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Clinical Neuropsychiatry (2004) 1, 1, 65-71
AUGMENTATION STRATEGIES FOR TREATMENT
RESISTANT OBSESSIVE COMPULSIVE DISORDER
Lorrin M. Koran
Summary
This article summarizes the literature and the author’s personal experience with augmentation strategies for treatmentresistant OCD. The article begins by noting that the literature on switching strategies is sparse. It then describes the
factors that may contribute to treatment-resistance. The first augmentation strategy considered is combination cognitivebehavioral therapy and pharmacotherapy if this combination has not been tried. The author then considers augmentation
of a serotonin reuptake inhibitor with a dopamine-blocking drug, followed by augmentation with pindolol, clomipramine
or buspirone. Strategies with less support, such as lithium, high dose trazodone, inositol, gabapentin, benzodiazepines
and l-trypophan are next described. The author mentions experimental strategies such as once weekly oral morphine
sulfate, daily tramadol and sumatriptan, and suggests that augmentation trials of anti-glutamate drugs such as memantine
and lamotrigine be undertaken. He recommends that the terminology conventions of the International Treatment Refractory
OCD Consortium be followed, and that investigators take care to report more completely the clinical characteristics of
subjects that may moderate treatment response.
Key words: Augmentation Strategies – Treatment-Resistant Obsessive-Compulsive Disorder – Cognitive-Behavioral
Therapy – Pharmacotherapy
Declaration of interest: Dr. Koran has research grants from Forest Pharmaceuticals, Inc.; Ortho-McNeil Pharmaceuticals; Eli Lilly; and Pfizer, Inc. He is a member of the Speakers Bureau for Forest Pharmaceuticals, Inc. and
Pfizer, Inc.
Lorrin M. Koran, M.D. Professor of Psychiatry, Department of Psychiatry and Behavioral Sciences, Stanford Medical Center,
Stanford, CA. OCD Clinic, Room 2363, 401 Quarry Road, Stanford, CA 94305, [email protected] – Telephone: 650/ 7235154 - Fax: 650/725-0363
When faced with human suffering, physicians want
to help. In the case of obsessive-compulsive disorder
(OCD), their first and even second efforts may bring
insufficient relief. This article reviews the augmentation
strategies that may benefit adult patients with treatmentresistant OCD. Both pharmacotherapies and psychotherapies are discussed. Although switching from one
medication to another is an alternate strategy, this
strategy is not explored in detail here. No published,
double-blind studies evaluate this strategy and the
available literature is sparse. In one of the few available
reports, Albert et al. (reported in Koran and Saxena 2000)
found a higher response rate (33-40%) in switching from
a selective serotonin reuptake inhibitor (SSRI) to
clomipramine (CMI) or vice versa than in switching
from one SSRI to another (0-20%). On the other hand,
Maraziti et al. (2001) reported that 14 of 18 OCD patients
resistant to at least two trials of SSRIs or CMI had a
good response to citalopram.
Scientific communication about treatment-resistant
OCD will be improved by use of a common language.
Therefore, this article follows the conventions
recommended by The International Treatment
Refractory OCD Consortium (ITROC) (Pallanti et al.
© 2004 Giovanni Fioriti Editore s.r.l.
2002). ITROC has proposed definitions for 10 levels of
non-response to treatment, with deeper levels of nonresponse as the patient fails more treatments. ITROC
considers “non-response” to a given treatment to be a
less that 25% decrease in the Yale-Brown ObsessiveCompulsive Scale (Y-BOCS) score (Goodman et al.
1989) in a patient with at least moderate OCD severity;
when no scale scores are available, one might substitute
a judgment of a Clinical Global ImpressionsImprovement (CGI-I) score of minimally improved (3)
or worse. In discussing augmentation strategies for
“treatment-resistant” OCD, I will be referring to patients
with non-response at Level I non-response, i.e.,
treatment with an SSRI or cognitive behavioral therapy
(CBT), Level II, i.e., treatment with an SSRI plus CBT,
Level III, i.e., treatment with two SSRIs plus CBT, Level
IV, i.e., 3 SSRIs plus CBT, or Level V, i.e., 3 SRIs
(including CMI) plus CBT. Most of the literature,
however, was either published before these definitions
were proposed, or has ignored them. Thus, one cannot
yet describe the efficacy of different augmentation
strategies for patients with different levels of treatment
resistance.
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Lorrin M. Koran
Factors That May Contribute To TreatmentResistance
Before concluding that a patient is Level I or II
non-responsive, the clinician must be sure that
confounding factors are not present. First, has an organic
cause of the OCD been missed? This is unlikely since
the organic conditions associated with OCD in adults
should be obvious – cerebrovascular accident,
neurodegenerative diseases such as Huntington’s chorea,
manganese poisoning, post-encephalitic OCD, carbon
monoxide poisoning or brain trauma or neurosurgery
(Koran 1999). OCD induced by illicit substance abuse
(stimulants) or by atypical antipsychotic drugs such as
clozapine, olanzapine or risperidone in patients with
schizophrenia should also be considered in appropriate
contexts (Koran 1999). Does the patient truly have OCD,
or is he suffering instead from depressive ruminations,
obsessions with weight and calories as symptoms of
anorexia nervosa, obsessions with body image as
symptoms of body dysmorphic disorder, or repetitive,
stereotyped behaviors that represent complex motor tics
seen in Tourette’s disorder or that are symptoms of
schizophrenia?
A second confounding factor is inadequate
medication dosing and/or inadequate treatment duration
before judging the degree of treatment response. The
ITROC definition of minimal adequate SSRI trials in
treating OCD are 12 weeks of: citalopram 40 mg/day,
fluoxetine 40 mg/day, fluvoxamine 200 mg/day,
paroxetine 40 mg/day, sertraline 200 mg/day and
venlafaxine 225 mg/day (Pallanti et al. 2002).
Escitalopram has not been studied in OCD, but I consider
20 mg/day an adequate, though not optimal, OCD trial.
Of course, some patients respond at lower doses
of these drugs. Some patients may not be able to tolerate
these doses, but they are better labeled “intolerant” rather
than “non-responders.” These doses are not the
maximum doses that can be tried. If patients can
comfortably tolerate them, I use the following maximum
doses: citalopram 100 mg/day, fluoxetine 80 mg/day,
fluvoxamine 400 mg/day, paroxetine 100 mg/day,
sertraline 400 mg/day, venlafaxine 375 mg/day and
escitalopram 40 mg/day. At venlafaxine doses of 150
mg/day or higher, one must be on the alert for druginduced hypertension. Some evidence suggests that nonresponders to moderate doses may become responders
if they simply continue the same dose for a second 12
weeks. For example, in a double-blind continuation trial,
34% of patients unresponsive to 16 weeks of sertraline
200 mg/day became responders after completing 12
additional weeks of treatment at this dose (versus 52%
who completed the second 12 weeks at doses of 250400 mg/day) (Koran et al. 2002).
Expert opinion, but not empirical data, defines an
adequate trial of CBT (taking the form of exposure and
response prevention [ERP]) as 13-20 sessions at a rate
of one to two per week (Expert Consensus Panel 1997).
Since most patients will prefer that new steps be taken
after a 12-week trial of medication or CBT, the clinician
should feel comfortable moving to an augmentation
strategy at this point.
Comorbid conditions are a third factor that can
contribute to treatment non-response. For example, a
double-blind trial indicates that OCD patients with
66
comorbid tics or Tourette’s Disorder will usually need a
dopamine-blocking medication added to their SSRI in
order to experience a good treatment response
(McDougle et al. 1994). An open-label trial suggests
that patients with comorbid schizotypal personality
disorder may also need an added dopamine blocker
(McDougle et al. 1990). Comorbid panic disorder may
necessitate a slower build-up of the SSRI dose, since
panic disorder can be exacerbated by SSRIs started at
usual therapeutic doses. In such cases, addition of low
doses of a benzodiazapine such as lorazepam or
clonazepam for the first four to six weeks may allow
more rapid increase in the SSRI dose. After four to six
weeks, the benzodiazepine can usually be tapered off.
Noncompliance is the fourth factor that can lead to
apparent treatment resistance. In some cases, the patient
dislikes the medication side effects, e.g., sexual side
effects or fatigue, and is reluctant to confess to the
physician that these side effects led him or her to
discontinue the drug or markedly reduce the dose. In
other cases, a family member or friend may tell the
patient that the medications are “addictive” or “bad for
your body,” or “an indication that you are weak and are
giving in to your problems.” To prevent such
misinformation from sabotaging treatment, the clinician
should provide all patients and their families with
educational materials. A scientifically sound and
helpful website is run by the OC Foundation at
www.ocfoundation.org. The website provides accurate
information reviewed by a scientific board of advisors,
an online bookstore, a place to ask experts questions, a
chat room in which to communicate with other sufferers
and links to other helpful sites. In addition, a number of
well thought out, reliable self-help books for OCD
sufferers have been published (see appendix).
Fifth, lack of treatment response may be due to a
stressful living situation. Stress both exacerbates OCD
symptoms and may contribute to lack of compliance
with treatment instructions. In such cases, helping the
patient relieve the stress, or arranging family therapy
when indicated, can improve the treatment outcome.
Family members must be helped to understand that
expressing hostility and other negative emotions can
exacerbate OCD by increasing the patient’s perceived
level of stress. Family members should also be counseled
to gradually stop colluding with the patient’s symptoms,
e.g., washing clothes daily for the patient, or providing
endless reassurance in response to questions about
contamination or about whether the patient has offended
them or whether a particular (irrational) danger is
present.
Sixth, a small percentage of patients may be rapid
metabolizers of various medications or have a
particularly dense blood/brain barrier and thus fail to
reach therapeutic drug levels at the neuronal sites of
action. At present, however, these possibilities remain
unproven hypotheses; available evidence shows no
relationship between plasma levels of certain SSRIs and
therapeutic response (Greist 1995, Koran et al. 1996)
Finally, lack of response may be related to the
heterogeneity of the pathophysiology of OCD. Clinical
consensus and some treatment trials indicate that the
hoarding variety of OCD is much less responsive to
pharmacotherapies and CBT than are other symptomatic
forms (Black et al. 1998, Winsberg et al. 1999, Mataix-
Clinical Neuropsychiatry (2004), 1, 1
Augmentation strategies for treatment resistant obsessive compulsive disorder
Cols 2002). A recent PET study indicates that OCD
hoarders exhibit a different pattern of abnormal cerebral
glucose metabolism than OCD patients with other
symptoms and than normal controls (Saxena et al. 2004).
This suggests that the pathophysiology in OCD hoarding
differs from that underlying other symptom types.
Patients with sexual, sacrilegious or other repugnant or
anxiogenic obsessions can be helped to make audio-loop
tapes of these obsessions in their own voice. The patient
should listen to these tapes for 10 minutes several times
a day. In a short time, this exposure will make the
thoughts boring rather than anxiety-provoking.
Augmentation Strategies
Augmentation of an SRI With a DopamineBlocking Drug
If the non-responsive patient has received only one
pharmacotherapy trial or CBT without pharmacotherapy
(resistance Level I), the first augmentation strategy to
consider is combining these two treatment modalities.
Some patients may be reluctant to take medications,
while others may be reluctant to confront their feared
stimuli, as ERP requires. The clinician should
nonetheless encourage combined treatment where
feasible. Although the evidence is only suggestive that
combined treatment is more effective than either
medications or ERP alone (Kobak et al. 1997), expert
opinion supports this approach (Expert Consensus
Guidelines 1997). Two small open studies suggest that
adding CBT in cases of SSRI non-response might be
helpful (Simpson et al. 1999, Kampman et al. 2002). In
both studies, however, the improvement may have been
due partly or wholly to longer time on medication. CBT
has the virtue that benefits may continue to be
experienced long after the treatment has been completed,
although “booster sessions” are often helpful or needed
(Foa and Franklin 2002). Because therapists trained in
CBT are in short supply, the clinician should not hesitate
to recommend the use of one of the CBT self-help books
(see appendix, e.g., Hyman and Pedrick, Baer, or
Schwartz) and to incorporate into weekly visits the
assignment of behavioral homework and the monitoring
of progress (Foa and Franklin 2002).
To begin CBT, the clinician should ask the patient
to make a list of compulsions and things that are avoided.
The patient then rearranges the compulsion list, placing
at the top the compulsion that, if not done, would arouse
the least anxiety, and at the bottom the compulsion that,
if not done, would arouse the most. The other
compulsions are ranked in between these. The patient
rearranges the list of things avoided in a hierarchy from
least-anxiety provoking to most-anxiety provoking. The
clinician then gives the patient the homework
assignment of exposing himself or herself to a mildly
anxiety-provoking stimulus from the list and refraining
from the associated compulsion. For example, a patient
with checking compulsions related to safety might be
told, as a starting point, to leave the house without
checking the door lock more than once. After daily
exposures to this task for a week or perhaps two, the
patient will find that foregoing the checking arouses very
little anxiety. After about a month, the urge to check the
door lock will have largely dissipated, although the
memory that door locks used to be checked may persist
beyond this point. The clinician helps the patient move
down the anxiety hierarchy at a rate of foregoing one to
two compulsions each week or two, i.e., a rate that allows
extinction of the anxiety aroused by the avoided stimuli
and foregone compulsions. For those patients with
obsessions but no compulsions, the clinician can utilize
the technique outlined by Schwartz (see appendix).
Clinical Neuropsychiatry (2004), 1, 1
The augmentation strategy best supported by
double-blind, placebo-controlled trials is the addition
of an atypical antipsychotic, specifically risperidone
(McDougle et al. 2000) or olanzapine (Bystritsky et al.
2004), to an SSRI. Open-label trials and case series also
support the use of quetiapine (summarized in Koran et
al. 2004). The responder rate for each of the atypicals
usually runs from 40-70% across trials (Koran et al.
2004). One cannot compare the results of different trials
because of differences in drug doses, trial duration, and
trial subjects’ characteristics, such as whether or not they
had failed one or more SRI trials, or one or more
augmentation trials of other atypical antipsychotic
medications. For example, olanzapine augmentation did
not separate from placebo in a recent double-blind trial
(Shapira et al. 2004). This is probably due to the trial
design, which began augmentation after only eight
weeks of SRI treatment, when further improvement in
both the olanzapine and placebo groups could be
expected simply from longer exposure to the SRI alone.
Whether patients who have failed more SRI trials
are less likely to respond to augmentation with an
atypical antipsychotic than those who have failed fewer
trials is unknown. In the risperidone augmentation trial
of McDougle et al. (2000), 6/9 (66%) subjects who had
failed one SRI trial responded, compared with 5/11
(45%) who had failed two or more. On the other had,
Denys et al. (2002) observed a responder rate of 70%
response rate to augmentation with quetiapine in subjects
who had failed at least three SRI trials. We have observed
a good response to quetiapine augmentation in a few
subjects who have failed to benefit from a trial of another
atypical antipsychotic (Koran et al. 2004). Other authors
do not report these data.
In general, therapeutic response to a given atypical
antipsychotic is evident within two weeks at a given
dose. Response tends to occur at low doses of
risperidone, i.e., 2 mg/day or less, or olanzapine, i.e.,
15 mg/day or less. Quetiapine usually must be dosed at
150 mg/day or more (Koran et al. 2004). Whether
prolonged trials would produce higher responder rates
is unknown, but my clinical practice is to abandon trials
after two to three weeks at the maximum comfortably
tolerated dose if a good response has not occurred by
then. I have had good response to augmentation with
ziprasidone up to 120 mg/day and of aripiprazole up to
30 mg/day, but no trials have yet been reported with
these agents. However, we are about to complete a
double-blind trial of ziprasidone augmentation that
should be published soon. In light of recent warnings
about weight gain and new onset diabetes mellitus in
patients treated with atypical antipsychotic drugs
(American Diabetes Association et al. 2004), clinicians
should weight the risk of these side effects heavily in
67
Lorrin M. Koran
choosing amongst the atypical antipsychotics. The best
dosing strategies and trial duration for each atypical
antipsychotic have yet to be established, as does a means
for matching patients and drugs to optimize the chance
of a favorable outcome.
Clinicians occasionally combine two SSRIs,
rather than an SSRI and CMI, in order to decrease the
side effect burden or increase treatment effect, but no
data are available to support this practice. In the absence
of data, this strategy deserves little attention.
Augmentation with Pindolol
Augmenting with Buspirone
Although an open-label trial (Blier and Bergeron
1996) and one double-blind, placebo-controlled trial of
pindolol augmentation (2.5 mg three times/day) (Danon
et al. 2000) found it efficacious, another similar study
did not (Mundo et al. 1998). Interestingly, subjects in
the positive trial (Danon et al. 2000) were quite treatment
resistant; they had not responded to at least two SRIs
and paroxetine before pindolol was added to paroxetine.
It has been suggested that doses of at least 10 mg/day
are needed to adequately block the presynaptic 5-HT1A
autoreceptor and thus enhance serotonergic
neurotransmission (Rabiner et al. 2001). Further study
of pindolol augmentation at higher doses is warranted.
The strategy of adding buspirone to an SSRI was
supported by open-label trials and case series, but two
double-blind, placebo-controlled trials were negative.
The first negative study (McDougle et al. 1993) utilized
60 mg/day for six weeks. However, these patients were
treatment-resistant (< 35% decrease in Y-BOCS score,
and rated “unimproved” by the investigators) rather than
partial responders for whom augmentation was sought.
The second study utilized a mean (SD) dose of 57 (7)
mg/day for 10 weeks after a two-week placebo control
period (Pigott et al. 1992a). In this study, 4 of 14 subjects
(29%) experienced a > = 25 % decrease in Y-BOCS
score, but the mean decrease from baseline for the entire
study group was not significant. In my clinical
experience about one in six patients who have failed
one or two SRI trials experiences a clinically meaningful
decrease in OCD symptoms after six weeks of treatment
with buspirone in doses of 60-90 mg/day. At doses of
60 mg/day or higher, however, irritability and
forgetfulness have been dose-limiting side effects.
Augmentation with Clomipramine
Several open-label trials support the strategy of
adding clomipramine (CMI) to an SSRI or vice versa.
My colleagues and I (Pallanti et al. 1999), in a
randomized, open-label, 90-day trial in patients who had
failed adequate trials of both CMI and fluoxetine,
observed a good response in nine of nine patients
randomized to addition of CMI 150 mg/day to
citalopram 40 mg/day. Only one of seven patients
assigned to citalopram alone experienced a good
response. Ravizza et al. (1996) reported a better response
and less side effects from adding sertraline 50 mg/day
to CMI 150 mg day than from raising the CMI dose to
250 mg/day in patients with an inadequate response to
six months of CMI 150 mg/day.
Before adding CMI in patients aged 40 and older
or suspected of cardiac disease, an EKG should be
obtained to guard against worsening an existing firstdegree heart block or other problem. In addition, plasma levels of CMI and its metabolite, desmethylclomipramine (DCMI), should be measured 12
hours after the dose, two to three weeks after adding an
initial dose of 50 mg/day to a modest dose of an SSRI.
(It takes this long to achieve steady state plasma levels).
The literature suggests but does not prove that higher
CMI plasma levels are associated with better response.
I aim at achieving plasma CMI levels of 200 ng/ml or
more. Total plasma concentration of CMI plus DCMI
should be kept at 450 ng/ml or less in order to avoid
cardiac and central nervous system toxicity (Koran
1999). Fluvoxamine can be utilized to achieve these plasma CMI concentrations, but one must be especially
careful. Fluvoxamine inhibits the metabolism of CMI,
raising CMI levels by a factor of about four while
keeping DCMI levels low. This combination may
convey a therapeutic advantage, since CMI is a
serotonergic reuptake inhibitor, whereas DCMI is a
noradrenaline reuptake inhibitor. Double-blind,
placebo-controlled trials of combining SSRIs and CMI
would be useful.
68
Augmentation Strategies with Scant or Mixed
Support
No other augmentation strategies are well
supported in the literature. Lithium augmentation,
despite positive case reports, was not helpful in two, 4week, double-blind placebo-controlled trials (Pigott et
al. 1991, McDougle et al. 1991). Given recent
demonstration of a neuroprotective effects and
promotion of synaptic growth (Bauer et al. 2003),
perhaps longer trials of lithium augmentation are in
order.
High dose trazodone (300-600 mg/day) has been
reported helpful in alleviating OCD as well as anxiety
and side effects of concomitant therapies (sleep
disturbance, gastrointestinal distress and sexual
dysfunction) in a case series (n=5) (Marazziti et al.
1999). Trazodone alone in doses of 500 mg/day was
helpful in one case series (Hermesh et al. 1990) and at
lower doses in case reports, but a controlled trial at a
mean dose of 235 mg/day found no effect (Pigott et al.
1992b).
In a double-blind, placebo-controlled, six-week per
phase, crossover trial, inositol 18 gm/day was beneficial
for 6 of 13 patients, compared to none in the placebo
phase (Fux et al. 1996). However, a subsequent openlabel trial was negative (Seedat et al. 1999) as was a
double-blind SRI augmentation trial (Fux et al. 1999).
In my clinical experience, only about 1 in 12 to 1 in 15
patients experiences benefit after a six-week trial, and
this may be simply a placebo response.
A small (n=6) six-week, open-label trial of
gabapentin, mean dose 2520 mg/day by week 6,
reported “marked subjective improvement” in anxiety
Clinical Neuropsychiatry (2004), 1, 1
Augmentation strategies for treatment resistant obsessive compulsive disorder
OCD and mood (Cora-Locatelli et al. 1998). In an
unpublished chart review of our experience with 36 OCD
patients, treated with 600-3600 mg/day of gabapentin,
we found only a small effect on core OCD symptoms.
Half the patients with marked anxiety or subsyndromal
depressive symptoms, however, reported meaningful
improvement in these symptoms. Lorazepam 1-3 mg/
day and clonazepam 1-3 mg/day may also relieve
anxiety in OCD, but in my experience have little effect
on the core OCD symptoms, i.e., frequency and duration
of obsessions and compulsive behaviors.
Support for augmentation with l-tryptophan is
limited to a case report (Rasmussen 1984) and a small
case series (Blier and Bergeron 1996). If this
augmentation strategy is utilized with SRIs, the clinician
should observe the patient carefully for early signs of
the serotonin syndrome.
Open augmentation trials of desipramine (Barr et
al. 1997), the androgen-receptor antagonist flutamide
(Altemus et al. 1999), and L-Triiodothyronine (Pigott
et al. 1991) have found no evidence of efficacy.
Augmentation Strategies Under Investigation
Promising preliminary results have been reported
from a double-blind, crossover augmentation trial
comparing once weekly oral morphine sulfate 30-45 mg,
lorazepam 0.5-1.5 mg and placebo (Franz et al, reported
in Hollander et al. 2002). Three of eight subjects had a
> = 40% decrease in Y-BOCS score in response to
morphine, and one had a decrease of 29%. These results
were significantly better than those during the lorazepam
experimental condition. No patient responded to placebo
augmentation. These results are consistent with a case
series reporting benefit from once weekly oral morphine
(Warnke 1997) and an open trial of daily doses of
tramadol (Shapira et al. 1997), a weak mu-receptor
agonist (and weak reuptake inhibitor of serotonin and
norepinephrine).
Given the recent finding of abnormally high levels
of glutamate in the caudate nucleus of children with
OCD before treatment, and the return to normal levels
in responders to paroxetine treatment (Rosenberg et al.
2000), exploratory augmentation trials of anti-glutamate
drugs such as memantine and lamotrigine should be
undertaken.
Clinical observations and serotonergic challenge
studies suggest that the 5-HT1D receptor may be
involved in the pathophysiology of OCD (Koran et al.
2001). Short-term (5-day), double-blind treatment with
the 5-HT1D agonist sumatriptan produced significant
worsening of OCD symptoms compared to placebo
(Koran et al. 2001). Longer term studies, utilizing
triptans with better penetration of the blood/brain barrier
would be of interest.
In addition to augmentation studies, of course,
studies are needed of new primary medications, e.g.,
glutamate antagonists, and perhaps of new routes of
administration, e.g., intravenous administration of
SSRIs. Pulse loading (2-day loading) of intravenous
citalopram, for example, produced a much quicker
response than gradually increased intravenous doses
(Koran et al. 1998). The data strongly suggested that
pulse loading also produces a much quicker response
Clinical Neuropsychiatry (2004), 1, 1
than usual oral titration methods – the pulse loading
completers exhibited a mean decrease in Y-BOCS score
of 32% five days after the pulse loading, a response never
reported this quickly in trials or orally administered
SRIs.
Methodological Improvements in Future
Studies
Future studies could advance clinical practice more
quickly if the investigators report more completely the
clinical characteristics of subjects entering the trials and
the differences between treatment responders and nonresponders. Characteristics such as age at onset, duration
of symptoms, most prominent symptom types, comorbid
conditions, number of failed adequate SRI trials, and
the number of failed adequate augmentation trials of
atypical antipsychotics and other agents mentioned in
this review. Detailed reporting would allow subsequent
meta-analyses to provide useful guidance. To promote
shared terminology, investigators should standardize on
the definitions of degrees of response and of treatment
resistance suggested by the International Treatment
Refractory OCD Consortium (ITROC) (Pallanti et al.
2002). Descriptions of treatment outcome would be
enriched by use of standardized scales measuring
patients’ quality of life (Koran 2000). Finally,
pharmacogenetic studies are needed to allow optimal
matching of patients to treatments. A recent study
comparing response to and tolerance of paroxetine
versus mirtazapine in geriatric depression provides an
excellent model. The investigators identified a genetic
marker that identifies those likely to have a speedy
response to mirtazapine (Murphy et al. 2003a) and a
variant of the 5-HT2A receptor that appears important
in determining side effect severity in paroxetine-treated
patients (Murphy et al. 2003b) . Similar studies in OCD
could produce results quite useful to clinicians and their
patients.
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Appendix
OCD Resources for Patients and Families:
Baer L (2000). Getting Control: Overcoming Your Obsessions
and Compulsions. New York: Penguin (Plume). (self-paced
cognitive behavioral therapy [CBT])
Chansky RE (2000). Freeing Your Child from Obsessive-Compulsive Disorder. New York: Crown. (help for parents of
children with OCD)
Ciarrocchi JW (1998). The Doubting Disease: Help for Scrupulosity and Religious Compulsions. Mahwah NJ: Paulist
Press. (for patients who obsess about religious failings and
moral mistakes)
Foa EB, Wilson R (1991). Stop Obsessing! How to Overcome Your
Obsessions and Compulsions. New York: Bantam. (instruction in combating obsessions and compulsions)
Gravitz HL (1998). Obsessive Compulsive Disorder: New Help
for the Family. Santa Barbara CA: Healing Visions Press.
(how family members can be helpful to OCD sufferers)
Hyman BM, Pedrick C (1999). The OCD Workbook: Your Guide
to Breaking Free from Obsessive Compulsive Disorder.
Oakland, CA: New Harbinger Publications. (detailed, selfpaced cognitive behavioral therapy [CBT].
Osborn I (1999). Tormenting Thoughts and Secret Rituals. New
York: Dell. (a psychiatrist with OCD explains the disorder
and ways to combat the symptoms)
Penzel F (2000). Obsessive-Compulsive Disorders: A Complete
Guide to Getting Well and Staying Well. New York: Oxford
University Press. (self-paced cognitive-behavioral therapy)
Schwartz JM (1996). Brain Lock: Free Yourself from Obsessive
Compulsive Disorder. New York: Harper Collins. (instruction in combating obsessions)
Waltz M (2000). Obsessive-Compulsive Disorder: Help for Children and Adolescents. Sebastopol CA: O’Reilly Press. (help
for parents of children with OCD)
OC Foundation: www.ocfoundation.org Tel 203/315-2190 (Connecticut, USA)
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