Background
Obsessive-compulsive disorder (OCD) is a prevalent, chronic and disabling disorder [1]. Controlled pharmacotherapy studies have established superiority of serotonin re-uptake inhibitors (SRI's) over noradrenaline reuptake inhibitors and over placebo in OCD and these currently form the cornerstone of pharmacotherapy management [2]. Despite the considerable advances made with the introduction of the SRI's into clinical practice, 40–60% of subjects still fail to respond adequately to initial therapy [3,4].
From this it is clear that a need exists to pursue more effective treatments for those with OCD who fail to respond or respond inadequately to SRI's. To this end, preliminary evidence supports a role for the addition of atypical antipsychotics to SRIs in OCD. These agents combine serotonin-dopamine antagonism with the advantage of being well tolerated including a low potential for inducing motor side-effects.
To date a number of open-label studies have suggested that augmenting SRI's with atypical antipsychotics is an effective strategy for treatment-refractory OCD. These include support for risperidone [5-7], olanzapine [8-13], and more recently amisulpride [14] and quetiapine [15-18]. A single open-label study using quetiapine as augmentation showed lack of effect in a small sample using low doses [19].
The outcome of the first controlled study in this area with the antipsychotic haloperidol demonstrated preferential benefit for refractory OCD subjects with co-morbid tic disorder [20]. In two subsequent studies the efficacy of risperidone in SRI refractory OCD has also been reported [21,22]. Interestingly the former study [21], did not replicate the particular advantage for subjects with co-morbid tic disorder. Efficacy has also been shown for quetiapine [23] and olanzapine [24] using similar designs, but the effects on co-morbid tic disorders were not reported. In contrast a recent controlled study using olanzapine failed to demonstrate efficacy over placebo in a six week study [25].
Despite some mixed evidence in this area, in general the available literature appears to support the use of relatively short trials with low doses of antipsychotic agents as augmentation to SRIs. Quetiapine has a particularly interesting profile in that it is the only available antipsychotic with significant 5-HT1D effects and this serotonin receptor subtype has been implicated in OCD [26,27].
Our objective was to examine the effects of quetiapine augmentation in subjects with OCD who had failed to respond adequately to a 12 week trial of an SRI, employing a double-blind, placebo-controlled, six week study design.