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Identifying Predictors of Drug Response in Patients With OCD

Identifying Predictors of Drug Response in Patients With OCD

Over the past decade, reports about obsessive-compulsive disorder (OCD) have gradually moved from the traditional and somewhat pessimistic points of view to a more defined and optimistic line of research: the "rare and intractable illness" has now become a paradigm for valid hypotheses in neurobiology and clinical psychopharmacology.

Data in the literature support the so-called "serotonin (5-HT) hypothesis" of OCD (Barr et al., 1992): peripheral markers of serotonin function (Bastani et al., 1991), pharmacologic challenge studies with serotonin agonists (Erzegovesi et al., 2001b) and, above all, drug-response data from serotonin reuptake inhibitors (SRIs) (Greist et al., 1995).

According to the serotonin hypothesis, patients with OCD have a dysregulation in the serotonergic system, with a hypersensitivity of postsynaptic 5-HT receptors, which could account for a different mechanism of action of SRIs in OCD (Billett et al., 1997; Zohar et al., 1987). For example, onset of therapeutic action is 10 to 12 weeks in OCD, compared to three to four weeks for mood disorders.

At the present time, SRIs represent the first-line strategy in drug treatment of OCD. Efficacy and tolerability have been proven in several controlled studies (Greist et al., 1995; Mundo et al., 1997; Tollefson et al., 1994; Zohar and Judge, 1996). According to available data, the different SRIs seem to be equivalent in treating OCD if employed at equivalent dosages.

However, a major concern in the clinical pharmacology of OCD is the number of non-responders to drug therapy. As many as 40% to 60% of patients treated with SRIs at full dosages for at least 12 weeks did not show a significant improvement in OC symptoms and global functioning.

How can we define good response to SRIs in patients with OCD? According to the literature, good response can be defined as at least a 35% reduction in total scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS).

In the last 10 years, several studies tried to identify possible response profiles among patients with OCD on SRI treatment (Ackerman et al., 1994; Baer et al., 1992; Carrasco et al., 1992; Cavedini et al., 1997; Mataix-Cols et al., 1999; McDougle et al., 1993; Ravizza et al., 1995). Early identification of good or poor responders could help physicians to optimize treatment with SRIs or make alternative choices such as add-on therapies.

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