3. 30 years ago…..
Being diagnosed with
obsessive-compulsive disorder
(OCD) was about the closest
thing the psychiatric world had
to being given a life
sentence…..
In addition to being seen as
extremely rare, ….prognosis for
those with a diagnosis of OCD
was very poor….,
…..with no effective truly
pharmacological or
psychological treatments
4. OCD
OCD is characterized by intrusive,
troubling thoughts (obsessions), and
repetitive, ritualistic behaviors
(compulsions) which are time
consuming, significantly impair
functioning and/or cause distress
When an obsession occurs, it almost
always corresponds with a massive
increase in anxiety and distress.
Subsequent compulsions serve to
reduce this associated anxiety/distress.
Lack CW, World J Psychiatry. 2012 Dec
22;2(6):86-90
5. Prevalence of OCD
The lifetime prevalence rate of OCD is estimated
at( USA)
2.3% in adults and
around 1%-2.3% in children and adolescents
under 18.
Sub-clinical” cases of OCD (around 5% of the
population)
Few epidemiological differences across different
countries and even between European and
Asian populations 1
Notably, 30-50% of patients develop OCD
starting in childhood 2
1. Lack CW , World J Psychiatry. 2012 Dec 22;2(6):86-
2. Brian P. Brennan et al, Biol Psychiatry. 2013 Jan 1;73
6. OCD in children and adolescents
Early-onset obsessive-
compulsive disorder (OCD) is
one of the more common
mental illnesses of children
and adolescents, with
prevalence of 1% to 3%.
Its manifestations often lead to
severe impairment and to
conflict in the family Walitza S et al, Dtsch Arztebl Int. 2011 Mar;108(11
8. The CSTC circuitry implicated in
OCD
Pittenger C et al, Pharmacol Ther. 2011 Dec;132(3):314
9. Wu et al. [16] summarized the prior literature on the
pivotal role of glutamate in corticostriatal-
thalamocortical (CSTC) models of OCD.
One of the leading OCD models is based on the
balance between direct and indirect pathways within
CSTC circuits.
According to this theory, reciprocal interaction
between direct (ultimately leads to thalamic
stimulation of the cortex) and indirect (ultimately leads
to thalamic inhibition of the cortex) pathways normally
resulted in a dynamic balance with no one pathway
predominating.
Hyperactivity of the direct pathway or hypoactivity of
the indirect pathway would disinhibit CSTC circuits
and promote consequent release of hardwired
behaviors (compulsions) and cognitions (obsessions)
that were normally held in check
10. Pathophysiology of OCD
As yet Unknown
Abnormalities in the orbital (OFC),
ventromedial (vmPFC-subgenual cingulate
and medial OFC), and dorsal anterior
cingulate (dACC) cortical-basal ganglia
circuits
OCD-linked patterns of activity in these PFC
regions are accentuated during provocation
of symptoms
They can predict treatment response
They tend to normalize following successful
treatment
Haber SN et al, Neuropsychopharmacology. 2013 Ja
11. Neurotransmitter alterations in OCD??
Linkage of OCD risk with polymorphisms in the serotonin
transporter
Increased serotonin in peripheral blood has been reported in
OCD
Abnormalities in dopamine neurotransmission in OCD: A
reduction in the dopamine D2 receptor
Abnormalities in glutamate neurotransmission and
homeostasis, especially in the CSTC circuitry
Pittenger C et al, Pharmacol Ther. 2011 Dec;132(3):314
12. NeuroCircuitry Abnormalities in OCD
Changes in vmPFC/OFC/dACC
activity
Overlap in the circuits
Dysfunction of the
vmPFC/OFC/dACC network
PFC regions associated with OCD
pathology
Haber SN et al, Neuropsychopharmacology. 2013 J
13. Genetic factors and OCD
Twin studies reveal a higher
concordance of OCD in
monozygotic twins (80–87%) than in
dizygotic twins (47–50%)
Genetic factors appear to have a
substantial role in the etiology of early-
onset OCD.
Wu K et al, Pharmacol Biochem Behav. 2012 Feb;100(4):726-3
14. Glutamate Related Genes implicated in OCD
Several glutamate-related genes have been
associated with OCD risk.
The glutamate transporter gene Slc1A1
The Sapap3 gene, is critical to the normal
localization of ionotropic glutamate receptors
The Grin2B gene may be associated with OCD
transmission
The Grik2 locus is involved in glutamate
neurotransmission
Pittenger C et al, Pharmacol Ther. 2011 Dec;132(
15. Disrupted neurotransmission of glutamate
in OCD
Disrupted neurotransmission of
glutamate within corticalstriatal-
thalamocortical (CSTC) circuitry
Plays a role in OCD pathogenesis.
Associations between variants for
SLC1A1
Wu K et al, Pharmacol Biochem Behav. 2012 Feb;1
16. Proinflammatory cytokines in OCD
Significant reduction in IL-1β
levels
Lower plasma IL-6 levels.
Elevated TNF-α levels in
individuals with comorbid
depression.
Gray SM et al, Curr Psychiatry Rep. 2012 Jun;14(3)
18. ICD-10 criteria for obsessive-compulsive
disorder (age-independent)*
For a definite diagnosis,
obsessional symptoms or
compulsive acts, or both, must
be present on most days for at
least 2 successive weeks and
be a source of distress or
interference with activities.
19. ICD-10 criteria for obsessive-compulsive
disorder (age-independent)*
The obsessional symptoms should have the
following characteristics:
They are acknowledged as originating in the mind of
the patient, and are not imposed by outside persons
or influences.
At least one obsession or compulsion must be
present which is unsuccessfully resisted.
Carrying out the obsessive thought or compulsive act
is not in itself pleasurable.
The thoughts, images, or impulses must be
unpleasantly repetitive
20. ICD-10 criteria for obsessive-compulsive
disorder (age-independent)*
The patient must suffer from obsessions and/or compulsions,
i.e., thoughts and/or behavioral impulses.
At least one of these obsessions and/or compulsions must be
resisted.
The patient does not perceive the manifestations of the disorder
as being pleasurable.
The obsessions and/or compulsions occur repetitively; the
patient is troubled by them and is markedly impaired by them.
21. DSM V and OCD changes : Unnecessay but
harmless?
The APA is considering changing the name of this
category to Anxiety and Obsessive-Compulsive
Spectrum Disorders.
Obsessive-Compulsive Disorder removed from the
Anxiety Disorders category, and reclassified in its
own category.
Reason : OCD has a neurological basis. …
22. DSM V and OCD changes
The DSM-IV focus was not on the cause of the but
rather on the presenting symptoms that define the
conditions.
One of the primary defining characteristics of OCD is
anxiety.
The one common factor - they are highly anxious
about their obsessive and compulsive symptoms.
23. OCD and DSM-V: Taking the “anxiety” out of
OCD
Psychiatrists and psychologists debate
whether or not OCD should continue to
be classified as an “anxiety disorder.”
In some ways, OCD overlaps with other
anxiety-related conditions, such as
panic disorder
Phobias
social anxiety disorder
generalized anxiety disorder, and
post-traumatic stress disorder (PTSD).
24. DSM V and OCD
The new Diagnostic and Statistical Manual of Mental Disorders, 5th
Edition (DSM-5)
Has a number of changes to obsessive-compulsive and related
disorders, such as hoarding and body dysmorphic disorder.
A separate chapter for OCD and related disorders
They are no longer considered “anxiety disorders.
Disorders in this chapter include
obsessive-compulsive disorder,
body dysmorphic disorder and
trichotillomania (hair-pulling disorder), as well as two new disorders:
hoarding disorder and excoriation (skin-picking) disorder.
25. DSM-5
Obsessive-compulsive and related disorders can
include
body-focused repetitive behavior disorder and
obsessional jealousy, or unspecified obsessive-
compulsive and related disorder.
Body-focused repetitive behavior disorder, is
characterized by recurrent behaviors other than hair
pulling and skin picking (e.g., nail biting, lip biting,
cheek chewing) and repeated attempts to decrease
or stop the behaviors.
Obsessional jealousy is characterized by
nondelusional preoccupation with a partner’s
perceived infidelity.
26. Diagnosis with the Y-BOCS
Define the range and severity of
OCD symptoms
The Yale-Brown Obsessive
Compulsive Scale (Y-BOCS) is a
good tool
Complete Mental Status
Examination
Look for comorbid symptoms and
27. Imaging studies
Functional MRI and PET scanning demosntrate
increase in blood flow and metabolic activity in the
orbitofrontal cortex, limbic structures, caudate, and
thalamus
with a trend toward right-sided predominance.
Areas of overactivity have been shown to normalize
following successful treatment with either SSRIs or
CBT.
These imaging modalities, are of value for research
They are not indicated for normal workups.
29. Common obsessions
Contamination fears
Worries about harm to self or
others
The need for symmetry,
exactness and order,
Religious/moralistic concerns
Forbidden thoughts (e.g.,
sexual or aggressive), or
A need to seek reassurance or
confess
Lack CW , World J Psychiatry. 2012 Dec 22;2
30. Common obsessions
Safety
Doubting one's memory or perception
Scrupulosity (need to do the right
thing, fear of committing a
transgression, often religious)
Need for order or symmetry
Unwanted, intrusive sexual/aggressive
thought
31. Common compulsions
Cleaning/washing
Checking
Counting
Repeating
Straightening
Routinized behaviors
Confessing
Praying
Seeking reassurance
Touching
Tapping or rubbing, and
Avoidance
Lack CW , World J Psychiatry. 2012 Dec 22;2
32. Common compulsions
Checking (eg, locks, stove, iron, safety of children)
Counting/repeating actions a certain number of times
or until it "feels right"
Arranging objects
Touching/tapping objects
Hoarding
Confessing/seeking reassurance
List making
33. Gender differences
More common in males in pediatric patients.
There are some differences in comorbidity as well.
Among men, hoarding symptoms are most often
associated with GAD and tic disorders.
In women social anxiety, PTSD, body dysmorphic
disorder, nail biting, and skin picking are more often
observed
Lack CW , World J Psychiatry. 2012 Dec 22;2
34. Cultural influences on symptom expression
Bali: Heavy emphasis on somatic symptoms and need to know
about members of their social network
Jews: Emphasis on cleanliness and order
Muslims : Religious obsessions in Muslim communities
South America : Aggressive aggressions
USA : Dirt and contamination worries
Lack CW , World J Psychiatry. 2012 Dec 22;2
36. OCD in children
Presentation of OCD symptoms is similar in children
and adults.
Younger children will not be able to recognize that
their obsessions and compulsions are both
unnecessary
In young children, compulsions often occur without
the patient being able to report their obsessions
Adolescents are often able to report multiple
obsessions and compulsions.
Lack CW , World J Psychiatry. 2012 Dec 22;2
37. OCD in children
Children and adolescents are also more likely to include family
members in their rituals
Can be highly demanding of adherence to rituals and rules,
leading to disruptive and oppositional behavior and even
episodes of rage.
Youth with OCD are generally more impaired than adults
with the same type of symptoms
Lack CW , World J Psychiatry. 2012 Dec 22;2
39. Comorbid disorders with OCD
Up to 75% of persons with OCD present with comorbid
disorders.
In pediatric cases : ADHD, disruptive behavior disorders, major
depression, and other anxiety disorders.
In adults: Social anxiety, major depression, and alcohol abuse.
Lack CW , World J Psychiatry. 2012 Dec 22;2
40. Comorbid disorders with OCD
Primary symmetry/ordering symptoms are often seen
with
comorbid tics
bipolar disorder
obsessive-compulsive personality disorder
panic disorder, and agoraphobia
Those with contamination/cleaning symptoms are
more likely to be diagnosed with an eating disorder.
Those with hoarding cluster symptoms, are likely to
be diagnosed with personality disorders, particularly
Cluster C disorders
Lack CW , World J Psychiatry. 2012 Dec 22;2
41. OCD and schizophrenia
The mean OCD prevalence is 13.6%
The prevalence rate of OCS, defined as any
obsession or compulsion is 30.7%
The prevalence of OCS and OCD in schizophrenia is
substantial, specifically in more chronic patient
populations
It is influenced by the method of assessment
Swets M, Schizophr Res. 2013 Dec 19. pii: S0920-9964(13)00
42. Prevalence estimations of OCS and OCD within
different samples of patients
Schirmbeck F, Front Pharmacol. 2013 Aug 9;4:99.
43. Onset of OCS
First onset of OCS has been described at different
stages during the course of psychotic illness:
Before psychosis as independent, co-existing
symptoms or diagnosed OCD.
Prior to psychotic manifestation as part of the at risk
mental state (ARMS).
Simultaneously with the first manifestation of
psychosis.
After the first psychotic episode during the course of
chronic schizophrenia.
As de novo OCS after initiation of antipsychotic
treatment. Schirmbeck F, Front Pharmacol. 2013 Aug 9;4:99.
44. OCS might manifest at
different time points
during the course of
schizophrenia illness
(A) Pre-existing and
persistent OCS.
(B) Intermittent OCS
during ARMS or later
in the clinical course.
(C) OCS-onset during
ARMS and persistent
course, strongly
associated to the
psychotic symptoms
(schizo-obsessive
concept).
(D) Fluctuating course of
OCS.
(E) Second-onset OCS
during antipsychotic
treatment
Schirmbeck F, Front Pharmacol. 2013 Aug
45. Identification of obsessive-compulsive symptoms in
schizophrenia.
Insight-criterion Patients suffering from OCD typically fulfill
three symptom characteristics: they attribute
the obsessions, impulsive symptoms and
compulsions to their own thinking, declare
with insight their unreasonableness and
show some degree of resistance against
them. In particular the first two properties
allow a differentiation from hallucinations
and delusions. Ruminations or stereotypic
ego-dystonic cognitions with direct relation
to the contents to psychotic thinking should
not be diagnosed as obsessions.
OCS not solely related to the psychotic
content
Cleaning or checking behavior should be
diagnosed as compulsions only if it is
accompanied by typical obsessions and not,
if the patient currently suffers from delusions
of contamination, intoxication or infection.
Re-evaluation of OCS after remission of
psychotic symptoms
If first manifestation of OCS occurs
simultaneously with the first psychotic
exacerbation, the final decision on a valid
comorbid condition should be postponed
until the remission of psychotic symptoms.
Schirmbeck F, Front Pharmacol. 2013 Aug 9;4
46. Identification of obsessive-compulsive symptoms in
schizophrenia.
Differentiation from catatonic symptoms Repetitive behavior or stereotypic actions
should carefully be discriminated from catatonic
symptoms most importantly in patients with so-
called “manieristic catatonia.”
Obsessions presented as pseudohallucinations A subgroups of OCS patients, who experience
their obsessions as extremely aversive and
burdening may try to distance themselves by
using expressions such as “voices” or “foreign
thought content”, but in most cases these
phenomena can be characterized as
pseudohallucinations.
SGA-induced OCS Patients without a previous history of OCS
might develop these phenomena during
antipsychotic treatment. This constellation hints
toward the unfavorable effect of second-onset
OCS induced by SGAs.
Schirmbeck F, Front Pharmacol. 2013 Aug 9;4:99.
47. Factors for occurrence of OCS
The additional occurrence of OCS is associated
with
high subjective burden of disease
additional neurocognitive impairment
poorer social and vocational functioning
greater service utilization
high levels of anxiety and depression.
Schirmbeck F,Front Pharmacol. 2013 Aug 9;4
48. Hypothesis for OCD + Schizophrenia
Patients with schizophrenia develop OCS as an
attempt to reduce psychotic symptoms ??
The presence of OCS was proposed to have
protective effects??
Negative correlations between specific OCS and
the severity of psychotic disorganization in
thinking and behavior, may be due to
compensating mechanisms??
Schirmbeck F,Front Pharmacol. 2013 Aug 9;4
49. Schizotypic OCD
Primary OCD-patients present beliefs, which can
be classified on a spectrum between obsessions
and delusions emphasizing the similarities as
being irrational thoughts, the first with insight and
the latter lacking insight.
Schirmbeck F,Front Pharmacol. 2013 Aug
50. Neurobiological mechanisms in OCD and
schzophrenia
Pronounced cognitive deficits reflect an
underlying neurobiological risk factor for
schizophrenia patients to develop OCS and
mirror at least partially overlapping
neurobiological mechanisms with OCD
Serotonergic dysfunctions, alterations in
dopaminergic activity and in glutamatergic
neurotransmission, have also been related to
OCD
Schirmbeck F,Front Pharmacol. 2013 Aug
51. Impact of OCD on QoL
Almost all adults and children with OCD report that
their obsessions cause them significant distress
and anxiety
A pervasive decrease in QOL
Youth show problematic peer relations, academic
difficulties, sleep problems, and participate in
fewer recreational activities
Lack CW , World J Psychiatry. 2012 Dec 22;2
52. OCD and bipolar disorder
Obsessive compulsive features occurring in mania
have been well documented.
There are very few case reports and studies in India
This is a complex comorbidity to treat as OCD
requires high doses of SSRIs which precipitates
mania.
A sound knowledge of etiology and the pathology
operating gives an insight into the comorbidity
Annigeri B, Indian J Psychol Med. 2011 Jan;33(1):83-5
53. Treatment of OCD and bipolar disorder
Treatment guidelines may differ as compared with
that of pure cases.
BPD also responds poorly to mood stabilizing
antipsychotics like olanzapine in the presence of
OCD.
BPD receives preference with regards to
treatment
Annigeri B, Indian J Psychol Med. 2011 Jan;33(1):83-5
55. Cognitive-behavioral therapy (CBT)
The psychological treatment of
choice for OCD
Effective in both adults and children
Is backed by numerous clinical trials
Particularly exposure with response
prevention (EX/RP)
Lack CW , World J Psychiatry. 2012 Dec 22;2
56.
57. CBT
It is superior to medications alone, with effect sizes
ranging from 1.16-1.72
There is a lower relapse rate than in medications (12%
vs 24%-89%)
Up to 25% of patients will drop out prior to completion
of treatment due to the nature of treatment.
The course of therapy generally lasts between 12-16
sessions
Lack CW , World J Psychiatry. 2012 Dec 22;2
58. Differing responses to CBT
Those with hoarding cluster
symptoms respond less well to
CBT
Accommodation by family
members in pediatric clients is
predictive of poorer treatment
response as well.
Intriguingly, group therapy that
uses CBT and EX/RP has been
shown to be equally as effective as
individual therapy
For persons with mild OCD,
computer-assisted self-treatment
has been shown to be very
effective
Lack CW , World J Psychiatry. 2012 Dec 22;2
59. Pharmacological treatment
Treatment is targeted primarily at monoaminergic
neurotransmission, particularly at the serotonin and
dopamine systems.
The SSRIs are the mainstay of pharmacotherapy
The SSRIs are of benefit in 50–60% of patients
Pittenger C et al, Pharmacol Ther. 2011 Dec;132
60. Drug therapy
First-line pharmacologic treatments consist of
5-HT reuptake inhibitors, such as the SSRIs
(fluoxetine, fluvoxamine, sertraline, paroxetine,
citalopram, escitalopram),
Clomipramine
TCA with 5-HT and NE reuptake inhibition.
Venlafaxine (SNRI).
61. SSRIs
SRIs can be successfully supplemented with
adjunctive antipsychotics
Only a third of patients will show improvements and
there are serious health concerns with their long-term
usage.
Lack CW, World J Psychiatry. 2012 Dec
22;2(6):86-90
62. Indian experience with SSRIs in OCD
The study examined the 5-year course prospectively in 115 OCD
outpatients who were mostly treated with serotonin reuptake
inhibitors (SRIs).
The outcome of OCD seems to be better than generally
assumed, at least in moderately ill outpatients.
Regular treatment over extended period may enhance likelihood
of remission.
Full remission should be the goal of treatment since it is
associated with lesser propensity for relapse.
Most patients remit in the first 2 years of treatment; therefore,
early detection and intervention may improve the outcome.
Cherian AV et al, J Affect Disord. 2014 Jan;152-
154:387-94
63. Clinical Pearls
Adding ERP to SRIs was superior to both
risperidone and pill placebo.
Patients with OCD receiving SRIs who continue
to have clinically significant symptoms should be
offered ERP before antipsychotics given its
superior efficacy and less negative adverse effect
profile.
Simpson HB JAMA Psychiatry. 2013 Nov;70(11):1190
64. Clinical Pearls
Augmenting SRIs with exposure and ritual
prevention versus stress management training
leads to better outcome after acute treatment and
24 weeks later
The response in combination group was
significantly higher starting from 9th week,
continuing up to 13th week. Mean symptom
reduction and mean percentage reduction of
symptoms were also higher in the case of
combination group.
Foa EB, J Clin Psychiatry. 2013 May;74(5):464-9
Giasuddin NA, Pak J Pharm Sci. 2013 Jan;26(1):95-8
65. Clinical Pearls
About one-third of SRI-resistant OCD patients
benefited from an augmentation strategy with
antipsychotics.
Based on the favourable risk:benefit ratio,
risperidone can be considered as the agent of
first choice and should be preferred to quetiapine
and olanzapine.
Dold M, Int J Neuropsychopharmacol. 2013 Apr;16(3):5
66. Sertraline for non responders of OCD
Greater symptom improvement was seen in the
high-dose sertraline group compared to the 200-
mg/day dose group during continuation treatment.
Both dosages have similar safety profiles.
Administration of higher than labeled doses of
selective serotonin reuptake inhibitors may be a
treatment option for certain OCD patients who fail
to respond to standard acute treatment
Ninan PT, J Clin Psychiatry. 2006 Jan;67(1):15
68. Fluvoxamine Vs Clomipramine in OCD
Presentation Title
Date
68
Study objective: To directly compare the efficacy and safety of
fluvoxamine and clomipramine in patients with OCD
Study Design: Double-blind, randomised, multicentre study
Patient population: 227 patients with a primary diagnosis of OCD
Evaluation parameters:
Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)
National Institute of Mental Health Obsessive-Compulsive (NIMH-OC)
scale
Global Improvement item of the Clinical Global Impression (CGI) scale
Mundo E. Hum Psychopharmacol. 2001 Aug;16(6):461-468.
69. Fluvoxamine Vs Clomipramine in OCD
69
Fluvoxamine and
clomipramine were
equally effective, both
resulting in clinically
significant
improvement
Mundo E. Hum Psychopharmacol. 2001 Aug;16(6):461-468.
70. Fluvoxamine Vs Clomipramine in OCD
70
Mundo E. Hum Psychopharmacol. 2001 Aug;16(6):461-468.
Fluvoxamine and
clomipramine were
equally effective on
secondary endpoints
variable
71. Fluvoxamine Vs Clomipramine in OCD
71
Mundo E. Hum Psychopharmacol. 2001 Aug;16(6):461-468.
Fluvoxamine was
better tolerated than
clomipramine
The overall incidence
of premature
withdrawal due to
adverse events was
twice as high as with
clomipramine than
with fluvoxamine
(16% Vs 8%)
72. Cognitive therapy versus fluvoxamine as a second-
step treatment in obsessive-compulsive disorder
nonresponsive to first-step behavior therapy
OCD patients who are nonresponsive to ERP
(exposure in vivo with response prevention) may
benefit more from a switch to treatment with an
antidepressant instead of switching to CT
In clinical practice, it may be important to motivate
this subgroup of patients to undergo
psychopharmacological treatment, as this may
improve their outcome considerably
van Balkom AJ, Psychother Psychosom. 2012;81(6):366-
73. Weight gain with SSRIs
Clomipramine,, citalopram, fluoxetine, fluvoxamine,
paroxetine, or sertraline
At the end of the 2.5-years patients had gained a
mean of 2.5% of their body weight with respect to
baseline (1.58 kg)
Higher proportion of clomipramine-treated patients
(34.8%) gained > or = 7% in weight as compared with
sertraline and fluoxetine
Sertraline and fluoxetine had the lowest percentage
of patients with a significant weight gain (4.5% and
8.7%, respectively),Maina G, J Clin Psychiatry. 2004 Oct;65(10):1365-71.
74. Clinical Pearls : Treatment predictors for
fluvoxamine
Pre-treatment activation in the
right cerebellum (Z-score=5.10, x,y,z=22,-84,-
18) and
the left STG (Z-score=4.95, x,y,z=-62,-22,0)
was positively correlated with the improvement
in the Y-BOCS score.
Pre-treatment activation in the right
cerebellum and in the left STG predict
subsequent reduction in OCD symptom
severity.
There is every possibility that fMRI can be
used as a tool to predict treatment response.
Sanematsu H et al, J Psychiatr Res. 2010 Mar;44(4):193-20
75. Major sites of action of glutamate-
modulating drugs
Pittenger C et al, Pharmacol Ther. 2011 Dec;132
76. Differing responses
The presence of tics appears to decrease selective
SRI effects in children, but it is unclear if it has the
same effect in adults.
Another known difference is that patients who have
OCD with comorbid tics respond better to neuroleptic
drugs than those who have OCD without tics
Lack CW, World J Psychiatry. 2012 Dec
22;2(6):86-90
77. Clinical Pearls
Unlike in the case of major depression, complete
or near-complete remission of OCD symptoms is
rare with only serotonergic antidepressant
treatment.
More typically, perhaps half of patients may
experience symptom reductions of 30-50%, with
many other patients failing to achieve even this
degree of relief.
Doses above those needed for treatment of
depression may be more effective for some
patients.
A therapeutic dose for 6-10 weeks may be
required to observe a clinical response.
Response tends to be slow and continues for at
least 12 weeks
78. Clinical Pearls
For reasons that remain unclear,
higher doses than those used
for depression are often required
for OCD
In disease refractory to these
agents, pharmacological
augmentation with neuroleptic
drugs, which antagonize the D2
dopamine receptor, can be
efficacious
Pittenger C et al, Pharmacol Ther. 2011 Dec;132
79. Clinical Pearls
Role of life events in obsessive
compulsive disorder.
Life events are significantly more
frequent in OCD patients
The severity of OC symptoms is
directly proportional to the number of
stressful life events experienced in the
last six months prior to onset.
Sarkhel S et al, Isr J Psychiatry Relat Sci. 2011;48(3):182-5.
80. Alternative agents
Use of specific glutamatergic agents (eg, memantine,
N -acetylcysteine, riluzole, topiramate, glycine)
Sarkhel S et al, Isr J Psychiatry Relat Sci.
2011;48(3):182-5.
81. ERP treatment
ERP is now usually administered as part of a broader program of
CBT specifically designed for OCD.
After making the patient aware of his or her irrational thoughts,
the therapist works to have the patient counter them with more
rational thoughts and do cost/benefit analyses regarding
performing his or her rituals.
82. Treatment resistance strategies
Strategies should always include an assessment of
complicating diagnoses
medication compliance
drug dose, and
duration of therapy.
Comorbid diagnosis such as depression or panic
disorder, can interfere with clinical recovery, and
identification may guide the choice of interventions.
William M Greenberg, Obsessive-Compulsive Disorder Treatment &
Management.www.medscape.com
83. Treatment resistance strategies
Interventions for patients with treatment resistance
include
Change or increase in medication
More intensive CBT
Other interventions, which have not received an
FDA indication for OCD include the following:
Addition of an NE reuptake inhibitor, such as
desipramine, to an SSRI, or a trial of venlafaxine
Addition of a typical or atypical antipsychotic,
especially in patients with a history of tics
William M Greenberg, Obsessive-Compulsive Disorder Treatment &
Management.www.medscape.com
84. Treatment resistance strategies
Interventions for patients with treatment resistance include
Augmentation with buspirone
Addition of inositol
Sole or augmented use of selected glutamatergic agents
Deep brain stimulation or cingulotomy neurosurgery or severe
and intractable cases
Some clinicians feel that individuals with comorbid Tourette
disorder or with hoarding as their principal OCD symptom may
be more likely to be treatment resistant, although there is
significant variation in treatment response, regardless of the
particular presenting symptomatology.
William M Greenberg, Obsessive-Compulsive Disorder Treatment &
Management.www.medscape.com
85. Low-frequency rTMS over the SMA for
treatment-refractory patients of OCD
Novel treatment strategies like
repetitive transcranial magnetic
stimulation (rTMS) have been
proposed for OCD refractory to
standard treatments
Low-frequency rTMS over the
SMA appears a promising
treatment strategy as an add-on
treatment in treatment-refractory
patients of OCD.
Kumar N et al,Indian J Psychiatry. 2011 Oct;5
86. Neurosurgical treatment of OCD
Neurosurgical treatment of OCD is reserved for
patients with severe and refractory symptoms.
The most common small series use a specific small
lesion (eg, cingulotomy) or deep brain stimulation.
Current clinical trials are also exploring the application
of transcranial magnetic stimulation (TMS), a
noninvasive treatment, for OCD.
William M Greenberg, Obsessive-Compulsive Disorder Treatment &
Management.www.medscape.com
87. Neurosurgical treatment of OCD
Stereotactic placement of bilateral lesions in the anterior
cingulate cortex: 28% response rate, with an additional 17%
showing a partial response.
A deep brain stimulation technique consists of implanting a
device to electrically stimulate the subthalamic nucleus
William M Greenberg, Obsessive-Compulsive Disorder Treatment &
Management.www.medscape.com
88. FUTURE DIRECTIONS FOR RESEARCH
Treatment dissemination, particularly for CBT and EX/RP,
remains an issue
Steps can and should be undertaken to improve
dissemination of CBT
Dissemination of both the safety and effectiveness of
exposure-based therapies to both the general public and
mental health clinicians
More research on how certain comorbidity patterns impact
treatment
89. Study further … New Promising approaches
Targeting the extinction learning core to EX/RP with
d-cycloserine , a partial agonist at the NMDA
receptor in the amygdala
Novel combinations of pre-existing treatments
90. End Note
There is truly not a better time in history to have
OCD than the present,….
…. given the multiple effective pharmacological
agents, psychological therapy, and ….an ever-
increasing understanding of the disorder itself.
This is not, however, the time to sit back and pat
our collective backs in triumph.
Editor's Notes
Convergent evidence from functional and structural neuroimaging suggests that abnormalities in the circuitry interconnecting the cortex, basal ganglia, and thalamus. The canonical connections forming these cortico-striato-thalamo-cortical (CSTC) loops is shown in simplified form here. Projections in this circuit use both the excitatory neurotransmitter glutamate and the inhibitory neurotransmitter GABA, as shown. Modulatory dopamine critically modulates information flow through this circuit. Other important modulatory neurotransmitters, such as acetylcholine, serotonin, and histamine, are excluded for clarity.
Changes in vmPFC/OFC/dACC activity have been linked to fear conditioning and recall in normal subjects with vmPFC activity and structure particularly relevant for fear extinction recall. Overlap in the circuits associated with fear conditioning and OCD dysfunction suggests that these patients may be less flexible in adjusting adverse responses based on new information.Dysfunction of the vmPFC/OFC/dACC network may lead to an increase in incentive-based fear learning and habit formationPFC regions associated with OCD pathology are not only involved in aversive behaviors and avoidance; they also mediate reward processing. Indeed, OCD patients are also impaired on tasks using rewarding outcomes
Presentation of OCD symptoms is similar in children and adults.Younger children will not be able to recognize that their obsessions and compulsions are both unnecessary (e.g., you don’t really need to wash your hands) and extreme (e.g., washing hands for 15-20 s is fine, but 5 min in scalding water is too much) in nature.In young children, compulsions often occur without the patient being able to report their obsessions, while adolescents are often able to report multiple obsessions and compulsions. Children and adolescents are also more likely to include family members in their rituals and can be highly demanding of adherence to rituals and rules, leading to disruptive and oppositional behavior and even episodes of rage.Youth with OCD are generally more impaired than adults with the same type of symptoms
Presentation of OCD symptoms is similar in children and adults.Younger children will not be able to recognize that their obsessions and compulsions are both unnecessary (e.g., you don’t really need to wash your hands) and extreme (e.g., washing hands for 15-20 s is fine, but 5 min in scalding water is too much) in nature.In young children, compulsions often occur without the patient being able to report their obsessions, while adolescents are often able to report multiple obsessions and compulsions. Children and adolescents are also more likely to include family members in their rituals and can be highly demanding of adherence to rituals and rules, leading to disruptive and oppositional behavior and even episodes of rage.Youth with OCD are generally more impaired than adults with the same type of symptoms
OCS might manifest at different time points during the course of schizophrenia illness. In addition, the clinical course is highly variable. Blue symbols indicate the onset and severity of OCS, red ones are related to psychotic symptoms. (A) Pre-existing and persistent OCS. (B) Intermittent OCS during ARMS or later in the clinical course. (C) OCS-onset during ARMS and persistent course, strongly associated to the psychotic symptoms (schizo-obsessive concept). (D) Fluctuating course of OCS. (E) Second-onset OCS during antipsychotic treatmentApart from OCS during the ARMS a growing body of evidence investigated the co-occurrence of OCS during manifest schizophrenia. A significant subgroup within these patients reports OCS development after treatment-start with second generation antipsychotic agents (SGA). The order of the three events “onset of psychosis,” “start with SGA treatment” and subsequent “de novo development of OCS” hints toward the involvement of pharmacodynamic mechanisms (
Approaching the co-occurrence from the OCD spectrum, the concept of “schizotypic OCD” has been described (Poyurovsky and Koran, 2005; Poyurovsky et al., 2008). This concept assumes that primary OCD-patients present beliefs, which can be classified on a spectrum between obsessions and delusions emphasizing the similarities as being irrational thoughts, the first with insight and the latter lacking insight. In line with this concept, the category of “obsessions without insight” was integrated into the fourth edition of the Diagnostic and Statistical Manual (DSM IV). OCD-patients without insight might therefore represent a subgroup with genetic, phenotypic and therapeutic vicinity to the schizophrenia-like spectrum
MA Psychiatry. 2013 Nov;70(11):1190-9. doi: 10.1001/jamapsychiatry.2013.1932.Cognitive-behavioral therapy vsrisperidone for augmenting serotonin reuptake inhibitors in obsessive-compulsive disorder: a randomized clinical trial.Simpson HB, Foa EB, Liebowitz MR, Huppert JD, Cahill S, Maher MJ, McLean CP, Bender J Jr, Marcus SM, Williams MT, Weaver J, Vermes D, Van Meter PE, Rodriguez CI, Powers M, Pinto A, Imms P, Hahn CG, Campeas R.Author information Department of Psychiatry, Columbia University, New York, New York2New York State Psychiatric Institute, New York, New York.AbstractIMPORTANCE: Obsessive-compulsive disorder (OCD) is one of the world's most disabling illnesses according to the World Health Organization. Serotonin reuptake inhibitors (SRIs) are the only medications approved by the Food and Drug Administration to treat OCD, but few patients achieve minimal symptoms from an SRI alone. In such cases, practice guidelines recommend adding antipsychotics or cognitive-behavioral therapy consisting of exposure and ritual prevention (EX/RP).OBJECTIVE: To compare the effects of these 2 SRI augmentation strategies vs pill placebo for the first time, to our knowledge, in adults with OCD.DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial (conducted January 2007-August 2012) at 2 academic outpatient research clinics that specialize in OCD and anxiety disorders. Patients (aged 18-70 years) were eligible if they had OCD of at least moderate severity despite a therapeutic SRI dose for at least 12 weeks prior to entry. Of 163 who were eligible, 100 were randomized (risperidone, n = 40; EX/RP, n = 40; and placebo, n = 20), and 86 completed the trial.INTERVENTIONS: While continuing their SRI at the same dose, patients were randomized to the addition of 8 weeks of risperidone (up to 4 mg/d), EX/RP (17 sessions delivered twice weekly), or pill placebo. Independent assessments were conducted every 4 weeks.MAIN OUTCOME AND MEASURE: The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to measure OCD severity.RESULTS: Patients randomized to EX/RP had significantly greater reduction in week 8 Y-BOCS scores based on mixed-effects models (vsrisperidone: mean [SE], -9.72 [1.38]; P < .001 vs placebo: mean [SE], -10.10 [1.68]; P < .001). Patients receiving risperidone did not significantly differ from those receiving placebo (mean [SE], -0.38 [1.72]; P = .83). More patients receiving EX/RP responded (Y-BOCS score decrease ≥25%: 80% for EX/RP, 23% for risperidone, and 15% for placebo; P < .001). More patients receiving EX/RP achieved minimal symptoms (Y-BOCS score ≤12: 43% for EX/RP, 13% for risperidone, and 5% for placebo; P = .001). Adding EX/RP was also superior to risperidone and placebo in improving insight, functioning, and quality of life.CONCLUSIONS AND RELEVANCE: Adding EX/RP to SRIs was superior to both risperidone and pill placebo. Patients with OCD receiving SRIs who continue to have clinically significant symptoms should be offered EX/RP before antipsychotics given its superior efficacy and less negative adverse effect profile.
J Clin Psychiatry. 2006 Jan;67(1):15-22.High-dose sertraline strategy for nonresponders to acute treatment for obsessive-compulsive disorder: a multicenter double-blind trial.Ninan PT, Koran LM, Kiev A, Davidson JR, Rasmussen SA, Zajecka JM, Robinson DG, Crits-Christoph P, Mandel FS, Austin C.Author information Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1841 Clifton Road, Atlanta, GA 30329, USA. pninan@emory.eduAbstractOBJECTIVE: To evaluate the efficacy and safety of high-dose sertraline for patients with obsessive-compulsive disorder (OCD) who failed to respond to standard sertraline acute treatment.METHOD: Sixty-six nonresponders to 16 weeks of sertraline treatment who met DSM-III-R criteria for current OCD were randomly assigned, in a double-blind continuation phase of a multicenter trial, either to continue on 200 mg/day of sertraline or to increase their dose to between 250 and 400 mg/day for 12 additional weeks. Efficacy measures included the Yale-Brown Obsessive Compulsive Scale (YBOCS), the National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH Global OC Scale), and the Clinical Global Impressions-Severity of Illness and -Improvement (CGI-I) scales. Data were collected from July 26, 1994, to October 26, 1995.RESULTS: The high-dose (250-400 mg/day, mean final dose = 357, SD = 60, N = 30) group showed significantly greater symptom improvement than the 200-mg/day group (N = 36) as measured by the YBOCS (p = .033), NIMH Global OC Scale (p = .003), and CGI-I (p = .011). Responder rates (decrease in YBOCS score of > or = 25% and a CGI-I rating < or = 3) were not significantly different for the 200-mg/day versus the high-dose sertraline group, either on completer analysis, 34% versus 52%, or on endpoint analysis, 33% versus 40%. Both treatments showed similar adverse event rates.CONCLUSION: Greater symptom improvement was seen in the high-dose sertraline group compared to the 200-mg/day dose group during continuation treatment. Both dosages yielded similar safety profiles. Administration of higher than labeled doses of selective serotonin reuptake inhibitors may be a treatment option for certain OCD patients who fail to respond to standard acute treatment
Psychother Psychosom. 2012;81(6):366-74. doi: 10.1159/000339369. Epub 2012 Sep 6.Cognitive therapy versus fluvoxamine as a second-step treatment in obsessive-compulsive disorder nonresponsive to first-step behavior therapy.van Balkom AJ, Emmelkamp PM, Eikelenboom M, Hoogendoorn AW, Smit JH, van Oppen P.Author information Department of Psychiatry and EMGO Institute, VU University Medical Center, Academic Outpatient Clinic for Anxiety Disorders, GGZinGeest, Amsterdam, The Netherlands. t.vanbalkom@ggzingeest.nlAbstractBACKGROUND: To compare the effectiveness of second-step treatment with cognitive therapy (CT) versus fluvoxamine in patients with obsessive-compulsive disorder (OCD) who are nonresponsive to exposure in vivo with response prevention (ERP).METHODS: A 12-week randomized controlled trial at an outpatient clinic in the Netherlands comparing CT with fluvoxamine in OCD. Of 118 subjects with OCD treated with 12 weeks of ERP, 48 appeared to be nonresponders (Y-BOCS improvement score of less than one third). These nonresponders were randomized to CT (n = 22) or fluvoxamine (n = 26). The main outcome measure was the Y-BOCS severity scale. Statistical analyses were conducted in the intention-to-treat sample (n = 45) on an 'as randomized basis' and in the per-protocol sample (n = 30). Due to selective dropout in the fluvoxamine group, two additional sensitivity analyses were performed.RESULTS: Complete data could be obtained from 45 subjects (94%) after 12 weeks. Fifty percent of the patients refused fluvoxamine after randomization compared to 13% who refused CT [χ(2)(1) = 7.10; p = 0.01]. CT as a second-step treatment did not appear to be effective in this sample of nonresponders. Fluvoxamine was significantly superior to CT in the intention-to-treat sample, in the per-protocol sample and in the two separately defined samples in which the sensitivity analyses were performed.CONCLUSIONS: OCD patients who are nonresponsive to ERP may benefit more from a switch to treatment with an antidepressant instead of switching to CT. In clinical practice, it may be important to motivate this subgroup of patients to undergo psychopharmacological treatment, as this may improve their outcome considerably.
J Clin Psychiatry. 2004 Oct;65(10):1365-71.Weight gain during long-term treatment of obsessive-compulsive disorder: a prospective comparison between serotonin reuptake inhibitors.Maina G, Albert U, Salvi V, Bogetto F.Author information Mood and Anxiety Disorders Unit, Department of Neuroscience, University of Turin, Torino, Italy. giuseppemaina@hotmail.comAbstractBACKGROUND: The effect of extended anti-depressant treatment on weight has been poorly investigated. Also unknown is whether different compounds have differential effects. The aim of the present study was to assess changes in weight in obsessive-compulsive disorder (OCD) patients treated for 2.5 years with clomipramine or selective serotonin reuptake inhibitors.METHOD: 138 DSM-IV OCD patients who responded to 6-month acute treatment at the Mood and Anxiety Disorders Unit, Department of Neuroscience, University of Turin, Italy, were followed-up for 2 years while receiving open-label clomipramine, citalopram, fluoxetine, fluvoxamine, paroxetine, or sertraline. Patients were consecutively recruited and followed from May 1998 to March 2003. The mean percentage change in weight was compared for each group, as was the proportion of patients who had a > or = 7% weight increase from baseline.RESULTS: At the end of the 2.5-year study period, patients had gained a mean of 2.5% of their body weight with respect to baseline (1.58 kg); 14.5% of the total sample experienced a significant (> or = 7%) weight increase. Within each but the fluoxetine treatment group, paired t tests showed a significant increase in weight from baseline to final visit. Analysis of variance showed a significant difference between treatment groups (p = .009), with clomipramine being associated with the highest weight increase and fluoxetine and sertraline with the lowest. A higher proportion of clomipramine-treated patients (34.8%) gained > or = 7% in weight as compared with sertraline and fluoxetine, which accounted for the lowest percentage of patients with a significant weight gain (4.5% and 8.7%, respectively), although this difference was not statistically significant.CONCLUSION: Risk of weight gain during extended serotonin reuptake inhibitor treatment for OCD differs depending on which compound is used. The differences among antiobsessive drugs may affect compliance with medication and health risks.
19.J Psychiatr Res. 2010 Mar;44(4):193-200. doi: 10.1016/j.jpsychires.2009.08.007. Epub 2009 Sep 15.Predictors of treatment response to fluvoxamine in obsessive-compulsive disorder: an fMRI study.Sanematsu H, Nakao T, Yoshiura T, Nabeyama M, Togao O, Tomita M, Masuda Y, Nakatani E, Nakagawa A, Kanba S.Author information Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.AbstractRecent neuroimaging studies suggest that the pathophysiology of obsessive-compulsive disorder (OCD) may involve more widely distributed large-scale brain systems, including the parietal, occipital, and cerebellar areas, rather than the conventional orbitofronto-striatal model. We hypothesized that not only orbitofrontal cortex and caudate nucleus activities but also posterior brain regions might be associated with subsequent treatment response to serotonin reuptake inhibitors in OCD. The participants were 17 patients with OCD. Each patient was required to undergo fluvoxamine pharmacotherapy for 12 weeks. Before treatment, fMRI images of the subjects were obtained in the context of a symptom-provocation paradigm. The percentage changes in total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores, from pre- to post-treatment, served as the index of treatment response. Statistical Parametric Mapping was used to identify brain loci where pre-treatment brain activation significantly correlated with the subsequent treatment response. Fifteen of 17 patients completed the 12-week treatment. During the symptom provocation task, patients showed brain activation in the left superior temporal gyrus (STG), left precuneus, left frontal cortices, right cerebellum, and right frontal cortices. We found that pre-treatment activation in the right cerebellum (Z-score=5.10, x,y,z=22,-84,-18) and the left STG (Z-score=4.95, x,y,z=-62,-22,0) was positively correlated with the improvement in the Y-BOCS score. Our results suggest that pre-treatment activation in the right cerebellum and in the left STG predict subsequent reduction in OCD symptom severity. There is every possibility that fMRI can be used as a tool to predict treatment response.
The glutamate modulator riluzole acts (i) by inhibiting axonal voltage-gated sodium channels (Na+) – a mechanism shared with the antiepileptic agent lamotrigine – thereby limiting glutamate release; and (ii) by enhancing glial uptake of extrasynaptic glutamate. The antioxidant N-acetylcysteine (NAC) also modulates extrasynaptic glutamate; it is converted into cystine and drives the extrusion of glutamate from astrocytes via the cystine-glutamate antiporter. The NMDA blockers memantine and ketamine block the pore of the NMDA receptor, preventing cation influx. Glycine, D-serine, and D-cycloserine (D-CS), in contrast, bind to the NMDA receptor coagonist site and potentiate activation of the receptor. Sarcosine (not shown) inhibits the glycine receptor Gly-T, increasing the endogenous levels of glycine
Stereotactic placement of bilateral lesions in the anterior cingulate cortex: 28% response rate, with an additional 17% showing a partial response. A deep brain stimulation technique consists of implanting a device to electrically stimulate the subthalamic nucleus. There was significantly more improvement during the active stimulation periods. However, serious adverse events were substantial and included intracerebralhemorrhage and infection.In February 2009, the FDA approved the use of Reclaim Deep Brain Stimulation Therapy for individuals with chronic, severe OCD. This device is an implanted medical device that is designed to target a region called the ventral capsule/ventral striatum, which is in the anterior limb of the internal capsule of the brain