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Gabbard’s Treatments of Psychiatric Disorders > Part VI. Anxiety Disorders, Dissociative Disorders, and Adjustment

Disorders >

Chapter 31. Obsessive-Compulsive Disorder

INTRODUCTION

Obsessive-compulsive disorder (OCD) is characterized by thoughts, images, or impulses that are

often experienced as intrusive and inappropriate (obsessions) and by repetitive behaviors or

mental acts that the person feels driven to perform to lessen their anxiety (compulsions)

(Rasmussen and Eisen 1989). For chronic and severe disorders such as OCD, many treatments are

attempted. Until recently, OCD was unresponsive to most remedies. Specific psychotherapeutic and

pharmacological approaches, however, now have established efficacy for this condition.

PSYCHOTHERAPIES

Behavior Therapy

In 1966, Meyer reported the successful behavioral treatment of two patients with severe

compulsive ritualizing through around-the-clock response (or ritual) prevention. A series of elegant

studies by other investigators (Foa et al. 1998; Marks et al. 1975; Rachman et al. 1973; Steketee et

1. 1982) confirmed that approximately 75% of OCD patients will engage in behavior therapy and

that most who do so faithfully show both acute (Foa et al. 1998) and sustained (O’Sullivan et al.

1991) improvement. Unsuccessful treatment is most often a result of noncompliance, which may

take the form of unrecognized mental rituals. Comorbid severe depression, misdiagnosis (e.g.,

when psychotic delusions are misinterpreted as obsessions), and state-dependent learning (usually

associated with high doses of central nervous system [CNS] depressant substances such as alcohol,

barbiturates, carbamates, or benzodiazepines) also interfere with response to behavior therapy.

Wolpe’s (1958) systematic desensitization was found to have weak efficacy for patients with OCD

(Cooper et al. 1965). Relaxation did not increase the benefit of effective exposure and ritual

prevention, and exposure in fantasy or imagination was not as effective as exposure in vivo

(Steketee et al. 1982).

Effective behavior therapy for OCD consists of exposure in vivo and ritual prevention (Abramowitz

1996). These simple concepts, systematically applied, lead to habituation of anxiety associated with

obsessions so that rituals are no longer necessary to reduce anxiety. Patients often, but imperfectly

and ineffectively, have tried this commonsense approach. The task of behavior therapy is to provide

the structure in which these basic principles are brought into effective practice.

Patients should be informed that their anxiety level will increase initially during exposure sessions

and that this anxiety and the time they must expend are the short-term costs of behavior therapy,

which produces long-term gains of reduced anxiety and dysfunction (Figure 31–1).

Figure 31–1. Sample rates of change with behavior therapy of an obsessive-compulsive disorder

ritual.Print: Chapter 31. Obsessive-Compulsive Disorder http://www.psychiatryonline.com/popup.aspx?aID=258458&print=yes…

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Source. Reprinted from Baer L: Getting Control: Overcoming Your Obsessions and Compulsions, Revised

Edition. Boston, MA, Little, Brown, 2000, p. 53. Copyright 2000. Used with permission.

The cognitive/affective lag reflected in this diagram is common; this phenomenon should be

explained to patients so that they expect it and are not surprised by their early improvement in

ritual behaviors with delayed reduction in obsessions and anxiety.

Rituals are performed because they work temporarily, reducing discomfort and the compulsion to

ritualize. Ritual prevention is also effective in reducing urge and discomfort but requires a longer

time to achieve similar reductions. With ritual prevention, however, OCD patients begin to learn

through the process of habituation that they can control discomfort from obsessions without

performing rituals. This demonstration of anxiety or discomfort reduction, when repeated through

systematic exposure and ritual prevention “homework assignments,” frees patients from

dependence on rituals.

Several patient guides to behavior therapy are available (Baer 2000; Foa and Wilson 1991;

Neziroglu and Yaryura-Tobias 1991; Steketee and White 1990). These manuals, coupled with

therapist willingness to try behavior therapy with obsessive-compulsive patients, often lead to

remarkably positive results. Although about 25% of obsessive-compulsive patients referred for

behavior therapy decline or are noncompliant with treatment, far more therapists, including

psychologists who espouse behavior therapy for OCD, fail to employ exposure and ritual prevention,

instead emphasizing cognitive restructuring and ineffective relaxation. A computer program to

guide patients in self-help homework exposure and ritual prevention treatment (E & RP) for OCD

was found to be as helpful in the 64% of patients who completed at least one E & RP session as 12

hours of clinician-directed E & RP, and both were significantly more effective than relaxation in this

randomized controlled trial (Greist et al. 2002).

Cognitive Therapy

Cognitive therapists seek to change thoughts, feelings, and behaviors. They hypothesize that faulty

cognitions permit and then maintain unpleasant affects and dysfunctional behaviors. Correcting

faulty cognitions should lead to more agreeable affects and more functional behaviors. However, it

is striking that in OCD, patients with insight have called their cognitions crazy thousands of times,

family members have argued against their obsessional fears, and clinicians have agreed that their

worries are unfounded, all without benefit.

Reviews (Deacon and Abramowitz 2004; Van Balkom et al. 1998) have documented efficacy for

cognitive procedures that address faulty risk assessment and exaggerated sense of responsibility.Print: Chapter 31. Obsessive-Compulsive Disorder http://www.psychiatryonline.com/popup.aspx?aID=258458&print=yes…

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Whether cognitive-behavioral therapy achieves its benefits directly through cognitive means or

indirectly by invoking exposure and ritual prevention (see above) is an important question.

Psychodynamic Psychotherapy

Despite Freud’s acclaimed success in curing the “Rat Man,” psychoanalytic approaches have not

been studied systematically or shown to be helpful. Dynamic therapies, taking their lead from

psychoanalysis, had been the main treatment of OCD before treatments of documented

effectiveness were developed. Improvements that occurred as the disorder waned spontaneously

were often interpreted as responses to dynamic psychotherapy, whereas worsening was thought to

represent effects of external stressors or resistance in therapy.

Gabbard (1992) acknowledged that “there is little evidence in the literature to suggest that

dynamic psychotherapy or psychoanalysis is effective in the treatment of obsessive-compulsive

disorder” (p. 993). On the other hand, he quite appropriately emphasized that a psychodynamic

perspective can often be a useful adjunct in the overall treatment of OCD, especially to enhance

compliance with other treatments and to address interpersonal problems.

Supportive psychotherapy, including empathy, minimization of limitations, support for strengths,

explanations regarding pathophysiology, and optimism about improvement, is appropriate for all

patients.

PHARMACOTHERAPY

Potent Serotonin Reuptake Inhibitors

Clomipramine

Numerous positive open trials of clomipramine in OCD were followed by at least 22 controlled trials

in which clomipramine was either more effective (11 trials) than placebo or tricyclic comparators or

equally as effective as selective serotonin reuptake inhibitor (SSRI) comparators (5 trials) (Greist

et al. 1995). Clinical opinion has generally led to dosing at the higher end of the dosing range for

these agents, although fixed-dose trials, when available, have usually found a flat dose–response

curve, suggesting that many patients receive more medication than necessary. Side effects of

clomipramine are typical of a tricyclic antidepressant and include anticholinergic, antihistaminergic,

and alpha-adrenergic blocking effects.

Selective Serotonin Reuptake Inhibitors

Multicenter placebo-controlled, parallel-design trials of fluoxetine (Tollefson et al. 1994),

fluvoxamine (Greist 1992), sertraline (Greist et al. 1992), and paroxetine (Wheadon et al. 1993)

have been completed and reported. Citalopram has also been studied in a controlled trial

(Montgomery et al. 2000). Each trial found the active compound significantly more effective than

placebo. As with clomipramine, onset of improvement was often delayed, with significant

differences only emerging between 2 and 6 weeks and continuing to increase to at least 10 weeks.

Trials of fluoxetine, sertraline, and paroxetine compared fixed doses, whereas the clomipramine

and fluvoxamine trials used an ascending-dose design (average final dosages of 227 and 249

mg/day, respectively). Although there were trends toward greater improvement with increasing

dosages of fluoxetine (20, 40, and 60 mg/day) and sertraline (50, 100, and 200 mg/day), no

statistically significant differences were seen. Paroxetine was significantly more effective than

placebo at 40 and 60 mg/day but not at 20 mg/day.

Although SSRIs have fewer side effects than clomipramine, it is surprising that dropout rates for

side effects were not greater in the U.S. Food and Drug Administration (FDA) registration

multicenter clomipramine trials (8%) than in the fluoxetine (12%), fluvoxamine (15%), or

sertraline (10%) trials. Delayed or inhibited orgasm is a common side effect of the potent serotonin

reuptake inhibitors (SRIs) (including clomipramine). Concerns about increased suicidal thoughts

and behaviors (suicidality) and possibly suicide has led to a recent class warning for all

antidepressants, including those with OCD indications.Print: Chapter 31. Obsessive-Compulsive Disorder http://www.psychiatryonline.com/popup.aspx?aID=258458&print=yes…

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As of early 2007, clomipramine, fluoxetine, fluvoxamine, paroxetine, and sertraline have FDA

indications for OCD in adults, and clomipramine, fluoxetine, fluvoxamine and sertraline also have

indications for pediatric populations of various ages.

Comparative Efficacy of Potent SRIs

A meta-analysis of the FDA registration multicenter controlled trials of clomipramine, fluoxetine,

fluvoxamine, and sertraline found clomipramine to be more efficacious than the SSRIs, which did

not differ from one another in efficacy (Figure 31–2) (Greist et al. 1995).

Figure 31–2. Mean change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score:

intent-to-treat analysis of drug minus placebo.

Pooled standard error of change score was used in error bars (available for endpoint only).

*

12 weeks of treatment for fluvoxamine and sertraline.

Source. Reprinted from Greist JH, Jefferson JW, Kobak KA, et al.: “Efficacy and Tolerability of Serotonin

Transport Inhibitors in Obsessive-Compulsive Disorder: A Meta-Analysis.” Archives of General Psychiatry

52:53–60, 1995. Copyright 1995, American Medical Association. Used with permission.

Indirect comparisons have limitations and must be viewed with caution, but double-blind,

head-to-head comparisons of clomipramine versus SSRIs are unmasked to some degree by tricyclic

side effects. Some studies have found comparable efficacy of SSRIs with clomipramine (Bisserbe et

1. 1997; Koran et al. 1996; Zohar and Judge 1996), whereas other studies continue to show at

least trends favoring clomipramine (Lopez-Ibor et al. 1996). Most meta-analyses (Ackerman and

Greenland 2002; Greist et al. 1995; Kobak et al. 1998; Piccinelli et al. 1995; Serretti et al. 1999;

Stein et al. 1995) of adult OCD SRI treatments have found clomipramine to be more efficacious, but

this advantage must be balanced against the greater side-effect burden of clomipramine.

Duration of SRI Pharmacotherapy

All reports of extended pharmacotherapy with potent SRIs indicate maintenance of or increase in

short-term gains for many months. Few discontinuation studies are available, but patients seem to

relapse rapidly whenever potent SRIs are discontinued (Pato et al. 1988; Ravizza et al. 1999).

Patients must continue to take the medication to maintain the gains achieved, although downward

titration to determine an optimal dose (maximum benefit with minimum side effects) is

appropriate.Print: Chapter 31. Obsessive-Compulsive Disorder http://www.psychiatryonline.com/popup.aspx?aID=258458&print=yes…

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Nonresponse to SRI Pharmacotherapy

Incomplete improvement is the rule for OCD patients treated with any therapeutic modality.

Nevertheless, symptomatic reductions of 25% (one standard of response) or more represent quite

worthwhile gains. Patients in the multicenter controlled trials typically had a decrease in time spent

with obsessions and rituals of at least 2 hours/day.

Patients who do not achieve worthwhile gains may have received treatment of insufficient duration.

Experts agree that at least 10 weeks of monotherapy must be completed before concluding that a

particular SRI is ineffective. If symptoms prove resistant to an adequate duration trial of the

maximum tolerated dose of one potent SRI, a trial of another potent SRI is appropriate. Many

clinicians believe that higher doses are required in OCD, and such may be the case for select

patients, although controlled studies do not support generally higher dosages. One study (Pato et

1. 1990) found that virtually all patients who relapsed when clomipramine (275 mg/day) was

discontinued responded when retreated at a lower dose (165 mg/day). Essentially flat

dose–response curves within a dose range equivalent to 20–80 mg of fluoxetine were confirmed in

the multicenter randomized controlled trials of fluoxetine and sertraline.

For patients unresponsive to or intolerant of clomipramine by mouth, intravenous clomipramine

given daily for 2 weeks at dosages increasing from 25 to 200 mg/day sometimes initiates

improvement that can be maintained with oral clomipramine (Fallon et al. 1998; Koran et al. 1997).

The intravenous advantage may result from lessened effects of first-pass hepatic metabolism,

yielding higher ratios of clomipramine to the more noradrenergic desmethylclomipramine.

Inhibiting the metabolism of clomipramine with fluvoxamine may be a convenient method for

producing “oral–intravenous clomipramine” (Szegedi et al. 1996).

SRI Augmentation Strategies

Proserotonergic Strategies

Proserotonergic augmentations are logical in a disorder so clearly responsive to potent SRIs,

particularly when there has been a partial response to a potent SRI. The combination of two potent

SRIs has not yet been subjected to controlled trials. Open-label augmentations with lithium,

tryptophan, fenfluramine (no longer available), and buspirone suggested benefit for each

proserotonergic augmentation, but controlled trials of lithium (McDougle et al. 1991; Pigott et al.

1991) and buspirone (Grady et al. 1993; McDougle et al. 1993; Pigott et al. 1992) found neither

drug significantly more effective than placebo (some patients did appear to have worthwhile

improvement).

Antipsychotics

Because patients have obsessions and rituals that they often view as “crazy” and that seem so at

some level to clinicians, it is understandable that antipsychotic medications would be used for OCD.

With the exceptions described below, typical antipsychotics have not been routinely helpful in the

treatment of OCD, and because of the common occurrence of extrapyramidal side effects and the

risk of tardive dyskinesia, they should not be used without careful thought and special effort to

ensure informed consent.

Most promising of the augmentation strategies is the addition of an antipsychotic drug to a potent

SRI (haloperidol plus fluvoxamine and risperidone plus clomipramine, fluoxetine, fluvoxamine,

paroxetine, or sertraline are the combinations that have been best studied). A double-blind,

placebo-controlled trial found that haloperidol (mean dosage: 6.2 mg/day) resulted in a worthwhile

augmentation of fluvoxamine in patients with OCD and Tourette’s disorder or multiple motor tics

(McDougle et al. 1994). A subsequent double-blind, placebo-controlled trial of risperidone

augmentation (mean dosage: 2.2 mg/day) of potent SRIs found that 50% of the risperidone

patients benefited substantially, with a mean Yale-Brown Obsessive Compulsive Scale (Y-BOCS)

score reduction of 8.7 points (vs. 2.6 for placebo) (McDougle et al. 2000). Recently, Sareen et al.

(2004) reported: “In the placebo-controlled trials with haloperidol, risperidone, olanzapine, andPrint: Chapter 31. Obsessive-Compulsive Disorder http://www.psychiatryonline.com/popup.aspx?aID=258458&print=yes…

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quetiapine, a significantly higher response rate (46%–71%) was found for the antipsychotic

groups, compared with no response for the placebo groups. Reports of exacerbation of OCD

symptoms with the use of atypical antipsychotics were limited to individuals with a primary

psychotic disorder” (p. 167). Discontinuation of a beneficial SRI augmentation by an antipsychotic

was associated with a relapse rate of 83.3% (Maina et al. 2003).

Monoamine Oxidase Inhibitors

Vallejo et al. (1992) conducted a 12-week placebo-controlled, double-blind, parallel-design

comparison of the monoamine oxidase inhibitor (MAOI) phenelzine with clomipramine. Both agents

were equally effective. Most recently, Jenike et al. (1997) found fluoxetine to be more effective

than phenelzine or placebo except for obsessions about symmetry, for which fluoxetine and

phenelzine were similarly more efficacious than placebo. MAOIs cannot be safely combined with

SRIs.

Antianxiety Agents

Benzodiazepines

Case reports and some case series suggested efficacy for alprazolam, bromazepam, clonazepam,

diazepam, and oxazepam.

The first controlled trial comparing a benzodiazepine with an effective pharmacological treatment

of OCD was a multiple crossover study with 28 subjects conducted by Hewlett et al. (1992). No

significant difference in efficacy was found between clomipramine and clonazepam at 6 weeks;

however, clonazepam improvement had plateaued by 3 weeks, whereas clomipramine improvement

was continuing at 6 weeks and was numerically greater than that for clonazepam (Y BOCS change

scores = 5.8 and 4.5, respectively). Clonazepam was less well tolerated and led to more dropouts

because of side effects (n = 5) than did clomipramine (n = 1). Because improvement with

clomipramine in other studies has continued for at least 10 weeks, 6-week trials are likely too short

to establish comparative efficacy of pharmacotherapies for OCD. Recently, other placebo-controlled

trials failed to find efficacy for clonazepam monotherapy (Hollander et al. 2003) or augmentation of

sertraline by clonazepam (Crockett et al. 2004).

Azapirones

Buspirone has serotonin type 1 (5-hydroxytryptamine [5-HT1A]) receptor partial-agonist effects

that are thought to account, in part, for its anti-anxiety effects. Although Jenike and Baer (1988)

found that buspirone was ineffective in an open trial with obsessive-compulsive patients, Pato et al.

(1991) found that buspirone (mean dosage: 58 mg/day) was as effective as clomipramine in a

small (n = 18) double-blind trial of only 6 weeks’ duration.

COMBINED BEHAVIOR THERAPY AND SRI PHARMACOTHERAPY

Several early studies suggested that the combination of a potent SRI and behavior therapy

accelerates and increases short- and long-term improvement (Cottraux et al. 1990; De Haan et al.

1998; Marks et al. 1988). Recently, important adult (Foa et al. 2005) and pediatric (Pediatric OCD

Treatment Study Team 2004) trials have been reported. In both trials, behavior therapy (exposure

and ritual prevention for adults and children plus cognitive components for children) proved more

efficacious (adults: P < 0.01) and trended toward greater benefit (children: effect size 0.97 vs.

0.67) than the SRIs with which they were compared. Combination treatment was not more

beneficial than behavior therapy alone. Relapse after SRI discontinuation is consistently and

significantly lower in adults who have also received behavior therapy (Simpson et al. 2004).

Medication treats accompanying or underlying depression and anxiety and may improve compliance

with behavior therapy, which in turn provides the possibility of discontinuing medication without

rapid and substantial relapse of OCD.

OTHER SOMATIC TREATMENTS

Neurosurgery and Deep Brain StimulationPrint: Chapter 31. Obsessive-Compulsive Disorder http://www.psychiatryonline.com/popup.aspx?aID=258458&print=yes…

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For the minority of obsessive-compulsive patients (perhaps 1 in 400) who do not respond to

adequate trials of behavior therapy and potent SRIs and have incapacitating OCD, consideration of

neurosurgical interventions is appropriate.

Modern neurosurgical techniques, involving careful patient selection and stereotactic placement of

lesions, are sometimes effective in patients with otherwise refractory OCD and have a low

morbidity and virtually no mortality (Baer et al. 1995). At present, anterior cingulotomy,

subcaudate tractotomy, their combination (called limbic leukotomy), and anterior capsulotomy are

all used. A comprehensive review (Greenberg et al. 2003) of modern neurosurgical procedures

found that “Existing data suggest that lesion procedures offer benefit to a large proportion (ranging

from about 35% to 70%) of patients with intractable OCD and depression” (Greenberg et al. 2003,

1. 209).

A further neurosurgical intervention is in the form of reversible electrical deep brain stimulation,

which permits removal of electrodes if worthwhile benefit is not achieved. Preliminary studies

involving bilateral anterior capsule electrode placement have been promising (Abelson et al. 2005).

Electroconvulsive Therapy

Because many OCD patients are depressed, electroconvulsive therapy has been tried, with

occasional benefit (Mellman and Gorman 1984), usually when obsessions and rituals are secondary

to a severe primary depression.

Promising Treatments Requiring Further Study

Inositol is a second-messenger precursor available in health food stores. In crossover designs,

inositol was significantly more effective than placebo as monotherapy for OCD (Fux et al. 1996),

but not as an augmentation for potent SRIs (Fux et al. 1999).

Opiates given every 4–7 days and opiate antagonists prescribed daily have been reported to help

some patients with OCD and OCD-spectrum impulse-control disorders (Koran et al. 2005a; Shapira

et al. 1997; Warneke 1997).

Mirtazapine appeared beneficial in both 12-week open-label and subsequent 8-week double-blind,

placebo-controlled responder discontinuation trials (Koran et al. 2005b).

Right lateral prefrontal transcranial magnetic stimulation reduced compulsive urges for up to 8

hours after the procedure (Greenberg et al. 1997), whereas left lateral prefrontal and mid-occipital

stimulation did not.

GUIDELINES FOR TREATMENT

Behavior therapy and potent SRIs are the cornerstones of effective treatment of OCD. Accumulating

evidence strongly supports the conclusion that behavior therapy is more efficacious than

medications, both acutely and in the long term. Behavior therapy’s limited availability is its greatest

limitation. If both modalities are available, patients may choose to begin with one or the other, but

combined treatment from the outset is also appropriate, as one cannot predict beforehand which

treatment may be most helpful for a particular patient.

Most patients obtain some benefit from potent SRIs; however, more patients obtain greater benefit

from behavior therapy than from SRIs. Although complete remission is unusual, patients complying

with both therapies have a high probability of significant gains (approximately 50% reduction in

obsessions and rituals). Most patients who have suffered silently for a decade or more are quite

appreciative of such improvements and feel and function much better.

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