Identifying Predictors of Drug Response in Patients With OCD
By Stefano Erzegovesi, M.D.
May 1, 2002
Dr. Erzegovesi is senior registrar at the OCD/Eating Disorders Clinical and Research Unit at San Raffaele Hospital, Vita-Salute San Raffaele University in Milan, Italy. His main research area is clinical psychopharmacology of OC spectrum disorders.
The Table illustrates several clinical features related to a poorer response to drug therapy. Some of these features (i.e., comorbid tic disorder, comorbid schizotypal personality disorder) seem to hypothesize different biological substrates in OCD. Beyond serotonin, other neurotransmitters (e.g., dopamine(Drug information on dopamine)) may be involved in OCD's pathophysiology. In fact, such comorbid conditions show a preferential response to an association therapy with SRIs and low-dose dopamine antagonists.
On the other hand, presence of early SRI-related side effects seems to be a positive predictor of response in OCD. According to the serotonin hypothesis of OCD, a hypersensitivity in post-synaptic serotonin receptors could account for some of this early response, for example initial nervousness and sexual complaints (Ackerman et al., 1999).
We have found that a positive family history for OCD in patients' first-degree relatives could be a predictor of good response (Erzegovesi et al., 2001a). To explain this result, we can hypothesize, in a biological and genetic perspective, that OCD is actually a heterogeneous disorder. Familial OCD could have a stronger biological liability, e.g., a greater serotonergic sensitivity, and therefore a greater sensitivity to the therapeutic effect of SRIs.
Another indirect support to the heterogeneity of OCD is the issue of poor insight. According to DSM-IV, there is a subgroup of patients with OCD who do not consider their symptoms to be senseless or excessive. This subtype, associated with a poorer response to SRIs treatment, could be the phenomenological expression of an underlying biological difference, e.g., the involvement of other neurotransmission systems such as dopamine (Erzegovesi et al., 2001a). Dopamine itself indirectly places a link between OCD and the comorbid conditions (tic disorders and schizotypal personality disorders) cited earlier as further negative predictors of response to antiobsessional therapy.
Somatic obsessions are a further confirmation of the significance of insight scoring in OCD (Erzegovesi et al., 2001a). Patients with somatic symptoms often show a poorer insight score.
These negative predictors can perhaps explain the growing interest in add-on therapies for non-responding patients. Several reports showed a significant effect of dopamine antagonists in SRI-resistant patients, either for typical (e.g., haloperidol(Drug information on haloperidol) [Haldol]) or atypical (e.g., risperidone(Drug information on risperidone) [Risperdal], olanzapine(Drug information on olanzapine) [Zyprexa]) antipsychotics (Koran et al., 2000; McDougle et al., 2000; McDougle et al., 1994; Ravizza et al., 1996; Saxena et al., 1996). Add-on therapies could confirm the presence of biologically heterogeneous subgroups of patients who are linked to biological markers other than serotonin.
In conclusion, recent findings about clinical psychopharmacology of OCD point out the importance of an accurate collection of clinical and familial data in the pretreatment assessment of patients. Collection of possible clinical predictors of drug response could be a valuable tool in the psychopharmacology of OCD. Before starting drug therapy with SRIs, the presence of some predictors can help us to foresee the final response or, alternatively, to set up an appropriate add-on therapy.
As for future perspectives on treating OCD, prospective follow-up studies are needed to identify specific subgroups of patients and, accordingly, to define a wide range of specific treatment strategies that improve the long-term outcome of patients with OCD.
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