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Psychogenic nonepileptic seizures: ways to win over skeptical patients; To best help them, clearly explain the diagnosis and treat underlying disorders.

Many patients with psychogenic nonepileptic seizures (PNES) dismiss the idea that their seizures are psychogenic, especially if the correct diagnosis comes after years of treatment for epilepsy. (1) In a recent study of 164 patients diagnosed with PNES, 82% were readmitted to neurologic wards within the next 10 years. (2)

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Getting patients to accept the diagnosis and appropriate treatment is possible, however. Depending on the severity of PNES' nearly ubiquitous psychiatric comorbidities, you may be able to defuse patients' anger by following protocols for presenting the PNES diagnosis, as described here. You can help PNES patients by:

* differentiating PNES from other conditions

* educating them to accept that psychological distress, not epilepsy, is causing their seizures

* treating underlying psychiatric illness.

CASE STUDY

Is it epilepsy?

Ms. P, age 61, is referred to a comprehensive epilepsy program for evaluation of unusual spells she's had since age 7 or 8. In childhood, the spells consisted of "spacey feelings" and epigastric discomfort. In her 30s she began to have other neurologic symptoms, such as numbness and tingling all over her body. At approximately age 50 she began experiencing confusional episodes lasting 1 to 2 minutes.

A neurologist evaluated Ms. P after she had a spell while hospitalized for angiography at age 59. This spell consisted of left hand shaking and stiffness and inability to respond without loss of awareness. Her spells decreased briefly after she was prescribed topiramate, 100 mg bid, but became increasingly more frequent and severe. MRI indicated an abnormality of the right mesiotemporal lobe with subcortical cystic changes and slight atrophy. PET indicated subtle hypoperfusion of the right medial temporal lobe. She was referred to the epilepsy program with a diagnosis of temporal lobe epilepsy.

Comorbid psychopathology is the rule

Although the precise incidence of PNES is unknown (Box 1), (1,3,4) nearly 100% of PNES patients have a history of psychiatric illness (Table 1). (5) The most commonly reported Axis I diagnoses are:

* somatoform or dissociative disorders

* affective disorders

* anxiety disorders, particularly posttraumatic stress disorder (PTSD). (1)

Depression is independently associated with poor quality of life whether patients have epilepsy or PNES. (6)

Maladaptive personalities. Personality disorders frequently are associated with PNES. (1) One systematic assessment of 45 PNES patients found that the most common personality presentation is not a single disorder but a confluence of maladaptive personality traits. (5)

In addition to DSM-IV-TR criteria, researchers have used other standard psychological assessments to examine PNES patients' personality traits. Typical results on the most commonly applied instrument--the Minnesota Multiphasic Personality Inventory (MMPI/MMPI-2) (7)--show marked elevations on the hysteria and hypochondriasis scale and a less marked elevation on the depression scale, which forms the classic conversion V pattern. Nonconversion patterns also have been reported. (8)

Studies conducted with the Dimensional Assessment of Personality Pathology-Basic Questionnaire (DAPP-BQ) and the Revised NEO Personality Inventory (NEO-PI-R) seem to confirm clusters of maladaptive personality styles among PNES patients. (7,8)

Regardless of assessment technique, a PNES patient's personality tends to include emotional dysregulation and poor coping style. Reuber et al (2) found that PNES patients' outcomes may be correlated with different personality feature clusters. Patients who scored lower on the high-order personality dimensions--inhibitedness, emotional dysregulation, and compulsivity--had fewer psychiatric hospitalizations and were more likely to be seizure-free at follow-up.

CASE CONTINUED

Distressed relationships

Ms. P's psychiatric history includes multiple sexual assaults by relatives, a former employer, and a former physician from her teens through age 40; one involuntary hospitalization for "paranoid ideation"; and a depression diagnosis. Ms. P is estranged from her parents, twin sister, and 2 children. Her only interpersonal relationship is with a live-in boyfriend with antisocial traits. Acquaintances have told Ms. P they believe she is depressed, but she denies depressive or anxious symptoms.

Ms. P undergoes comprehensive neuropsychological evaluation, including multiple cognitive measures and personality testing. Cognition is intact; MMPI responses--though somewhat defensive--are valid and reveal elevations of the hypochondriasis and hysteria scales with a lesser elevation of the depression scale. This "conversion V pattern" suggests mild emotional distress, characterized by tension and very mild dysphoria in the context of strong tendency toward somatization. Her character structure is consistent with borderline personality organization.

Differential diagnosis

Diagnostic evaluation of a patient who presents with seizure-like behaviors begins with taking a history of the illness and psychiatric history, considering the patient's medical status, and ordering baseline laboratory tests (Table 2). (9)

Physiologic seizures. PNES must be differentiated from physiologic nonepileptic paroxysmal events, including:

* syncopal episodes

* complicated migraines

* panic attacks

* transient ischemic events.

PNES must also be differentiated from paroxysmal events with other medical causes--such as autonomic dysfunction, cardiac arrhythmias, hypoglycemia, and drug or alcohol intoxication or withdrawal--and from movement disorders, sleep disorders, or vestibular symptoms. (10)

Epilepsy. Patients with PNES are often misdiagnosed with and treated for epilepsy. (1) Although epilepsy is considered a risk factor for PNES, epilepsy is found in only 5% to 10% of PNES patients--much less frequently than was once thought. (11,12) Among patients with refractory seizure disorder, 15% to 20% eventually are diagnosed with PNES. (13)

The psychiatric history often suggests PNES. Psychiatric disorders are more common in persons with epilepsy than those without, however, so the presence of a comorbid psychiatric diagnosis has low sensitivity or specificity for PNES. (6,14)

Classic semiologic details such as rhythmic pelvic movements, asynchronous limb movements, and side-to-side head shaking are specific to PNES but lack sensitivity. (1) A more recent retrospective study found that ictal eye closure had a sensitivity and specificity of 96% and 98%, respectively, for PNES. (15) Fifty of 52 PNES patients consistently closed their eyes during seizures, whereas 152 of 156 epilepsy patients kept them open. Not all clinicians agree, however, that any semiologic features of seizures are specific to PNES and reliable enough to establish the diagnosis. (16)

Serum prolactin levels rise after generalized tonic-clonic or partial seizures but not after other types of paroxysmal episodes. Normal serum prolactin is 2 to 18 ng/mL for men, 3 to 29 ng/mL for nonpregnant women, and 10 to 209 ng/mL for pregnant women. An elevated serum prolactin assay, when measured in the appropriate clinical setting 10 to 20 minutes after a suspected event, can be a useful adjunct for differentiating generalized tonic-clonic or partial seizures from PNES in adults or older children. (17) Serum prolactin assay does not, however, distinguish epileptic seizures from syncope, nor is it helpful in distinguishing PNES from absence, simple partial, or frontal lobe seizures.

Video electroencephalography. Ensure that any patient with a PNES diagnosis has had the diagnosis confirmed by video electroencephalography (VEEG) performed at an epilepsy center. A prospective study of VEEG and refractory epilepsy found the pre-VEEG clinical diagnosis of PNES was incorrect 22% of the time and the pre-VEEG clinical diagnosis of epilepsy was incorrect 52% of the time. (18)

During VEEG, patients are monitored by video camera and EEG for several hours to several days. If the patient experiences a typical paraoxysmal event with no corresponding EEG change, a trained epileptologist can diagnose PNES with near certainty. An epileptologist's expertise is required because while recording an episode with no epileptiform EEG discharge is necessary for a PNES diagnosis, it's not sufficient--certain types of epileptic seizures, such as simple partial seizures, will not show an ictal discharge on surface EEG.

CASE STUDY

Diagnosis confirmed

The childhood onset of Ms. P's seizures, the semiology of those spells, and her abnormal MRI strongly suggest epileptic seizure. However, her current psychologic profile, recent seizure semiology, and treatment refractoriness raise the potential for PNES. The psychiatrist refers Ms. P to an epilepsy center for VEEG. The results reveal an interictal EEG without epileptiform discharges. Monitoring captures 2 typical spells consisting of head shaking, intermittent upper body jerks, and unresponsiveness. These spells were not accompanied by EEG changes. The diagnosis is PNES, and Ms. P is referred for outpatient psychotherapy.

Voluntary symptom production

In most patients, PNES are an unconscious manifestation of psychopathology. However, a small subgroup of patients consciously produces symptoms for unconscious (factitious) or conscious (malingering) gain. (19) Symptom validity testing can help distinguish factitious disorder and malingering (see "Neurocognitive impairment: Feigned, exaggerated, or real?" CURRENT PSYCHIATRY, August 2007, p. 19-37).

Diagnosis is part of treatment

Outcomes in PNES are generally poor: 71% of PNES patients continue to have seizures 4 years after diagnosis, and 56% are dependent on Social Security assistance. (2) Neurologic and psychiatric factors associated with poor outcome include: (2,10,20,21)

* history of epilepsy

* abnormal MRI

* presence of a psychiatric diagnosis

* age >30 years

* duration of illness (the longer the patient has been treated for epilepsy, the worse the prognosis).

Treatment begins with a secure diagnosis and clear patient communication. Diagnosis alone may be therapeutic. Studies have found that patients have significantly fewer seizures (22) and use less medical services (23) after PNES diagnosis. One small study, however, found that substantial reductions in PNES frequency are not maintained long term. (24)

One potentially modifiable factor that appears to affect outcome is whether patients accept the PNES diagnosis. (25) Reuber et al (2) found approximately 8 out of 10 patients do not. Protocols can help you structure how you present the diagnosis to reduce patient anger and increase acceptance of the diagnosis and treatment (Table 3, page 24). (26) Explain a PNES diagnosis in unambiguous terms that patients will understand, such as "psychological" and "emotional."

Physician attitude might negatively impact PNES treatment. Only 18% of psychiatrists report being confident of a PNES diagnosis based on VEEG. (27)

Scant evidence for treatments

A recent review (28) found no reliable evidence to support the use of any intervention for persons with nonepileptic seizures. Treatments are based on expert opinion, case reports, and--in some cases--open trials.

Pharmacotherapy. Based on expert opinion, psychopharmacology for patients with only PNES begins with tapering and discontinuing ineffective antiepileptic drugs (AEDs), unless a specific AED has a documented beneficial effect for that patient. (29) Treat comorbid mood, anxiety, or psychotic disorders with appropriate psychopharmacologic agents. PNES may be a manifestation of other psychiatric disorders; therefore, treating the predisposing disorder will likely improve PNES. Regardless of PNES outcome, improving comorbid disorders improves PNES patients' quality of life. (21,30)

The National Institute of Neurological Disorders and Stroke is supporting a prospective double-blind, placebo-controlled trial of the selective serotonin reuptake inhibitor sertraline for treating PNES. The pilot study of 50 patients with PNES and comorbid depression, anxiety, and impulsivity is expected to be completed in March. (31)

Psychotherapy. A recent review (28) found only 3 studies of psychotherapy for PNES treatment--2 assessing hypnosis, 1 examining paradoxical therapy--that were randomized or quasi-randomized. All 3 studies were methodologically poor, and none provided detailed data regarding PNES frequency or severity. A 6-month randomized trial of cognitive-behavioral therapy (CBT) vs family therapy is underway at Rhode Island Hospital; data from this study are not yet available (LaFrance WC, personal communication, November 2007).

Single case reports, case series, and retrospective chart reviews have reported various psychotherapies to be successful for PNES, including CBT, eye movement desensitization and reprocessing, group psychoeducation, group psychotherapy, operant conditioning, occupational therapy, and nonspecific psychotherapy. (32)

Psychotherapy for PNES is similar to the pharmacotherapy approach:

* Evaluate the patient for comorbid Axis I or Axis II disorders.

* Provide evidence-based treatment for those disorders.

Goals of treatment. Despite a lack of systematic trials evaluating psychotherapy for PNES, patients continue to present for treatment. Seizure remission as a treatment goal is debatable and likely unrealistic. (33)

Although data supporting any specific PNES treatment are scant, very strong evidence supports treating the most common comorbid illnesses. In our experience, engaging patients in therapy and providing evidence-based treatment for psychiatric comorbidity often reduces PNES and nearly always improves patients' quality of life (Box 2, page 33).

CASE CONTINUED

A rejected diagnosis

Ms. P's psychotherapy focuses on her tendency to isolation of affect, dysfunctional interpersonal relations, and maladaptive coping. She participates in 5 sessions but has limited insight and never accepts the diagnosis of PNES. She withdraws from therapy after the therapist shares with her results of the psychometric testing and plans for psychiatric treatment.

References

1. Reuber M, Elger CE. Psychogenic nonepileptic seizures: review and update. Epilepsy Behav 2003;4:205-16.

2. Reuber M, Pukrop R, Bauer J, et al. Outcome in psychogenic nonepileptic seizures: 1 to 10 year follow-up in 164 patients. Ann Neurol 2003;53:305-11.

3. Benbadis SR, Hauser WA. An estimate of the prevalence of psychogenic non-epileptic seizures. Seizure 2000;9:280-1.

4. Kotagal P, Costa M, Wyllie E, Wolgamuth B. Paroxysmal nonepileptic events in children and adolescents. Pediatrics 2002;110(4):46-51.

5. Bowman ES, Markand ON. Psychodynamics and psychiatric diagnoses of pseudoseizure subjects. Am J Psychiatry 1996; 135:57-63.

6. Szaflarski J, Szaflarski M, Hughes C, et al. Psychopathology and quality of life: psychogenic nonepileptic seizures versus epilepsy. Med Sci Monit 2003;9(4):CR165-70.

7. Reuber M, Pukrop R, Bauer J, et al. Multidimensional assessment of personality in patients with psychogenic non-epileptic seizures. J Neurol Neurosurg Psychiatry 2004; 75:743-8.

8. Cragar DE, Berry DT, Schmitt FA, Fakhoury TA. Cluster analysis of normal personality traits in patients with psychogenic nonepileptic seizures. Epilepsy Behav 2005;6:593-600.

9. Benbadis SR. Psychogenic non-epileptic seizures. In: Wyllie E, ed. The treatment of epilepsy: principles and practice. 4th ed. Philadelphia: Lippincott, Williams & Wilkins; 2005:623-30.

10. Alsaadi TM, Marquez AV. Psychogenic nonepileptic seizures. Am Fam Phy 2005;72(5):849-56.

11. Martin R, Burneo JG, Prasad A, et al. Frequency of epilepsy in patients with psychogenic seizures monitored by video-EEG. Neurology 2003;61:1791-2.

12. Benbadis SR, Agrawal V, Tatum WO IV. How many patients with psychogenic nonepileptic seizures also have epilepsy? Neurology 2001;57:915-7.

13. Benbadis SR, Tatum WO IV, Vale FL. When drugs don't work: an algorithmic approach to medically intractable epilepsy. Neurology 2000;55(12):1780-4.

14. Galimberti CA, Ratti MT, Murelli R, et al. Patients with psychogenic nonepileptic seizures, alone or epilepsy-associated, share a psychological profile distinct from that of epilepsy patients. J Neurol 2003;250(3):338-46.

15. Chung SS, Gerber P, Kirlin KA. Ictal eye closure is a reliable indicator for psychogenic nonepileptic seizures. Neurology 2006;66(11):1730-1.

16. Iriarte J, Parra J, Urrestarazu E, Kuyk J. Controversies in the diagnosis and management of psychogenic pseudoseizures. Epilepsy Behav 2003;4(3):354-9.

17. Chen DK, So YT, Fisher RS. Use of serum prolactin in diagnosing epileptic seizures: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2005;65(5):668-75.

18. Parra J, Iriarte J, Kanner AM. Are we overusing the diagnosis of psychogenic non-epileptic events? Seizure 1999;8(4):223-7.

19. Reuber M, Baker GA, Gill R, et al. Failure to recognize psychogenic nonepileptic seizures may cause death. Neurology 2004;62(5):834-5.

20. Kanner A, Parra J, Frey M, et al. Psychiatric and neurologic predictors of psychogenic pseudoseizure outcome. Neurology 1999;53(5):933-8.

21. Walczak TS, Papacostas S, Williams DT, et al. Outcome after diagnosis of psychogenic nonepileptic seizures. Epilepsia 1995;36(11):1131-7.

22. Farias ST, Thieman C, Alsaadi TM. Psychogenic nonepileptic seizures: acute change in event frequency after presentation of the diagnosis. Epilepsy Behav 2003;4(4):424-9.

23. Martin RC, Gillian FG, Kilgore M, et al. Improved health care resource utilization following video-EEG-confirmed diagnosis of nonepileptic psychogenic seizures. Seizure 1998;7(5):385-90.

24. Wilder C, Marquez AV, Farias ST, et al. Long-term follow up study of patients with PNES. Epilepsia 2004;45(suppl 7):349.

25. LaFrance WC Jr, Alper K, Babcock D, et al. Nonepileptic seizures treatment workshop summary. Epilepsy Behav 2006;8:451-61.

26. Shen W, Bowman ES, Markan ON. Presenting the diagnosis of pseudoseizure. Neurology 1990;40(5):756-9.

27. Harden CL, Burgut FT, Kanner AM. The diagnostic significance of video-EEG monitoring findings on pseudoseizure patients differs between neurologists and psychiatrists. Epilepsia 2003;44(3):453-6.

28. Baker G, Brooks JL, Goodfellow L, et al. Treatments for non-epileptic attack disorder. Cochrane Database Syst Rev 2007;(1):CD006370.

29. LaFrance WC Jr, Devinsky O. Treatment of nonepileptic seizures. Epilepsy Behav 2002;3(suppl 1):S19-23.

30. Quigg M, Armstrong RF, Farace E, Fountain NB. Quality of life outcome is associated with cessation rather than reduction of psychogenic nonepileptic seizures. Epilepsy Behav 2002;3:455-9.

31. ClinicalTrials.gov. Treatments for psychogenic nonepileptic seizures (NES). NCT00159965. Available at: http://www.clinicaltrials.gov/ct/show/NCT00159965?order=1. Accessed October 19, 2007.

32. Reuber M, Howlett S, Kemp S. Psychologic treatment of patients with psychogenic nonepileptic seizures. Expert Rev Neurother 2005;5(6):737-52.

33. Reuber M, Mitchel AJ, Howlett S, Elger CE, Measuring outcome in psychogenic nonepileptic seizure: how relevant is seizure remission? Epilepsia 2005;46(11);1788-95.

ONLINE EXCLUSIVE

Video of a PNES episode

Visit CurrentPsychiatry.com

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Patrick Marsh, MD

Assistant professor

Department of psychiatry

Selim Benbadis, MD

Director, Comprehensive Epilepsy Program

Professor, Department of neurology and neurosurgery

Francisco Fernandez, MD

Professor and Chair

Department of psychiatry

....

University of South Florida College of Medicine

Tampa, FL

Box 1 How many patients develop PNES?

Studies of patients referred to neurologic centers have reported an incidence of 1.5 to 3 psychogenic nonepileptic seizure (PNES) cases per 100,000 patients per year. (1) However, these studies counted only cases diagnosed by video electroencephalography.

Based on the overall prevalence of epilepsy and proportion of PNES in patients referred for refractory epilepsy, the estimated incidence of PNES in the general population is 2 to 33 cases per 100,000 patients per year--making PNES about as common as multiple sclerosis. (3) This estimated range is wide because of variability in estimates of intractable epilepsy, referral patterns, and PNES diagnosis, in particular.

PNES typically occur in patients age 20 to 30 but have been reported in those as young as 4 and in patients older than 70. Three-quarters of adults with PNES are women. (1) Among patients age 5 to 12, the condition is more common in boys than in girls, but by adolescence the reverse is true. (4)

Box 2 Successful depression treatment halts this patient's PNES

Mrs. A, age 31, is referred for psychiatric evaluation by a neurologist who suspects she is having psychogenic nonepileptic seizures (PNES). A teacher and mother of a young child, Mrs. A reports first experiencing a seizure after an argument during which she thought her husband was going to strike her. The neurologist prescribed phenytoin, 900 mg/d.

On clinical examination Mrs. A has moderately severe depressive symptoms. She is angry that the neurologist referred her to a psychiatrist and refuses to discuss the PNES diagnosis.

Mrs. A's psychiatric history includes recurrent depression that has been treated with antidepressants, although she is not taking an antidepressant at this time. Her psychosocial history is consistent with early developmental deprivation.

The psychiatrist tactfully shares the results of the psychological evaluation with Mrs. A and--at her request--her husband. Both reluctantly agree to the psychiatrist's recommendations that she begin cognitive-behavioral therapy (CBT) and resume antidepressant therapy with venlafaxine XR, titrated over several weeks to 300 mg/d. They decline couples' therapy.

Mrs. A understands and accepts the need to treat her depression but refuses to discontinue phenytoin. She doubts the need for CBT and often cancels sessions. As the focus of therapy becomes more supportive, her PNES episodes decrease but are not eliminated, even after her mood improves.

After Mrs. A has been in treatment 14 months, her husband leaves her. Her depression is greatly ameliorated, and her seizures cease. After another 2 months of treatment, the psychiatrist transfers Mrs. A's care to her primary care physician.

Related Resources

Clinician resource

LaFrance WC Jr, Kanner AM, Barry JJ. Treating patients with psychological nonepileptic seizures. In: Ettinger AB, Kanner AM, eds. Psychiatric issues in epilepsy: a practical guide to diagnosis and treatment. 2nd ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2007:461-88.

Patient resource

Benbadis SR, Heriaud L. Psychogenic (non-epileptic) seizures. A guide for patients & families. http://hsc.usf.edu/COM/epilepsy/PNESbrochure.pdf.

Drug Brand Names

Phenytoin * Dilantin

Sertraline * Zoloft

Venlafaxine * Effexor

Disclosures

Drs. Marsh and Benbadis report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Fernandez receives research support from Cyberonics Inc., Dainippon Sumitomo Pharma, Pfizer Inc., the Florida Department of Elder Affairs, and the National Institutes of Health. He is a speaker for Wyeth Pharmaceuticals.

RELATED ARTICLE: Bottom Line

Patients with psychogenic nonepileptic seizures (PNES) almost always have comorbid psychiatric illness. Providing effective patient education can improve patient acceptance of the diagnosis and outcomes. Evaluate PNES patients for underlying psychiatric illness, and provide evidence-based pharmacotherapy and psychotherapy for those comorbidities.
Table 1 PNES: Most common comorbid psychiatric diagnoses

Diagnosis                             Lifetime  Current

Any somatoform disorder               98%       89%
Conversion seizure                    89%       78%
Conversion, nonseizure                82%        4%
Dissociative disorder                 93%       91%
Any personality disorder              *         62%
Major depressive disorder             80%       47%
Any mood disorder                     98%       64%
Posttraumatic stress disorder (PTSD)  58%       49%
Non-PTSD anxiety disorder             51%       47%

*Data were not reported
Source: Reference 5

Table 2 Baseline exam when you suspect PNES

History of present illness
Take detailed symptom profile. Emphasize recent stressful events to
  differentiate diagnostic possibilities (panic, depression,
  dissociative disorder, posttraumatic stress disorder, etc.)
Evaluate for other primary Axis I and Axis II disorders with comorbid
  anxiety and depression (bereavement, adjustment disorders, borderline
  personality disorder, antisocial personality disorder, etc.)

Psychiatric history
Ascertain past symptoms and treatments
Emphasize prior trauma
Examine drug and alcohol history

Medical status
Assess for pulmonary disease, cardiac disease, endocrine disturbances,
  neurologic disease, etc.
Document medication history, including over-the-counter medications and
  herbal therapies

Video EEG
Obtain adequate neurologic workup, including PNES diagnosis by an
  experienced epileptologist using video electroencephalography

Source: Reference 9

Table 3 Presenting patients with a diagnosis of PNES

Review the video electroencephalography-recorded seizure with the
  patient and someone who has witnessed the patient's previous events to
  ensure the event was typical
Explain the diagnosis in positive terms ("good news"); emphasize that
  the seizures are not a result of the brain firing out of control
Acknowledge that the precise cause of the seizures has not yet been
  established and may not be found
Suggest that in many cases the seizures may be related to psychological
  factors such as stress or negative emotions
State that the diagnosis does not imply the patient is "crazy"
Suggest that the seizures may resolve on their own

Source: Reference 26
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Author:Marsh, Patrick; Benbadis, Selim; Fernandez, Francisco
Publication:Current Psychiatry
Geographic Code:1USA
Date:Jan 1, 2008
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