ABSTRACT

BACKGROUND: Age-related macular degeneration (ARMD) is the leading cause of blindness in the United States among people aged 65 years or older. Observational and experimental data suggest that antioxidant or zinc supplements may delay progression of ARMD and visual loss.

POPULATION STUDIED: Eleven retinal specialty clinics enrolled participants aged 55 to 80 years in 4 ARMD categories determined by the size and extent of drusen and retinal pigment epithelial abnormalities in each eye, the presence of advanced ARMD (each determined by evaluation of color photographs at a reading center), and visual acuity. Persons in category 1 had no ARMD; those in category 2 had mild or borderline ARMD; those in category 3 had moderate ARMD; and those in category 4 had advanced ARMD. At least 1 eye had a best corrected visual acuity of 20/32 or better (the study eye). Among participants, 56% were women, 96% were white, and the median age was 69 years. Potential participants were excluded for illness or disorders (history of cancer with a poor 7-year prognosis, major cardiovascular or cerebrovascular event within the previous year, or hemochromatosis) that would have made long-term follow-up or compliance with the study protocol unlikely or difficult.

STUDY DESIGN AND VALIDITY: This was a randomized, double-masked, placebo-controlled trial (concealed allocation assignment). Participants were assigned to 1 of 4 treatment groups: (1) antioxidants (500 mg vitamin C, 400 IU vitamin E, 15 mg beta carotene); (2) 80 mg zinc as zinc oxide and copper, 2 mg as cupric oxide; (3) antioxidants plus zinc; or (4) placebo. The groups did not differ in their baseline characteristics. Average follow-up was 6.3 years, with 2.4% lost to follow-up. Analysis was by intention to treat. The judicial assessors of outcomes were masked to treatment group assignment.

OUTCOMES MEASURED: Two primary outcomes were defined for study eyes in the ARMD trial: (1) progression to advanced ARMD and (2) at least a 15-letter decrease in visual acuity score.

RESULTS: Patients with no ARMD (category 1) and mild or borderline ARMD (category 2) did not benefit from antioxidant and/or zinc supplementation. However, participants in the moderate and advanced ARMD groups (categories 3 and 4) had a lower risk of progression to advanced ARMD and visual acuity loss in the good eye if they took both zinc and antioxidants compared with placebo for 7 years (35.7% vs 26.7%, respectively; P < .001; number needed to treat = 11).

ABSTRACT

BACKGROUND: Age-related macular degeneration (ARMD) is the leading cause of blindness in the United States among people aged 65 years or older. Observational and experimental data suggest that antioxidant or zinc supplements may delay progression of ARMD and visual loss.

POPULATION STUDIED: Eleven retinal specialty clinics enrolled participants aged 55 to 80 years in 4 ARMD categories determined by the size and extent of drusen and retinal pigment epithelial abnormalities in each eye, the presence of advanced ARMD (each determined by evaluation of color photographs at a reading center), and visual acuity. Persons in category 1 had no ARMD; those in category 2 had mild or borderline ARMD; those in category 3 had moderate ARMD; and those in category 4 had advanced ARMD. At least 1 eye had a best corrected visual acuity of 20/32 or better (the study eye). Among participants, 56% were women, 96% were white, and the median age was 69 years. Potential participants were excluded for illness or disorders (history of cancer with a poor 7-year prognosis, major cardiovascular or cerebrovascular event within the previous year, or hemochromatosis) that would have made long-term follow-up or compliance with the study protocol unlikely or difficult.

STUDY DESIGN AND VALIDITY: This was a randomized, double-masked, placebo-controlled trial (concealed allocation assignment). Participants were assigned to 1 of 4 treatment groups: (1) antioxidants (500 mg vitamin C, 400 IU vitamin E, 15 mg beta carotene); (2) 80 mg zinc as zinc oxide and copper, 2 mg as cupric oxide; (3) antioxidants plus zinc; or (4) placebo. The groups did not differ in their baseline characteristics. Average follow-up was 6.3 years, with 2.4% lost to follow-up. Analysis was by intention to treat. The judicial assessors of outcomes were masked to treatment group assignment.

OUTCOMES MEASURED: Two primary outcomes were defined for study eyes in the ARMD trial: (1) progression to advanced ARMD and (2) at least a 15-letter decrease in visual acuity score.

RESULTS: Patients with no ARMD (category 1) and mild or borderline ARMD (category 2) did not benefit from antioxidant and/or zinc supplementation. However, participants in the moderate and advanced ARMD groups (categories 3 and 4) had a lower risk of progression to advanced ARMD and visual acuity loss in the good eye if they took both zinc and antioxidants compared with placebo for 7 years (35.7% vs 26.7%, respectively; P < .001; number needed to treat = 11).

ABSTRACT

BACKGROUND: Age-related macular degeneration (ARMD) is the leading cause of blindness in the United States among people aged 65 years or older. Observational and experimental data suggest that antioxidant or zinc supplements may delay progression of ARMD and visual loss.

POPULATION STUDIED: Eleven retinal specialty clinics enrolled participants aged 55 to 80 years in 4 ARMD categories determined by the size and extent of drusen and retinal pigment epithelial abnormalities in each eye, the presence of advanced ARMD (each determined by evaluation of color photographs at a reading center), and visual acuity. Persons in category 1 had no ARMD; those in category 2 had mild or borderline ARMD; those in category 3 had moderate ARMD; and those in category 4 had advanced ARMD. At least 1 eye had a best corrected visual acuity of 20/32 or better (the study eye). Among participants, 56% were women, 96% were white, and the median age was 69 years. Potential participants were excluded for illness or disorders (history of cancer with a poor 7-year prognosis, major cardiovascular or cerebrovascular event within the previous year, or hemochromatosis) that would have made long-term follow-up or compliance with the study protocol unlikely or difficult.

STUDY DESIGN AND VALIDITY: This was a randomized, double-masked, placebo-controlled trial (concealed allocation assignment). Participants were assigned to 1 of 4 treatment groups: (1) antioxidants (500 mg vitamin C, 400 IU vitamin E, 15 mg beta carotene); (2) 80 mg zinc as zinc oxide and copper, 2 mg as cupric oxide; (3) antioxidants plus zinc; or (4) placebo. The groups did not differ in their baseline characteristics. Average follow-up was 6.3 years, with 2.4% lost to follow-up. Analysis was by intention to treat. The judicial assessors of outcomes were masked to treatment group assignment.

OUTCOMES MEASURED: Two primary outcomes were defined for study eyes in the ARMD trial: (1) progression to advanced ARMD and (2) at least a 15-letter decrease in visual acuity score.

RESULTS: Patients with no ARMD (category 1) and mild or borderline ARMD (category 2) did not benefit from antioxidant and/or zinc supplementation. However, participants in the moderate and advanced ARMD groups (categories 3 and 4) had a lower risk of progression to advanced ARMD and visual acuity loss in the good eye if they took both zinc and antioxidants compared with placebo for 7 years (35.7% vs 26.7%, respectively; P < .001; number needed to treat = 11).

When you suspect a patient has obsessive-compulsive disorder (OCD) (Box 1), how can you differentiate OCD from psychosis? Once you have made the diagnosis, what critical factors suggest treatment will be successful—or unsuccessful? Is behavioral therapy more effective than medication? Which medications are most likely to be effective? The answers to these questions can help you improve the well-being of your patients with OCD.

Differential diagnosis

Unfortunately, many patients with severe OCD are misdiagnosed with psychosis or schizophrenia spectrum disorder and spend many years suffering without proper treatment.³ Despite many similarities between patients with severe OCD and psychosis—including rigid belief systems, unrealistic concerns, magical thinking, and odd behaviors—patients with OCD can recognize the irrational nature of their beliefs when they are not in the throes of anxiety.

Patients with OCD also will usually respond to behavioral interventions within a few weeks while patients who are psychotic usually get progressively worse. Treatment must be given time as both cohorts will get anxious or increase their negative symptoms initially, but patients with OCD should soon habituate and find symptom relief.

Some patients have OCD with psychotic features and tend to have more difficulty responding to behavior therapy without medication. Patients with both OCD and schizotypal personalities respond poorly to both behavior therapy and psychotropic medications.⁴

Box 1

Predictors for successful treatment

Insight Researchers³ found that about 52% of patients with insight into the reasonableness of their obsessions responded to medications, while none who lacked insight responded. Therefore, it pays to assess patients’ insight and ability to recognize the long-term consequences of OCD to themselves and those around them.

Some patients who have suffered with treatment-refractory OCD for most of their lives lack a premorbid high level of functioning to serve as a reference for normalized behavior. Educating these patients to see the advantages of living without certain negative behaviors improves their receptivity to treatment.

Patients who lack insight often refuse to acknowledge that many of their behaviors are manifestations of OCD. Such patients, however, are usually more amenable to giving up or modifying their dysfunctional behaviors—and the clinician more likely to avoid confrontations—if they are shown how certain behaviors undermine their goals.

Cost-benefit analysis Because of the aversive nature of exposure and response prevention therapy (ERP) and the negative side effects of many medications, some patients may find it easier to live with their symptoms, as painful as they are, rather than undergo the discomfort of behavior therapy. Because the prognosis is poor in such cases, patients need to be convinced that the discomfort of treatment is merely short-term, while the discomfort of the illness could last forever if left untreated.

Motivation In our experience, motivation has played a crucial role in determining treatment outcome for severe refractory OCD. And regardless of the severity of their symptoms, patients who are fed up with their symptoms, or are tired of living a life controlled by their obsessions, usually are excellent candidates for treatment.

Conversely, those who enter treatment as a result of external pressure from spouses or family face a less positive prognosis. High emotional expressiveness, overinvolvement, and hostility by relatives is related to higher attrition rates in treatment.³ Because ERP is so aversive, these patients will find ways to dilute the treatment’s effectiveness. In many cases, they do the minimal amount of work required to stay in treatment to avoid whatever consequences their families would impose for not adhering to treatment.

One marker to assess compliance is whether the clinician feels he or she is investing more time and effort into the patient’s treatment than the patient is. If so, this should be addressed in a timely manner. Also, sporadic attendance at sessions and noncompliance with medications, homework, and behavior therapy assignments may also portend a poor outcome. Remember, though, that noncompliance and lack of motivation are fluid states; many previously noncompliant patients later return to treatment better motivated and more compliant.

Predictors for a lower success rate

Secondary gain Researchers⁴ found that patients who were enabled by their families had more severe symptoms than those who were not. These relational and environmental factors should be discussed openly. If the patient finds that many of his or her life needs are being met secondary to the illness, that patient might not agree to an aversive treatment.

To overcome this, urge family members or other individuals who provide dysfunctional reinforcers to remove them from the environment. Meet with the patient and family/friends and frankly point out dysfunctional gains and the ways in which family members unknowingly allow the gains to continue (e.g., giving the patient more money after he or she overspent his or her allowance). A family behavioral contract should be devised to address how these gains will be reasonably eliminated.

Recognize, too, that a patient may find it difficult to give up the secondary gains, detrimental as they may be, without adequate skills or coping mechanisms to fill the void. So in some cases, it is best not to remove all the secondary gains at once; this can cause many patients to terminate treatment prematurely.

Trauma or abuse history Many patients with treatment refractory OCD have trauma histories and cannot habituate to the behavioral tasks because of dissociation, emotional numbing, or some form of distraction that mediates their anxiety and prevents proper habituation. If the patient is adequately complying with the exposures, yet still is unable to confront every feared stimulus, inquire about a trauma or abuse history (Box 2).

Substance abuse The stress that is inherent to ERP can cause many patients to relapse or abuse illicit substances to manage their anxiety. Therefore, patients with severe substance abuse problems often have great difficulty handling ERP, as they are asked to experience the very discomfort that initially caused them to abuse drugs and alcohol.

Box 2

In such cases, a patient cannot realistically be asked to give up a coping mechanism, faulty as it may be, until a more functional reinforcer takes its place. Hence, skills training is a crucial part of treatment for this group.

Residential treatment for OCD patients with comorbid substance abuse in remission may be necessary to ensure a positive outcome. Patients should continue recovery work concurrent to behavior therapy to prevent relapse.

High-risk OCD symptoms Patients who have more traditional OCD symptoms usually have a good prognosis. Unfortunately some symptoms do not respond to ERP treatment. These include:

• Repeating, hoarding, and symmetry. Though evidence suggests that hoarding is predictive of poor outcomes,⁵ treatment carried out in the home can be effective over a 24-week trial.⁶
• Incompletion, or the need for things to feel right.
• Rigid and overvalued belief systems.
• Sexual and religious obsessions. These appear to be more resistant to behavior therapy and selective serotonin reuptake inhibitors (SSRIs).⁷

More research needs to be conducted to offer patients with these symptoms better respite.

Researchers also found that patients with childhood and adolescent onset of symptoms, tics, history of hospitalization, and terminated treatment against medical advice are more likely than other OCD patients to develop more severe symptoms in adulthood.⁸ Patients with OCD who also suffer from generalized anxiety disorders are more likely than those without GAD to drop out of treatment.⁹

Behavior therapy: first choice

ERP is considered the premier treatment for OCD and is suitable for both adults and children.¹⁰ Exposure forces patients to confront their feared stimuli. Response prevention blocks patients from engaging in compulsions or avoidance behaviors intended to reduce their discomfort. Patients are asked to identify situations that trigger their obsession and compulsions and rank them along a fear hierarchy. Patients confront a moderately rated situation and, once they become habituated to it, move up the fear hierarchy to the next situation.

ERP has been proven effective for OCD not only as an individual behavior treatment, but also when done in a group setting¹¹ or when delivered online or by telephone.¹²

Table 1

Dosage levels for SRIs in OCD

Some clinicians prefer cognitive behavioral therapy (CBT) to ERP because it is less aversive. Researchers found that patients who were treated with either CBT or ERP improved. Patients treated with ERP, however, were more likely to maintain their gains in recovery 3 months after treatment concluded.¹³ Evidence suggests that ERP or CBT when implemented alone, or when applied in conjunction with fluvoxamine,¹⁴ are equally effective.

ERP should be managed only by clinicians specially trained in this modality. Several treatment centers across the country provide specialized care for OCD patients. For the nearest treatment center in your community that accepts referrals for ERP, contact the OC Foundation in North Branford, Conn. (See Related Resources.)

Medication for OCD: SRIs as first-line therapy

Experts agree that first-line somatic treatments for OCD include not only behavior therapy but also serotonin reuptake inhibitors (SRIs),¹⁵ that is, clomipramine or selective serotonin reuptake inhibitors, (SSRIs) (Table 1).

Caution: Many patients who “respond” to treatment in clinical studies remain symptomatic and meaningfully affected by their residual illness. Therefore, it is critical that you inform patients at the outset that 100% reduction in symptoms is rare.

SRIs Overwhelming evidence from multiple randomized, double-blind, placebo-controlled studies support the efficacy of SRIs. In adults, well-designed and controlled trials have demonstrated the relative efficacy of clomipramine, fluoxetine, sertraline, paroxetine, and fluvoxamine vs. placebo.

SRIs also have been shown to be significantly more effective than tricyclic antidepressants (TCAs) in both placebo-controlled and non-placebo-controlled studies.

Despite initial reports that clomipramine may be more effective than SSRIs, a growing number of studies and a recent comprehensive literature review suggest that the SRIs all have comparable efficacy.¹⁶ Because clomipramine has significantly more anticholinergic- and antiadrenergic-mediated side effects than the SSRIs, however, many clinicians choose SSRIs as the initial agent.

When using SRIs, remember that response is typically delayed; an adequate trial requires at least 10 weeks. Indeed, a meaningful proportion of responders continue to emerge past the 8-week mark. Experts suggest that optimal dosages of SRIs for OCD may exceed those typically used for major depression. Guidelines for SRI dosage ranges for OCD appear in (Table 1).

Data regarding treatment duration also suggest that discontinuation of SRIs results in a high relapse rate, though the use of lower maintenance dosages of SRIs is still debated.

Table 2

Ratings of SRI-augmenting agents for OCD treatment

Augmentation of SRIs When first-line interventions fail, second-line pharmacological approaches include augmentation of SRIs with additional medications (Table 2). Numerous agents have been tried for patients who were unresponsive or only partially responsive to SRIs alone.¹⁷ Few controlled trials of such strategies have been conducted, however. The most impressive data document the benefits of adding low doses of dopamine antagonists (both conventional and atypical neuroleptics).

Table 3

Using alternative monotherapies

Recent uncontrolled studies of augmentation with atypical neuroleptics have yielded encouraging preliminary results, as has one controlled trial of augmentation of an SRI with risperidone. Other data suggest that lithium, buspirone, and clonazepam may also be effective.

Numerous other agents have been tried in combination with SRIs, including clonidine, tryptophan, fenfluramine, pindolol, trazodone, nortriptyline, and other antidepressants. The small number of subjects, lack of sufficient controls, and mixed results preclude drawing even preliminary conclusions as to the potential efficacy of such strategies.

Alternative Monotherapies For patients who do not respond satisfactorily to trials of SRIs alone or to augmentation strategies, consider alternative monotherapies in place of SRIs (Table 3). In addition to uncontrolled data, positive controlled studies lend some support for trials of clonazepam, monoamine oxidase (MAO) inhibitors, and buspirone.

Pertinent negative findings are worthy of mention. In contrast to promising results with risperidone as an augmenter, an open trial of the atypical antipsychotic clozapine suggests inefficacy as a monotherapy. Several case reports suggest that clozapine can actually precipitate obsessive-compulsive symptoms in patients with psychotic disorders.¹⁸ Controlled trials have not demonstrated the efficacy of trazodone, clonidine, and diphenhydramine as monotherapies.

Pharmacotherapy + or vs. behavioral therapy

Only a few studies directly comparing behavior therapy vs. medication have been reported. In practice, the two are routinely used in concert. Experts have long recommended this treatment approach. Two recent studies^19,20 have demonstrated that the combination is more effective than either treatment alone.

In another study, behavior therapy significantly outperformed clomipramine; no significant incremental benefit was seen from the two treatments in combination.²¹ However, the dosages of clomipramine were relatively low (mean=164 mg/d and maximum=225 mg/d) and of inadequate duration (6 weeks). Still another older head-to-head comparison of behavior therapy and clomipramine showed that medication was better for reducing obsessional doubt, whereas behavior therapy more effectively reduced compulsive rituals.

Third-line treatments may include the unproven augmentation therapies described above, or intravenous clomipramine if available.²²

Treatments of last resort

Finally, other nonpharmacologic treatments, including neurosurgery and electroconvulsive therapy (ECT), have remained controversial and are reserved for particular clinical situations or as treatments of last resort.

Despite a large body of uncontrolled data reporting antiobsessional benefits from a variety of neurosurgical procedures, ethical considerations and technical limitations have precluded the performance of sham-controlled studies to definitively establish the efficacy of these strategies.

Neurosurgical treatment of OCD is reserved for patients with severe and debilitating illness who have failed an exhaustive array of other available treatment options and who provide informed consent or assent. Currently, the most commonly employed neurosurgical treatments for OCD include anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leukotomy. In recent prospective trials of cingulotomy and capsulotomy, approximately 45% of patients experienced a 35% or more symptom reduction.

With the advent of innovative surgical devices that allow functional neurosurgery without craniotomy (e.g., by gamma knife), the performance of ethical, double-blind, sham-controlled trials of neurosurgery for OCD is now feasible. A team of investigators from Brown University and Massachusetts General Hospital is conducting one such study that tests the efficacy of anterior capsulotomy.

There are no controlled data regarding the efficacy of ECT for OCD. Given the high comorbidity of major affective illness in OCD and the well-established efficacy of ECT for major depression, it is not surprising that some patients with OCD have reportedly shown clinical improvement after ECT. Several limited case series and anecdotal reports suggest that ECT may help in some circumstances, and such intervention would seem prudent in some cases where severe, comorbid affective illness is present.²³

Related resources

• Jenike MA, Baer, L, Minichiello WE, eds. Obsessive Compulsive Disorders: Practical Management. 3rd ed. Boston: Mosby, 1998.
• Jenike MA. An update on obsessive-compulsive disorder. Bulletin of the Menninger Clinic. 2001;65:4-25.
• Obsessive-Compulsive Foundation, (203) 315-2190, www.ocfoundation.org

Drug brand names

• Buspirone • BuSpar, BuSpar DIVIDOSE
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clonazepam • Ativar, Diastat, Halcion
• Clonidine • Catapres, Catapres TTS-1
• Clozapine • Clozaril
• Fenfluramine • Pondimin
• Fluoxetine • Prozac, Prozac Weekly
• Fluvoxamine • Luvox
• Paroxetine • Paxil
• Phenelzine • Nardil, Parnate
• Pindolol • Inderol, Corgard, Betaloc
• Risperidone • Risperidal
• Sertaline • Zoloft
• Trazodone • Desyrel
• Tryptophan* • L-Tryptophan, Alti-trytophan

Disclosure

Dr. Boxill and Ms. Shapiro report no affiliation or financial arrangement with any of the companies whose products are mentioned in this article.

Dr. Dougherty reports conflicts of interest with Pfizer Inc., Forest Pharmaceuticals, and Solvay Pharmaceuticals.

When you suspect a patient has obsessive-compulsive disorder (OCD) (Box 1), how can you differentiate OCD from psychosis? Once you have made the diagnosis, what critical factors suggest treatment will be successful—or unsuccessful? Is behavioral therapy more effective than medication? Which medications are most likely to be effective? The answers to these questions can help you improve the well-being of your patients with OCD.

Differential diagnosis

Unfortunately, many patients with severe OCD are misdiagnosed with psychosis or schizophrenia spectrum disorder and spend many years suffering without proper treatment.³ Despite many similarities between patients with severe OCD and psychosis—including rigid belief systems, unrealistic concerns, magical thinking, and odd behaviors—patients with OCD can recognize the irrational nature of their beliefs when they are not in the throes of anxiety.

Patients with OCD also will usually respond to behavioral interventions within a few weeks while patients who are psychotic usually get progressively worse. Treatment must be given time as both cohorts will get anxious or increase their negative symptoms initially, but patients with OCD should soon habituate and find symptom relief.

Some patients have OCD with psychotic features and tend to have more difficulty responding to behavior therapy without medication. Patients with both OCD and schizotypal personalities respond poorly to both behavior therapy and psychotropic medications.⁴

Box 1

Predictors for successful treatment

Insight Researchers³ found that about 52% of patients with insight into the reasonableness of their obsessions responded to medications, while none who lacked insight responded. Therefore, it pays to assess patients’ insight and ability to recognize the long-term consequences of OCD to themselves and those around them.

Some patients who have suffered with treatment-refractory OCD for most of their lives lack a premorbid high level of functioning to serve as a reference for normalized behavior. Educating these patients to see the advantages of living without certain negative behaviors improves their receptivity to treatment.

Patients who lack insight often refuse to acknowledge that many of their behaviors are manifestations of OCD. Such patients, however, are usually more amenable to giving up or modifying their dysfunctional behaviors—and the clinician more likely to avoid confrontations—if they are shown how certain behaviors undermine their goals.

Cost-benefit analysis Because of the aversive nature of exposure and response prevention therapy (ERP) and the negative side effects of many medications, some patients may find it easier to live with their symptoms, as painful as they are, rather than undergo the discomfort of behavior therapy. Because the prognosis is poor in such cases, patients need to be convinced that the discomfort of treatment is merely short-term, while the discomfort of the illness could last forever if left untreated.

Motivation In our experience, motivation has played a crucial role in determining treatment outcome for severe refractory OCD. And regardless of the severity of their symptoms, patients who are fed up with their symptoms, or are tired of living a life controlled by their obsessions, usually are excellent candidates for treatment.

Conversely, those who enter treatment as a result of external pressure from spouses or family face a less positive prognosis. High emotional expressiveness, overinvolvement, and hostility by relatives is related to higher attrition rates in treatment.³ Because ERP is so aversive, these patients will find ways to dilute the treatment’s effectiveness. In many cases, they do the minimal amount of work required to stay in treatment to avoid whatever consequences their families would impose for not adhering to treatment.

One marker to assess compliance is whether the clinician feels he or she is investing more time and effort into the patient’s treatment than the patient is. If so, this should be addressed in a timely manner. Also, sporadic attendance at sessions and noncompliance with medications, homework, and behavior therapy assignments may also portend a poor outcome. Remember, though, that noncompliance and lack of motivation are fluid states; many previously noncompliant patients later return to treatment better motivated and more compliant.

Predictors for a lower success rate

Secondary gain Researchers⁴ found that patients who were enabled by their families had more severe symptoms than those who were not. These relational and environmental factors should be discussed openly. If the patient finds that many of his or her life needs are being met secondary to the illness, that patient might not agree to an aversive treatment.

To overcome this, urge family members or other individuals who provide dysfunctional reinforcers to remove them from the environment. Meet with the patient and family/friends and frankly point out dysfunctional gains and the ways in which family members unknowingly allow the gains to continue (e.g., giving the patient more money after he or she overspent his or her allowance). A family behavioral contract should be devised to address how these gains will be reasonably eliminated.

Recognize, too, that a patient may find it difficult to give up the secondary gains, detrimental as they may be, without adequate skills or coping mechanisms to fill the void. So in some cases, it is best not to remove all the secondary gains at once; this can cause many patients to terminate treatment prematurely.

Trauma or abuse history Many patients with treatment refractory OCD have trauma histories and cannot habituate to the behavioral tasks because of dissociation, emotional numbing, or some form of distraction that mediates their anxiety and prevents proper habituation. If the patient is adequately complying with the exposures, yet still is unable to confront every feared stimulus, inquire about a trauma or abuse history (Box 2).

Substance abuse The stress that is inherent to ERP can cause many patients to relapse or abuse illicit substances to manage their anxiety. Therefore, patients with severe substance abuse problems often have great difficulty handling ERP, as they are asked to experience the very discomfort that initially caused them to abuse drugs and alcohol.

Box 2

In such cases, a patient cannot realistically be asked to give up a coping mechanism, faulty as it may be, until a more functional reinforcer takes its place. Hence, skills training is a crucial part of treatment for this group.

Residential treatment for OCD patients with comorbid substance abuse in remission may be necessary to ensure a positive outcome. Patients should continue recovery work concurrent to behavior therapy to prevent relapse.

High-risk OCD symptoms Patients who have more traditional OCD symptoms usually have a good prognosis. Unfortunately some symptoms do not respond to ERP treatment. These include:

• Repeating, hoarding, and symmetry. Though evidence suggests that hoarding is predictive of poor outcomes,⁵ treatment carried out in the home can be effective over a 24-week trial.⁶
• Incompletion, or the need for things to feel right.
• Rigid and overvalued belief systems.
• Sexual and religious obsessions. These appear to be more resistant to behavior therapy and selective serotonin reuptake inhibitors (SSRIs).⁷

More research needs to be conducted to offer patients with these symptoms better respite.

Researchers also found that patients with childhood and adolescent onset of symptoms, tics, history of hospitalization, and terminated treatment against medical advice are more likely than other OCD patients to develop more severe symptoms in adulthood.⁸ Patients with OCD who also suffer from generalized anxiety disorders are more likely than those without GAD to drop out of treatment.⁹

Behavior therapy: first choice

ERP is considered the premier treatment for OCD and is suitable for both adults and children.¹⁰ Exposure forces patients to confront their feared stimuli. Response prevention blocks patients from engaging in compulsions or avoidance behaviors intended to reduce their discomfort. Patients are asked to identify situations that trigger their obsession and compulsions and rank them along a fear hierarchy. Patients confront a moderately rated situation and, once they become habituated to it, move up the fear hierarchy to the next situation.

ERP has been proven effective for OCD not only as an individual behavior treatment, but also when done in a group setting¹¹ or when delivered online or by telephone.¹²

Table 1

Dosage levels for SRIs in OCD

Some clinicians prefer cognitive behavioral therapy (CBT) to ERP because it is less aversive. Researchers found that patients who were treated with either CBT or ERP improved. Patients treated with ERP, however, were more likely to maintain their gains in recovery 3 months after treatment concluded.¹³ Evidence suggests that ERP or CBT when implemented alone, or when applied in conjunction with fluvoxamine,¹⁴ are equally effective.

ERP should be managed only by clinicians specially trained in this modality. Several treatment centers across the country provide specialized care for OCD patients. For the nearest treatment center in your community that accepts referrals for ERP, contact the OC Foundation in North Branford, Conn. (See Related Resources.)

Medication for OCD: SRIs as first-line therapy

Experts agree that first-line somatic treatments for OCD include not only behavior therapy but also serotonin reuptake inhibitors (SRIs),¹⁵ that is, clomipramine or selective serotonin reuptake inhibitors, (SSRIs) (Table 1).

Caution: Many patients who “respond” to treatment in clinical studies remain symptomatic and meaningfully affected by their residual illness. Therefore, it is critical that you inform patients at the outset that 100% reduction in symptoms is rare.

SRIs Overwhelming evidence from multiple randomized, double-blind, placebo-controlled studies support the efficacy of SRIs. In adults, well-designed and controlled trials have demonstrated the relative efficacy of clomipramine, fluoxetine, sertraline, paroxetine, and fluvoxamine vs. placebo.

SRIs also have been shown to be significantly more effective than tricyclic antidepressants (TCAs) in both placebo-controlled and non-placebo-controlled studies.

Despite initial reports that clomipramine may be more effective than SSRIs, a growing number of studies and a recent comprehensive literature review suggest that the SRIs all have comparable efficacy.¹⁶ Because clomipramine has significantly more anticholinergic- and antiadrenergic-mediated side effects than the SSRIs, however, many clinicians choose SSRIs as the initial agent.

When using SRIs, remember that response is typically delayed; an adequate trial requires at least 10 weeks. Indeed, a meaningful proportion of responders continue to emerge past the 8-week mark. Experts suggest that optimal dosages of SRIs for OCD may exceed those typically used for major depression. Guidelines for SRI dosage ranges for OCD appear in (Table 1).

Data regarding treatment duration also suggest that discontinuation of SRIs results in a high relapse rate, though the use of lower maintenance dosages of SRIs is still debated.

Table 2

Ratings of SRI-augmenting agents for OCD treatment

Augmentation of SRIs When first-line interventions fail, second-line pharmacological approaches include augmentation of SRIs with additional medications (Table 2). Numerous agents have been tried for patients who were unresponsive or only partially responsive to SRIs alone.¹⁷ Few controlled trials of such strategies have been conducted, however. The most impressive data document the benefits of adding low doses of dopamine antagonists (both conventional and atypical neuroleptics).

Table 3

Using alternative monotherapies

Recent uncontrolled studies of augmentation with atypical neuroleptics have yielded encouraging preliminary results, as has one controlled trial of augmentation of an SRI with risperidone. Other data suggest that lithium, buspirone, and clonazepam may also be effective.

Numerous other agents have been tried in combination with SRIs, including clonidine, tryptophan, fenfluramine, pindolol, trazodone, nortriptyline, and other antidepressants. The small number of subjects, lack of sufficient controls, and mixed results preclude drawing even preliminary conclusions as to the potential efficacy of such strategies.

Alternative Monotherapies For patients who do not respond satisfactorily to trials of SRIs alone or to augmentation strategies, consider alternative monotherapies in place of SRIs (Table 3). In addition to uncontrolled data, positive controlled studies lend some support for trials of clonazepam, monoamine oxidase (MAO) inhibitors, and buspirone.

Pertinent negative findings are worthy of mention. In contrast to promising results with risperidone as an augmenter, an open trial of the atypical antipsychotic clozapine suggests inefficacy as a monotherapy. Several case reports suggest that clozapine can actually precipitate obsessive-compulsive symptoms in patients with psychotic disorders.¹⁸ Controlled trials have not demonstrated the efficacy of trazodone, clonidine, and diphenhydramine as monotherapies.

Pharmacotherapy + or vs. behavioral therapy

Only a few studies directly comparing behavior therapy vs. medication have been reported. In practice, the two are routinely used in concert. Experts have long recommended this treatment approach. Two recent studies^19,20 have demonstrated that the combination is more effective than either treatment alone.

In another study, behavior therapy significantly outperformed clomipramine; no significant incremental benefit was seen from the two treatments in combination.²¹ However, the dosages of clomipramine were relatively low (mean=164 mg/d and maximum=225 mg/d) and of inadequate duration (6 weeks). Still another older head-to-head comparison of behavior therapy and clomipramine showed that medication was better for reducing obsessional doubt, whereas behavior therapy more effectively reduced compulsive rituals.

Third-line treatments may include the unproven augmentation therapies described above, or intravenous clomipramine if available.²²

Treatments of last resort

Finally, other nonpharmacologic treatments, including neurosurgery and electroconvulsive therapy (ECT), have remained controversial and are reserved for particular clinical situations or as treatments of last resort.

Despite a large body of uncontrolled data reporting antiobsessional benefits from a variety of neurosurgical procedures, ethical considerations and technical limitations have precluded the performance of sham-controlled studies to definitively establish the efficacy of these strategies.

Neurosurgical treatment of OCD is reserved for patients with severe and debilitating illness who have failed an exhaustive array of other available treatment options and who provide informed consent or assent. Currently, the most commonly employed neurosurgical treatments for OCD include anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leukotomy. In recent prospective trials of cingulotomy and capsulotomy, approximately 45% of patients experienced a 35% or more symptom reduction.

With the advent of innovative surgical devices that allow functional neurosurgery without craniotomy (e.g., by gamma knife), the performance of ethical, double-blind, sham-controlled trials of neurosurgery for OCD is now feasible. A team of investigators from Brown University and Massachusetts General Hospital is conducting one such study that tests the efficacy of anterior capsulotomy.

There are no controlled data regarding the efficacy of ECT for OCD. Given the high comorbidity of major affective illness in OCD and the well-established efficacy of ECT for major depression, it is not surprising that some patients with OCD have reportedly shown clinical improvement after ECT. Several limited case series and anecdotal reports suggest that ECT may help in some circumstances, and such intervention would seem prudent in some cases where severe, comorbid affective illness is present.²³

Related resources

• Jenike MA, Baer, L, Minichiello WE, eds. Obsessive Compulsive Disorders: Practical Management. 3rd ed. Boston: Mosby, 1998.
• Jenike MA. An update on obsessive-compulsive disorder. Bulletin of the Menninger Clinic. 2001;65:4-25.
• Obsessive-Compulsive Foundation, (203) 315-2190, www.ocfoundation.org

Drug brand names

• Buspirone • BuSpar, BuSpar DIVIDOSE
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clonazepam • Ativar, Diastat, Halcion
• Clonidine • Catapres, Catapres TTS-1
• Clozapine • Clozaril
• Fenfluramine • Pondimin
• Fluoxetine • Prozac, Prozac Weekly
• Fluvoxamine • Luvox
• Paroxetine • Paxil
• Phenelzine • Nardil, Parnate
• Pindolol • Inderol, Corgard, Betaloc
• Risperidone • Risperidal
• Sertaline • Zoloft
• Trazodone • Desyrel
• Tryptophan* • L-Tryptophan, Alti-trytophan

Disclosure

Dr. Boxill and Ms. Shapiro report no affiliation or financial arrangement with any of the companies whose products are mentioned in this article.

Dr. Dougherty reports conflicts of interest with Pfizer Inc., Forest Pharmaceuticals, and Solvay Pharmaceuticals.

When you suspect a patient has obsessive-compulsive disorder (OCD) (Box 1), how can you differentiate OCD from psychosis? Once you have made the diagnosis, what critical factors suggest treatment will be successful—or unsuccessful? Is behavioral therapy more effective than medication? Which medications are most likely to be effective? The answers to these questions can help you improve the well-being of your patients with OCD.

Differential diagnosis

Unfortunately, many patients with severe OCD are misdiagnosed with psychosis or schizophrenia spectrum disorder and spend many years suffering without proper treatment.³ Despite many similarities between patients with severe OCD and psychosis—including rigid belief systems, unrealistic concerns, magical thinking, and odd behaviors—patients with OCD can recognize the irrational nature of their beliefs when they are not in the throes of anxiety.

Patients with OCD also will usually respond to behavioral interventions within a few weeks while patients who are psychotic usually get progressively worse. Treatment must be given time as both cohorts will get anxious or increase their negative symptoms initially, but patients with OCD should soon habituate and find symptom relief.

Some patients have OCD with psychotic features and tend to have more difficulty responding to behavior therapy without medication. Patients with both OCD and schizotypal personalities respond poorly to both behavior therapy and psychotropic medications.⁴

Box 1

Predictors for successful treatment

Insight Researchers³ found that about 52% of patients with insight into the reasonableness of their obsessions responded to medications, while none who lacked insight responded. Therefore, it pays to assess patients’ insight and ability to recognize the long-term consequences of OCD to themselves and those around them.

Some patients who have suffered with treatment-refractory OCD for most of their lives lack a premorbid high level of functioning to serve as a reference for normalized behavior. Educating these patients to see the advantages of living without certain negative behaviors improves their receptivity to treatment.

Patients who lack insight often refuse to acknowledge that many of their behaviors are manifestations of OCD. Such patients, however, are usually more amenable to giving up or modifying their dysfunctional behaviors—and the clinician more likely to avoid confrontations—if they are shown how certain behaviors undermine their goals.

Cost-benefit analysis Because of the aversive nature of exposure and response prevention therapy (ERP) and the negative side effects of many medications, some patients may find it easier to live with their symptoms, as painful as they are, rather than undergo the discomfort of behavior therapy. Because the prognosis is poor in such cases, patients need to be convinced that the discomfort of treatment is merely short-term, while the discomfort of the illness could last forever if left untreated.

Motivation In our experience, motivation has played a crucial role in determining treatment outcome for severe refractory OCD. And regardless of the severity of their symptoms, patients who are fed up with their symptoms, or are tired of living a life controlled by their obsessions, usually are excellent candidates for treatment.

Conversely, those who enter treatment as a result of external pressure from spouses or family face a less positive prognosis. High emotional expressiveness, overinvolvement, and hostility by relatives is related to higher attrition rates in treatment.³ Because ERP is so aversive, these patients will find ways to dilute the treatment’s effectiveness. In many cases, they do the minimal amount of work required to stay in treatment to avoid whatever consequences their families would impose for not adhering to treatment.

One marker to assess compliance is whether the clinician feels he or she is investing more time and effort into the patient’s treatment than the patient is. If so, this should be addressed in a timely manner. Also, sporadic attendance at sessions and noncompliance with medications, homework, and behavior therapy assignments may also portend a poor outcome. Remember, though, that noncompliance and lack of motivation are fluid states; many previously noncompliant patients later return to treatment better motivated and more compliant.

Predictors for a lower success rate

Secondary gain Researchers⁴ found that patients who were enabled by their families had more severe symptoms than those who were not. These relational and environmental factors should be discussed openly. If the patient finds that many of his or her life needs are being met secondary to the illness, that patient might not agree to an aversive treatment.

To overcome this, urge family members or other individuals who provide dysfunctional reinforcers to remove them from the environment. Meet with the patient and family/friends and frankly point out dysfunctional gains and the ways in which family members unknowingly allow the gains to continue (e.g., giving the patient more money after he or she overspent his or her allowance). A family behavioral contract should be devised to address how these gains will be reasonably eliminated.

Recognize, too, that a patient may find it difficult to give up the secondary gains, detrimental as they may be, without adequate skills or coping mechanisms to fill the void. So in some cases, it is best not to remove all the secondary gains at once; this can cause many patients to terminate treatment prematurely.

Trauma or abuse history Many patients with treatment refractory OCD have trauma histories and cannot habituate to the behavioral tasks because of dissociation, emotional numbing, or some form of distraction that mediates their anxiety and prevents proper habituation. If the patient is adequately complying with the exposures, yet still is unable to confront every feared stimulus, inquire about a trauma or abuse history (Box 2).

Substance abuse The stress that is inherent to ERP can cause many patients to relapse or abuse illicit substances to manage their anxiety. Therefore, patients with severe substance abuse problems often have great difficulty handling ERP, as they are asked to experience the very discomfort that initially caused them to abuse drugs and alcohol.

Box 2

In such cases, a patient cannot realistically be asked to give up a coping mechanism, faulty as it may be, until a more functional reinforcer takes its place. Hence, skills training is a crucial part of treatment for this group.

Residential treatment for OCD patients with comorbid substance abuse in remission may be necessary to ensure a positive outcome. Patients should continue recovery work concurrent to behavior therapy to prevent relapse.

High-risk OCD symptoms Patients who have more traditional OCD symptoms usually have a good prognosis. Unfortunately some symptoms do not respond to ERP treatment. These include:

• Repeating, hoarding, and symmetry. Though evidence suggests that hoarding is predictive of poor outcomes,⁵ treatment carried out in the home can be effective over a 24-week trial.⁶
• Incompletion, or the need for things to feel right.
• Rigid and overvalued belief systems.
• Sexual and religious obsessions. These appear to be more resistant to behavior therapy and selective serotonin reuptake inhibitors (SSRIs).⁷

More research needs to be conducted to offer patients with these symptoms better respite.

Researchers also found that patients with childhood and adolescent onset of symptoms, tics, history of hospitalization, and terminated treatment against medical advice are more likely than other OCD patients to develop more severe symptoms in adulthood.⁸ Patients with OCD who also suffer from generalized anxiety disorders are more likely than those without GAD to drop out of treatment.⁹

Behavior therapy: first choice

ERP is considered the premier treatment for OCD and is suitable for both adults and children.¹⁰ Exposure forces patients to confront their feared stimuli. Response prevention blocks patients from engaging in compulsions or avoidance behaviors intended to reduce their discomfort. Patients are asked to identify situations that trigger their obsession and compulsions and rank them along a fear hierarchy. Patients confront a moderately rated situation and, once they become habituated to it, move up the fear hierarchy to the next situation.

ERP has been proven effective for OCD not only as an individual behavior treatment, but also when done in a group setting¹¹ or when delivered online or by telephone.¹²

Table 1

Dosage levels for SRIs in OCD

Some clinicians prefer cognitive behavioral therapy (CBT) to ERP because it is less aversive. Researchers found that patients who were treated with either CBT or ERP improved. Patients treated with ERP, however, were more likely to maintain their gains in recovery 3 months after treatment concluded.¹³ Evidence suggests that ERP or CBT when implemented alone, or when applied in conjunction with fluvoxamine,¹⁴ are equally effective.

ERP should be managed only by clinicians specially trained in this modality. Several treatment centers across the country provide specialized care for OCD patients. For the nearest treatment center in your community that accepts referrals for ERP, contact the OC Foundation in North Branford, Conn. (See Related Resources.)

Medication for OCD: SRIs as first-line therapy

Experts agree that first-line somatic treatments for OCD include not only behavior therapy but also serotonin reuptake inhibitors (SRIs),¹⁵ that is, clomipramine or selective serotonin reuptake inhibitors, (SSRIs) (Table 1).

Caution: Many patients who “respond” to treatment in clinical studies remain symptomatic and meaningfully affected by their residual illness. Therefore, it is critical that you inform patients at the outset that 100% reduction in symptoms is rare.

SRIs Overwhelming evidence from multiple randomized, double-blind, placebo-controlled studies support the efficacy of SRIs. In adults, well-designed and controlled trials have demonstrated the relative efficacy of clomipramine, fluoxetine, sertraline, paroxetine, and fluvoxamine vs. placebo.

SRIs also have been shown to be significantly more effective than tricyclic antidepressants (TCAs) in both placebo-controlled and non-placebo-controlled studies.

Despite initial reports that clomipramine may be more effective than SSRIs, a growing number of studies and a recent comprehensive literature review suggest that the SRIs all have comparable efficacy.¹⁶ Because clomipramine has significantly more anticholinergic- and antiadrenergic-mediated side effects than the SSRIs, however, many clinicians choose SSRIs as the initial agent.

When using SRIs, remember that response is typically delayed; an adequate trial requires at least 10 weeks. Indeed, a meaningful proportion of responders continue to emerge past the 8-week mark. Experts suggest that optimal dosages of SRIs for OCD may exceed those typically used for major depression. Guidelines for SRI dosage ranges for OCD appear in (Table 1).

Data regarding treatment duration also suggest that discontinuation of SRIs results in a high relapse rate, though the use of lower maintenance dosages of SRIs is still debated.

Table 2

Ratings of SRI-augmenting agents for OCD treatment

Augmentation of SRIs When first-line interventions fail, second-line pharmacological approaches include augmentation of SRIs with additional medications (Table 2). Numerous agents have been tried for patients who were unresponsive or only partially responsive to SRIs alone.¹⁷ Few controlled trials of such strategies have been conducted, however. The most impressive data document the benefits of adding low doses of dopamine antagonists (both conventional and atypical neuroleptics).

Table 3

Using alternative monotherapies

Recent uncontrolled studies of augmentation with atypical neuroleptics have yielded encouraging preliminary results, as has one controlled trial of augmentation of an SRI with risperidone. Other data suggest that lithium, buspirone, and clonazepam may also be effective.

Numerous other agents have been tried in combination with SRIs, including clonidine, tryptophan, fenfluramine, pindolol, trazodone, nortriptyline, and other antidepressants. The small number of subjects, lack of sufficient controls, and mixed results preclude drawing even preliminary conclusions as to the potential efficacy of such strategies.

Alternative Monotherapies For patients who do not respond satisfactorily to trials of SRIs alone or to augmentation strategies, consider alternative monotherapies in place of SRIs (Table 3). In addition to uncontrolled data, positive controlled studies lend some support for trials of clonazepam, monoamine oxidase (MAO) inhibitors, and buspirone.

Pertinent negative findings are worthy of mention. In contrast to promising results with risperidone as an augmenter, an open trial of the atypical antipsychotic clozapine suggests inefficacy as a monotherapy. Several case reports suggest that clozapine can actually precipitate obsessive-compulsive symptoms in patients with psychotic disorders.¹⁸ Controlled trials have not demonstrated the efficacy of trazodone, clonidine, and diphenhydramine as monotherapies.

Pharmacotherapy + or vs. behavioral therapy

Only a few studies directly comparing behavior therapy vs. medication have been reported. In practice, the two are routinely used in concert. Experts have long recommended this treatment approach. Two recent studies^19,20 have demonstrated that the combination is more effective than either treatment alone.

In another study, behavior therapy significantly outperformed clomipramine; no significant incremental benefit was seen from the two treatments in combination.²¹ However, the dosages of clomipramine were relatively low (mean=164 mg/d and maximum=225 mg/d) and of inadequate duration (6 weeks). Still another older head-to-head comparison of behavior therapy and clomipramine showed that medication was better for reducing obsessional doubt, whereas behavior therapy more effectively reduced compulsive rituals.

Third-line treatments may include the unproven augmentation therapies described above, or intravenous clomipramine if available.²²

Treatments of last resort

Finally, other nonpharmacologic treatments, including neurosurgery and electroconvulsive therapy (ECT), have remained controversial and are reserved for particular clinical situations or as treatments of last resort.

Despite a large body of uncontrolled data reporting antiobsessional benefits from a variety of neurosurgical procedures, ethical considerations and technical limitations have precluded the performance of sham-controlled studies to definitively establish the efficacy of these strategies.

Neurosurgical treatment of OCD is reserved for patients with severe and debilitating illness who have failed an exhaustive array of other available treatment options and who provide informed consent or assent. Currently, the most commonly employed neurosurgical treatments for OCD include anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leukotomy. In recent prospective trials of cingulotomy and capsulotomy, approximately 45% of patients experienced a 35% or more symptom reduction.

With the advent of innovative surgical devices that allow functional neurosurgery without craniotomy (e.g., by gamma knife), the performance of ethical, double-blind, sham-controlled trials of neurosurgery for OCD is now feasible. A team of investigators from Brown University and Massachusetts General Hospital is conducting one such study that tests the efficacy of anterior capsulotomy.

There are no controlled data regarding the efficacy of ECT for OCD. Given the high comorbidity of major affective illness in OCD and the well-established efficacy of ECT for major depression, it is not surprising that some patients with OCD have reportedly shown clinical improvement after ECT. Several limited case series and anecdotal reports suggest that ECT may help in some circumstances, and such intervention would seem prudent in some cases where severe, comorbid affective illness is present.²³

Related resources

• Jenike MA, Baer, L, Minichiello WE, eds. Obsessive Compulsive Disorders: Practical Management. 3rd ed. Boston: Mosby, 1998.
• Jenike MA. An update on obsessive-compulsive disorder. Bulletin of the Menninger Clinic. 2001;65:4-25.
• Obsessive-Compulsive Foundation, (203) 315-2190, www.ocfoundation.org

Drug brand names

• Buspirone • BuSpar, BuSpar DIVIDOSE
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clonazepam • Ativar, Diastat, Halcion
• Clonidine • Catapres, Catapres TTS-1
• Clozapine • Clozaril
• Fenfluramine • Pondimin
• Fluoxetine • Prozac, Prozac Weekly
• Fluvoxamine • Luvox
• Paroxetine • Paxil
• Phenelzine • Nardil, Parnate
• Pindolol • Inderol, Corgard, Betaloc
• Risperidone • Risperidal
• Sertaline • Zoloft
• Trazodone • Desyrel
• Tryptophan* • L-Tryptophan, Alti-trytophan

Disclosure

Dr. Boxill and Ms. Shapiro report no affiliation or financial arrangement with any of the companies whose products are mentioned in this article.

Dr. Dougherty reports conflicts of interest with Pfizer Inc., Forest Pharmaceuticals, and Solvay Pharmaceuticals.

When you suspect a patient has obsessive-compulsive disorder (OCD) (Box 1), how can you differentiate OCD from psychosis? Once you have made the diagnosis, what critical factors suggest treatment will be successful—or unsuccessful? Is behavioral therapy more effective than medication? Which medications are most likely to be effective? The answers to these questions can help you improve the well-being of your patients with OCD.

Differential diagnosis

Unfortunately, many patients with severe OCD are misdiagnosed with psychosis or schizophrenia spectrum disorder and spend many years suffering without proper treatment.³ Despite many similarities between patients with severe OCD and psychosis—including rigid belief systems, unrealistic concerns, magical thinking, and odd behaviors—patients with OCD can recognize the irrational nature of their beliefs when they are not in the throes of anxiety.

Patients with OCD also will usually respond to behavioral interventions within a few weeks while patients who are psychotic usually get progressively worse. Treatment must be given time as both cohorts will get anxious or increase their negative symptoms initially, but patients with OCD should soon habituate and find symptom relief.

Some patients have OCD with psychotic features and tend to have more difficulty responding to behavior therapy without medication. Patients with both OCD and schizotypal personalities respond poorly to both behavior therapy and psychotropic medications.⁴

Box 1

Predictors for successful treatment

Insight Researchers³ found that about 52% of patients with insight into the reasonableness of their obsessions responded to medications, while none who lacked insight responded. Therefore, it pays to assess patients’ insight and ability to recognize the long-term consequences of OCD to themselves and those around them.

Some patients who have suffered with treatment-refractory OCD for most of their lives lack a premorbid high level of functioning to serve as a reference for normalized behavior. Educating these patients to see the advantages of living without certain negative behaviors improves their receptivity to treatment.

Patients who lack insight often refuse to acknowledge that many of their behaviors are manifestations of OCD. Such patients, however, are usually more amenable to giving up or modifying their dysfunctional behaviors—and the clinician more likely to avoid confrontations—if they are shown how certain behaviors undermine their goals.

Cost-benefit analysis Because of the aversive nature of exposure and response prevention therapy (ERP) and the negative side effects of many medications, some patients may find it easier to live with their symptoms, as painful as they are, rather than undergo the discomfort of behavior therapy. Because the prognosis is poor in such cases, patients need to be convinced that the discomfort of treatment is merely short-term, while the discomfort of the illness could last forever if left untreated.

Motivation In our experience, motivation has played a crucial role in determining treatment outcome for severe refractory OCD. And regardless of the severity of their symptoms, patients who are fed up with their symptoms, or are tired of living a life controlled by their obsessions, usually are excellent candidates for treatment.

Conversely, those who enter treatment as a result of external pressure from spouses or family face a less positive prognosis. High emotional expressiveness, overinvolvement, and hostility by relatives is related to higher attrition rates in treatment.³ Because ERP is so aversive, these patients will find ways to dilute the treatment’s effectiveness. In many cases, they do the minimal amount of work required to stay in treatment to avoid whatever consequences their families would impose for not adhering to treatment.

One marker to assess compliance is whether the clinician feels he or she is investing more time and effort into the patient’s treatment than the patient is. If so, this should be addressed in a timely manner. Also, sporadic attendance at sessions and noncompliance with medications, homework, and behavior therapy assignments may also portend a poor outcome. Remember, though, that noncompliance and lack of motivation are fluid states; many previously noncompliant patients later return to treatment better motivated and more compliant.

Predictors for a lower success rate

Secondary gain Researchers⁴ found that patients who were enabled by their families had more severe symptoms than those who were not. These relational and environmental factors should be discussed openly. If the patient finds that many of his or her life needs are being met secondary to the illness, that patient might not agree to an aversive treatment.

To overcome this, urge family members or other individuals who provide dysfunctional reinforcers to remove them from the environment. Meet with the patient and family/friends and frankly point out dysfunctional gains and the ways in which family members unknowingly allow the gains to continue (e.g., giving the patient more money after he or she overspent his or her allowance). A family behavioral contract should be devised to address how these gains will be reasonably eliminated.

Recognize, too, that a patient may find it difficult to give up the secondary gains, detrimental as they may be, without adequate skills or coping mechanisms to fill the void. So in some cases, it is best not to remove all the secondary gains at once; this can cause many patients to terminate treatment prematurely.

Trauma or abuse history Many patients with treatment refractory OCD have trauma histories and cannot habituate to the behavioral tasks because of dissociation, emotional numbing, or some form of distraction that mediates their anxiety and prevents proper habituation. If the patient is adequately complying with the exposures, yet still is unable to confront every feared stimulus, inquire about a trauma or abuse history (Box 2).

Substance abuse The stress that is inherent to ERP can cause many patients to relapse or abuse illicit substances to manage their anxiety. Therefore, patients with severe substance abuse problems often have great difficulty handling ERP, as they are asked to experience the very discomfort that initially caused them to abuse drugs and alcohol.

Box 2

In such cases, a patient cannot realistically be asked to give up a coping mechanism, faulty as it may be, until a more functional reinforcer takes its place. Hence, skills training is a crucial part of treatment for this group.

Residential treatment for OCD patients with comorbid substance abuse in remission may be necessary to ensure a positive outcome. Patients should continue recovery work concurrent to behavior therapy to prevent relapse.

High-risk OCD symptoms Patients who have more traditional OCD symptoms usually have a good prognosis. Unfortunately some symptoms do not respond to ERP treatment. These include:

• Repeating, hoarding, and symmetry. Though evidence suggests that hoarding is predictive of poor outcomes,⁵ treatment carried out in the home can be effective over a 24-week trial.⁶
• Incompletion, or the need for things to feel right.
• Rigid and overvalued belief systems.
• Sexual and religious obsessions. These appear to be more resistant to behavior therapy and selective serotonin reuptake inhibitors (SSRIs).⁷

More research needs to be conducted to offer patients with these symptoms better respite.

Researchers also found that patients with childhood and adolescent onset of symptoms, tics, history of hospitalization, and terminated treatment against medical advice are more likely than other OCD patients to develop more severe symptoms in adulthood.⁸ Patients with OCD who also suffer from generalized anxiety disorders are more likely than those without GAD to drop out of treatment.⁹

Behavior therapy: first choice

ERP is considered the premier treatment for OCD and is suitable for both adults and children.¹⁰ Exposure forces patients to confront their feared stimuli. Response prevention blocks patients from engaging in compulsions or avoidance behaviors intended to reduce their discomfort. Patients are asked to identify situations that trigger their obsession and compulsions and rank them along a fear hierarchy. Patients confront a moderately rated situation and, once they become habituated to it, move up the fear hierarchy to the next situation.

ERP has been proven effective for OCD not only as an individual behavior treatment, but also when done in a group setting¹¹ or when delivered online or by telephone.¹²

Table 1

Dosage levels for SRIs in OCD

Some clinicians prefer cognitive behavioral therapy (CBT) to ERP because it is less aversive. Researchers found that patients who were treated with either CBT or ERP improved. Patients treated with ERP, however, were more likely to maintain their gains in recovery 3 months after treatment concluded.¹³ Evidence suggests that ERP or CBT when implemented alone, or when applied in conjunction with fluvoxamine,¹⁴ are equally effective.

ERP should be managed only by clinicians specially trained in this modality. Several treatment centers across the country provide specialized care for OCD patients. For the nearest treatment center in your community that accepts referrals for ERP, contact the OC Foundation in North Branford, Conn. (See Related Resources.)

Medication for OCD: SRIs as first-line therapy

Experts agree that first-line somatic treatments for OCD include not only behavior therapy but also serotonin reuptake inhibitors (SRIs),¹⁵ that is, clomipramine or selective serotonin reuptake inhibitors, (SSRIs) (Table 1).

Caution: Many patients who “respond” to treatment in clinical studies remain symptomatic and meaningfully affected by their residual illness. Therefore, it is critical that you inform patients at the outset that 100% reduction in symptoms is rare.

SRIs Overwhelming evidence from multiple randomized, double-blind, placebo-controlled studies support the efficacy of SRIs. In adults, well-designed and controlled trials have demonstrated the relative efficacy of clomipramine, fluoxetine, sertraline, paroxetine, and fluvoxamine vs. placebo.

SRIs also have been shown to be significantly more effective than tricyclic antidepressants (TCAs) in both placebo-controlled and non-placebo-controlled studies.

Despite initial reports that clomipramine may be more effective than SSRIs, a growing number of studies and a recent comprehensive literature review suggest that the SRIs all have comparable efficacy.¹⁶ Because clomipramine has significantly more anticholinergic- and antiadrenergic-mediated side effects than the SSRIs, however, many clinicians choose SSRIs as the initial agent.

When using SRIs, remember that response is typically delayed; an adequate trial requires at least 10 weeks. Indeed, a meaningful proportion of responders continue to emerge past the 8-week mark. Experts suggest that optimal dosages of SRIs for OCD may exceed those typically used for major depression. Guidelines for SRI dosage ranges for OCD appear in (Table 1).

Data regarding treatment duration also suggest that discontinuation of SRIs results in a high relapse rate, though the use of lower maintenance dosages of SRIs is still debated.

Table 2

Ratings of SRI-augmenting agents for OCD treatment

Augmentation of SRIs When first-line interventions fail, second-line pharmacological approaches include augmentation of SRIs with additional medications (Table 2). Numerous agents have been tried for patients who were unresponsive or only partially responsive to SRIs alone.¹⁷ Few controlled trials of such strategies have been conducted, however. The most impressive data document the benefits of adding low doses of dopamine antagonists (both conventional and atypical neuroleptics).

Table 3

Using alternative monotherapies

Recent uncontrolled studies of augmentation with atypical neuroleptics have yielded encouraging preliminary results, as has one controlled trial of augmentation of an SRI with risperidone. Other data suggest that lithium, buspirone, and clonazepam may also be effective.

Numerous other agents have been tried in combination with SRIs, including clonidine, tryptophan, fenfluramine, pindolol, trazodone, nortriptyline, and other antidepressants. The small number of subjects, lack of sufficient controls, and mixed results preclude drawing even preliminary conclusions as to the potential efficacy of such strategies.

Alternative Monotherapies For patients who do not respond satisfactorily to trials of SRIs alone or to augmentation strategies, consider alternative monotherapies in place of SRIs (Table 3). In addition to uncontrolled data, positive controlled studies lend some support for trials of clonazepam, monoamine oxidase (MAO) inhibitors, and buspirone.

Pertinent negative findings are worthy of mention. In contrast to promising results with risperidone as an augmenter, an open trial of the atypical antipsychotic clozapine suggests inefficacy as a monotherapy. Several case reports suggest that clozapine can actually precipitate obsessive-compulsive symptoms in patients with psychotic disorders.¹⁸ Controlled trials have not demonstrated the efficacy of trazodone, clonidine, and diphenhydramine as monotherapies.

Pharmacotherapy + or vs. behavioral therapy

Only a few studies directly comparing behavior therapy vs. medication have been reported. In practice, the two are routinely used in concert. Experts have long recommended this treatment approach. Two recent studies^19,20 have demonstrated that the combination is more effective than either treatment alone.

In another study, behavior therapy significantly outperformed clomipramine; no significant incremental benefit was seen from the two treatments in combination.²¹ However, the dosages of clomipramine were relatively low (mean=164 mg/d and maximum=225 mg/d) and of inadequate duration (6 weeks). Still another older head-to-head comparison of behavior therapy and clomipramine showed that medication was better for reducing obsessional doubt, whereas behavior therapy more effectively reduced compulsive rituals.

Third-line treatments may include the unproven augmentation therapies described above, or intravenous clomipramine if available.²²

Treatments of last resort

Finally, other nonpharmacologic treatments, including neurosurgery and electroconvulsive therapy (ECT), have remained controversial and are reserved for particular clinical situations or as treatments of last resort.

Despite a large body of uncontrolled data reporting antiobsessional benefits from a variety of neurosurgical procedures, ethical considerations and technical limitations have precluded the performance of sham-controlled studies to definitively establish the efficacy of these strategies.

Neurosurgical treatment of OCD is reserved for patients with severe and debilitating illness who have failed an exhaustive array of other available treatment options and who provide informed consent or assent. Currently, the most commonly employed neurosurgical treatments for OCD include anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leukotomy. In recent prospective trials of cingulotomy and capsulotomy, approximately 45% of patients experienced a 35% or more symptom reduction.

With the advent of innovative surgical devices that allow functional neurosurgery without craniotomy (e.g., by gamma knife), the performance of ethical, double-blind, sham-controlled trials of neurosurgery for OCD is now feasible. A team of investigators from Brown University and Massachusetts General Hospital is conducting one such study that tests the efficacy of anterior capsulotomy.

There are no controlled data regarding the efficacy of ECT for OCD. Given the high comorbidity of major affective illness in OCD and the well-established efficacy of ECT for major depression, it is not surprising that some patients with OCD have reportedly shown clinical improvement after ECT. Several limited case series and anecdotal reports suggest that ECT may help in some circumstances, and such intervention would seem prudent in some cases where severe, comorbid affective illness is present.²³

Related resources

• Jenike MA, Baer, L, Minichiello WE, eds. Obsessive Compulsive Disorders: Practical Management. 3rd ed. Boston: Mosby, 1998.
• Jenike MA. An update on obsessive-compulsive disorder. Bulletin of the Menninger Clinic. 2001;65:4-25.
• Obsessive-Compulsive Foundation, (203) 315-2190, www.ocfoundation.org

Drug brand names

• Buspirone • BuSpar, BuSpar DIVIDOSE
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clonazepam • Ativar, Diastat, Halcion
• Clonidine • Catapres, Catapres TTS-1
• Clozapine • Clozaril
• Fenfluramine • Pondimin
• Fluoxetine • Prozac, Prozac Weekly
• Fluvoxamine • Luvox
• Paroxetine • Paxil
• Phenelzine • Nardil, Parnate
• Pindolol • Inderol, Corgard, Betaloc
• Risperidone • Risperidal
• Sertaline • Zoloft
• Trazodone • Desyrel
• Tryptophan* • L-Tryptophan, Alti-trytophan

Disclosure

Dr. Boxill and Ms. Shapiro report no affiliation or financial arrangement with any of the companies whose products are mentioned in this article.

Dr. Dougherty reports conflicts of interest with Pfizer Inc., Forest Pharmaceuticals, and Solvay Pharmaceuticals.

When you suspect a patient has obsessive-compulsive disorder (OCD) (Box 1), how can you differentiate OCD from psychosis? Once you have made the diagnosis, what critical factors suggest treatment will be successful—or unsuccessful? Is behavioral therapy more effective than medication? Which medications are most likely to be effective? The answers to these questions can help you improve the well-being of your patients with OCD.

Differential diagnosis

Unfortunately, many patients with severe OCD are misdiagnosed with psychosis or schizophrenia spectrum disorder and spend many years suffering without proper treatment.³ Despite many similarities between patients with severe OCD and psychosis—including rigid belief systems, unrealistic concerns, magical thinking, and odd behaviors—patients with OCD can recognize the irrational nature of their beliefs when they are not in the throes of anxiety.

Patients with OCD also will usually respond to behavioral interventions within a few weeks while patients who are psychotic usually get progressively worse. Treatment must be given time as both cohorts will get anxious or increase their negative symptoms initially, but patients with OCD should soon habituate and find symptom relief.

Some patients have OCD with psychotic features and tend to have more difficulty responding to behavior therapy without medication. Patients with both OCD and schizotypal personalities respond poorly to both behavior therapy and psychotropic medications.⁴

Box 1

Predictors for successful treatment

Insight Researchers³ found that about 52% of patients with insight into the reasonableness of their obsessions responded to medications, while none who lacked insight responded. Therefore, it pays to assess patients’ insight and ability to recognize the long-term consequences of OCD to themselves and those around them.

Some patients who have suffered with treatment-refractory OCD for most of their lives lack a premorbid high level of functioning to serve as a reference for normalized behavior. Educating these patients to see the advantages of living without certain negative behaviors improves their receptivity to treatment.

Patients who lack insight often refuse to acknowledge that many of their behaviors are manifestations of OCD. Such patients, however, are usually more amenable to giving up or modifying their dysfunctional behaviors—and the clinician more likely to avoid confrontations—if they are shown how certain behaviors undermine their goals.

Cost-benefit analysis Because of the aversive nature of exposure and response prevention therapy (ERP) and the negative side effects of many medications, some patients may find it easier to live with their symptoms, as painful as they are, rather than undergo the discomfort of behavior therapy. Because the prognosis is poor in such cases, patients need to be convinced that the discomfort of treatment is merely short-term, while the discomfort of the illness could last forever if left untreated.

Motivation In our experience, motivation has played a crucial role in determining treatment outcome for severe refractory OCD. And regardless of the severity of their symptoms, patients who are fed up with their symptoms, or are tired of living a life controlled by their obsessions, usually are excellent candidates for treatment.

Conversely, those who enter treatment as a result of external pressure from spouses or family face a less positive prognosis. High emotional expressiveness, overinvolvement, and hostility by relatives is related to higher attrition rates in treatment.³ Because ERP is so aversive, these patients will find ways to dilute the treatment’s effectiveness. In many cases, they do the minimal amount of work required to stay in treatment to avoid whatever consequences their families would impose for not adhering to treatment.

One marker to assess compliance is whether the clinician feels he or she is investing more time and effort into the patient’s treatment than the patient is. If so, this should be addressed in a timely manner. Also, sporadic attendance at sessions and noncompliance with medications, homework, and behavior therapy assignments may also portend a poor outcome. Remember, though, that noncompliance and lack of motivation are fluid states; many previously noncompliant patients later return to treatment better motivated and more compliant.

Predictors for a lower success rate

Secondary gain Researchers⁴ found that patients who were enabled by their families had more severe symptoms than those who were not. These relational and environmental factors should be discussed openly. If the patient finds that many of his or her life needs are being met secondary to the illness, that patient might not agree to an aversive treatment.

To overcome this, urge family members or other individuals who provide dysfunctional reinforcers to remove them from the environment. Meet with the patient and family/friends and frankly point out dysfunctional gains and the ways in which family members unknowingly allow the gains to continue (e.g., giving the patient more money after he or she overspent his or her allowance). A family behavioral contract should be devised to address how these gains will be reasonably eliminated.

Recognize, too, that a patient may find it difficult to give up the secondary gains, detrimental as they may be, without adequate skills or coping mechanisms to fill the void. So in some cases, it is best not to remove all the secondary gains at once; this can cause many patients to terminate treatment prematurely.

Trauma or abuse history Many patients with treatment refractory OCD have trauma histories and cannot habituate to the behavioral tasks because of dissociation, emotional numbing, or some form of distraction that mediates their anxiety and prevents proper habituation. If the patient is adequately complying with the exposures, yet still is unable to confront every feared stimulus, inquire about a trauma or abuse history (Box 2).

Substance abuse The stress that is inherent to ERP can cause many patients to relapse or abuse illicit substances to manage their anxiety. Therefore, patients with severe substance abuse problems often have great difficulty handling ERP, as they are asked to experience the very discomfort that initially caused them to abuse drugs and alcohol.

Box 2

In such cases, a patient cannot realistically be asked to give up a coping mechanism, faulty as it may be, until a more functional reinforcer takes its place. Hence, skills training is a crucial part of treatment for this group.

Residential treatment for OCD patients with comorbid substance abuse in remission may be necessary to ensure a positive outcome. Patients should continue recovery work concurrent to behavior therapy to prevent relapse.

High-risk OCD symptoms Patients who have more traditional OCD symptoms usually have a good prognosis. Unfortunately some symptoms do not respond to ERP treatment. These include:

• Repeating, hoarding, and symmetry. Though evidence suggests that hoarding is predictive of poor outcomes,⁵ treatment carried out in the home can be effective over a 24-week trial.⁶
• Incompletion, or the need for things to feel right.
• Rigid and overvalued belief systems.
• Sexual and religious obsessions. These appear to be more resistant to behavior therapy and selective serotonin reuptake inhibitors (SSRIs).⁷

More research needs to be conducted to offer patients with these symptoms better respite.

Researchers also found that patients with childhood and adolescent onset of symptoms, tics, history of hospitalization, and terminated treatment against medical advice are more likely than other OCD patients to develop more severe symptoms in adulthood.⁸ Patients with OCD who also suffer from generalized anxiety disorders are more likely than those without GAD to drop out of treatment.⁹

Behavior therapy: first choice

ERP is considered the premier treatment for OCD and is suitable for both adults and children.¹⁰ Exposure forces patients to confront their feared stimuli. Response prevention blocks patients from engaging in compulsions or avoidance behaviors intended to reduce their discomfort. Patients are asked to identify situations that trigger their obsession and compulsions and rank them along a fear hierarchy. Patients confront a moderately rated situation and, once they become habituated to it, move up the fear hierarchy to the next situation.

ERP has been proven effective for OCD not only as an individual behavior treatment, but also when done in a group setting¹¹ or when delivered online or by telephone.¹²

Table 1

Dosage levels for SRIs in OCD

Some clinicians prefer cognitive behavioral therapy (CBT) to ERP because it is less aversive. Researchers found that patients who were treated with either CBT or ERP improved. Patients treated with ERP, however, were more likely to maintain their gains in recovery 3 months after treatment concluded.¹³ Evidence suggests that ERP or CBT when implemented alone, or when applied in conjunction with fluvoxamine,¹⁴ are equally effective.

ERP should be managed only by clinicians specially trained in this modality. Several treatment centers across the country provide specialized care for OCD patients. For the nearest treatment center in your community that accepts referrals for ERP, contact the OC Foundation in North Branford, Conn. (See Related Resources.)

Medication for OCD: SRIs as first-line therapy

Experts agree that first-line somatic treatments for OCD include not only behavior therapy but also serotonin reuptake inhibitors (SRIs),¹⁵ that is, clomipramine or selective serotonin reuptake inhibitors, (SSRIs) (Table 1).

Caution: Many patients who “respond” to treatment in clinical studies remain symptomatic and meaningfully affected by their residual illness. Therefore, it is critical that you inform patients at the outset that 100% reduction in symptoms is rare.

SRIs Overwhelming evidence from multiple randomized, double-blind, placebo-controlled studies support the efficacy of SRIs. In adults, well-designed and controlled trials have demonstrated the relative efficacy of clomipramine, fluoxetine, sertraline, paroxetine, and fluvoxamine vs. placebo.

SRIs also have been shown to be significantly more effective than tricyclic antidepressants (TCAs) in both placebo-controlled and non-placebo-controlled studies.

Despite initial reports that clomipramine may be more effective than SSRIs, a growing number of studies and a recent comprehensive literature review suggest that the SRIs all have comparable efficacy.¹⁶ Because clomipramine has significantly more anticholinergic- and antiadrenergic-mediated side effects than the SSRIs, however, many clinicians choose SSRIs as the initial agent.

When using SRIs, remember that response is typically delayed; an adequate trial requires at least 10 weeks. Indeed, a meaningful proportion of responders continue to emerge past the 8-week mark. Experts suggest that optimal dosages of SRIs for OCD may exceed those typically used for major depression. Guidelines for SRI dosage ranges for OCD appear in (Table 1).

Data regarding treatment duration also suggest that discontinuation of SRIs results in a high relapse rate, though the use of lower maintenance dosages of SRIs is still debated.

Table 2

Ratings of SRI-augmenting agents for OCD treatment

Augmentation of SRIs When first-line interventions fail, second-line pharmacological approaches include augmentation of SRIs with additional medications (Table 2). Numerous agents have been tried for patients who were unresponsive or only partially responsive to SRIs alone.¹⁷ Few controlled trials of such strategies have been conducted, however. The most impressive data document the benefits of adding low doses of dopamine antagonists (both conventional and atypical neuroleptics).

Table 3

Using alternative monotherapies

Recent uncontrolled studies of augmentation with atypical neuroleptics have yielded encouraging preliminary results, as has one controlled trial of augmentation of an SRI with risperidone. Other data suggest that lithium, buspirone, and clonazepam may also be effective.

Numerous other agents have been tried in combination with SRIs, including clonidine, tryptophan, fenfluramine, pindolol, trazodone, nortriptyline, and other antidepressants. The small number of subjects, lack of sufficient controls, and mixed results preclude drawing even preliminary conclusions as to the potential efficacy of such strategies.

Alternative Monotherapies For patients who do not respond satisfactorily to trials of SRIs alone or to augmentation strategies, consider alternative monotherapies in place of SRIs (Table 3). In addition to uncontrolled data, positive controlled studies lend some support for trials of clonazepam, monoamine oxidase (MAO) inhibitors, and buspirone.

Pertinent negative findings are worthy of mention. In contrast to promising results with risperidone as an augmenter, an open trial of the atypical antipsychotic clozapine suggests inefficacy as a monotherapy. Several case reports suggest that clozapine can actually precipitate obsessive-compulsive symptoms in patients with psychotic disorders.¹⁸ Controlled trials have not demonstrated the efficacy of trazodone, clonidine, and diphenhydramine as monotherapies.

Pharmacotherapy + or vs. behavioral therapy

Only a few studies directly comparing behavior therapy vs. medication have been reported. In practice, the two are routinely used in concert. Experts have long recommended this treatment approach. Two recent studies^19,20 have demonstrated that the combination is more effective than either treatment alone.

In another study, behavior therapy significantly outperformed clomipramine; no significant incremental benefit was seen from the two treatments in combination.²¹ However, the dosages of clomipramine were relatively low (mean=164 mg/d and maximum=225 mg/d) and of inadequate duration (6 weeks). Still another older head-to-head comparison of behavior therapy and clomipramine showed that medication was better for reducing obsessional doubt, whereas behavior therapy more effectively reduced compulsive rituals.

Third-line treatments may include the unproven augmentation therapies described above, or intravenous clomipramine if available.²²

Treatments of last resort

Finally, other nonpharmacologic treatments, including neurosurgery and electroconvulsive therapy (ECT), have remained controversial and are reserved for particular clinical situations or as treatments of last resort.

Despite a large body of uncontrolled data reporting antiobsessional benefits from a variety of neurosurgical procedures, ethical considerations and technical limitations have precluded the performance of sham-controlled studies to definitively establish the efficacy of these strategies.

Neurosurgical treatment of OCD is reserved for patients with severe and debilitating illness who have failed an exhaustive array of other available treatment options and who provide informed consent or assent. Currently, the most commonly employed neurosurgical treatments for OCD include anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leukotomy. In recent prospective trials of cingulotomy and capsulotomy, approximately 45% of patients experienced a 35% or more symptom reduction.

With the advent of innovative surgical devices that allow functional neurosurgery without craniotomy (e.g., by gamma knife), the performance of ethical, double-blind, sham-controlled trials of neurosurgery for OCD is now feasible. A team of investigators from Brown University and Massachusetts General Hospital is conducting one such study that tests the efficacy of anterior capsulotomy.

There are no controlled data regarding the efficacy of ECT for OCD. Given the high comorbidity of major affective illness in OCD and the well-established efficacy of ECT for major depression, it is not surprising that some patients with OCD have reportedly shown clinical improvement after ECT. Several limited case series and anecdotal reports suggest that ECT may help in some circumstances, and such intervention would seem prudent in some cases where severe, comorbid affective illness is present.²³

Related resources

• Jenike MA, Baer, L, Minichiello WE, eds. Obsessive Compulsive Disorders: Practical Management. 3rd ed. Boston: Mosby, 1998.
• Jenike MA. An update on obsessive-compulsive disorder. Bulletin of the Menninger Clinic. 2001;65:4-25.
• Obsessive-Compulsive Foundation, (203) 315-2190, www.ocfoundation.org

Drug brand names

• Buspirone • BuSpar, BuSpar DIVIDOSE
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clonazepam • Ativar, Diastat, Halcion
• Clonidine • Catapres, Catapres TTS-1
• Clozapine • Clozaril
• Fenfluramine • Pondimin
• Fluoxetine • Prozac, Prozac Weekly
• Fluvoxamine • Luvox
• Paroxetine • Paxil
• Phenelzine • Nardil, Parnate
• Pindolol • Inderol, Corgard, Betaloc
• Risperidone • Risperidal
• Sertaline • Zoloft
• Trazodone • Desyrel
• Tryptophan* • L-Tryptophan, Alti-trytophan

Disclosure

Dr. Boxill and Ms. Shapiro report no affiliation or financial arrangement with any of the companies whose products are mentioned in this article.

Dr. Dougherty reports conflicts of interest with Pfizer Inc., Forest Pharmaceuticals, and Solvay Pharmaceuticals.

When you suspect a patient has obsessive-compulsive disorder (OCD) (Box 1), how can you differentiate OCD from psychosis? Once you have made the diagnosis, what critical factors suggest treatment will be successful—or unsuccessful? Is behavioral therapy more effective than medication? Which medications are most likely to be effective? The answers to these questions can help you improve the well-being of your patients with OCD.

Differential diagnosis

Unfortunately, many patients with severe OCD are misdiagnosed with psychosis or schizophrenia spectrum disorder and spend many years suffering without proper treatment.³ Despite many similarities between patients with severe OCD and psychosis—including rigid belief systems, unrealistic concerns, magical thinking, and odd behaviors—patients with OCD can recognize the irrational nature of their beliefs when they are not in the throes of anxiety.

Patients with OCD also will usually respond to behavioral interventions within a few weeks while patients who are psychotic usually get progressively worse. Treatment must be given time as both cohorts will get anxious or increase their negative symptoms initially, but patients with OCD should soon habituate and find symptom relief.

Some patients have OCD with psychotic features and tend to have more difficulty responding to behavior therapy without medication. Patients with both OCD and schizotypal personalities respond poorly to both behavior therapy and psychotropic medications.⁴

Box 1

Predictors for successful treatment

Insight Researchers³ found that about 52% of patients with insight into the reasonableness of their obsessions responded to medications, while none who lacked insight responded. Therefore, it pays to assess patients’ insight and ability to recognize the long-term consequences of OCD to themselves and those around them.

Some patients who have suffered with treatment-refractory OCD for most of their lives lack a premorbid high level of functioning to serve as a reference for normalized behavior. Educating these patients to see the advantages of living without certain negative behaviors improves their receptivity to treatment.

Patients who lack insight often refuse to acknowledge that many of their behaviors are manifestations of OCD. Such patients, however, are usually more amenable to giving up or modifying their dysfunctional behaviors—and the clinician more likely to avoid confrontations—if they are shown how certain behaviors undermine their goals.

Cost-benefit analysis Because of the aversive nature of exposure and response prevention therapy (ERP) and the negative side effects of many medications, some patients may find it easier to live with their symptoms, as painful as they are, rather than undergo the discomfort of behavior therapy. Because the prognosis is poor in such cases, patients need to be convinced that the discomfort of treatment is merely short-term, while the discomfort of the illness could last forever if left untreated.

Motivation In our experience, motivation has played a crucial role in determining treatment outcome for severe refractory OCD. And regardless of the severity of their symptoms, patients who are fed up with their symptoms, or are tired of living a life controlled by their obsessions, usually are excellent candidates for treatment.

Conversely, those who enter treatment as a result of external pressure from spouses or family face a less positive prognosis. High emotional expressiveness, overinvolvement, and hostility by relatives is related to higher attrition rates in treatment.³ Because ERP is so aversive, these patients will find ways to dilute the treatment’s effectiveness. In many cases, they do the minimal amount of work required to stay in treatment to avoid whatever consequences their families would impose for not adhering to treatment.

One marker to assess compliance is whether the clinician feels he or she is investing more time and effort into the patient’s treatment than the patient is. If so, this should be addressed in a timely manner. Also, sporadic attendance at sessions and noncompliance with medications, homework, and behavior therapy assignments may also portend a poor outcome. Remember, though, that noncompliance and lack of motivation are fluid states; many previously noncompliant patients later return to treatment better motivated and more compliant.

Predictors for a lower success rate

Secondary gain Researchers⁴ found that patients who were enabled by their families had more severe symptoms than those who were not. These relational and environmental factors should be discussed openly. If the patient finds that many of his or her life needs are being met secondary to the illness, that patient might not agree to an aversive treatment.

To overcome this, urge family members or other individuals who provide dysfunctional reinforcers to remove them from the environment. Meet with the patient and family/friends and frankly point out dysfunctional gains and the ways in which family members unknowingly allow the gains to continue (e.g., giving the patient more money after he or she overspent his or her allowance). A family behavioral contract should be devised to address how these gains will be reasonably eliminated.

Recognize, too, that a patient may find it difficult to give up the secondary gains, detrimental as they may be, without adequate skills or coping mechanisms to fill the void. So in some cases, it is best not to remove all the secondary gains at once; this can cause many patients to terminate treatment prematurely.

Trauma or abuse history Many patients with treatment refractory OCD have trauma histories and cannot habituate to the behavioral tasks because of dissociation, emotional numbing, or some form of distraction that mediates their anxiety and prevents proper habituation. If the patient is adequately complying with the exposures, yet still is unable to confront every feared stimulus, inquire about a trauma or abuse history (Box 2).

Substance abuse The stress that is inherent to ERP can cause many patients to relapse or abuse illicit substances to manage their anxiety. Therefore, patients with severe substance abuse problems often have great difficulty handling ERP, as they are asked to experience the very discomfort that initially caused them to abuse drugs and alcohol.

Box 2

In such cases, a patient cannot realistically be asked to give up a coping mechanism, faulty as it may be, until a more functional reinforcer takes its place. Hence, skills training is a crucial part of treatment for this group.

Residential treatment for OCD patients with comorbid substance abuse in remission may be necessary to ensure a positive outcome. Patients should continue recovery work concurrent to behavior therapy to prevent relapse.

High-risk OCD symptoms Patients who have more traditional OCD symptoms usually have a good prognosis. Unfortunately some symptoms do not respond to ERP treatment. These include:

• Repeating, hoarding, and symmetry. Though evidence suggests that hoarding is predictive of poor outcomes,⁵ treatment carried out in the home can be effective over a 24-week trial.⁶
• Incompletion, or the need for things to feel right.
• Rigid and overvalued belief systems.
• Sexual and religious obsessions. These appear to be more resistant to behavior therapy and selective serotonin reuptake inhibitors (SSRIs).⁷

More research needs to be conducted to offer patients with these symptoms better respite.

Researchers also found that patients with childhood and adolescent onset of symptoms, tics, history of hospitalization, and terminated treatment against medical advice are more likely than other OCD patients to develop more severe symptoms in adulthood.⁸ Patients with OCD who also suffer from generalized anxiety disorders are more likely than those without GAD to drop out of treatment.⁹

Behavior therapy: first choice

ERP is considered the premier treatment for OCD and is suitable for both adults and children.¹⁰ Exposure forces patients to confront their feared stimuli. Response prevention blocks patients from engaging in compulsions or avoidance behaviors intended to reduce their discomfort. Patients are asked to identify situations that trigger their obsession and compulsions and rank them along a fear hierarchy. Patients confront a moderately rated situation and, once they become habituated to it, move up the fear hierarchy to the next situation.

ERP has been proven effective for OCD not only as an individual behavior treatment, but also when done in a group setting¹¹ or when delivered online or by telephone.¹²

Table 1

Dosage levels for SRIs in OCD

Some clinicians prefer cognitive behavioral therapy (CBT) to ERP because it is less aversive. Researchers found that patients who were treated with either CBT or ERP improved. Patients treated with ERP, however, were more likely to maintain their gains in recovery 3 months after treatment concluded.¹³ Evidence suggests that ERP or CBT when implemented alone, or when applied in conjunction with fluvoxamine,¹⁴ are equally effective.

ERP should be managed only by clinicians specially trained in this modality. Several treatment centers across the country provide specialized care for OCD patients. For the nearest treatment center in your community that accepts referrals for ERP, contact the OC Foundation in North Branford, Conn. (See Related Resources.)

Medication for OCD: SRIs as first-line therapy

Experts agree that first-line somatic treatments for OCD include not only behavior therapy but also serotonin reuptake inhibitors (SRIs),¹⁵ that is, clomipramine or selective serotonin reuptake inhibitors, (SSRIs) (Table 1).

Caution: Many patients who “respond” to treatment in clinical studies remain symptomatic and meaningfully affected by their residual illness. Therefore, it is critical that you inform patients at the outset that 100% reduction in symptoms is rare.

SRIs Overwhelming evidence from multiple randomized, double-blind, placebo-controlled studies support the efficacy of SRIs. In adults, well-designed and controlled trials have demonstrated the relative efficacy of clomipramine, fluoxetine, sertraline, paroxetine, and fluvoxamine vs. placebo.

SRIs also have been shown to be significantly more effective than tricyclic antidepressants (TCAs) in both placebo-controlled and non-placebo-controlled studies.

Despite initial reports that clomipramine may be more effective than SSRIs, a growing number of studies and a recent comprehensive literature review suggest that the SRIs all have comparable efficacy.¹⁶ Because clomipramine has significantly more anticholinergic- and antiadrenergic-mediated side effects than the SSRIs, however, many clinicians choose SSRIs as the initial agent.

When using SRIs, remember that response is typically delayed; an adequate trial requires at least 10 weeks. Indeed, a meaningful proportion of responders continue to emerge past the 8-week mark. Experts suggest that optimal dosages of SRIs for OCD may exceed those typically used for major depression. Guidelines for SRI dosage ranges for OCD appear in (Table 1).

Data regarding treatment duration also suggest that discontinuation of SRIs results in a high relapse rate, though the use of lower maintenance dosages of SRIs is still debated.

Table 2

Ratings of SRI-augmenting agents for OCD treatment

Augmentation of SRIs When first-line interventions fail, second-line pharmacological approaches include augmentation of SRIs with additional medications (Table 2). Numerous agents have been tried for patients who were unresponsive or only partially responsive to SRIs alone.¹⁷ Few controlled trials of such strategies have been conducted, however. The most impressive data document the benefits of adding low doses of dopamine antagonists (both conventional and atypical neuroleptics).

Table 3

Using alternative monotherapies

Recent uncontrolled studies of augmentation with atypical neuroleptics have yielded encouraging preliminary results, as has one controlled trial of augmentation of an SRI with risperidone. Other data suggest that lithium, buspirone, and clonazepam may also be effective.

Numerous other agents have been tried in combination with SRIs, including clonidine, tryptophan, fenfluramine, pindolol, trazodone, nortriptyline, and other antidepressants. The small number of subjects, lack of sufficient controls, and mixed results preclude drawing even preliminary conclusions as to the potential efficacy of such strategies.

Alternative Monotherapies For patients who do not respond satisfactorily to trials of SRIs alone or to augmentation strategies, consider alternative monotherapies in place of SRIs (Table 3). In addition to uncontrolled data, positive controlled studies lend some support for trials of clonazepam, monoamine oxidase (MAO) inhibitors, and buspirone.

Pertinent negative findings are worthy of mention. In contrast to promising results with risperidone as an augmenter, an open trial of the atypical antipsychotic clozapine suggests inefficacy as a monotherapy. Several case reports suggest that clozapine can actually precipitate obsessive-compulsive symptoms in patients with psychotic disorders.¹⁸ Controlled trials have not demonstrated the efficacy of trazodone, clonidine, and diphenhydramine as monotherapies.

Pharmacotherapy + or vs. behavioral therapy

Only a few studies directly comparing behavior therapy vs. medication have been reported. In practice, the two are routinely used in concert. Experts have long recommended this treatment approach. Two recent studies^19,20 have demonstrated that the combination is more effective than either treatment alone.

In another study, behavior therapy significantly outperformed clomipramine; no significant incremental benefit was seen from the two treatments in combination.²¹ However, the dosages of clomipramine were relatively low (mean=164 mg/d and maximum=225 mg/d) and of inadequate duration (6 weeks). Still another older head-to-head comparison of behavior therapy and clomipramine showed that medication was better for reducing obsessional doubt, whereas behavior therapy more effectively reduced compulsive rituals.

Third-line treatments may include the unproven augmentation therapies described above, or intravenous clomipramine if available.²²

Treatments of last resort

Finally, other nonpharmacologic treatments, including neurosurgery and electroconvulsive therapy (ECT), have remained controversial and are reserved for particular clinical situations or as treatments of last resort.

Despite a large body of uncontrolled data reporting antiobsessional benefits from a variety of neurosurgical procedures, ethical considerations and technical limitations have precluded the performance of sham-controlled studies to definitively establish the efficacy of these strategies.

Neurosurgical treatment of OCD is reserved for patients with severe and debilitating illness who have failed an exhaustive array of other available treatment options and who provide informed consent or assent. Currently, the most commonly employed neurosurgical treatments for OCD include anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leukotomy. In recent prospective trials of cingulotomy and capsulotomy, approximately 45% of patients experienced a 35% or more symptom reduction.

With the advent of innovative surgical devices that allow functional neurosurgery without craniotomy (e.g., by gamma knife), the performance of ethical, double-blind, sham-controlled trials of neurosurgery for OCD is now feasible. A team of investigators from Brown University and Massachusetts General Hospital is conducting one such study that tests the efficacy of anterior capsulotomy.

There are no controlled data regarding the efficacy of ECT for OCD. Given the high comorbidity of major affective illness in OCD and the well-established efficacy of ECT for major depression, it is not surprising that some patients with OCD have reportedly shown clinical improvement after ECT. Several limited case series and anecdotal reports suggest that ECT may help in some circumstances, and such intervention would seem prudent in some cases where severe, comorbid affective illness is present.²³

Related resources

• Jenike MA, Baer, L, Minichiello WE, eds. Obsessive Compulsive Disorders: Practical Management. 3rd ed. Boston: Mosby, 1998.
• Jenike MA. An update on obsessive-compulsive disorder. Bulletin of the Menninger Clinic. 2001;65:4-25.
• Obsessive-Compulsive Foundation, (203) 315-2190, www.ocfoundation.org

Drug brand names

• Buspirone • BuSpar, BuSpar DIVIDOSE
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clonazepam • Ativar, Diastat, Halcion
• Clonidine • Catapres, Catapres TTS-1
• Clozapine • Clozaril
• Fenfluramine • Pondimin
• Fluoxetine • Prozac, Prozac Weekly
• Fluvoxamine • Luvox
• Paroxetine • Paxil
• Phenelzine • Nardil, Parnate
• Pindolol • Inderol, Corgard, Betaloc
• Risperidone • Risperidal
• Sertaline • Zoloft
• Trazodone • Desyrel
• Tryptophan* • L-Tryptophan, Alti-trytophan

Disclosure

Dr. Boxill and Ms. Shapiro report no affiliation or financial arrangement with any of the companies whose products are mentioned in this article.

Dr. Dougherty reports conflicts of interest with Pfizer Inc., Forest Pharmaceuticals, and Solvay Pharmaceuticals.

Since September 11, America has carried on under a cloud of fear. Though the cloud is lifting, it will not disappear for months or years. The terrorist attacks on New York City and Washington, DC, the resultant military action in Afghanistan, and the anthrax scare—combined with pervasive, nagging doubts about homeland security and the specter of another possible future terrorist attack—all are straining the nation’s collective emotional well-being.

Psychiatrists in America have reported new cases of terror-inspired acute stress disorder, anxiety, depression, and other illnesses, as well as recurrences of posttraumatic stress disorder (PTSD) in existing patients, in the weeks after the recent attacks and the anthrax scare. What will be the impact on psychiatric practice in the coming months and years?

“We are all at ground zero,” says Kenneth S. Thompson, MD, of Pittsburgh, an experienced disaster psychiatrist. But he and other subspecialists have identified four critical areas in which psychiatrists should be prepared:

1. Identifying how terrorist attacks and scares can exacerbate symptoms in patients now in your practice;
2. Diagnosing PTSD among comorbid conditions present in existing or new patients;
3. Treating—and avoiding over-treatment—of patients with acute stress disorder and PTSD;
4. Managing fear in your communities—in response to the Sept. 11 attacks, to the anthrax scare, or in anticipation of an impending catastrophe.

To bring you this special report, the editors of Current Psychiatry have reviewed the literature and interviewed psychiatrists nationwide and in countries such as Israel and Colombia, where terrorism has been a fact of life for years (see “PTSD lessons from Israel, Colombia,”).

Terror and your patients

Which symptoms are you most likely to see in existing patients subsequent to recent events? In the weeks following the Sept. 11 attacks, psychiatrists reported the most commonly seen symptoms as increased anxiety and worsened depression. Sleep disturbances, agoraphobia, suicidality, and severe reactions among patients with personality disorders also were reported.

Patients with previous PTSD or exposure to trauma face a high risk of new or recurrent PTSD in the wake of Sept. 11 than do those not previously exposed to trauma.¹ War veterans with prior posttraumatic symptoms have been particularly prone to recurrent PTSD after the attacks. James Allen, MD, of the Department of Psychiatry and Behavioral Sciences at the University of Oklahoma Health Sciences Center, calls this the “additive effect”: patients traumatized by military service in Vietnam experience a recurrence after seeing a major disaster or atrocity. Dr. Allen, who was extensively involved with Oklahoma City’s disaster psychiatry effort after the 1995 bombing there, recalls seeing patients who were traumatized in Vietnam suffer a recurrence after the Alfred P. Murrah Building attack, and then another relapse after Sept. 11.

“The Sept. 11 attacks were very similar to the war for them,” says Juan Corvalan, MD, of the PTSD Unit of the St. Louis Veterans Administration Medical Center, referring to the numerous war veterans he treated after the atrocities. “Seeing it on TV triggered many memories.” By early November, however, many who experienced recurrent PTSD had returned to their pre-Sept. 11 mental states.

Craig Katz, MD, director of emergency psychiatry services at New York’s Mount Sinai Medical Center, says that a patient’s psychiatric history is crucial to determining risk for PTSD or other terror-related sequelae:

“You can recognize that a given person is at high risk for PTSD post-trauma, based on any combination of these factors—having a psychiatric history, past trauma, high exposure to the event, psychosocial problems pre-disaster, or lack of supports post-disaster.”

The clinical interview is a vital tool in assessing patients with suspected PTSD or posttraumatic sequelae, says Arieh Shalev, MD, of the department of psychiatry at Hadassah University Hospital in Jerusalem, Israel. “It provides the opportunity to discuss the traumatic event with the patient, and to listen to his or her perceptions of the event and its effects” in order to carefully appraise the patient’s symptoms.²

The guidelines set forth in the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) remain the gold standard for confirming a diagnosis of PTSD and discerning long-term posttraumatic sequelae from temporary acute stress disorder (Box 1). The guidelines have proved far from foolproof, however, and the existence of psychiatric comorbidities often clouds the picture.

Box 1

DSM-IV DIAGNOSTIC CRITERIA FOR PTSD

1. Exposure to a traumatic event with both of the following present:
2. The traumatic event is persistently reexperienced in one or more of the following ways:
3. Persistent avoidance of stimuli associated with the trauma and numbing of general responsiveness (not present before the trauma), as indicated by three or more of the following:
4. Persistent symptoms of increased arousal (not present before the trauma), as indicated by two or more of the following:
5. Duration of symptoms in criteria B, C or D exceeds 1 month.
6. Disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Specify if; Acute: if duration of symptoms is less than 3 months.

Chronic: if symptoms persist 3 months or more.

With delayed onset: if onset of symptoms is at least 6 months after the stressor.

Acute stress disorder, whose symptom pattern is similar to that of PTSD, is distinguished from PTSD because the symptom pattern must occur and resolve within 4 weeks of the traumatic event. If the symptoms persist for more than 1 month and meet the criteria for PTSD, the diagnosis is changed from acute stress disorder to PTSD.

Differential diagnosis of PTSD

Patients with PTSD are more likely to have substantial psychiatric comorbidity than are those without the disorder.³ Possible reasons include suspected self-medication of PTSD symptoms, particularly among patients with substance abuse, and the possible overreporting of symptoms by patients. Psychiatrists should maintain a high level of suspicion for PTSD when managing a new or existing patient with psychopathology.

Citing data from the National Comorbidity Study of the Institute for Social Research at the University of Michigan, Kessler and others in 1995 noted that more than 80 percent of individuals with PTSD meet criteria for at least one other psychiatric diagnosis. Roughly half of PTSD sufferers met criteria for three or more comorbidities.³

Kathleen Brady, MD, professor of psychiatry at the Medical University of South Carolina in Charleston, noted in a 1997 study that affective disorders, other anxiety disorders, somatization, substance abuse, and dissociative disorders are common comorbidities of PTSD.⁵ Dr. Shalev and colleagues in one study found that a history of major depressive disorder may increase the severity of posttraumatic morbidity.⁶ Dr. Brady and others also have found that PTSD patients with a comorbid substance abuse disorder experience severe PTSD symptoms while in a withdrawal state.⁷

Box 2

PTSD often is overlooked in the presence of other psychiatric diagnoses. Meuser et al in 1998 studied 275 patients with schizophrenia and bipolar disorder. As many as 98 percent of patients reported lifetime exposure to at least one traumatic event. The researchers found diagnosable PTSD in 119 (43 %) of the subjects, but only three (2%) had the diagnosis in their charts.⁸

In a later study, Dr. Brady and others cited substantial symptom overlap between PTSD and other psychiatric diagnoses, particularly major depressive disorder. This can contribute to underdiagnosis of PTSD, the researchers found.⁷ (Box 2).

Box 3

WATCH FOR SIGNS OF PTSD IN CHILDREN

Children also have been experiencing stress disorders since Sept. 11, says Arshad Husain, MD, professor and chief of child and adolescent psychiatry and director of the International Center for Psychosocial Trauma at the University of Missouri-Columbia. Such disorders manifest as sleep disturbances, anxiety, hyperarousal/hyperactivity, and nightmares.

Young children regress and cling to their parents, and are frightened of the dark or noises, Dr, Husain notes. Those who are toilet-trained can suddenly wet the bed, become neurotic, and demand attention. School-age children are more fearful; they may not want to go to school, their schoolwork may decline, and they may have trouble paying attention. Dr. Husain suggests discussing the trauma and devising a plan of action with them in case the trauma recurs.

The media’s role in reporting on the aftermath of the attacks—and triggering traumatic reactions as an unintended consequence—cannot be overlooked. Two recent studies performed after the Oklahoma City bombing suggest that television reports of that atrocity precipitated PTSD symptoms in middle-school children 7 weeks after the bombing,²³ and in geographically distant sixth-graders 2 years after the attack.¹² It was not clear whether any of these students had prior PTSD or other psychopathology.

Psychiatric education in the schools is especially crucial in light of the school violence that has occurred in America in recent years. Dr. Husain believes that the children who commit violence are victims of abuse. If teachers early on can identify children who show evidence of stress disorders, they can refer them to trained psychiatrists, catching those who need help before tragedies occur. “It is the psychiatric equivalent of CPR,” Dr. Husain says.

Dr. Brady recommends that psychiatrists and primary care physicians routinely screen patients for exposure to traumatic events. Ask patients specifically about their reaction to such events and encourage them to talk about it. Patients often feel either guilty or embarrassed about the traumatic event, or do not believe it affects their presenting complaints, she notes. Other approaches may be needed to identify the risk of PTSD in children (Box 3).

Identifying a traumatic event of an extreme nature, for example, a life-threatening experience, is key to diagnosing PTSD in the presence of comorbidities, Dr. Corvalan says. “Some of the symptoms—such as avoidance, numbing, and increased arousal—are present in other disorders and may have occurred before exposure to the traumatic event.” If they did, he says, PTSD is ruled out.

Gauging the extent of the patient’s exposure to the traumatic event is critical to determining the likelihood of PTSD onset. Dr. Allen, of Oklahoma City, points to studies that show that the closer and longer the patient has been exposed to a catastrophic event, the more likely he or she will develop PTSD.^9,10

Julia Frank, MD, associate professor and director of student education and psychiatry at George Washington University in Washington, DC, suggests screening for symptoms that are unique to PTSD as stated in the DSM-IV, such as nightmares, difficulty remembering the traumatic event, and extreme reactions to reminders of the trauma. She also proposes analyzing the past event and the patient’s reaction to it to confirm that it is a source of trauma.

Patients with PTSD symptoms are easily startled by loud or piercing noises. Dr. Shalev says this characteristic sets true PTSD cases apart from other psychopathology, particularly depression. In one study, Israeli combat veterans with PTSD exhibited a more pronounced heart rate and skin conductance when exposed to auditory stimuli than did combat veterans with no PTSD symptoms.¹¹

Drs. Allen and Frank note that patients who have anthrax-related fears and no prior PTSD symptoms are not likely to develop PTSD. They may, however, manifest symptoms of chronic fatigue, fibromyalgia, and generalized anxiety disorder. Patients may be jumpy, intense, or lethargic, with autonomic instability and rapid heart rate. They may feel alienated and mistrustful of the government. A nonspecific stress disorder and mixed anxiety depression are other possible effects.

Who to treat—and how

Psychiatrists nationwide have reported increased patient presentations after the Sept. 11 attacks and throughout the anthrax scare. Studies conducted after the Oklahoma City bombing also suggest that psychiatrists could be seeing more patients in the coming months.^12,13 As caseloads increase, so do the questions about who to treat, how, and how to avoid the possibility of overtreatment.

“In order to provide effective care to our patients it is necessary to have clear ideas on how to follow criteria for diagnosis and as a consequence for treatment,” Dr. Corvalan says. “The field at times is confusing; patients do not always follow the diagnostic criteria. The needs of the moment, limitations of recourses, intensity and variety of symptoms, urgency of the situation, etc., all conspire to make the job more difficult.”

Patients with anthrax-related anxiety should be encouraged to “try to function as normally as possible and keep an open communication with peers and those who they look to for information,” Dr. Frank notes. Dr. Allen adds that his patients with anthrax-inspired stress have responded well to breathing, meditation and other relaxation techniques.

Treatment of patients who are severely traumatized and exhibit true PTSD symptoms will vary based on severity of exposure, history of prior PTSD, and existence of comorbidities. A combination of pharmacological and psychosocial therapy is the common first-line treatment.

The selective serotonin reuptake inhibitor (SSRI) sertraline is specifically indicated for treating confirmed PTSD symptoms, and several studies have documented the agent’s effectiveness for this use.^14,15 Dr. Frank recommends dosages between 50 and 200 mg/d depending on the patient’s body weight or complaint of side effects (e.g., diarrhea, nausea, or sexual dysfunction). Other SSRIs, as well as tricyclics and MAO inhibitors, are alternatives. Fluoxetine, amitriptyline, phenelzine, and imipramine have all been found more effective than a placebo;^16-18 paroxetine also has been shown effective in specific populations.¹⁹

Box 4

Benzodiazapenes also may be prescribed to manage PTSD symptoms. Patients should be counseled against taking these sedating agents in the daytime, however, as they can lead to fogginess, detachment, and trouble functioning.

Assessing the patient’s available social support also is crucial to PTSD treatment. “Do patients talk to other people about the event?” Dr. Frank asks. “Are they trying to get back to a daily routine? Can they make sense of this experience? Are they incorporating the event into a world view?”

Dr. Thompson, the Pittsburgh disaster psychiatrist, agrees. Psychiatrists should encourage their patients to talk more about their trauma and how fear is affecting their lives. “We don’t discuss with our trauma patients as much as we might what the experience has been like for them,” he says.

Small-group therapy is the most conducive approach to psychotherapy for PTSD, according to Dr. Frank, although individual counseling can work in many cases. Several studies have found group therapy effective,^20,21 and 12-step group therapy has shown promise in PTSD patients with comorbid substance abuse disorder.²²

Managing fear

Just as people grieve and confront death in stages, Dr. Thompson, who helped coordinate Oklahoma City’s disaster psychiatry effort, has discovered that the public usually employs a similar subconscious process to cope with a traumatic event (Box 4).

But Americans have had no time to recover. As U.S. troops seek justice in Afghanistan, back home people grapple with the threat of anthrax contamination and the prospect of another terrorist attack. The ominously enhanced presence of security at airports, major bridges, sporting and entertainment events, and in other aspects of everyday life, has further fueled the sensation that all is not right.

“The September 11 tragedy brings trauma home,” adds Arshad Husain, MD, professor and chief of child and adolescent psychiatry and director of the International Center for Psychosocial Trauma at the University of Missouri-Columbia. “The anthrax scare and the Nov. 12 plane crash of American Airlines Flight 587 only further remind people of their vulnerability and fears. If the anthrax scare were an accident, people would have been relieved. Since the plane crash was ruled an accident, it has offered people a chance to feel more in control. Accidents can be fixed with better maintenance. Terrorism cannot.”

Dr. Katz of New York City and other disaster psychiatrists are urging their colleagues to help manage public fear by reaching out through community efforts.

Dr. Katz is president of the volunteer group Disaster Psychiatry Outreach, which helped coordinate the city’s post-Sept. 11 trauma psychiatry effort. Visitors waiting at New York’s Family Assistance Center, a referral and help center for people who lost family and friends in the World Trade Center attack, were approached by Dr. Katz and other colleagues to let them know that psychiatric services were available if needed. By doing this, he says, Disaster Psychiatry Outreach clinicians have identified, treated, and referred scores of patients with terror-related stress who otherwise would have gone untreated.

Joseph Dorzab, MD, of the Holt-Krock Clinic in Fort Smith, Ark., also has offered his services. Members of his clinic’s psychiatry department have made several TV appearances, and have given and coordinated area lectures. Working with the local mental health association, the department also is starting a community forum called Mental Health Mondays, an open discussion group with coffee and cookies at a local coffee shop.

In Pittsburgh, Dr. Thompson is encouraging psychiatrists to educate their communities about how traumatic events affect the public. He proposes:

• Staging community meetings to brief religious and other leaders on how to manage traumatized people;
• Informing local news editors about the nature of psychiatric disorders;
• Instructing school administrators about detecting signs of distress in children;
• Contacting local government officials to offer input in devising the town’s emergency response plan.

Psychiatrists also can educate themselves about managing public trauma, thanks to scores of studies that have been done in recent years following major man-made and natural disasters, from Mount St. Helens and Hurricane Andrew, to Chernobyl and the Yom Kippur War. Dr. Thompson urges psychiatrists to seek out the papers of prominent leaders in trauma-related psychiatry, mentioning studies by Carol North, MD, Betty Pfefferbaum, MD, and Robert Ursano, MD, as examples. Other sources include the Web sites of the American Psychiatric Association and National Center for PTSD. (See Related Resources.)

In the end, psychiatrists have been well primed for dealing with public disaster—just by treating individual patients whose psychiatric disorders emanated from everyday life, Dr. Thompson says. “Psychiatrists know more about trauma than they recognize.”

Related resources

• National Center for PTSD Web site
• National Institute of Mental Health:
• Linenthal EJ. The Unfinished Bombing: Oklahoma City in American Memory. Oxford University Press, 2001.
• Norwood AE, Ursano RJ, Fullerton CS. Disaster psychiatry: principles of practice. Psychiatr Q. 2000; 71(3):207-226.
• American Psychiatric Association Web site:
• The Psychiatric Training Manual for Teachers and Mental Health Professionals

Drug brand names

• Amitriptyline • Elavil
• Bupropion • Wellbutrin
• Fluoxetine • Prozac
• Imipramine • Tofranil
• Paroxetine • Paxil
• Phenelzine • Nardil
• Sertraline • Zoloft

Since September 11, America has carried on under a cloud of fear. Though the cloud is lifting, it will not disappear for months or years. The terrorist attacks on New York City and Washington, DC, the resultant military action in Afghanistan, and the anthrax scare—combined with pervasive, nagging doubts about homeland security and the specter of another possible future terrorist attack—all are straining the nation’s collective emotional well-being.

Psychiatrists in America have reported new cases of terror-inspired acute stress disorder, anxiety, depression, and other illnesses, as well as recurrences of posttraumatic stress disorder (PTSD) in existing patients, in the weeks after the recent attacks and the anthrax scare. What will be the impact on psychiatric practice in the coming months and years?

“We are all at ground zero,” says Kenneth S. Thompson, MD, of Pittsburgh, an experienced disaster psychiatrist. But he and other subspecialists have identified four critical areas in which psychiatrists should be prepared:

1. Identifying how terrorist attacks and scares can exacerbate symptoms in patients now in your practice;
2. Diagnosing PTSD among comorbid conditions present in existing or new patients;
3. Treating—and avoiding over-treatment—of patients with acute stress disorder and PTSD;
4. Managing fear in your communities—in response to the Sept. 11 attacks, to the anthrax scare, or in anticipation of an impending catastrophe.

To bring you this special report, the editors of Current Psychiatry have reviewed the literature and interviewed psychiatrists nationwide and in countries such as Israel and Colombia, where terrorism has been a fact of life for years (see “PTSD lessons from Israel, Colombia,”).

Terror and your patients

Which symptoms are you most likely to see in existing patients subsequent to recent events? In the weeks following the Sept. 11 attacks, psychiatrists reported the most commonly seen symptoms as increased anxiety and worsened depression. Sleep disturbances, agoraphobia, suicidality, and severe reactions among patients with personality disorders also were reported.

Patients with previous PTSD or exposure to trauma face a high risk of new or recurrent PTSD in the wake of Sept. 11 than do those not previously exposed to trauma.¹ War veterans with prior posttraumatic symptoms have been particularly prone to recurrent PTSD after the attacks. James Allen, MD, of the Department of Psychiatry and Behavioral Sciences at the University of Oklahoma Health Sciences Center, calls this the “additive effect”: patients traumatized by military service in Vietnam experience a recurrence after seeing a major disaster or atrocity. Dr. Allen, who was extensively involved with Oklahoma City’s disaster psychiatry effort after the 1995 bombing there, recalls seeing patients who were traumatized in Vietnam suffer a recurrence after the Alfred P. Murrah Building attack, and then another relapse after Sept. 11.

“The Sept. 11 attacks were very similar to the war for them,” says Juan Corvalan, MD, of the PTSD Unit of the St. Louis Veterans Administration Medical Center, referring to the numerous war veterans he treated after the atrocities. “Seeing it on TV triggered many memories.” By early November, however, many who experienced recurrent PTSD had returned to their pre-Sept. 11 mental states.

Craig Katz, MD, director of emergency psychiatry services at New York’s Mount Sinai Medical Center, says that a patient’s psychiatric history is crucial to determining risk for PTSD or other terror-related sequelae:

“You can recognize that a given person is at high risk for PTSD post-trauma, based on any combination of these factors—having a psychiatric history, past trauma, high exposure to the event, psychosocial problems pre-disaster, or lack of supports post-disaster.”

The clinical interview is a vital tool in assessing patients with suspected PTSD or posttraumatic sequelae, says Arieh Shalev, MD, of the department of psychiatry at Hadassah University Hospital in Jerusalem, Israel. “It provides the opportunity to discuss the traumatic event with the patient, and to listen to his or her perceptions of the event and its effects” in order to carefully appraise the patient’s symptoms.²

The guidelines set forth in the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) remain the gold standard for confirming a diagnosis of PTSD and discerning long-term posttraumatic sequelae from temporary acute stress disorder (Box 1). The guidelines have proved far from foolproof, however, and the existence of psychiatric comorbidities often clouds the picture.

Box 1

DSM-IV DIAGNOSTIC CRITERIA FOR PTSD

1. Exposure to a traumatic event with both of the following present:
2. The traumatic event is persistently reexperienced in one or more of the following ways:
3. Persistent avoidance of stimuli associated with the trauma and numbing of general responsiveness (not present before the trauma), as indicated by three or more of the following:
4. Persistent symptoms of increased arousal (not present before the trauma), as indicated by two or more of the following:
5. Duration of symptoms in criteria B, C or D exceeds 1 month.
6. Disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Specify if; Acute: if duration of symptoms is less than 3 months.

Chronic: if symptoms persist 3 months or more.

With delayed onset: if onset of symptoms is at least 6 months after the stressor.

Acute stress disorder, whose symptom pattern is similar to that of PTSD, is distinguished from PTSD because the symptom pattern must occur and resolve within 4 weeks of the traumatic event. If the symptoms persist for more than 1 month and meet the criteria for PTSD, the diagnosis is changed from acute stress disorder to PTSD.

Differential diagnosis of PTSD

Patients with PTSD are more likely to have substantial psychiatric comorbidity than are those without the disorder.³ Possible reasons include suspected self-medication of PTSD symptoms, particularly among patients with substance abuse, and the possible overreporting of symptoms by patients. Psychiatrists should maintain a high level of suspicion for PTSD when managing a new or existing patient with psychopathology.

Citing data from the National Comorbidity Study of the Institute for Social Research at the University of Michigan, Kessler and others in 1995 noted that more than 80 percent of individuals with PTSD meet criteria for at least one other psychiatric diagnosis. Roughly half of PTSD sufferers met criteria for three or more comorbidities.³

Kathleen Brady, MD, professor of psychiatry at the Medical University of South Carolina in Charleston, noted in a 1997 study that affective disorders, other anxiety disorders, somatization, substance abuse, and dissociative disorders are common comorbidities of PTSD.⁵ Dr. Shalev and colleagues in one study found that a history of major depressive disorder may increase the severity of posttraumatic morbidity.⁶ Dr. Brady and others also have found that PTSD patients with a comorbid substance abuse disorder experience severe PTSD symptoms while in a withdrawal state.⁷

Box 2

PTSD often is overlooked in the presence of other psychiatric diagnoses. Meuser et al in 1998 studied 275 patients with schizophrenia and bipolar disorder. As many as 98 percent of patients reported lifetime exposure to at least one traumatic event. The researchers found diagnosable PTSD in 119 (43 %) of the subjects, but only three (2%) had the diagnosis in their charts.⁸

In a later study, Dr. Brady and others cited substantial symptom overlap between PTSD and other psychiatric diagnoses, particularly major depressive disorder. This can contribute to underdiagnosis of PTSD, the researchers found.⁷ (Box 2).

Box 3

WATCH FOR SIGNS OF PTSD IN CHILDREN

Children also have been experiencing stress disorders since Sept. 11, says Arshad Husain, MD, professor and chief of child and adolescent psychiatry and director of the International Center for Psychosocial Trauma at the University of Missouri-Columbia. Such disorders manifest as sleep disturbances, anxiety, hyperarousal/hyperactivity, and nightmares.

Young children regress and cling to their parents, and are frightened of the dark or noises, Dr, Husain notes. Those who are toilet-trained can suddenly wet the bed, become neurotic, and demand attention. School-age children are more fearful; they may not want to go to school, their schoolwork may decline, and they may have trouble paying attention. Dr. Husain suggests discussing the trauma and devising a plan of action with them in case the trauma recurs.

The media’s role in reporting on the aftermath of the attacks—and triggering traumatic reactions as an unintended consequence—cannot be overlooked. Two recent studies performed after the Oklahoma City bombing suggest that television reports of that atrocity precipitated PTSD symptoms in middle-school children 7 weeks after the bombing,²³ and in geographically distant sixth-graders 2 years after the attack.¹² It was not clear whether any of these students had prior PTSD or other psychopathology.

Psychiatric education in the schools is especially crucial in light of the school violence that has occurred in America in recent years. Dr. Husain believes that the children who commit violence are victims of abuse. If teachers early on can identify children who show evidence of stress disorders, they can refer them to trained psychiatrists, catching those who need help before tragedies occur. “It is the psychiatric equivalent of CPR,” Dr. Husain says.

Dr. Brady recommends that psychiatrists and primary care physicians routinely screen patients for exposure to traumatic events. Ask patients specifically about their reaction to such events and encourage them to talk about it. Patients often feel either guilty or embarrassed about the traumatic event, or do not believe it affects their presenting complaints, she notes. Other approaches may be needed to identify the risk of PTSD in children (Box 3).

Identifying a traumatic event of an extreme nature, for example, a life-threatening experience, is key to diagnosing PTSD in the presence of comorbidities, Dr. Corvalan says. “Some of the symptoms—such as avoidance, numbing, and increased arousal—are present in other disorders and may have occurred before exposure to the traumatic event.” If they did, he says, PTSD is ruled out.

Gauging the extent of the patient’s exposure to the traumatic event is critical to determining the likelihood of PTSD onset. Dr. Allen, of Oklahoma City, points to studies that show that the closer and longer the patient has been exposed to a catastrophic event, the more likely he or she will develop PTSD.^9,10

Julia Frank, MD, associate professor and director of student education and psychiatry at George Washington University in Washington, DC, suggests screening for symptoms that are unique to PTSD as stated in the DSM-IV, such as nightmares, difficulty remembering the traumatic event, and extreme reactions to reminders of the trauma. She also proposes analyzing the past event and the patient’s reaction to it to confirm that it is a source of trauma.

Patients with PTSD symptoms are easily startled by loud or piercing noises. Dr. Shalev says this characteristic sets true PTSD cases apart from other psychopathology, particularly depression. In one study, Israeli combat veterans with PTSD exhibited a more pronounced heart rate and skin conductance when exposed to auditory stimuli than did combat veterans with no PTSD symptoms.¹¹

Drs. Allen and Frank note that patients who have anthrax-related fears and no prior PTSD symptoms are not likely to develop PTSD. They may, however, manifest symptoms of chronic fatigue, fibromyalgia, and generalized anxiety disorder. Patients may be jumpy, intense, or lethargic, with autonomic instability and rapid heart rate. They may feel alienated and mistrustful of the government. A nonspecific stress disorder and mixed anxiety depression are other possible effects.

Who to treat—and how

Psychiatrists nationwide have reported increased patient presentations after the Sept. 11 attacks and throughout the anthrax scare. Studies conducted after the Oklahoma City bombing also suggest that psychiatrists could be seeing more patients in the coming months.^12,13 As caseloads increase, so do the questions about who to treat, how, and how to avoid the possibility of overtreatment.

“In order to provide effective care to our patients it is necessary to have clear ideas on how to follow criteria for diagnosis and as a consequence for treatment,” Dr. Corvalan says. “The field at times is confusing; patients do not always follow the diagnostic criteria. The needs of the moment, limitations of recourses, intensity and variety of symptoms, urgency of the situation, etc., all conspire to make the job more difficult.”

Patients with anthrax-related anxiety should be encouraged to “try to function as normally as possible and keep an open communication with peers and those who they look to for information,” Dr. Frank notes. Dr. Allen adds that his patients with anthrax-inspired stress have responded well to breathing, meditation and other relaxation techniques.

Treatment of patients who are severely traumatized and exhibit true PTSD symptoms will vary based on severity of exposure, history of prior PTSD, and existence of comorbidities. A combination of pharmacological and psychosocial therapy is the common first-line treatment.

The selective serotonin reuptake inhibitor (SSRI) sertraline is specifically indicated for treating confirmed PTSD symptoms, and several studies have documented the agent’s effectiveness for this use.^14,15 Dr. Frank recommends dosages between 50 and 200 mg/d depending on the patient’s body weight or complaint of side effects (e.g., diarrhea, nausea, or sexual dysfunction). Other SSRIs, as well as tricyclics and MAO inhibitors, are alternatives. Fluoxetine, amitriptyline, phenelzine, and imipramine have all been found more effective than a placebo;^16-18 paroxetine also has been shown effective in specific populations.¹⁹

Box 4

Benzodiazapenes also may be prescribed to manage PTSD symptoms. Patients should be counseled against taking these sedating agents in the daytime, however, as they can lead to fogginess, detachment, and trouble functioning.

Assessing the patient’s available social support also is crucial to PTSD treatment. “Do patients talk to other people about the event?” Dr. Frank asks. “Are they trying to get back to a daily routine? Can they make sense of this experience? Are they incorporating the event into a world view?”

Dr. Thompson, the Pittsburgh disaster psychiatrist, agrees. Psychiatrists should encourage their patients to talk more about their trauma and how fear is affecting their lives. “We don’t discuss with our trauma patients as much as we might what the experience has been like for them,” he says.

Small-group therapy is the most conducive approach to psychotherapy for PTSD, according to Dr. Frank, although individual counseling can work in many cases. Several studies have found group therapy effective,^20,21 and 12-step group therapy has shown promise in PTSD patients with comorbid substance abuse disorder.²²

Managing fear

Just as people grieve and confront death in stages, Dr. Thompson, who helped coordinate Oklahoma City’s disaster psychiatry effort, has discovered that the public usually employs a similar subconscious process to cope with a traumatic event (Box 4).

But Americans have had no time to recover. As U.S. troops seek justice in Afghanistan, back home people grapple with the threat of anthrax contamination and the prospect of another terrorist attack. The ominously enhanced presence of security at airports, major bridges, sporting and entertainment events, and in other aspects of everyday life, has further fueled the sensation that all is not right.

“The September 11 tragedy brings trauma home,” adds Arshad Husain, MD, professor and chief of child and adolescent psychiatry and director of the International Center for Psychosocial Trauma at the University of Missouri-Columbia. “The anthrax scare and the Nov. 12 plane crash of American Airlines Flight 587 only further remind people of their vulnerability and fears. If the anthrax scare were an accident, people would have been relieved. Since the plane crash was ruled an accident, it has offered people a chance to feel more in control. Accidents can be fixed with better maintenance. Terrorism cannot.”

Dr. Katz of New York City and other disaster psychiatrists are urging their colleagues to help manage public fear by reaching out through community efforts.

Dr. Katz is president of the volunteer group Disaster Psychiatry Outreach, which helped coordinate the city’s post-Sept. 11 trauma psychiatry effort. Visitors waiting at New York’s Family Assistance Center, a referral and help center for people who lost family and friends in the World Trade Center attack, were approached by Dr. Katz and other colleagues to let them know that psychiatric services were available if needed. By doing this, he says, Disaster Psychiatry Outreach clinicians have identified, treated, and referred scores of patients with terror-related stress who otherwise would have gone untreated.

Joseph Dorzab, MD, of the Holt-Krock Clinic in Fort Smith, Ark., also has offered his services. Members of his clinic’s psychiatry department have made several TV appearances, and have given and coordinated area lectures. Working with the local mental health association, the department also is starting a community forum called Mental Health Mondays, an open discussion group with coffee and cookies at a local coffee shop.

In Pittsburgh, Dr. Thompson is encouraging psychiatrists to educate their communities about how traumatic events affect the public. He proposes:

• Staging community meetings to brief religious and other leaders on how to manage traumatized people;
• Informing local news editors about the nature of psychiatric disorders;
• Instructing school administrators about detecting signs of distress in children;
• Contacting local government officials to offer input in devising the town’s emergency response plan.

Psychiatrists also can educate themselves about managing public trauma, thanks to scores of studies that have been done in recent years following major man-made and natural disasters, from Mount St. Helens and Hurricane Andrew, to Chernobyl and the Yom Kippur War. Dr. Thompson urges psychiatrists to seek out the papers of prominent leaders in trauma-related psychiatry, mentioning studies by Carol North, MD, Betty Pfefferbaum, MD, and Robert Ursano, MD, as examples. Other sources include the Web sites of the American Psychiatric Association and National Center for PTSD. (See Related Resources.)

In the end, psychiatrists have been well primed for dealing with public disaster—just by treating individual patients whose psychiatric disorders emanated from everyday life, Dr. Thompson says. “Psychiatrists know more about trauma than they recognize.”

Related resources

• National Center for PTSD Web site
• National Institute of Mental Health:
• Linenthal EJ. The Unfinished Bombing: Oklahoma City in American Memory. Oxford University Press, 2001.
• Norwood AE, Ursano RJ, Fullerton CS. Disaster psychiatry: principles of practice. Psychiatr Q. 2000; 71(3):207-226.
• American Psychiatric Association Web site:
• The Psychiatric Training Manual for Teachers and Mental Health Professionals

Drug brand names

• Amitriptyline • Elavil
• Bupropion • Wellbutrin
• Fluoxetine • Prozac
• Imipramine • Tofranil
• Paroxetine • Paxil
• Phenelzine • Nardil
• Sertraline • Zoloft

Since September 11, America has carried on under a cloud of fear. Though the cloud is lifting, it will not disappear for months or years. The terrorist attacks on New York City and Washington, DC, the resultant military action in Afghanistan, and the anthrax scare—combined with pervasive, nagging doubts about homeland security and the specter of another possible future terrorist attack—all are straining the nation’s collective emotional well-being.

Psychiatrists in America have reported new cases of terror-inspired acute stress disorder, anxiety, depression, and other illnesses, as well as recurrences of posttraumatic stress disorder (PTSD) in existing patients, in the weeks after the recent attacks and the anthrax scare. What will be the impact on psychiatric practice in the coming months and years?

“We are all at ground zero,” says Kenneth S. Thompson, MD, of Pittsburgh, an experienced disaster psychiatrist. But he and other subspecialists have identified four critical areas in which psychiatrists should be prepared:

1. Identifying how terrorist attacks and scares can exacerbate symptoms in patients now in your practice;
2. Diagnosing PTSD among comorbid conditions present in existing or new patients;
3. Treating—and avoiding over-treatment—of patients with acute stress disorder and PTSD;
4. Managing fear in your communities—in response to the Sept. 11 attacks, to the anthrax scare, or in anticipation of an impending catastrophe.

To bring you this special report, the editors of Current Psychiatry have reviewed the literature and interviewed psychiatrists nationwide and in countries such as Israel and Colombia, where terrorism has been a fact of life for years (see “PTSD lessons from Israel, Colombia,”).

Terror and your patients

Which symptoms are you most likely to see in existing patients subsequent to recent events? In the weeks following the Sept. 11 attacks, psychiatrists reported the most commonly seen symptoms as increased anxiety and worsened depression. Sleep disturbances, agoraphobia, suicidality, and severe reactions among patients with personality disorders also were reported.

Patients with previous PTSD or exposure to trauma face a high risk of new or recurrent PTSD in the wake of Sept. 11 than do those not previously exposed to trauma.¹ War veterans with prior posttraumatic symptoms have been particularly prone to recurrent PTSD after the attacks. James Allen, MD, of the Department of Psychiatry and Behavioral Sciences at the University of Oklahoma Health Sciences Center, calls this the “additive effect”: patients traumatized by military service in Vietnam experience a recurrence after seeing a major disaster or atrocity. Dr. Allen, who was extensively involved with Oklahoma City’s disaster psychiatry effort after the 1995 bombing there, recalls seeing patients who were traumatized in Vietnam suffer a recurrence after the Alfred P. Murrah Building attack, and then another relapse after Sept. 11.

“The Sept. 11 attacks were very similar to the war for them,” says Juan Corvalan, MD, of the PTSD Unit of the St. Louis Veterans Administration Medical Center, referring to the numerous war veterans he treated after the atrocities. “Seeing it on TV triggered many memories.” By early November, however, many who experienced recurrent PTSD had returned to their pre-Sept. 11 mental states.

Craig Katz, MD, director of emergency psychiatry services at New York’s Mount Sinai Medical Center, says that a patient’s psychiatric history is crucial to determining risk for PTSD or other terror-related sequelae:

“You can recognize that a given person is at high risk for PTSD post-trauma, based on any combination of these factors—having a psychiatric history, past trauma, high exposure to the event, psychosocial problems pre-disaster, or lack of supports post-disaster.”

The clinical interview is a vital tool in assessing patients with suspected PTSD or posttraumatic sequelae, says Arieh Shalev, MD, of the department of psychiatry at Hadassah University Hospital in Jerusalem, Israel. “It provides the opportunity to discuss the traumatic event with the patient, and to listen to his or her perceptions of the event and its effects” in order to carefully appraise the patient’s symptoms.²

The guidelines set forth in the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) remain the gold standard for confirming a diagnosis of PTSD and discerning long-term posttraumatic sequelae from temporary acute stress disorder (Box 1). The guidelines have proved far from foolproof, however, and the existence of psychiatric comorbidities often clouds the picture.

Box 1

DSM-IV DIAGNOSTIC CRITERIA FOR PTSD

1. Exposure to a traumatic event with both of the following present:
2. The traumatic event is persistently reexperienced in one or more of the following ways:
3. Persistent avoidance of stimuli associated with the trauma and numbing of general responsiveness (not present before the trauma), as indicated by three or more of the following:
4. Persistent symptoms of increased arousal (not present before the trauma), as indicated by two or more of the following:
5. Duration of symptoms in criteria B, C or D exceeds 1 month.
6. Disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Specify if; Acute: if duration of symptoms is less than 3 months.

Chronic: if symptoms persist 3 months or more.

With delayed onset: if onset of symptoms is at least 6 months after the stressor.

Acute stress disorder, whose symptom pattern is similar to that of PTSD, is distinguished from PTSD because the symptom pattern must occur and resolve within 4 weeks of the traumatic event. If the symptoms persist for more than 1 month and meet the criteria for PTSD, the diagnosis is changed from acute stress disorder to PTSD.

Differential diagnosis of PTSD

Patients with PTSD are more likely to have substantial psychiatric comorbidity than are those without the disorder.³ Possible reasons include suspected self-medication of PTSD symptoms, particularly among patients with substance abuse, and the possible overreporting of symptoms by patients. Psychiatrists should maintain a high level of suspicion for PTSD when managing a new or existing patient with psychopathology.

Citing data from the National Comorbidity Study of the Institute for Social Research at the University of Michigan, Kessler and others in 1995 noted that more than 80 percent of individuals with PTSD meet criteria for at least one other psychiatric diagnosis. Roughly half of PTSD sufferers met criteria for three or more comorbidities.³

Kathleen Brady, MD, professor of psychiatry at the Medical University of South Carolina in Charleston, noted in a 1997 study that affective disorders, other anxiety disorders, somatization, substance abuse, and dissociative disorders are common comorbidities of PTSD.⁵ Dr. Shalev and colleagues in one study found that a history of major depressive disorder may increase the severity of posttraumatic morbidity.⁶ Dr. Brady and others also have found that PTSD patients with a comorbid substance abuse disorder experience severe PTSD symptoms while in a withdrawal state.⁷

Box 2

PTSD often is overlooked in the presence of other psychiatric diagnoses. Meuser et al in 1998 studied 275 patients with schizophrenia and bipolar disorder. As many as 98 percent of patients reported lifetime exposure to at least one traumatic event. The researchers found diagnosable PTSD in 119 (43 %) of the subjects, but only three (2%) had the diagnosis in their charts.⁸

In a later study, Dr. Brady and others cited substantial symptom overlap between PTSD and other psychiatric diagnoses, particularly major depressive disorder. This can contribute to underdiagnosis of PTSD, the researchers found.⁷ (Box 2).

Box 3

WATCH FOR SIGNS OF PTSD IN CHILDREN

Children also have been experiencing stress disorders since Sept. 11, says Arshad Husain, MD, professor and chief of child and adolescent psychiatry and director of the International Center for Psychosocial Trauma at the University of Missouri-Columbia. Such disorders manifest as sleep disturbances, anxiety, hyperarousal/hyperactivity, and nightmares.

Young children regress and cling to their parents, and are frightened of the dark or noises, Dr, Husain notes. Those who are toilet-trained can suddenly wet the bed, become neurotic, and demand attention. School-age children are more fearful; they may not want to go to school, their schoolwork may decline, and they may have trouble paying attention. Dr. Husain suggests discussing the trauma and devising a plan of action with them in case the trauma recurs.

The media’s role in reporting on the aftermath of the attacks—and triggering traumatic reactions as an unintended consequence—cannot be overlooked. Two recent studies performed after the Oklahoma City bombing suggest that television reports of that atrocity precipitated PTSD symptoms in middle-school children 7 weeks after the bombing,²³ and in geographically distant sixth-graders 2 years after the attack.¹² It was not clear whether any of these students had prior PTSD or other psychopathology.

Psychiatric education in the schools is especially crucial in light of the school violence that has occurred in America in recent years. Dr. Husain believes that the children who commit violence are victims of abuse. If teachers early on can identify children who show evidence of stress disorders, they can refer them to trained psychiatrists, catching those who need help before tragedies occur. “It is the psychiatric equivalent of CPR,” Dr. Husain says.

Dr. Brady recommends that psychiatrists and primary care physicians routinely screen patients for exposure to traumatic events. Ask patients specifically about their reaction to such events and encourage them to talk about it. Patients often feel either guilty or embarrassed about the traumatic event, or do not believe it affects their presenting complaints, she notes. Other approaches may be needed to identify the risk of PTSD in children (Box 3).

Identifying a traumatic event of an extreme nature, for example, a life-threatening experience, is key to diagnosing PTSD in the presence of comorbidities, Dr. Corvalan says. “Some of the symptoms—such as avoidance, numbing, and increased arousal—are present in other disorders and may have occurred before exposure to the traumatic event.” If they did, he says, PTSD is ruled out.

Gauging the extent of the patient’s exposure to the traumatic event is critical to determining the likelihood of PTSD onset. Dr. Allen, of Oklahoma City, points to studies that show that the closer and longer the patient has been exposed to a catastrophic event, the more likely he or she will develop PTSD.^9,10

Julia Frank, MD, associate professor and director of student education and psychiatry at George Washington University in Washington, DC, suggests screening for symptoms that are unique to PTSD as stated in the DSM-IV, such as nightmares, difficulty remembering the traumatic event, and extreme reactions to reminders of the trauma. She also proposes analyzing the past event and the patient’s reaction to it to confirm that it is a source of trauma.

Patients with PTSD symptoms are easily startled by loud or piercing noises. Dr. Shalev says this characteristic sets true PTSD cases apart from other psychopathology, particularly depression. In one study, Israeli combat veterans with PTSD exhibited a more pronounced heart rate and skin conductance when exposed to auditory stimuli than did combat veterans with no PTSD symptoms.¹¹

Drs. Allen and Frank note that patients who have anthrax-related fears and no prior PTSD symptoms are not likely to develop PTSD. They may, however, manifest symptoms of chronic fatigue, fibromyalgia, and generalized anxiety disorder. Patients may be jumpy, intense, or lethargic, with autonomic instability and rapid heart rate. They may feel alienated and mistrustful of the government. A nonspecific stress disorder and mixed anxiety depression are other possible effects.

Who to treat—and how

Psychiatrists nationwide have reported increased patient presentations after the Sept. 11 attacks and throughout the anthrax scare. Studies conducted after the Oklahoma City bombing also suggest that psychiatrists could be seeing more patients in the coming months.^12,13 As caseloads increase, so do the questions about who to treat, how, and how to avoid the possibility of overtreatment.

“In order to provide effective care to our patients it is necessary to have clear ideas on how to follow criteria for diagnosis and as a consequence for treatment,” Dr. Corvalan says. “The field at times is confusing; patients do not always follow the diagnostic criteria. The needs of the moment, limitations of recourses, intensity and variety of symptoms, urgency of the situation, etc., all conspire to make the job more difficult.”

Patients with anthrax-related anxiety should be encouraged to “try to function as normally as possible and keep an open communication with peers and those who they look to for information,” Dr. Frank notes. Dr. Allen adds that his patients with anthrax-inspired stress have responded well to breathing, meditation and other relaxation techniques.

Treatment of patients who are severely traumatized and exhibit true PTSD symptoms will vary based on severity of exposure, history of prior PTSD, and existence of comorbidities. A combination of pharmacological and psychosocial therapy is the common first-line treatment.

The selective serotonin reuptake inhibitor (SSRI) sertraline is specifically indicated for treating confirmed PTSD symptoms, and several studies have documented the agent’s effectiveness for this use.^14,15 Dr. Frank recommends dosages between 50 and 200 mg/d depending on the patient’s body weight or complaint of side effects (e.g., diarrhea, nausea, or sexual dysfunction). Other SSRIs, as well as tricyclics and MAO inhibitors, are alternatives. Fluoxetine, amitriptyline, phenelzine, and imipramine have all been found more effective than a placebo;^16-18 paroxetine also has been shown effective in specific populations.¹⁹

Box 4

Benzodiazapenes also may be prescribed to manage PTSD symptoms. Patients should be counseled against taking these sedating agents in the daytime, however, as they can lead to fogginess, detachment, and trouble functioning.

Assessing the patient’s available social support also is crucial to PTSD treatment. “Do patients talk to other people about the event?” Dr. Frank asks. “Are they trying to get back to a daily routine? Can they make sense of this experience? Are they incorporating the event into a world view?”

Dr. Thompson, the Pittsburgh disaster psychiatrist, agrees. Psychiatrists should encourage their patients to talk more about their trauma and how fear is affecting their lives. “We don’t discuss with our trauma patients as much as we might what the experience has been like for them,” he says.

Small-group therapy is the most conducive approach to psychotherapy for PTSD, according to Dr. Frank, although individual counseling can work in many cases. Several studies have found group therapy effective,^20,21 and 12-step group therapy has shown promise in PTSD patients with comorbid substance abuse disorder.²²

Managing fear

Just as people grieve and confront death in stages, Dr. Thompson, who helped coordinate Oklahoma City’s disaster psychiatry effort, has discovered that the public usually employs a similar subconscious process to cope with a traumatic event (Box 4).

But Americans have had no time to recover. As U.S. troops seek justice in Afghanistan, back home people grapple with the threat of anthrax contamination and the prospect of another terrorist attack. The ominously enhanced presence of security at airports, major bridges, sporting and entertainment events, and in other aspects of everyday life, has further fueled the sensation that all is not right.

“The September 11 tragedy brings trauma home,” adds Arshad Husain, MD, professor and chief of child and adolescent psychiatry and director of the International Center for Psychosocial Trauma at the University of Missouri-Columbia. “The anthrax scare and the Nov. 12 plane crash of American Airlines Flight 587 only further remind people of their vulnerability and fears. If the anthrax scare were an accident, people would have been relieved. Since the plane crash was ruled an accident, it has offered people a chance to feel more in control. Accidents can be fixed with better maintenance. Terrorism cannot.”

Dr. Katz of New York City and other disaster psychiatrists are urging their colleagues to help manage public fear by reaching out through community efforts.

Dr. Katz is president of the volunteer group Disaster Psychiatry Outreach, which helped coordinate the city’s post-Sept. 11 trauma psychiatry effort. Visitors waiting at New York’s Family Assistance Center, a referral and help center for people who lost family and friends in the World Trade Center attack, were approached by Dr. Katz and other colleagues to let them know that psychiatric services were available if needed. By doing this, he says, Disaster Psychiatry Outreach clinicians have identified, treated, and referred scores of patients with terror-related stress who otherwise would have gone untreated.

Joseph Dorzab, MD, of the Holt-Krock Clinic in Fort Smith, Ark., also has offered his services. Members of his clinic’s psychiatry department have made several TV appearances, and have given and coordinated area lectures. Working with the local mental health association, the department also is starting a community forum called Mental Health Mondays, an open discussion group with coffee and cookies at a local coffee shop.

In Pittsburgh, Dr. Thompson is encouraging psychiatrists to educate their communities about how traumatic events affect the public. He proposes:

• Staging community meetings to brief religious and other leaders on how to manage traumatized people;
• Informing local news editors about the nature of psychiatric disorders;
• Instructing school administrators about detecting signs of distress in children;
• Contacting local government officials to offer input in devising the town’s emergency response plan.

Psychiatrists also can educate themselves about managing public trauma, thanks to scores of studies that have been done in recent years following major man-made and natural disasters, from Mount St. Helens and Hurricane Andrew, to Chernobyl and the Yom Kippur War. Dr. Thompson urges psychiatrists to seek out the papers of prominent leaders in trauma-related psychiatry, mentioning studies by Carol North, MD, Betty Pfefferbaum, MD, and Robert Ursano, MD, as examples. Other sources include the Web sites of the American Psychiatric Association and National Center for PTSD. (See Related Resources.)

In the end, psychiatrists have been well primed for dealing with public disaster—just by treating individual patients whose psychiatric disorders emanated from everyday life, Dr. Thompson says. “Psychiatrists know more about trauma than they recognize.”

Related resources

• National Center for PTSD Web site
• National Institute of Mental Health:
• Linenthal EJ. The Unfinished Bombing: Oklahoma City in American Memory. Oxford University Press, 2001.
• Norwood AE, Ursano RJ, Fullerton CS. Disaster psychiatry: principles of practice. Psychiatr Q. 2000; 71(3):207-226.
• American Psychiatric Association Web site:
• The Psychiatric Training Manual for Teachers and Mental Health Professionals

Drug brand names

• Amitriptyline • Elavil
• Bupropion • Wellbutrin
• Fluoxetine • Prozac
• Imipramine • Tofranil
• Paroxetine • Paxil
• Phenelzine • Nardil
• Sertraline • Zoloft