COMORBID RECURRENT DEPRESSION IN OBSESSIVE-COMPULSIVE DISORDER A CASE REPORT



Similar documents
Psychopharmacotherapy for Children and Adolescents

Obsessive Compulsive Disorder: a pharmacological treatment approach

Recognizing and Treating Depression in Children and Adolescents.

OCD & Anxiety: Helen Blair Simpson, M.D., Ph.D.

Improving the Recognition and Treatment of Bipolar Depression

Obsessive Compulsive Disorder What you need to know to help your patients

Major Depression. What is major depression?

MAJOR DEPRESSION DURING CONCEPTION AND PREGNANCY: A Guide for Patients and Families

Update on guidelines on biological treatment of depressive disorder. Dr. Henry CHEUNG Psychiatrist in private practice

The Priory Group. What is obsessive-compulsive disorder?

Neuroscience An extra bit. Dr Sasha Gartside Institute of Neuroscience Newcastle University

TITLE: Cannabinoids for the Treatment of Post-Traumatic Stress Disorder: A Review of the Clinical Effectiveness and Guidelines

Recognition and Treatment of Depression in Parkinson s Disease

Depre r s e sio i n o i n i a dults Yousuf Al Farsi

Rogers Memorial Hospital (Wisconsin).

What are the best treatments?

BRIEF NOTES ON THE MENTAL HEALTH OF CHILDREN AND ADOLESCENTS

Questions & Answers About OCD In Children and Adolescents

ESCITALOPRAM IN THE TREATMENT OF OBSESSIVE-COMPULSIVE DISORDER: A DOUBLE BLIND PLACEBO CONTROL TRIAL

Depressive disorders among older residents in a Chinese rural community. Risk for Depression by Age and Sex. Risk for Depression by Age and Sex

DEPRESSION Depression Assessment PHQ-9 Screening tool Depression treatment Treatment flow chart Medications Patient Resource

NICE Clinical guideline 23

Treatments for Major Depression. Drug Treatments The two (2) classes of drugs that are typical antidepressants are:

MOH CLINICAL PRACTICE GUIDELINES 6/2011 DEPRESSION

Best Practices Treatment Guideline for Major Depression

IMR ISSUES, DECISIONS AND RATIONALES The Final Determination was based on decisions for the disputed items/services set forth below:

Maintenance treatment for obsessivecompulsive disorder: Findings from a naturalistic setting

CLINICIAN INTERVIEW COMPLEXITIES OF BIPOLAR DISORDER. Interview with Charles B. Nemeroff, MD, PhD

Antidepressants and suicidal thoughts and behaviour. Pharmacovigilance Working Party. January 2008

Depression in the Elderly: Recognition, Diagnosis, and Treatment

PSYCHOPHARMACOLOGY AND WORKING WITH PSYCHIATRY PROVIDERS. Juanaelena Garcia, MD Psychiatry Director Institute for Family Health

TREATMENT-RESISTANT DEPRESSION AND ANXIETY

COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP)

TREATING MAJOR DEPRESSIVE DISORDER

Overview of Mental Health Medication Trends

Psychopharmacology. Psychopharmacology. Hamish McAllister-Williams Reader in Clinical. Department of Psychiatry, RVI

Bipolar Disorder. Mania is the word that describes the activated phase of bipolar disorder. The symptoms of mania may include:

Conjoint Professor Brian Draper

Selective serotonin re-uptake inhibitors in child and adolescent depression

and body dysmorphic disorder (BDD) in adults, children and young people Issue date: November 2005

MEDICATIONS AND TOURETTE S DISORDER: COMBINED PHARMACOTHERAPY AND DRUG INTERACTIONS. Barbara Coffey, M.D., Cheston Berlin, M.D., Alan Naarden, M.D.

Mood Disorders. What Are Mood Disorders? Unipolar vs. Bipolar

1. Which of the following SSRIs requires up to a 5-week washout period because of the

DEPRESSION DURING THE TRANSITION TO MENOPAUSE: A Guide for Patients and Families

Algorithm for Initiating Antidepressant Therapy in Depression

Depression Treatment Guide

Child & Adolescent Anxiety: Psychopathology and Neuroscience

CLASS OBJECTIVE: What is Obsessive-Compulsive Disorder? What is OCD?

Comorbid Conditions in Autism Spectrum Illness. David Ermer MD June 13, 2014

Some helpful reminders on depression in children and young people. Maria Moldavsky Consultant Child and Adolescent Psychiatrist

Introduction to Exposure Therapy for Obsessive Compulsive Disorder

How to Recognize Depression and Its Related Mood and Emotional Disorders

DEPRESSION CARE PROCESS STEP EXPECTATIONS RATIONALE

Preferred Practice Guidelines Bipolar Disorder in Children and Adolescents

Depression Flow Chart

Psychiatric Comorbidity in Methamphetamine-Dependent Patients

Clinical Practice Guideline: Depression in Primary Care, Adult 4 Taft Court Rockville, MD

Depression Overview. Symptoms

Generalised anxiety disorder in adults

Depression is a medical illness that causes a persistent feeling of sadness and loss of interest. Depression can cause physical symptoms, too.

Depression in Older Persons

Co-Occurring Substance Use and Mental Health Disorders. Joy Chudzynski, PsyD UCLA Integrated Substance Abuse Programs

Suicide in Bipolar Disorder. Julie Anderson, MD Oregon State Hospital Psychiatrist OHSU Assistant Professor September 25, 2012

Topics In Addictions and Mental Health: Concurrent disorders and Community resources. Laurence Bosley, MD, FRCPC

EFFECTIVENESS OF PSYCHOLOGICAL AND PHARMACOLOGICAL TREATMENTS FOR OBSESSIVE- COMPULSIVE DISORDER: A QUALITATIVE REVIEW

Medication Management of Depressive Disorders in Children and Adolescents. Satya Tata, M.D. Kansas University Medical Center

DSM 5 AND DISRUPTIVE MOOD DYSREGULATION DISORDER Gail Fernandez, M.D.

MOH CLINICAL PRACTICE GUIDELINES 2/2008 Prescribing of Benzodiazepines

Depression: Facility Assessment Checklists

Revised 7/05. Copyright 2005 St. Jude Children's Research Hospital Page 1 of 6

Treatment of Bipolar Disorders with Second Generation Antipsychotic Medications

Depression: What You Need to Know

SLEEP DISTURBANCE AND PSYCHIATRIC DISORDERS

Depression Assessment & Treatment

Depression in children and adolescents

placebo-controlledcontrolled double-blind, blind,

Depression, Mental Health and Native American Youth

Are You Considering Medication for Depression?

CLINICAL PRACTICE GUIDELINES. Depression

MOLINA HEALTHCARE OF CALIFORNIA

Alcohol and Health. Alcohol and Mental Illness

Obsessive Compulsive Disorders. Treatment

`çããçå=jéåí~ä= aáëçêçéêëw=^åñáéíó=~åç= aééêéëëáçå. aêk=`=f=lâçåü~ jéçáå~ä=aáêéåíçê lñäé~ë=kep=cçìåç~íáçå=qêìëí=

A Sierra Tucson Publication. An Introduction to Mood Disorders & Treatment Options

Elizabeth A. Crocco, MD Assistant Clinical Professor Chief, Division of Geriatric Psychiatry Department of Psychiatry and Behavioral Sciences Miller

DEMENTIA EDUCATION & TRAINING PROGRAM

Obsessive- Compulsive Disorder:

Transcription:

CLINICAL CASE COMORBID RECURRENT DEPRESSION IN OBSESSIVE-COMPULSIVE DISORDER A CASE REPORT 1 2 3 4 Anamaria Vasilache, Alina Beldie, Elena Cãlinescu, Iuliana Cozac Abstract: We reported a case study of a 57-year-old man who presented at Prof. Dr. Alexandru Obregia Clinical Hospital of Psychiatry with symptoms associated with obsessive-compulsive and depressive disorder: obsessive ideas, compulsions, depressive ruminations, depressive mood, anxiety related to the obsessive thoughts, anhedonia, ideas of incurability, feelings of worthlessness, social withdrawal, multiple somatic complains, fatigue, insomnia. We discuss therapeutic and prognostic implications of the association between the two disorders. The occurring of depressive simptomatology may complicate treatment adherence and response therefore it is crucial to evaluate the affective patterns in obsessivecompulsive patients presenting for treatment. Key words: obsessive ideas, depressive simptomatology, SSRIs, antipsychotic drugs. Rezumat: Prezentãm cazul unui bãrbat în vârstã de 57 ani care s-a prezentat la Spitalul Clinic de Psihiatrie Prof. Dr. Alexandru Obregia pentru simptome asociate cu Tulburarea obsesivo-compulsivã ºi cu Tulburare depresivã recurentã: idei obsesive, compulsii, ruminaþii depresive, dispoziþie depresivã, anxietate legate de ideile obsesive, anhedonie, idei de incurabilitate, sentimente de inutilitate, retragere socialã, multiple simptome, obosealã, insomnie. Am discutat implicaþiile terapeutice ºi prognostice ale asocierii dintre cele douã tulburãri. Apariþia simptomatologiei depresive poate complica complianþa ºi rãspunsul la tratament, prin urmare, este crucial sã se evalueze simptomele afective la pacienþii care se prezintã pentru tratamentul Tulburãrii obsesivocompulsive. Cuvinte cheie: idei obsesive, simptome depresive, ISRS, antipsihotice. People with obsessive-compulsive disorder (OCD) frequently experience, throughout their life, additional psychiatric disorders such as: affective, OCD spectrum, anxiety, tic, personality disorders and drug addiction (1, 2). Depression is the most frequent comorbid condition in OCD in adult and children with a prevalence that range from 30% to 80% in clinical and general population. The comorbidity of major depressive disorder (MDD) in OCD has been related to unfavorable prognosis and poor treatment response (1, 4). Several factors are positively correlated with the association of depressive disorders in obsessivecompulsive patients. Among them, the early onset and diagnosis and severity of OCD are significantly associated with development of recurrent major depressive disorder. The early age at onset has been a hallmark for genetic predisposition to many diseases that aggregate in families, therefore it was assumed that OCD with comorbid depression may identify a more homogenous group with a genetic predisposition. Alternatively, the patients with early onset and more severely impairing symptoms may become more discouraged, stigmatized, and ultimately liable to depression because of the impact of the illness on their emotional and social life (1, 4). It was found that aggressive, philosophical, existential, odd or superstitious obsession are more common in patients with both OCD and MDD and that sexual and religious obsessions are more frequent in patients with comorbid of recurrent major depressive disorder (1, 5). We report the case of a 57-year-old man, hospitalized the following reasons: obsessive ideas with aggressive content ( I've lost a screwdriver and I'm thinking that someone might find and use it to harm someone with it. ; Someone died and I'm thinking that maybe he was murdered with the screwdriver I've lost ; I was walking by a car and I smashed it's mirror, now I'm obsessed with the idea that the owner of that car had an accident because of me ), sexual obsessions and ruminations ( As a child, I tried to have intimate relations with my sisters and my mother. Now I'm obsessed with what I have done to my mother and my sisters...i know I haven't done anything but what if I did? ), compulsions ( Every evening I check the gas tank and the door lock several times ; I tie my shoelaces several times to be sure they are properly done ; If I don't step correctly, I turn back and redo the steps again ; I don't touch anyone, and if I do I wash my hands immediately. ), depressive ruminations ( I believe that I killed a woman I was working with, even though I'm sure I didn't. I'm thinking I killed that woman but I don't know when that happened. ), depressive mood ( I feel sad, maybe it's the weather, my thoughts won't leave me alone. ; Today I feel sad because of my thoughts. ); anxiety related to the obsessive thoughts, anhedonia ( I feel like doing nothing. ; I can't work anymore, I have no pleasures. ), ideas of incurability ( I don't believe that I will ever get better. ), suicidal ideation ( I'm thinking to take my life. ), feelings of worthlessness ( It feels like my life has no meaning. ), social withdrawal, multiple somatic complains: cervical and occipital paresthesia ( I feel numbness in the back of my head and down my neck, the feeling gets stronger when my thoughts appea. ), 1, 2, 3, 4 Resident in Psychiatry, Clinical Hospital of Psychiatry Prof. Dr. Alexandru Obregia, Bucharest, Romania. Contact e-mail: ana_vslch@yahoo.com 118

Romanian Journal of Psychiatry, vol. XII, No.3, 2010 dizziness, pain in the right upper abdomen, fatigue, insomnia ( I haven't slept all night. ). Symptoms appeared insidiously and then progressively developed over financial difficulties that the patient had for about 12 months History According to patient, the onset of the obsessive symptoms held around age of 15 when he was first hospitalized. Depressive symptoms first appeared around the age of 27 when he divorced his first wife. He later had several hospitalisations until the age of 40 when he received electroconvulsivant therapy. After that, he had neither hospitalisations nor treatment until the age of 57. The only symptoms present in this period were compulsions, but their frequency and intensity haven't had a significant influence on patient's life. From the patient's heredocolateral history we found that his mother suffered from a psychiatric disorder and had an infection with hepatitis B virus, and his father was a chronic alcohol user. From the social history we found that the patient divorced at age 27 an remarried 3 years later. He has 4 children (1 daughter from the first marriage, 2 sons from the second and 1 adopted daughter). He's living with his wife and one son. After graduating a vocational school, he worked as a mechanic and a master aid (12 years in a toxic environment at an Aluminium Plant ) until 2002 when he reached the retirement age. The paraclinical examinations (laboratory, cerebral CT, EEG) didn't show any relevant abnormalities. The patient met the DSM-IV-TR criteria for OCD and recurrent, major depressive disorder. Severe, prolonged episode. Management We started the treatment with citalopram (increased until the maximum dosage of 60mg/day), lorazepam (3mg/day) and zolpidem 10mg/day. After 6 weeks the obsessive symptoms didn't improved, depresive symptoms were persisting and general improvement was minimal (CGI=3). We added quetiapine (300mg/zi) which we had to interrupt because of it's side effects: drowsiness, dizziness, headache and postural hypotension. Consequently we chose another atypical antipsychotic, risperdone (2mg/day). After 2 weeks obsessive symptoms improved and depressive symptoms remitted. Lorazepam was gradually stopped and afterwards, zolpidem was removed too. Citalopram dosage was reduced to 40 mg/day. The general improvement was significant (CGI=2) and the patient was released with the prescription of citalopram 40 mg/day, risperidone 2 mg/day and zolpidem 10 mg/day if needed. He returnead after 3 months with recurrent depressive and obsessive symptoms which emerged because the patient stopped the treatment. The previous drug prescription was restarted and the symptoms remited after 8 weeks alowing the patient's release. After aproximately 2 months the patient's condition got worse, despite the treatment, with predominant somatic symptoms (anhedonia, depressive mood, ideas of incurability, feelings of worthlessness). Citalopram (40 mg/day) was gradually replaced with escitalopram. Rispolept (2 mg/day) and zolpidem (10mg/day) were maintained and there was added sodium valproate (500 mg/day). After 6 weeks of treatment symptoms remited and the patient was released once again. DISCUSSION Coexistence of major depression with OCD was found to be related to chronicity and severity of obsessivecompulsive symptoms, poor response to treatment, a higher number of suicide attempts and hospitalizations and bad prognosis, conclusions wich are confirmed by other international researches (6). A recent study that compared depressive symptoms of pure MDD with those from OCD complicated with depressive symptoms of equal severity showed that patients suffering from both OCD and MDD scored significantly and substantially higher on MADRS items for anxiety and pessimistic thoughts and significantly and substantially lower on the items reflecting vegetative symptoms (7). In uncomplicated OCD, both SSRIs and Cognitive behavioral therapy (CBT) in the form of exposure and response prevention (ERP) are evidence based first-line treatments (8). Co-occurring MDD has been associated with a less satisfactory outcome in many ERP monotherapy trials of patients with OCD, and limited evidence from controlled trials supports the use of ERP in combination with fluvoxamine or imipramine in such cases. Evidence suggests that for some patients with uncomplicated OCD, combining an SSRI and CBT is more effective than either treatment as monotherapy (9,10). No useful predictive factors exist to orient the choice of SSRI. and limited information is currently available comparing SSRIs among each other. There does not seem to be any clear therapeutic advantage associated with any particular SSRI. Therefore, the choice should be based on their particular side effect profiles and on their potential for drug drug interactions (11). Patients with concomitant major depression and OCD may have a poorer response to treatment than non depressed patients (12), but there are studies showing that the presence of MDD does not necessarilly predict a low response of OCD to SSRI treatment (13), although occasionally SSRI treatment may relieve the OCD but increase the patient's depression (14). A recent study suggests that this may indicate differences in the neurobiological substrates for OCD and MDD response in patients with both disorders (15). Results from a case series suggest that when an SSRI relieves OCD and simultaneously worsens MDD, the depression may respond to the addition of an antidepressant that inhibits norepinephrine reuptake (14). However, the addition of the noradrenergic antidepressant desipramine to SSRIs in a double-blind, placebo-controlled trial in treatmentresistant OCD did not improve OCD response (16). Although SSRIs are first-line pharmacological agents in the treatment of OCD, approximately 40 60% of patients with the disorder do not respond to this treatment (17, 18). This suggests a role in OCD for other neurotransmitters such as the dopaminergic system, which has recently been a particular focus of interest (19). Augmentation of SSRIs by traditional and atypical antipsychotics in treatment-resistant OCD can lead to symptom improvement (20). The duration of the adjunct therapy has been reported to be significantly associated 119

Anamaria Vasilache, Alina Beldie, Elena Cãlinescu, Iuliana Cozac: Comorbid Recurrent Depression In Obsessivecompulsive Disorder A Case Report with a better outcome; at least 8 weeks of therapy appears to be required to determine anti psychotic-related effectiveness in the treatment of OCD. In a systematic review, Skapinakis et al (21) have summarized the results of previous studies of use of various antipsychotic drugs as adjunct therapy in refractory OCD. In this review, haloperidol, olanzapine, quetiapine and risperidone were found to be effective in refractory OCD. In a retrospective, comparative study that compared the efficacy of quetiapine and ziprasidone as adjuncts for treatment-resistant OCD, clinical improvement was established in 80% of the quetiapine group and in 44.4% of the ziprasidone group (22). There is evidence indicating that a hyperglutamatergic activity is involved in OCD. Therefore, a drug that could directly decrease GLU neurotransmission would in theory induce a rapid onset of action, in contrast to SSRIs, which take several weeks to enhance inhibitory 5-HT transmission (23, 24). Such a net effect could be obtained by pre- or postsynaptic action in the GLU system. A first possibility would be to decrease GLU release. Recently, riluzole, a medication thought to act in amyotrophic lateral sclerosis by exerting this very effect, has been reported to be effective in treating SSRI-resistant OCD patients (25). Another possibility would be to activate inhibitory autoreceptors on GLU terminals to turn down excessive GLU release. These neurons are endowed with just such a subtype of autoreceptor, the mglur type 2, which exerts an inhibiting effect only when GLU release is increased (26). Such an agent has already been tested in humans, with positive results in an experimental model of anxiety (27). More potent and bioavailable compounds should allow the testing of this hypothesis in OCD. The early diagnosis of depressive disorders has an important impact among the evolution, prognosis in OCD. Because co-occurring depressive simptomatology may complicate treatment adherence and response, it is crucial to evaluate these affective patterns in the OCD patients presenting for treatment. REFERENCES 1. Hong JP, Samuels J, Bienvenu OJ et al. Clinical correlates of recurrent major depression in obsessive-compulsive disorder. Depression and anxiety 2004; 20:86-91. 2. Fireman B, Koran LM, Leventhal JL, Jacobson A. The prevalence of clinically recognized obsessive compulsive disorder in a large health maintenance organization. The American Journal of Psychiatry 2001; 158(11):1904 10. 3. Kolada JL, Bland RC, Newman SC. Obsessive-compulsive disorder. Acta Psychiatr Scand 1994; 376:24-35. 4. Perugi G, Akiskal HS, Pfanner C et al. The clinical impact of bipolar and unipolar affective comorbidity on obsessive-compulsive disorder. J Affect Disord 1997; 46:15-22. 5. Summerfeldt LJ, Richter MA, Antony MM, Swinson RP. Symptom structure in obsessive-compulsive disorder: A confirmatory factor-analitic study. Behav Res Ther 1999; 37:297-311. 6. Angst J, Gamma A, Endrass J et al. Obsessive-compulsive syndromes and disorders: significance of comorbidity with bipolar and anxiety syndromes. Eur Arch Psychiatry and Neurosci 2005; 255:65 71. 7. Fineberg NA, Fourie H, Gale TM et al. Comorbid depression in obsessive compulsive disorder (OCD):symptomatic differences to major depressive disorder. J Affect Disord 2005; 87:327-30. 8. Eddy KT, Dutra L, Bradley R et al. A multidimensional metaanalysis of psychotherapy and pharmacotherapy for obsessivecompulsive disorder. Clin Psychol Rev 2004; 24:1011 30. 9. Cottraux J, Bouvard MA, Milliery M. Combining pharmacotherapy with cognitive-behavioral interventions for obsessive compulsive disorder. Cogn Behav Ther 2005; 34:185 92. 10. Foa EB, Liebowitz MR, Kozak MJ et al. Randomized, placebocontrolled trial of exposure and ritual prevention, clomipramine, and their combination in the treatment of obsessivecompulsive disorder. Am J Psychiatry 2005; 162:151 61. 11. Bergeron R, Ravindran AV. Chaput Y et al. Sertraline and tluoxetine treatment of obsessive-eompulsive disorder: results of a double-blind, 6-month treatment study. J Clin Psychophamiacol 2002; 22:148-54. 12. Tükel R, Meteris H, Koyuncu A, Tecer A, Yazici O. The clinical impact of mood disorder comorbidity on obsessivecompulsive disorder. European Archives of Psychiatry and Clinical Neuroscience 2006; 256:240 245. 13. Ackerman DL, Greenland S. Multivariate meta-analysis of controlled drug studies for obsessive-compulsive disorder. J Clin Psychopharmacol 2002; 22:309 17. 14. Mancini C, Van Ameringen M, Farvolden P. Does SSRI augmentation with antidepressants that influence noradrenergic function resolve depression in obsessive compulsive disorder? J Affect Disord 2002; 68:59 65. 15. Saxena S, Brody AL, Ho ML et al. Differential brain metabolic predictors of response to paroxetine in obsessive-compulsive disorder versus major depression. Am J Psychiatry 2003; 160:522 32. 16. Barr LC, Goodman WK, Anand A et al. Addition of desipramine to serotonin reuptake inhibitors in treatment-resistant obsessivecompulsive disorder. Am J Psychiatry 1997; 154:1293 5. 17. Fineberg NA, Gale TM. Evidence-based pharmacotherapy of obsessive-compulsive disorder. Int J Neuropsychopharmacol 2005; 8:107-29. 18. Pallanti S, Hollander E, Bienstock C, et al. Treatment nonresponse in OCD: methodological issues and operational definitions. Int J Neuropsychopharmacol 2002; 5:181-91. 19.Goodman WK, McDougle CJ, Price LH, et al. Beyond the serotonin hypothesis: a role for dopamine in some forms of obsessive compulsive disorder? J Clin Psychiatry 1996; 57:36 43. 20. Mohr N, Vythilingum B, Emsley RA, et al. Quetiapine augmentation of serotonin reuptake inhibitors in obsessive-compulsive disorder. Int Clin Psychopharmacol 2002; 7:37-40. 21. Skapinakis P, Papatheodorou T, Mavreas V. Antipsychotic augmentation of serotonergic antidepressants in treatment-resistant obsessive-compulsive disorder: a meta-analysis of the randomized controlled trials. Eur Neuropsychopharmacol 2007; 17:79-93. 22. Haluk A, Mehmet Z, Murat E. Quetiapine and Ziprasidone as Adjuncts in Treatment-Resistant Obsessive-Compulsive Disorder A Retrospective Comparative Study Clinical Drug Investigation 2008; 28(7):439-42. 23. Rosenberg DR, MacMaster FP,Keshavan MS, Fitzgerald KD. Stewart CM. Moore GJ. Decrease in caudate glutamatergic concentrations in pediatric obsessive-compulsive disorder patients taking paroxetine. J Am Acad Child Adolesc Psychiatry 2000; 39:1096-103. 24. Rosenberg DR, MacMillan SN, Moore GJ. Brain anatomy and chemistry may predict treatment response in paediatric obsessivecompulsive disorder. Int J Neuropsychopharmacol 2001; 4:179-90. 25. Coric V, Taskiran S, Pittenger C et al. Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial. Biol Psychiany 2005; 58:424-8. 26. Schoepp DD, Wright RA, Levine LR, Gaydos B, Potter WZ. LY354740, an mglu2/3 receptor agonist as a novel approach to treat anxieiy/stress. Stress 2003; 6:189-97. 27. Grilion C, Cordova J, Levine LR, Morgan CA. Anxiolytic effects of a novel group II metabotropic glutamate receptor agonist (LY354740) in the fear-potentiated startle paradigm in humans. Psychopharmacology 2003; 168:446-54. 120