with an atypical antipsychotic, it is important to monitor them for metabolic syndrome.

When treatments are discontinued, studies seem to show lower relapse rates for CBT than are found for medication treatment.68 This is especially true when the CBT includes consideration of relapse prevention.69 However, to date adequate head-to-head trials are not available. Likewise, there is some evidence that CBT in combination with SRIs may help prevent relapse. Definitive research is needed,70 yet, it seems reasonable to recommend CBT for patients in need of long-term medication treatment.

Conclusion

Treatment for patients with OCD has improved dramatically in recent years. Primary care physicians may be the first healthcare professionals consulted by these patients, and they can provide appropriate pharmacologic treatment and therapeutic guidance. Psychiatric consultations may be needed for refractory cases or those complicated by comorbid psychiatric conditions. PP

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Dr. Allen is assistant professor of psychiatry in the Department of Psychiatry at Mount Sinai School of Medicine in New York City. Dr. Hollander is professor of psychiatry in the Department of Psychiatry and director of the Compulsive, Impulsive and Anxiety Disorders Program at Mount Sinai School of Medicine.


Disclosure: Dr. Allen has received research/grant support from the National Institute of Mental Health (NIMH). Dr. Hollander has received research/grant support from Abbott, Eli Lilly, the Food and Drug Administration, GlaxoSmithKline, NIMH, the National Institute of Neurological Disorders and Stroke, the National Institute on Drug Abuse, Pfizer, and Solvay.

Please direct all correspondence to: Andrea Allen, PhD, Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029; Tel: 212-241-3176; Fax: 212-987-4031; E-mail: andrea.allen@mssm.edu.