PSYCHOPHARMACOLOGY OF OCD AND SOCIAL PHOBIA
From Advances in Psychopharmacology Throughout the Life Span, presented by the University of California, San Diego,
School of Medicine
Sanjaya Saxena, MD, Associate Professor of Psychiatry, Director, UCSD Obsessive-Compulsive Disorders Program,
University of California, San Diego, School of Medicine and Director, Veterans Affairs Anxiety Disorders Clinic, La Jolla,
CA
| Introduction: before prescribing medication, physician must know 1) what is being treated (eg, specific target symptoms,
specific syndromes, differentiating between syndromes), 2) which medications effective and which not, and
3) how medications work, ie, their mechanisms and loci of action, brain systems and neurochemical and neuroanatomic
systems affected, and downstream effects
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| Anxiety disorders: not all same; variability occurs among and within disorders; 4-compartment model of anxiety
posits that anxiety disorders affect compartments of cognitions, emotions, somatic responses, and behaviors, and
pathology can occur in any compartment or combination of compartments; cognitions—specific; include thoughts,
beliefs, predictions, and appraisal of danger; in differentiating anxiety disorders, essential to accurately and completely
assess cognitions; emotions—include fear and anticipatory anxiety; somatic responses—nonspecific; include
autonomic arousal (eg, tachycardia, palpitations, shortness of breath, sweating, dizziness, tremors, vigilance,
restlessness, insomnia) and muscle tension; behaviors—specific or nonspecific; all anxiety disorders marked by
avoidance, but only some marked by compulsions
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| General principles of psychopharmacology of anxiety disorders: different symptom clusters respond to medications
to different degrees and at different rates; in anxiety disorders, medications work well for psychic fear, somatic
symptoms, and overall functioning, but not well for avoidance or agoraphobia; in obsessive-compulsive
disorder (OCD), some symptom factors do not respond as well as others to given medication class, eg, selective serotonin
reuptake inhibitors (SSRIs); combination of medications and cognitive behavioral therapy (CBT) generally
better than either alone for initial efficacy and relapse prevention; most anxiety disorders chronic conditions that require
long-term treatment
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| Management: thorough assessment crucial for making accurate diagnosis and determining symptom pattern, comorbidity,
history of treatment and side effects, patient’s beliefs and expectations about disorder and treatment (as well
as beliefs of family members and significant others), and predictors of response to specific medications (eg, particular
symptom variables, demographic variables)
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| OCD symptom factors: doubt underlying feature of OCD; studies show OCD consists of 5 major domains; 1) obsessions
relating to harm and/or aggression that lead to checking and repeating compulsions (≈60% of patients); 2)
contamination obsessions with cleaning compulsions (40% to 50% incidence); 3) symmetry and order-related obsessions
with arranging, repeating, and/or counting compulsions; 4) hoarding and loss obsessions with hoarding,
saving, and/or acquiring compulsions; 5) thoughts of unacceptable nature, often about sex or religion, with mental
compulsions
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| Recognizing OCD: patients usually present with general complaints of anxiety or irrational somatic complaints, not
of obsessions that lead to compulsions; look for telltale signs such as red hands or dermatitis from excessive
washing, repetitive movements, and complaints by patients of being unable to finish tasks
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 | Screening questions: sensitivity and specificity of first 3 questions >80%; fourth question also identifies obsessive-
compulsive (OC) spectrum disorders; screen all patients with symptoms of anxiety or depression with the following
questions 1) do you wash your hands over and over? 2) do you have to check things repeatedly? 3) do you
have repetitive thoughts that distress you and that you cannot get rid of? 4) do you have any repetitive behaviors
that are difficult to control? positive response to any of these questions suggests more specific screening with
Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and symptom checklist; screen for comorbidities with Mini
International Neuropsychiatric Interview (MINI), Hamilton Depression Scale (HAM-D), Hamilton Anxiety
Scale (HAM-A), Global Assessment of Functioning (GAF), or other screening instruments
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| Treatment planning: know treatments available, and which effective and ineffective; assess patient’s insight and
motivation; determine most appropriate treatment setting (inpatient or outpatient); combine medications and
CBT whenever possible; treat comorbid disorders; address family and environmental factors
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| Treatment for OCD: first-line treatments include pharmacotherapy (primarily SSRIs) and CBT that uses exposure
and response prevention; forms of psychotherapy that do not include behavior modification and electroconvulsive
therapy (ECT) shown not to be effective for OCD, but may help with comorbid conditions; neurosurgical approaches
used only as last resort; combination of CBT and medication best
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| Pharmacotherapy for OCD: medications approved (or in approval process) by Food and Drug Administration
(FDA) for OCD include citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, clomipramine, and escitalopram;
treat OCD with higher daily doses than those for major depression or other anxiety disorders; allow minimum
10- to 12-wk trial of full dose of any medication before changing or augmenting; in patients with
depression and OCD, depressive symptoms often abate first; in patients who respond, continue maintenance
therapy for at least 12 mo; slow withdrawal recommended for all agents; if initial response not favorable, switch
to another agent in same class; some studies show that venlafaxine may be effective in patients who have failed
SSRIs; higher doses mean more side effects, so educate patient and family accordingly; 40% to 60% of patients
respond to SSRIs, with mean improvement in symptoms of 40% to 50%; relapse rate very high if medication discontinued
without behavioral therapy
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| Predictors of poor response to SSRIs: greater symptom severity; early onset or longer duration of OCD; higher
number and frequency of compulsions; sexual or religious obsessions; greater number of washing/cleaning rituals;
poor insight; sensory phenomena that lead to compulsions; early studies suggested that hoarding and saving
were relative predictors of poor response, but more recent studies have not shown that; comorbid tic disorder or
history of tic disorder; schizo-obsessive disorder (“grab bag that includes patients who have some mild schizotypal
traits all the way up to patients who have full-blown primary psychotic disorders, such as schizoaffective
disorder or schizophrenia”); severe personality disorder; family history of psychiatric illness
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| Augmentation strategies: atypical antipsychotic medica-tions—good studies for risperidone, olanzapine, and quetiapine;
trials in progress for ziprasidone; case series only for aripiprazole; used in smaller doses than those used
for primary treatment of schizophrenia or bipolar disorder; typical antipsychotic medications—seldom used because
of side effect profiles, “but they do work”; especially effective for tic-related and schizo-obsessive OCD,
but also effective for “garden variety” OCD; clomipramine—add 50 to 100 mg at night; strongly sedating; strong
anticholinergic effect can produce blurry vision, constipation, and urinary retention; pindolol—“mixed track
record”; results of studies conflicting; generally favorable side effect profile; because it is β-blocker, it can reduce
blood pressure and heart rate (monitor carefully); also has serotonin 1A-blocking effect, which may be what
makes it effective for augmentation of antidepressants and antiobsessional agents; mirtazapine—still in early
studies; one trial showed possible efficacy as monotherapy, but results not yet replicated; in one study of mirtazapine
for augmentation, 30% to 40% of patients got worse; another study showed that if mirtazapine and SSRI
started simultaneously, response accelerated; speaker recommends waiting for more data before augmenting
with mirtazapine; agents with no controlled studies—may have been found effective in open trial or case series;
morphine (one controlled study); tramadol; buspirone; trazodone; glutamate antagonists under intensive study,
but no controlled study results so far; stimulants may be helpful in patients with comorbid attention-deficit/hyperactivity
disorder (ADHD); speaker occasionally uses long-acting benzodiazepine, but reluctant to use short-acting
formulations; “mood stabilizers have not panned out”; 2 case series suggested nicotine may help
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| Behavioral therapy for OCD: must incorporate exposure and response prevention (“neither one by itself will
work”); meta-analysis found that of patients who completed trials of exposure and response prevention, 50% had
>70% symptom reduction, another 35% to 38% had moderate improvement, and only ≈10% had no improvement;
however, dropout and refusal rate 24% (speaker attributes this to therapists not being proficient in behavioral therapy)
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| Practice guidelines: will be published by American Psychiatric Association (APA) in 2008; candidates for CBT
alone—children and adolescents; adults with mild or moderate OCD without significant comorbid depression, substance
abuse, or other major psychiatric disorder; patients who decline medication; women currently pregnant or
lactating; candidates for medication alone—patients with low motivation or poor insight; patients with cognitive
impairment that prevents them from following instructions or complying with CBT; patients who decline or do not
have access to CBT; candidates for combination therapy—everyone else; better efficacy than SSRI alone; possibly
better than CBT alone for adults; better than CBT alone for children and adolescents, especially those with obsessions
with minimal compulsions and those with depressive symptoms; better for first 2 mo of treatment in adults;
combined treatment yields lower relapse rates after treatment discontinuation than treatment with SSRI alone; adding
CBT to ongoing treatment with SSRI produces additional improvement in Y-BOCS scores and converts >50%
of nonresponders to responders
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| Social phobia: distinguished from OCD and other anxiety disorders by fear of negative evaluation; all humans have
some fear of being judged negatively, but when excessive, it becomes pathologic; can produce “tremendous” distress
and impairment in social, occupational, school, relationship, and other situations; criteria include—excessive
and persistent fear of social situations; excessive anxiety and arousal in social situations; anticipatory worry about
social situations; avoidance (or endurance with distress); individual recognizes that his or her fear excessive;
subtypes—specific (also called discrete social phobia or performance anxiety); generalized subtype tends to have
earlier onset and to be more severe; patients tend to be afraid of variety of social situations (eg, groups, one-on-one
situations, fun and work situations, eating in public)
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| General considerations: specific subtype usually does not have heritable component and can begin at any age in person
who has negative experience; generalized subtype has strong heritable component and almost always starts in
childhood; targets of treatment—fear and anticipatory anxiety; physical arousal symptoms; avoidance; overall functioning;
medications improve all; common comorbidities—major depression; alcohol abuse; panic disorder; agoraphobia
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| Specific medications: β-blockers—work only for specific social phobia (performance anxiety); not effective for generalized
social phobia; SSRIs—treatment of choice for generalized social phobia; all (except possibly fluoxetine)
equally effective; response rate 40% to 65%, vs 25% to 35% for placebo; average symptom reduction 40% to 50%;
dosing range intermediate between dosage for major depression and dosage for OCD; effective for comorbid depression,
and possibly effective for comorbid alcohol abuse; monoamine oxidase inhibitors (MAOIs)—70% response
rate with phenelzine vs 20% for placebo; reversible MAOIs less effective than irreversible MAOIs; venla-
faxine—response rate better than that of placebo, similar to that of SSRIs; mirtazapine—may be effective; only one
placebo-controlled study; bupropion and reboxetine—may be effective, but studied only in open trials; benzo-
diazepines—clonazepam superior to placebo, but inferior to SSRIs or venlafaxine; alprazolam only mildly better
than placebo; side effects include sedation, dependence, and abuse potential; not helpful for comorbid depression;
not recommended as first-line agents, but may be useful as adjunct to SSRIs; in one study, combination of paroxetine
and clonazepam better than combination of paroxetine and placebo; anticonvulsants—gabapentin, pregabalin,
and levetiracetam better than placebo, but effects weak; olanzapine better than placebo in one small trial; other
medications—ondansetron and clonidine helpful in case reports, but no controlled studies; ineffective—tricyclic antidepressants;
buspirone; valproate; pergolide; pindolol; St. John’s wort; nefazodone effective in open trials but not
in placebo-controlled trial
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| Predictors of poor response: early onset; greater severity of illness; alcohol abuse; greater autonomic arousal (eg,
higher blood pressure and heart rate); borderline and passive-dependent personality disorders; short duration of
treatment; s/s genotype of 5HTTLPR
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| Other considerations: high rate of relapse after medication discontinued unless CBT substituted; treat for ≥1 yr; medications
act more rapidly than CBT in beginning, but after 12 to 24 wk, both treatments equivalent; higher relapse rate
if medications discontinued in first few months, lower if medications discontinued with slow titration after 1 yr; CBT
endures and lowers future relapse rate; unclear whether combination treatment better than either treatment alone
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| Conclusions: studies show that effects on brain of SSRIs differ by disorder; different symptom clusters mediated by
different brain circuits and require different treatment approaches
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Suggested Reading
Brown RA et al: A pilot study of moderate-intensity aerobic exercise for obsessive compulsive disorder. J Nerv Ment
Dis 195:514, 2007; Bystritsky A et al: Augmentation of serotonin reuptake inhibitors in refractory obsessive-compulsive
disorder using adjunctive olanzapine: a placebo-controlled trial. J Clin Psychiatry 65:565, 2004; Calamari JE
et al: Obsessive-compulsive disorder subgroups: a symptom-based clustering approach. Behav Res Ther 37:113,
1999; Cosgrove GR: Surgery for psychiatric disorders. CNS Spectr 5:43, 2000; Cyr NR: Obsessive compulsive disorder.
AORN J 86:277, 2007; Dell’Osso B et al: Diagnosis and treatment of obsessive-compulsive disorder and related
disorders. Int J Clin Pract 61:98, 2007; Denys D et al: Prediction of response to paroxetine and venlafaxine by
serotonin-related genes in obsessive-compulsive disorder in a randomized, double-blind trial. J Clin Psychiatry
68:747, 2007; Fineberg NA et al: Obsessive-compulsive disorder: boundary issues. CNS Spectr 12:359, 2007; Galvao-de
Almeida A et al: Obsessive-compulsive disorder: an open-label pilot trial of escitalopram. CNS Spectr
12:519, 2007; Grados M, Wilcox HC: Genetics of obsessive-compulsive disorder: a research update. Expert Rev
Neurother 7:967, 2007; Hummelen B et al: The relationship between avoidant personality disorder and social phobia.
Compr Psychiatry 48:348, 2007; Lipsman N et al: Deep brain stimulation for treatment-refractory obsessive-
compulsive disorder: the search for a valid target. Neurosurgery 61:1, 2007; Math SB, Janardhan Reddy YC: Issues
in the pharmacological treatment of obsessive-compulsive disorder. Int J Clin Pract 61:1188, 2007; Saxena S et al:
Paroxetine treatment of compulsive hoarding. J Psychiatr Res 41:481, 2007; Summerfeldt LJ et al: Symptom structure
in obsessive-compulsive disorder: a confirmatory factor-analytic study. Behav Res Ther 37:297, 1999; Tumur I
et al: Computerised cognitive behaviour therapy for obsessive-compulsive disorder: a systematic review. Psychother
Psychosom 76:196, 2007.
Educational Objectives
| The goal of this program is to improve the diagnosis and treatment of obsessive-compulsive disorder (OCD) and social
phobia. After hearing and assimilating this program, the clinician will be better able to:
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| 1. Distinguish OCD from other anxiety disorders.
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| 2. Select appropriate medications for treating OCD.
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| 3. Discuss the importance of cognitive behavioral therapy in the treatment of OCD.
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| 4. Differentiate between specific social phobia (performance anxiety) and generalized social phobia.
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| 5. Describe treatment options for both subtypes of social phobia.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, the Audio-Digest Foundation requires all faculty members
to disclose relevant financial relationships within the past 12 months that might create any personal conflict of
interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care
education and not a proprietary business or commercial interest. For this program, Dr. Saxena reported nothing to disclose.
Acknowledgements
Dr. Saxena was recorded at Advances in Psychopharmacology Throughout the Life Span, held April 12-14, 2007, in San
Diego, CA, and sponsored by the University of California, San Diego, School of Medicine. The Audio-Digest Foundation
thanks Dr. Saxena and UCSD for their cooperation in the production of this program.
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