Double-blind, placebo-controlled, and active-comparator studies
indicate that fluvoxamine is significantly more effective than placebo
and equal in efficacy to clomipramine and certain SSRIs (citalopram,
paroxetine), although the sample size for the latter comparison
was small. Compared with clomipramine, fluvoxamine showed fewer
anticholinergic side effects and better tolerability. Whether the
combination of fluvoxamine and CBT (particularly ERP) is more effective
than CBT alone is uncertain because of methodological shortcomings
in available studies.
An early double-blind, placebo-controlled trial (408)
reported positive findings when 42 OCD patientshalf of
whom also had depressive symptomswere randomly assigned
to receive fluvoxamine (up to 300 mg/day, mean final dose = 255 mg/day)
or placebo for 6–8 weeks. Nine of 21 fluvoxamine patients
were CGI-I:1,2 responders (mean Y-BOCS score decrease from baseline = 42%)
versus none in the placebo group. The majority of week 6 partial
responders became full responders at week 8 of fluvoxamine treatment, suggesting
that at least 8 weeks of treatment are needed to detect a full clinical
A 10-week, double-blind trial (409) randomly
assigned 40 OCD subjects to receive fluvoxamine (up to 300 mg/day,
mean maximum dose = 294 mg/day) or placebo and
reported a statistically significant greater improvement for fluvoxamine
than for placebo on Y-BOCS and NIMH-OC but not CGI measures.
Two pivotal 10-week, multicenter, double-blind,
placebo-controlled studies with identical study protocols provide
convincing evidence for the therapeutic efficacy of fluvoxamine
in OCD (410, 411). Subjects met DSM-III-R
criteria for OCD of at least 12 months' duration and had
an NIMH-OC scale score of 7 and a 17-item
Hamilton Depression Rating Scale (Ham-D) score of 19.
Seventy-nine (410) and 78 (411) fluvoxamine-treated
subjects and 78 (410) and 80 (411) placebo-treated
subjects completed the studies. Fluvoxamine was flexibly titrated
to 100–300 mg/day. At week 10, the mean fluvoxamine
doses were 245 and 251 mg/day, at which time the mean Y-BOCS
score had fallen 21% in the fluvoxamine groups compared
with 7% in the placebo groups (among patients who received
at least one postbaseline rating). A statistically significant difference
between the two groups was first observed at week 6. CGI-I:1,2 response
(ITT) was achieved in 33% and 38% of fluvoxamine
subjects compared with 9% and 15% of placebo subjects.
In the largest double-blind, placebo-controlled fluvoxamine
trial (412), 253 OCD subjects were randomly assigned
to receive fluvoxamine controlled release or placebo (efficacy analyses: n = 237,
117 fluvoxamine controlled release, 120 placebo). After 12 weeks,
fluvoxamine was significantly more effective than placebo on all
efficacy measures, including the Y-BOCS and CGI scales. YBOCS-25% and
YBOCS-35% response rates were significantly higher in the
fluvoxamine group, as were remission rates (44% vs. 31% and
18% vs. 8%, with Y-BOCS score definitions of
respectively). Therapeutic effects were evident at week 2, which
is earlier than reported in other fluvoxamine versus placebo studies,
with the earlier onset of effects perhaps attributable to the higher
starting dose (100 mg/day). Fluvoxamine, although having
more side effects (e.g., insomnia, nausea, somnolence) than placebo,
was safe and generally well tolerated.
In double-blind, active-comparator studies, fluvoxamine was
superior to desipramine and as efficacious as other SRIs (clomipramine
and some SSRIs); however, the lack of placebo control groups prevents
calculating the net drug effect (i.e., active drug effect minus
In an 8-week trial (413), OCD subjects were randomly
assigned to receive fluvoxamine (up to 300 mg/day, mean
final dose = 214 mg/day) or desipramine (up to
300 mg/day, mean final dose = 223 mg/day).
Forty subjects completed at least 2 weeks of treatment and were
included in the efficacy analysis. The mean Y-BOCS score decreased
29% from baseline in the fluvoxamine group and was virtually unchanged
in the desipramine group.
In a 12-week trial (414), 12 OCD subjects were
randomly assigned to receive fluvoxamine or clomipramine (both up
to 200 mg/day). For the 10 subjects who completed the study,
the Y-BOCS score decreases were similar in the treatment groups;
however, the small number of subjects limits the power to detect differences.
In a 10-week multicenter trial (396), fluvoxamine
(up to 250 mg/day, mean final dose = 200 mg/day)
was as effective as clomipramine (up to 250 mg/day, mean
final dose = 200 mg/day). Endpoint Y-BOCS scores
among the 64 randomly assigned subjects with at least one postbaseline
rating did not significantly differ between the two treatment groups.
Fluvoxamine produced fewer anticholinergic side effects and less
sexual dysfunction than clomipramine. These findings were replicated
in a subsequent 10-week study (397) that involved 79
OCD subjects randomly assigned to receive fluvoxamine (up to 300
mg/day, mean final dose = 225 mg/day)
or clomipramine (up to 300 mg/day, mean final
dose = 201 mg/day). Among the 73 subjects with
at least one postbaseline rating, the percentage of Y-BOCS-25% responders
in the two groups showed no difference at any time. The mean Y-BOCS
score decrease was 30% in both treatment groups. The fluvoxamine
group experienced fewer anticholinergic side effects.
In a large, 10-week, multicenter, double-blind trial, 227
OCD subjects were randomly assigned to receive fluvoxamine (up to
300 mg/day) or clomipramine (up to 300 mg/day)
(415). Both groups experienced a marked improvement
in OCD as evidenced by Y-BOCS, NIMH-OC, and CGI scores. Fluvoxamine
was better tolerated primarily because troubling anticholinergic side
effects were more common in the clomipramine group. In a small,
10-week, single-blind trial, 30 OCD patients were randomly assigned
to receive fluvoxamine (up to 300 mg/day, mean final
dose = 290 mg/day), paroxetine (up to 60 mg/day,
mean final dose = 53.3 mg/day), or citalopram
(up to 60 mg/day, mean final dose = 50.9
mg/day); all patients completed the study (416).
At trial endpoint the percentage of responders (with response defined
as YBOCS-35% and a CGI-I
improved]) showed no statistically significant differences,
suggesting similar effectiveness. However, the small number of subjects
in each group severely limited the power to detect differences between
Two double-blind studies compared the efficacy of fluvoxamine
combined with different forms of CBT to the efficacy of CBT alone
or of CBT combined with placebo. In a combined single- and double-blind
trial, 60 patients were randomly assigned to receive fluvoxamine
and antiexposure therapy, fluvoxamine and ERP, or placebo and ERP
(165). Pharmacotherapy (fluvoxamine up to 300 mg/day,
mean dose = 282 mg/day) lasted for 24 weeks. The
medication was then tapered over a 4-week period and discontinued,
and patients were then free to seek treatment as desired. Evaluations
were conducted after 2 months of active treatment (n = 50)
and at the end of active treatment (6 months, n = 44).
Follow-up evaluations by a blinded rater were done at 1 year (n = 37)
and 18 months (n = 33).
Fluvoxamine with ERP and fluvoxamine with antiexposure therapy yielded
greater reduction in rituals at week 8 than placebo with ERP, but
this superiority disappeared at 1 year. By week 24, all
treatments had reduced OCD symptoms, with no significant between-group
differences. Fluvoxamine plus antiexposure and fluvoxamine plus
ERP had more effect on depressive measures than did ERP plus placebo.
However, the lack of a standard response measure (Y-BOCS), the small
number of subjects in each treatment group, and varying treatments
subjects received during follow-up limit interpretation of the results.
Hohagen et al. (164) randomly assigned 60 OCD
inpatients to receive 10 weeks of either fluvoxamine (up to 300 mg/day,
mean dose = 288 mg/day) plus CBT or placebo plus
CBT. The CBT consisted of therapist-aided ERP plus cognitive restructuring.
In the 49 patients who completed the study, both treatments significantly
reduced OCD symptoms. However, there were significantly more YBOCS-35% responders
in the fluvoxamine plus CBT group (87.5%) than in the placebo
plus CBT group (60%). Post hoc analyses suggested that
patients with OCD and depression benefited more from fluvoxamine
plus CBT than from placebo plus CBT. However, this conclusion must
be viewed cautiously, as no information was given on the two groups' degree
of response to prior treatments, and the analyses excluded nine
subjects in order to equalize the two groups' baseline
Van Balkom et al. (61) randomly assigned 117
outpatients to five treatment conditions: fluvoxamine plus cognitive therapy,
fluvoxamine plus self-guided ERP, cognitive therapy alone, self-guided
ERP alone, or an 8-week wait-list control. Fluvoxamine was titrated
to 300 mg/day, with a mean endpoint dose in the two drug
groups of 197 mg/day. Pharmacotherapy lasted 16 weeks,
and a naturalistic follow-up measurement was made at 6 months. Completer
and ITT analyses posttreatment revealed no differences in effects
(Y-BOCS, SCL-90, BDI) between the four active treatment conditions; however,
this result may be due to inadequate power. Overall, 36% of
subjects who completed the study were responders (Y-BOCS score
and 6-point improvement). No evidence was found that the combination
of fluvoxamine with cognitive therapy or ERP was superior to the
cognitive therapy or ERP alone. However, neither the ERP nor the
fluvoxamine dosing was optimized. Moreover, because of the absence
of a group treated with fluvoxamine alone and of a control group
for the duration of the study, the differential efficacy of fluvoxamine,
cognitive therapy, or self-guided ERP at week 16 cannot be determined.
A recent follow-up study (66) assessed 62 OCD
subjects who completed controlled trials (23 treated with CBT consisting
of ERP alone, 24 with SRI alone [fluvoxamine or clomipramine],
15 with ERP plus medication) and found that most subjects showed
long-term improvement following either ERP or medication treatment.
The small number of patients in each group, however, limited the
power to detect differences between the groups.
One fluvoxamine study supports the hypothesis that OCD with
co-occurring chronic tic disorders may be a clinically meaningful
subtype. An 8-week open-label trial (223) assessed
the efficacy of fluvoxamine in 66 OCD patients, of whom 33 had tic
disorders. Of the OCD patients with co-occurring chronic tic disorders,
21% were fluvoxamine YBOCS-35% and CGI-I:1,2
responders compared with 52% of the OCD patients without
co-occurring chronic tics. The authors concluded that fluvoxamine
monotherapy may be less efficacious in OCD patients with tics than
in those free of this condition. A clomipramine study, however,
found no reduction in effectiveness in OCD patients with tics (224).
Three randomized, double-blind, placebo-controlled studies
show that fluoxetine is significantly more effective than placebo.
In addition, double-blind active-comparator studies suggest fluoxetine
is comparable in efficacy to clomipramine and sertraline and superior
in efficacy to phenelzine. Compared with clomipramine, fluoxetine
exhibited fewer side effects in one study. In other studies, fluoxetine
was well tolerated, with side effects comparable to those of the
Two large, randomized, double-blind, placebo-controlled studies
demonstrated the effectiveness of fluoxetine in the treatment of
adults with DSM-III-R OCD. In an 8-week double-blind study
(417), 214 subjects were randomly assigned to receive
fluoxetine 20, 40, or 60 mg/day or placebo. Fluoxetine
response (defined as YBOCS-25% and CGI-I:1,2)
rates were significantly higher in the 40 mg/day
and 60 mg/day groups (48% and 47%, respectively)
than in the placebo group (26%), but the response rate
in the 20 mg/day group (36%) was not. In a 16-week
extension, subjects who had not responded to 20 mg/day
or 40 mg/day and who took fluoxetine 60 mg/day
experienced a highly significant decrease in Y-BOCS scores. Fluoxetine
and placebo dropout rates did not differ significantly.
A 13-week, randomized, double-blind trial (83)
assessed the effects of fluoxetine 20, 40, or 60 mg/day
versus placebo in 355 outpatients with OCD. At each dose, fluoxetine
was significantly superior to placebo on the Y-BOCS and other efficacy
measures, with statistical significance reached by week 5. The fluoxetine
groups had YBOCS-35% response rates of 32%, 32%,
and 35%, respectively, with a trend for greater improvement
in the 60 mg/day group. The YBOCS-35% response
rate in the placebo group was 8.5%. The safety and efficacy
of fluoxetine in the acute treatment of OCD are further supported by
open trials (418–421).
Two studies compared fluoxetine with clomipramine in the treatment
of DSM-III-R OCD without using a placebo control group (394, 395).
In the first study, involving crossover designs with 10 weeks of
treatment, 4 weeks of drug washout, and samples of 6 and 20 subjects,
fluoxetine up to 80 mg/day was as effective as clomipramine
up to 250 mg/day (394). Both drugs produced a significant
decrease in the Y-BOCS score, although clomipramine was associated
with more adverse events. The second study, an 8-week, double-blind,
randomized trial, compared fluoxetine 40 mg/day (n = 30)
with clomipramine 150 mg/day (n = 25)
(395). The two drugs appeared equally effective over this short
treatment period. The YBOCS-25% responder rate, but not
the YBOCS-35% responder rate, was higher with clomipramine.
The discontinuation rates for adverse events were 3% for
fluoxetine and 4% for clomipramine.
A 24-week, randomized, double-blind trial compared the efficacy
and tolerability of fluoxetine (mean dose = 57 ± 23 mg/day)
and sertraline (mean dose = 140 ± 59 mg/day) in
outpatients with DSM-IV OCD (422). Equivalent and significant
improvement was found at week 24 in Y-BOCS and NIMH-OC scale scores.
Remission rates (defined as Y-BOCS score 11 and CGI-I:1,2)
at weeks 12 and 24 were significantly higher for sertraline (36% vs.
22% at week 24). Subjects treated with sertraline showed
an earlier improvement on some, but not all, efficacy measures.
Both medications were well tolerated; rates of discontinuation due
to adverse events were 14% for fluoxetine and 19% for
A 10-week randomized trial compared fluoxetine 80 mg/day,
phenelzine 60 mg/day (both doses achieved by the
end of week 3), and placebo in 64 adults with DMS-III-R OCD (423).
Fluoxetine was superior to placebo at weeks 6 and 10 as well as
to phenelzine at week 10. Symmetry obsessions and lower baseline
Y-BOCS scores were significantly more common in phenelzine responders
than in fluoxetine responders; however, this post hoc analysis provides only
weak evidence for a phenelzine effect in this subgroup.
The long-term treatment of OCD with fluoxetine has been examined
to a limited extent. In a continuation of the 13-week, double-blind,
placebo-controlled, fixed-dose fluoxetine study (83),
treatment responders continued their blinded treatment, whereas
nonresponders began a 24-week open-label trial of maximally tolerated
doses up to 80 mg/day (81). Among acute-phase
responders, all three doses of fluoxetine (20, 40, and 60 mg/day)
were associated with further Y-BOCS improvement. The acute-phase
nonresponders benefited from upward dose titration, with two-thirds
achieving a YBOCS-35% response. Another study assessed
the efficacy and safety of 52 weeks of fluoxetine or placebo treatment
in patients with DSM-IV OCD who had responded to single-blind fluoxetine
for 20 weeks (201). Patients who received fluoxetine
had numerically lower relapse rates compared with those who received
placebo, although the difference was not significant (see Section
V.E for details).
Three double-blind placebo-controlled trials show paroxetine
to be more effective than placebo acutely; an additional double-blind
study shows the superiority of paroxetine relative to placebo in
maintaining response over 6 months of continuation treatment.
A double-blind active-comparator study suggests that paroxetine
is comparable in efficacy to clomipramine. Compared with venlafaxine,
the relative efficacy of paroxetine is less clear, as findings vary
with the definition of treatment response. Paroxetine's
tolerability is comparable to that of other SSRIs. Some evidence (424),
but not all (80), suggests paroxetine is more likely
to be associated with significant weight gain. Paroxetine is more
likely to induce anticholinergic side effects than are other SSRIs
(118, 425). It also carries a greater
risk of an unpleasant withdrawal syndrome, comparable to the risk
associated with venlafaxine (426).
In a 12-week double-blind trial (80), OCD patients
without co-occurring major depression, tics, or Tourette's
disorder were randomly assigned to receive paroxetine 20 mg/day
(n = 88), 40 mg/day
(n = 86), 60 mg/day
(n = 85), or placebo (n = 89).
A little more than half of subjects had had a prior SRI trial. Endpoint
response rates (defined as YBOCS-25% or Clinical
Global Impression–Severity [CGI-S] score
decrease of 2 points) for paroxetine 40 mg/day
(25%) and 60 mg/day (29%), but not 20
mg/day (16%), were significantly greater than
for placebo (13%). In a 12-week, double-blind, flexible-dose
study (427), 191 subjects were randomly assigned to
receive placebo or paroxetine, with the dose increasing from 20
mg/day to 40 mg/day by week 3 and up
to 50 mg/day from week 8 onward. The CGI-I:1,2 response
rate was significantly greater in the paroxetine (50%)
than in the placebo group (24%). A significantly greater
response rate was similarly observed in subjects randomly assigned to
receive 12 weeks of flexibly dosed paroxetine 20–60 mg/day
(mean dose = 37 mg/day) (n = 201)
or placebo (n = 99) (393).
More than half (55%) of the paroxetine subjects were YBOCS-25% responders
compared with 35% of placebo subjects. The active comparator,
flexibly dosed clomipramine (150–250 mg/day, mean
dose = 113 mg/day), produced the same responder
rate as paroxetine.
A 12-week, randomized, double-blind, flexible-dose study (172)
comparing paroxetine with venlafaxine found no significant difference
in YBOCS-35% responder rates for paroxetine at doses up
to 60 mg/day (44%) (n = 76)
and venlafaxine at doses up to 300 mg/day (37%)
(n = 75), although the
YBOCS-25% responder rate was higher for paroxetine (66%)
than for venlafaxine (49%). When the medication for nonresponders
in this study was switched to the alternative medication in a double-blind
fashion, a higher YBOCS-25% responder rate was observed
for paroxetine (56% [15/27])
than for venlafaxine (19% [3/19])
Long-term effectiveness of paroxetine has been observed in
one study. Responders to paroxetine in a 12-week double-blind study
and its 6-month open-label, flexible-dose extension phase (N = 105)
were randomly assigned to receive 6 months of double-blind
paroxetine or placebo (80). Relapse was defined as
a return to the baseline Y-BOCS score or an increase of 1 point
in the CGI-S score for more than one visit. Subjects assigned to
placebo had a significantly higher relapse rate (59%) than
those assigned to paroxetine (38%). The mean time to relapse
was 29 days in the placebo group and 63 days in the paroxetine group.
Two double-blind, placebo-controlled trials demonstrated the
efficacy of sertraline in treating OCD. In double-blind active-comparator
studies, sertraline appeared comparable in efficacy to fluoxetine.
Sertraline was superior in efficacy to clomipramine (although methodological
shortcomings influenced the latter comparison) and, in subjects
with co-occurring depression, was superior to desipramine. Finally,
in an open-label trial, subjects who responded to 1 year
of treatment with sertraline experienced further small but noticeable
decreases in symptoms when treatment was extended to 2 years.
In a 12-week, randomized, fixed-dose trial (82),
subjects were assigned to sertraline 50 mg/day (n = 80),
100 mg/day (n = 81),
200 mg/day (n = 80),
or placebo (n = 84). Sertraline
at doses of 50 mg/day and 200 mg/day was significantly
superior to placebo with regard to change in Y-BOCS, NIMH-OC, CGI-S,
and CGI-I scores, but at 100 mg/day sertraline was only
superior in terms of the NIMH-OC, probably because of the high dropout
rate (33%) in this group. At endpoint, CGI:1,2 responder
rates were 39% for sertraline and 30% for placebo.
A 12-week, double-blind, randomized study of flexibly-dosed sertraline
50–200 mg/day (mean maximum dose at endpoint = 165
± 55 mg/day) found the drug (n = 86)
more effective than placebo (n = 81)
with regard to change in Y-BOCS, NIMH-OC, and CGI-S scores (428).
The CGI-I:1,2 responder rate was numerically but not significantly
higher for sertraline (41%) than for placebo (23%).
In a 24-week, double-blind, randomized, flexible-dose comparison
of sertraline 50–200 mg/day (mean endpoint dose = 140
± 59 mg/day) (n = 77)
versus fluoxetine 20–80 mg/day (mean endpoint
dose = 57 ± 23 mg/day), the differences in CGI-I:1,2
responder rates (60% and 60%) and remission (defined
as CGI-I:1,2 plus Y-BOCS < 12)
rates (36% vs. 22%) were not significant (422).
A 16-week double-blind study compared sertraline and clomipramine
50 mg/day for 4 weeks followed by flexible increases in
dose to 200 mg/day (mean final dose = 132 mg/day
for sertraline and 101 mg/day for clomipramine) (401).
The sertraline group had significantly greater improvement as measured
by the Y-BOCS, NIMH-OC, and CGI-S. Inappropriately high starting
doses of clomipramine (50 mg/day), producing a high dropout
rate and low maximum clomipramine dose, strongly influenced the
comparative result. Among subjects treated for at least 4 weeks,
the two drugs produced equal results, but the mean final clomipramine
dose was relatively low. The Y-BOCS-35% responder rates
were 72% for sertraline and 65% for clomipramine.
In another double-blind, flexible-dose study (429), OCD patients
with co-occurring depression were randomly assigned to receive sertraline
50–200 mg/day (mean endpoint dose = 160
± 50 mg/day) or desipramine 50–300 mg/day
(mean endpoint dose = 194 ± 90 mg/day). Sertraline
(n = 79) was more effective
than desipramine (n = 85)
in bringing about "robust improvement in OCD symptoms" (Y-BOCS
score decrease 40%).
A second completed year of continued treatment with open-label
sertraline flexibly dosed from 50 mg/day to 200 mg/day
was associated with a mean decrease in Y-BOCS scores from about
12 to about 9 in 38 subjects (430) who had been CGI-I:1,2
responders in a 1-year, fixed-dose, double-blind study (431).
Finally, after 1 year of single-blind treatment, sertraline
responders rarely relapsed over 28 weeks regardless of whether they
were maintained on flexibly dosed sertraline (50–200 mg/day)
(3/108, or 3%) or switched over 2 weeks
to placebo (5/113, or 4%) (200) (see
Section V.E. for details).
A double-blind, placebo-controlled trial showed citalopram
to be more effective than placebo, with a trend for greater efficacy
and more rapid response at a higher dose. Several open trials suggest
efficacy for citalopram in individuals whose OCD has not responded
to other SRIs. In addition, several open-label trials suggest comparable
efficacy to other SRIs. The active isomer in citalopram, escitalopram,
is now marketed as a separate SSRI in the United States.
In the only double-blind, placebo-controlled, randomized trial,
12 weeks of treatment with fixed-dose citalopram 20 mg/day
(n = 102), 40 mg/day
(n = 98), or 60 mg/day
(n = 100) produced higher
YBOCS-25% response rates (57%, 52%, and
65%, respectively) than did placebo (n = 101)
(37%) (432). There were trends for the highest
dose to be associated with a more rapid response.
A small open-label trial suggests that citalopram (n = 11;
mean dose = 51 mg/day) and paroxetine (n = 9;
mean dose = 53 mg/day) bring about similar YBOCS-35% responder
rates (40% and 45%, respectively) in inpatients
(416). The response rate to fluvoxamine (n = 10;
mean dose = 290 mg/ day) (60%) was numerically
but not statistically significantly higher. An open-label, random-assignment,
flexible-dose study utilizing a blinded rater found no significant
difference in YBOCS-35% responder rates to 12 weeks of
citalopram 40–60 mg/day (n = 23)
(48%), fluvoxamine 200–300 mg/day (n = 83)
(55%), clomipramine 150–250 mg/ day (n = 37)
(48%), or paroxetine 40–60 mg/day (n = 16)
A single case report described a patient whose OCD was unresponsive
after 3 months of citalopram 80 mg/day but subsequently
responded to 160 mg/day, which was well tolerated over
several months (436). Intravenous citalopram (unavailable
in the United States) was well tolerated in one study at doses of
20–80 mg/day and may have a faster onset of action
than oral citalopram (437).
Escitalopram was as effective as paroxetine for OCD in a European
multicenter double-blind, active-comparator trial (437a) and was
superior to placebo in preventing OCD relapse in a second large
European double-blind trial (437b).
Venlafaxine is a serotonin-norepinephrine reuptake inhibitor
(SNRI) that does not have an FDA indication for OCD. A small, double-blind,
placebo-controlled trial with venlafaxine was negative, but several
open-label trials showed robust responses in OCD symptoms at doses
of at least 225 mg/day. In addition, double-blind active-comparator
studies suggest venlafaxine is comparable in efficacy to clomipramine
and perhaps to paroxetine. Venlafaxine has been generally well tolerated.
In the only double-blind, placebo-controlled trial (438),
30 OCD patients were randomly assigned to receive placebo or venlafaxine
(up to 225 mg/day) for 8 weeks. At endpoint, there were
no statistically significant differences in response, although there
was a trend for greater response in the venlafaxine group. The study's
small sample size, short trial length, low venlafaxine dose, and
lack of standard outcome measures (Clinical Global Impression, ratings
of avoidance) severely constrain interpretation.
In a 12-week, double-blind, active-comparator study (172),
150 OCD patients were randomly assigned to receive venlafaxine XR
(up to 300 mg/day) or paroxetine (up to 60 mg/day).
Full response was defined as a Y-BOCS score decrease of 50% and
partial response as a decrease of 35%. An ITT LOCF analysis
demonstrated no significant differences in responder rates (full response:
24% venlafaxine vs. 22% paroxetine; partial response:
37% venlafaxine vs. 44% paroxetine). Only a small
percentage of patients (5%) dropped out because of adverse
effects. The study's methodological limitations include
the absence of a placebo control group and venlafaxine doses not
exceeding 300 mg/day. In addition, the venlafaxine group
had undergone more unsuccessful medication trials.
Nonresponders (Y-BOCS decrease < 25%) in this
study (n = 43) were treated
for 12 additional weeks with the alternative medication (171).
A significantly higher proportion of those whose medication was
switched to paroxetine (56%, 15/27) were YBOCS-25% responders
compared with those whose medication was switched to venlafaxine
XR (19%, 3/16). However, the small sample size,
the lack of a placebo control group, and a less stringent response
criterion are methodological limitations in this second study.
In a 12-week double-blind trial (173), 73 OCD
subjects were randomly assigned to receive venlafaxine (225–350
mg/day, mean dose = 265 mg/day) or clomipramine
(150–225 mg/day, mean dose = 168 mg/day).
Visitwise and LOCF analyses at study end revealed no statistically
significant difference between the groups in YBOCS-35% and CGI-I:1,2
responder rates (visitwise responder rates: venlafaxine 36% vs.
clomipramine 50%; LOCF responder rates: venlafaxine 35% vs.
clomipramine 43%). The investigators concluded that venlafaxine
at these doses may be as effective acutely as clomipramine, with
fewer side effects. However, confidence in these results is again
limited by the lack of a placebo control group, the small size of
the study, and by the relatively low mean clomipramine dose.
An open, naturalistic, retrospective study examined treatment
results for 39 OCD patients (29 who were "nonresponders" [undefined] to
one or more SRI trials) after treatment for a mean of 18 months
(range 1–56 months) with venlafaxine up to 450 mg/day
(mean final dose = 230 mg/day) (439).
At study end, 69% of subjects entering the study were CGI-I:1,2
responders. Of note, 76% of the "nonresponders" to
one or more SRI trials, and 82% of the "nonresponders" to
two or more SRI trials were sustained responders. Venlafaxine even
at the higher end of the dosing range was well tolerated.
An 8-week open-label trial in which 12 OCD patients were treated
with venlafaxine 150–300 mg/day reported responder
rates of 75% (YBOCS-35%) and 35% (CGI-I:1,2)
(440) without substantial side effects. A 12-week open-label
trial utilizing venlafaxine 150–350 mg/day in 10
OCD patients reported responder rates of 30% (YBOCS-35%)
and 40% (CGI–I:1,2), with a more robust response
in treatment-naive patients (441). Marazziti (442)
reported five patients whose OCD was resistant to SSRIs
who improved (Y-BOCS, Ham-D, and other clinical evaluations) for
at least 1 year with venlafaxine 150–225 mg/day.