2008年1月27日 星期日

Effectiveness of Psychological and Pharmacological Treatments for Obsessive–Compulsive Disorder: A Quantitative Review

Effectiveness of Psychological and Pharmacological Treatments for Obsessive–Compulsive Disorder: A Quantitative Review
[Regular Articles]
Abramowitz, Jonathan S.1,2
1The University of Memphis.
2Correspondence concerning this article should be addressed to Jonathan S. Abramowitz, Department of Psychology, The University of Memphis, Memphis, Tennessee 38152. Electronic mail may be sent via Internet to jabramowitz@cc.memphis.edu.
I thank the following people for their assistance and helpful suggestions during various stages of this research: Leslie Robinson, Guy Mittleman, John Richter, Will Shadish, Gail Steketee, Fugen Neziroglu, and John Greist. I also express special thanks and appreciation to Art Houts for his invaluable support.
Received Date: September 11, 1995; Revised Date: December 19, 1995; Accepted Date: March 21, 1996
Abstract
Quantitative review of the controlled treatment outcome literature for obsessive–compulsive disorder (OCD) showed that exposure with response prevention was highly effective in reducing OCD symptoms. Cognitive approaches were also found to be at least as effective as exposure procedures. It appears that both cognitive and exposure interventions involve some overlapping procedures and capitalize on similar mechanisms of change. Serotonergic medication, particularly clomipramine, also substantially reduced OCD symptoms. However, clomipramine may not be particularly superior to other serotonergic medication. The relationship between side effects and effect size in medication trials was explored.
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Obsessive–compulsive disorder (OCD) involves (a) intrusive and unwanted thoughts, ideas, or images (obsessions) that lead to increased anxiety; and (b) repetitious, intentional rituals (compulsions) performed to neutralize the anxiety. Because people who show this behavior pattern spend excessive amounts of time obsessing and ritualizing, they typically experience significant impairment in occupational and social functioning. Ritualizing often involves friends or family members who may devote considerable time to care for the person. In severe cases, ritualizing can dominate the entire day and sometimes involve self-injury, such as skin damage from excessive hand washing. Usually, OCD symptoms wax and wane throughout the course of the disorder (American Psychiatric Association, 1994; Rachman & Hodgson, 1980; Rasmussen & Tsuang, 1986; Riggs & Foa, 1993).
Until a decade ago, OCD was thought to be a rare condition with a poor prognosis. Recently, the Epidemiological Catchment Area survey estimated that the lifetime prevalence rate could be as high as 2.5% in the United States (Karno, Golding, Sorenson, & Burnam, 1988). Because they fear embarrassment, individuals with OCD often attempt to hide their symptoms from others. As a result, it is common for people to suffer with obsessions and compulsions for several years before seeking treatment (Steketee, 1993). Consistent findings show the average age of onset to be in the early twenties (Minichiello, Baer, Jenike, & Holland, 1990). Considering the personal cost and prevalence, OCD is a significant public health concern, and identifying effective interventions for this disorder is important.
Current treatments for OCD can be divided into psychological and pharmacological approaches. Psychological interventions have included exposure-based procedures (Riggs & Foa, 1993; Steketee, 1993) and cognitively oriented strategies such as Ellis's rational emotive behavior therapy (REBT; Ellis, 1994),1 a cognitive treatment based on Beck's (1976) cognitive therapy for depression (van Oppen & Arntz, 1994), and thought stopping (Hackman & McLean, 1975). Pharmacotherapy has been dominated by the use of antidepressants, particularly the serotonin reuptake inhibitors (SRIs; Jenike, Baer, & Greist, 1990). Although clomipramine, an SRI, has received more research attention than any other single medication to date, newer SRIs such as fluoxetine, fluvoxamine, and sertraline have become the focus of recent controlled clinical trials. Behavior therapy and medication have also been used in combination, most often in cases of severe OCD or when patients failed to respond to behavior therapy alone. Previous reviews of this outcome literature have generally concluded that the behavioral, cognitive, and pharmacological treatments developed over the past 3 decades were more effective than the psychoanalytically oriented therapies used previously (e.g., Stanley & Turner, 1995).
One procedure, exposure with response prevention (ERP), is often considered the psychological treatment of choice for OCD (Riggs & Foa, 1993; Steketee, 1993). Conclusions that ERP is more effective than other psychological treatments have been based on research studies that represent a variety of methodological designs and patient characteristics. Many have been single-case reports and uncontrolled trials rather than the methodologically preferable comparisons between patients randomly assigned to treatment and control groups. Uncontrolled trials should be interpreted with caution because they merely reflect within-group changes over time (pre- to posttest) without taking into account the effects of nonspecific factors on treatment. For example, there are natural fluctuations in symptom severity that occur throughout the course of OCD. Because people are inclined to seek treatment when their symptoms are more severe, changes in the direction of improvement would be expected from normal fluctuations of symptoms. In the present review, I avoid these problems by focusing exclusively on studies that contained direct comparisons between randomly assigned groups.
In the late 1970s and early 1980s, studies of pharmacological treatments for OCD mainly concerned tricyclic antidepressants (e.g., Mavissakalian, Turner, Michelson, & Jacob, 1985). Although case studies and open trials provided preliminary evidence that some of these medications were effective, well-executed randomized comparisons usually demonstrated the superiority of clomipramine (Perse, 1988). Because clomipramine (a tricyclic antidepressant and SRI) increased levels of available serotonin, hypotheses about a relationship between serotonin and obsessional symptoms emerged (Insel, Mueller, Alterman, Linnoila, & Murphy, 1985). Recent medication trials have focused more narrowly on other serotonergic antidepressants, such as fluoxetine (e.g., Tollefson et al., 1994), fluvoxamine (e.g., Jenike, Hyman, et al., 1990), and sertraline (Jenike, Baer, et al., 1990). These medications are thought to be more serotonin selective in their action. Reviews of this literature have concluded that, although other serotonergic antidepressants were somewhat helpful in treating OCD, clomipramine was still the most effective (e.g., Stanley & Turner, 1995). Whereas researchers have occasionally assessed moderating variables peripheral to the actual medication, such as levels of depression in study participants (e.g., DeVeaugh-Geiss, Katz, Landau, Goodman, & Rasmussen, 1990), length of treatment (e.g., Mallya, White, Waternaux, & Quay, 1992), medication dosage levels (e.g., Tollefson et al., 1994), and side effects (Jenike, Baer, & Greist, 1990), the relationships between these variables and medication effects across studies have not been systematically assessed. This review used methods of quantitative synthesis to examine these moderating variables.
In a meta-analysis of the OCD literature through 1984, Christensen, Hadzi-Pavlovic, Andrews, and Mattick (1987) concluded that both behavior therapies and tricyclic medications resulted in substantial improvement from pretest to posttest and that there was no difference in their relative efficacy. In a more recent review, van Balkom et al. (1994) reported that groups treated with serotonergic antidepressants, behavior therapy, and the combination of the two, had significantly larger treatment gains from pretest to posttest than groups given placebo treatment. On the basis of the improvement of treatment groups combined across different studies, van Balkom et al. (1994) concluded that behavior therapy was more effective than serotonergic antidepressants and that the combination of serotonergic antidepressants and behavior therapy was superior to the medication alone.
It is important to note that van Balkom et al.'s (1994) effect sizes for all treatment and placebo groups were calculated by subtracting a group's posttest mean from its pretest mean and dividing by the pooled within-group standard deviation. This represents a standardized measure of improvement from pre- to posttest on a group-by-group basis. Ordinarily, effect size is calculated by dividing the difference in means by the pooled between-groups standard deviation. All else being equal, a smaller pooled standard deviation will yield a larger effect size estimate. The van Balkom et al. (1994) method of calculating effect sizes yielded larger effect sizes because the pooled standard deviation was relatively smaller because of the same patients being measured at both pre- and posttreatment. In Lipsey and Wilson's (1993) quantitative reanalysis of previously completed quantitative reviews, the average effect sizes for pretest–posttest (pre-post) designs were significantly larger than for any other type of design. Thus, the conclusions that van Balkom et al. (1994) drew from their analyses may be based on overestimations of OCD treatment effects. Also, van Balkom et al.'s (1994) conclusions about the relative benefits of OCD treatments were based on comparisons between effect sizes that were calculated from different sets of treatment trials. Thus, differences between effect sizes were confounded with differences in treatment trial characteristics, such as types of patients and treatment duration.
In this review, we included only studies with multiple treatment or control groups to which participants were randomly assigned. Our effect sizes were calculated as the difference between the two groups' posttest scores divided by a standard deviation that was pooled from both groups. The absolute efficacy of each treatment was, therefore, derived only from direct comparisons between groups who were given that treatment and a control group. The relative efficacy of a treatment was derived from studies in which a treatment group was compared with another treatment group within the same study. These selection criteria and the method of effect size calculation provided two advantages over the approach taken in the previous reviews. First, they yielded a more precise estimate of the effects of treatment by capitalizing on the internal validity gained from random assignment of patients to a treatment or control group. Second, they allowed better statistical control over subtle background variables because these variables did not differ between groups within the same study. Also, the present sample of studies included all of the appropriate literature through December, 1995.
It has been suggested that effect sizes from double-blind studies may be inflated because of biases that spoil the “blindedness” of these trials (Fisher & Greenberg, 1993). Research in this area has shown that the effects of psychotropic medications relative to placebo appear greater as the degree of “blindedness” of the researchers decreases (Greenberg, Bornstein, Greenberg, & Fisher, 1992; Greenberg, Bornstein, Zborowski, Fisher, & Greenberg, 1994). Fisher and Greenberg (1993) speculated that the double-blind design was compromised when a greater side-effect profile for active medication, compared with placebo, was noticed by those involved in the research. Greenberg et al. (1994) empirically illustrated this phenomenon by finding that effect sizes in double-blind studies of fluoxetine increased as the proportion of patients who had telltale side effects from active medication increased. Thus, which group the patients were in was actually revealed by the side effects of the medication. This might especially bias clinician ratings of pharmacological efficacy if the same raters evaluate both the medicated group and the placebo group. In placebo-controlled trials, one might expect at least a moderate contrast in side effects between the placebo group and the active medication group. However, in comparisons between two active medications, this difference might be somewhat smaller. In further examination of this issue of “blindness,” a measure of relative side effects was included in the present analysis.
The present review addressed two major questions: First, what is the overall efficacy of treatments for OCD? Second, are certain types of treatment more effective than others? In addition to assessing these broad questions, the effects of research and participant variables such as age, duration of OCD symptoms, level of concurrent depression, intensity of ERP procedures, length of treatment, medication dosage, type of outcome measure, and drug side effects were also addressed.
Method
Studies
OCD treatment studies were identified through searches of the following media: PsycLIT and MedLine databases, reference lists from published material concerning OCD, and an issue-by-issue examination of the relevant journals.2 As in the previous OCD reviews, only published research was considered for inclusion. Four inclusion criteria were used. First, only investigations of adult samples with a primary diagnosis of OCD, or the former label obsessive–compulsive neurosis, were used. Studies including samples that had concurrent diagnoses of OCD along with active phases of other disorders (e.g., major depression) were excluded. Also, trials in which investigators failed to use explicit, standardized diagnostic criteria were excluded. Second, only studies containing comparisons between two or more randomly assigned treatment groups or control groups were included. Third, only reports that provided outcome measures of OCD symptoms at posttreatment or at a follow-up assessment were included. Fourth, to rule out carryover effects, studies using crossover designs were included only if outcomes were reported for each group separately before the crossover point.
Fifty-two studies met the initial criteria for inclusion. However, 20 studies contained comparisons between treatments that only appeared once in the literature. Thus, these studies could not be included in the analyses. The remaining 32 studies included a total of 37 treatment comparisons.3 Year of publication ranged from 1975 to 1995. Descriptive characteristics of the studies can be found in Table 1. Although all participants in the included studies met DSM criteria for OCD, it should be noted that the samples of the 32 studies were rather heterogeneous with respect to other potentially meaningful variables (e.g., amount of previous treatment for OCD).

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Table 1 Characteristics of OCD Treatment Outcome Studies
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Treatment Types
Current OCD treatment manuals describe an ERP procedure that includes both (a) daily sessions of deliberate exposure to anxiety-provoking situations lasting until significant habituation occurs, and (b) strict abstinence from performing rituals (Riggs & Foa, 1993; Steketee, 1993). Thus, in the present review, only comparisons involving treatments similar to the ERP procedure described above were included in the analyses. Different studies used modified versions of the ERP procedure described above. In some trials, the patient, rather than the therapist, determined the course of the treatment. Some investigators used “flooding,” a more rapid exposure procedure, rather than gradual exposure according to a hierarchy. Whether exposure was performed in vivo or in imagination was also varied along with the occasional use of modeling. Treatment session length, the number of sessions, and the spacing of sessions also varied greatly between studies. A strength of the quantitative review technique is that it allows for statistical control over the types of variables described above. Coding for the differences in ERP procedures made it possible to assess whether these treatment variables affect outcome.
Eight comparisons between ERP and other psychological interventions were located. These studies compared ERP with relaxation, cognitive therapies such as thought stopping or REBT, and the single-treatment components (e.g., exposure or response prevention alone). Guided by descriptions of ERP procedures in treatment manuals (Riggs & Foa, 1993; Steketee, 1993), the following variables were coded: total number of sessions, number of sessions per week, total number of hours spent in therapist-guided exposure, total number of hours spent in therapist-guided exposure per week, whether complete or partial response prevention was used, and dropout rate.
The pharmacological trials examined a total of 16 different medications. Both SRIs and non-serotonergic medications were studied extensively, and these two classes of medications were analyzed separately. Among the SRIs, multiple placebo-controlled studies of clomipramine, fluvoxamine, sertraline, and fluoxetine were found. Because each non-serotonergic agent appeared in only one placebo-controlled study, effect sizes for these medications were combined in the analyses. Ten comparisons between clomipramine and other medications were included in the review. Again, none of the pharmacotherapies that were compared with clomipramine appeared more than once. Therefore, these studies were combined into a broad category called clomipramine versus other medications.
Estimating Treatment Effects
For comparison of the effects of treatments across different measures of outcome, the results of each comparison were represented in terms of Cohen's (1977) d, a standardized measure of effect size. Cohen's d is defined as

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Equation (Uncited)
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where m1 and m2 represent group means and s is the pooled standard deviation. Effect sizes were calculated in a consistent manner so that in comparisons between control participants and treated clients, the control group's mean was always subtracted from the treatment group's mean. For comparisons between different types of treatments, such as between ERP and relaxation, one treatment group's mean was always subtracted from the other every time the two were compared (e.g., subtracting the ERP group's mean from the relaxation group's mean in every comparison between these two types of treatment). When group means, standard deviations, and sample size were not available, the statistical procedures described by Glass, McGaw, and Smith (1981 Chap. 5) were used to estimate the effect size. Where authors described results as “nonsignificant,” the effect size was conservatively estimated to be zero. Hedges' (1982, Formula 4) correction for small sample bias was applied to all effect sizes reported in this review.
Outcome data are likely to yield various results depending on whether they are obtained by means of clinician ratings or patient self-ratings. Because combining data across different modes of assessment is likely to introduce a measurement bias, effect sizes were only calculated for behavioral measures of OCD (e.g., time spent ritualizing) and for measures of OCD symptom severity with known psychometric properties (e.g., Yale–Brown Obsessive–Compulsive Scale [Y-BOCS]; Goodman, Price, Rasmussen, Mazure, et al., 1989). Additionally, the rater of each outcome measure (self or clinician assessed) was also coded. Because many studies used more than one outcome measure there were often multiple self- and clinician-rated effect sizes per treatment comparison. In these cases, effect sizes for each mode of assessment were averaged separately so that clinician- and patient-rated outcomes could be analyzed separately. Table 2 displays the outcome measures used to calculate effect sizes in this review.

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Table 2 Outcome Measures Used to Calculate Effect Sizes from OCD Treatment Studies
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Contrast of Medication Side Effects
Fisher and Greenberg (1993) suggested that the contrast in side-effect profiles between active medication and placebo might reveal to both the investigators and research participants which participants were receiving which treatments. As suggested by Greenberg et al. (1994), the proportion of patients in each group that reported the side effects variable was coded. The side-effect profile contrast within a comparison was defined as the difference between these proportions. For example, if .75 of a medicated group and .25 of a placebo group reported side effects, the side effect profile contrast for this comparison was .75 - .25, or .50. Of the 24 pharmacological studies, 21 provided enough information to estimate the proportion of participants in each group that reported side effects.
Results
Psychological Treatments
Table 3 shows the effect sizes for comparisons between psychological treatments. Except for one study (Fals-Stewart, Marks, & Schafer, 1993), all psychological treatment trials reported outcome on only self-rated measures. A particularly large effect favoring ERP was found in two comparisons to progressive muscle relaxation used as a control treatment. In contrast, a small and nonsignificant effect size in favor of cognitive therapy was found in comparisons between ERP and cognitive therapy. There was no reliable difference in efficacy between ERP and either exposure alone or response prevention alone.

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Table 3 Comparisons Between Psychological Treatments for Obsessive-Compulsive Disorder at Posttreatment
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Correlations were computed to examine the relationship between effect sizes for the treatment comparisons and the following study characteristics: year of publication, number of participants in the study, pretreatment duration of OCD symptoms, number of weeks of treatment, total number of hours in therapist-guided exposure, number of hours in therapist-guided exposure per week, total number of sessions, number of sessions per week, degree of response prevention, and dropout rate. A significant correlation was found between effect size and the total number of hours spent in therapist-guided exposure, r(8) = .87, p = .005. The more hours spent in therapist-guided exposure, the better the relative efficacy of the treatment procedure.
Pharmacological Treatments
Effect sizes for comparisons between pharmacological treatments appear in Table 4. On both self- and clinician-rated outcome measures, SRIs produced significant reductions in OCD symptoms at posttreatment, compared with placebo. Clomipramine's effect, as measured by clinician ratings, was the largest and most reliable of the SRIs. In contrast, small and nonsignificant effects were found in comparisons between non-SRIs and placebo. In trials that directly compared clomipramine with non-SRIs, both self- and clinician-rated outcomes yielded significant effect sizes in favor of clomipramine. This effect was large on patients' self ratings, yet only moderate on clinician-rated measures. No reliable difference was found between clomipramine and other SRIs.

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Table 4 Efficacy of Pharmacological Treatments for Obsessive-Compulsive Disorder at Posttreatment
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The mean contrast in side effects for each pharmacological treatment comparison is shown in the far right column of Table 4. The mean contrast within placebo-controlled studies of clomipramine (M = 0.54, SD = 0.20) was significantly larger than the mean contrast in studies that compared clomipramine with non-SRI medication (M = 0.12, SD = 0.06), F(6, 17) = 7.84, p < .001. Furthermore, for all pharmacotherapy studies that involved clomipramine, from which the contrast in side-effect profiles could be calculated, the correlation between effect size and side-effect contrast was r(10) = .92, p < .001. Thus, using clinician-rated measures, clomipramine was more effective in studies in which there were greater contrasts in the side-effect profiles between groups.
The mean clinician-rated effect size for clomipramine-versus-placebo trials, that would be predicted if the difference in side-effect profiles was equal to zero, was calculated from the regression equation for the relationship between effect size and side-effect contrast. An adjusted mean effect size of d = 0.83 was found. This is more similar to the patient-rated effect size found in comparisons between clomipramine and non-SRIs. It is also similar to the adjusted clinician-rated effect size for all trials of SRIs versus placebo, which was d = 0.80.
Correlations were computed to determine whether the following variables were related to effect size across all pharmacological trials: year of publication, average age of the subjects, pre-treatment OCD symptom duration, severity of depression in subjects, length of the trial, number of professional contacts during the trial, dosage of the medication, and side effect contrast. Only side-effect contrast was significantly correlated with effect size, r(21) = .62, p < .01. Across all pharmacological studies for which the side-effect contrast could be determined, larger effect sizes were associated with larger differences between groups in terms of relative proportion of participants who experienced side effects.
Discussion
The purpose of this research was to present a quantitative review of the controlled OCD treatment outcome literature. By calculating effect size as the standardized difference between treatments at posttest, rather than as the change from pre- to posttest, this review capitalized on the internal validity of randomized, controlled experiments. Meta-analytic techniques allowed for a quantitative summary of the effects of treatment variables across studies in which ERP procedures had been modified. These techniques were also used to assess the relationship between effect size and side effect profiles in pharmacological treatment trials.
Although the OCD outcome literature contains numerous uncontrolled single-group and case studies of psychological interventions, there have been relatively few randomized, controlled comparisons detailing the efficacy of these treatments. It is particularly surprising that there were only two trials comparing ERP with control treatments and none comparing ERP with no-treatment or waiting-list control groups. Although results from uncontrolled trials have suggested that the majority of OCD patients did experience at least moderate improvement when ERP procedures were used (e.g., Foa & Goldstein, 1978), a controlled research design that includes direct comparisons between a treated group and a control group would offer a more convincing argument that this treatment, rather than spontaneous fluctuations in symptoms, produces symptom relief.
The excellent improvement rates in OCD patients treated with ERP are among the most consistent findings in the literature on the treatment of behavior disorders. In agreement, we found that ERP produced substantial change relative to a progressive muscle relaxation control treatment. Although this conclusion is only based on two treatment trials, the importance of confronting feared stimuli for extinguishing anxiety is highlighted by many behaviorally oriented researchers (e.g., Foa & Kozak, 1986). Clear effects of exposure therapies have also been demonstrated in the treatment of social phobia (Feske & Chambliss, 1995) and agoraphobia (Emmelkamp & Kuipers, 1979).
The results of this review also suggest that cognitive approaches to treating OCD were at least as effective as exposure procedures. This is not in accord with previous reviewers' conclusions that ERP was more effective than other treatments (e.g., van Balkom et al., 1994). The use of REBT and cognitive interventions along the lines of Beck's (1976) therapy for depression (van Oppen & Arntz, 1994) have been developed from cognitive theories of OCD that emphasize the role of cognitive distortions about perceived responsibility and the overestimation of catastrophes (Salkovskis, 1985, 1989). In this review, all three of the studies that compared ERP with this type of cognitive intervention (Emmelkamp & Beens, 1991; Emmelkamp, Visser, & Hoekstra, 1988; van Oppen et al., 1995) reported a small advantage for the cognitive therapy. The only study in which there was no advantage for cognitive therapy used thought stopping, an imaginal technique aimed at reducing preoccupations with obsessional or compulsive thoughts (Hackman & McLean, 1975). Although thought stopping is often regarded as a weak intervention for OCD (Steketee, 1993), it was found to be equally as effective as ERP when directly compared.
As discussed above, cognitive therapy and ERP have been derived from distinct theoretical approaches to OCD. However, the finding that these interventions are equally effective leads to speculation about how these procedures work. One plausible explanation is that the treatments work by means of specific and distinct psychological mechanisms that happen to lead to similar degrees of improvement. An alternative interpretation is that the treatments share a common psychological mechanism. These hypotheses may be explored within the context of the present review.
If patients who received cognitive therapy responded significantly better on a cognitive measure than those who received ERP, and groups treated with ERP responded better on physiological measures of anxiety, it could be argued that the treatments work by means of distinct mechanisms. Of the studies included in this review that compared ERP and cognitive therapy, none assessed outcome with physiological measures. Only an Oppen et al. (1995) reported results on a cognitive outcome measure—the Irrational Beliefs Inventory (Koopmans, Sanderman, Timmerman, & Emmelkamp, 1994). However, no differences between the treatment groups were found on this measure at the end of treatment. van Oppen et al. (1995) also explored whether the two types of therapy had differential effects on obsessions or compulsions. However, no between-group differences were found on the obsessions or compulsions subscales of the Y-BOCS. At the present time, the available literature provides no support for the notion that cognitive therapy and ERP work by separate mechanisms.
The other possibility is that the two treatments share the same mechanism of change. Because the effects of ERP were quite robust compared with those of relaxation treatment (Fals-Stewart et al., 1993), one would presumably look beyond nonspecific factors such as the amount of time spent with the therapist or the simple discussion of symptoms. Close examination of the treatment protocols suggest that both cognitive therapy and ERP implicitly contain elements of each other. For example, REBT and thought stopping involve thinking about and processing situations that result in anxiety, similar to imaginal exposure procedures. van Oppen and Arntz's cognitive intervention involved live behavioral experiments that were “used to test out the empirical basis of dysfunctional assumptions” (1994, p. 381). This procedure appears comparable with in vivo exposure. Similarly, ERP may indirectly influence cognition. Foa and Kozak (1986) argued that the aim of prolonged exposure is to modify the patient's cognitive appraisal of threat. Furthermore, ERP protocols suggest the use of cognitive restructuring to persuade patients to attempt difficult exposures (Steketee, 1993). The procedural overlap and the similarity in efficacy suggest that ERP and cognitive therapy may share a common active ingredient. Cognitive therapy produces different beliefs by means of direct verbal challenges, and behavioral procedures provide exposure to conditions that lead to the disconfirmation of dysfunctional beliefs.
The procedures used for ERP treatment varied across the studies in this review. Only one variant was found to be significantly related to outcome. More time spent in therapist-assisted exposure was related to increased effectiveness of ERP. This result is supported by research that has demonstrated that longer exposure results in increased habituation to feared stimuli and better outcome (Foa & Chambliss, 1978). It is likely, however, that other variations affect outcome with ERP, such as in vivo or imaginal exposure, complete or partial response prevention, and home- or office-based treatment. Further investigation in this area may lead to uncovering whether specific types of OCD patients benefit from certain procedural variations.
Serotonergic medication was effective in reducing OCD symptoms, whereas nonserotonergic medication was not. On the basis of the placebo-controlled research, the medication associated with the greatest and most reliable symptom reduction was clomipramine. However, because the absolute effect sizes for fluoxetine and sertraline were computed using only two studies, caution in interpreting these effects is warranted. Overall, these results replicate previous quantitative reviews that also found larger effect sizes for serotonergic antidepressants, particularly clomipramine (Jenike, Baer, & Greist, 1990; van Balkom et al., 1994).
Is clomipramine more effective than other medications for reducing OCD symptoms? The present results suggest that the answer is yes; however, the difference between clomipramine and other SRIs may not be that large. Given the difference in clinician-rated effect sizes between placebo-controlled studies of clomipramine and those of non-SRIs, it was surprising that the advantage for clomipramine in head-to-head comparisons with non-SRIs, on clinician-rated measures, was only modest. As a possible explanation, I considered Fisher and Greenberg's (1993) suggestion that the difference in side-effect profiles between the active medication and placebo group compromises the “blindedness” in double-blind studies. Indeed, in my sample, the contrast in side-effect profiles within studies predicted relative treatment effectiveness. Considering the statistically significant difference in side effect profiles between placebo-controlled studies and direct comparisons between active medications, I interpreted this evidence to suggest that when two groups have markedly different side-effect profiles, such as in a placebo-controlled trial, there is potential for a loss of blindedness, which could give way to biases in favor of the active medication. In direct comparisons between clomipramine and other antidepressants, the ambiguity in side-effect symptoms was probably better at preserving the double-blind design. In further support of the idea that researchers are not necessarily “blind” in double-blind trials, clinician ratings of outcome produced larger significant effect sizes than patients' self ratings in comparisons between clomipramine and placebo. However, in direct comparisons between clomipramine and other medications, significant effect sizes for clinician ratings were smaller than self-ratings.
The mean effect size for clomipramine versus placebo when the difference between side-effect profiles in the placebo-controlled studies of clomipramine was statistically adjusted to zero was very similar to the adjusted mean for all of the SRIs. Thus, although clomipramine is clearly effective in reducing OCD symptoms, it may not be greatly superior to other serotonergic medications such as fluvoxamine, sertraline, or fluoxetine. To date, only two direct comparisons between clomipramine and other SRIs have been published (Pigott et al., 1990; Smiraldi et al., 1992). The collection of further data, with consideration to patient variables that likely moderate response to medication, should help to further clarify which SRI is likely to be of greatest benefit in severe cases of OCD.
An alternative explanation for these findings may be that higher blood levels of medication are related to both side effects and efficacy. This would also suggest that people who are helped by the medication are also those more likely to experience more serious side effects (Greenberg, Bornstein, Greenberg, & Fisher, 1992; Greenberg, Bornstein, Zborowski, et al., 1994).
The present findings could also be understood by the explanation that the efficacy of antidepressant medication is enhanced by its side effects. By such a mechanism, side effects act to distract antidepressant users from their usual daily routines. Therefore, the patient does not experience the usual cues that have generated obsessive-compulsive symptoms. Future work can pursue these hypotheses by including measures of drug plasma levels in results of studies. Currently, few studies report all of this information. In addition, the use of an active, side effect producing placebo has been suggested for use in double-blind studies to help make drug side effect profiles more ambiguous (Fisher & Greenberg, 1993). The potential for bias in clinician ratings can further be reduced with the use of computer interview methods such as the interactive computer administered version of the Y-BOCS (Rosenfeld, Dar, Anderson, Kobak, & Greist, 1992).
Overall, ERP and serotonergic medication appear to produce substantial OCD symptom reduction on their own at posttreatment. Unfortunately, follow-up data were not reported by enough studies to allow for meaningful analyses. Two additional studies have investigated the effects of combining psychological and pharmacological treatments; however, because of their complicated designs and the lack of clear control groups, these studies were omitted from the quantitative analyses. Nevertheless, a brief narrative summary of the findings in this area is appropriate. In short, Marks et al. (1988) concluded that exposure, when assigned for homework, enhanced the effects of clomipramine. Cottraux, Mollard, Bouvard, et al. (1990) found that the combination of fluvoxamine plus exposure was more effective than exposure plus placebo or than fluvoxamine plus a nonexposure procedure. A controlled comparison between combination treatments, single treatments, and placebo would best help in assessing the advantage of combining medication and cognitive–behavioral therapy.
The present analyses could not identify any patient variables that predicted outcome. This was probably because of the heterogeneity of the samples used in many of these treatment studies. Although I attempted to control for comorbid depression, given the high incidence of depressive symptoms in people with OCD, it is unknown how well this control was achieved. Consideration should be given to such variables in future outcome research so that particular aspects such as types of obsessions or compulsions, concurrent diagnoses, or insight into the irrationality of fears, can be isolated as predictors of response to psychological treatments.
Additionally, no treatment studies that directly compare medication to ERP currently exist in the published literature. For determining the relative efficacy of these two treatments, such a design is needed. Advantages of such a study might also help to identify characteristics of patients with severe cases of OCD who benefit most from ERP or who require medication. In this era of increasing popularity of medication for the treatment of behavior disorders, future research on behaviorally oriented treatments seems to be a worthy endeavor.
References
References marked with an asterisk indicate studies included in the meta-analysis.
American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: Author. [Context Link]
*Anath, J., Pecknold, J. C., van den Steen, N., & Engelsmann, F. (1981). Double-blind comparative study of clomipramine and amitriptyline in obsessive neurosis. Progress in Neuro-Psychopharmacology, 5, 257–262.
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1This intervention was formerly known as rational-emotive therapy (RET). [Context Link]
2The issue-by-issue search was conducted for the following journals: American Journal of Psychiatry; Archives of General Psychiatry; Behavior Therapy; Behavior Research and Therapy; British Journal of Clinical Psychology; British Journal of Psychiatry; Journal of Behavior Therapy and Experimental Psychiatry; Journal of Clinical Psychology; Journal of Consulting and Clinical Psychology; Journal of Nervous and Mental Disease; and Psychopharmacology Bulletin. [Context Link]
3Jonathan S. Abramowitz. [Context Link]
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