Exploring OCD Subtypes and Treatment Resistance

Patients with OCD exhibit a wide range of insight; about 5% to 25% have partial insight or lack of insight.²⁷ Some reports indicate that patients with OCD and poor insight do not differ substantially from those with full insight in demographic and clinical characteristics or in their response to SRIs or CBT.²⁷ Insight in OCD may fluctuate with environmental influences (eg, stress) or may parallel response to treatment. In an open-label, 16-week study with sertraline(Drug information on sertraline), researchers found that a decrease in OCD symptom severity corresponded with improvement in insight.²⁷ Similarly, 56% (14 of 25) of patients no longer exhibited poor insight, and this improvement was associated with reduced severity of obsessive-compulsive and depressive symptoms at the end of a 6-month trial with combined clomipramine(Drug information on clomipramine) and CBT.²⁸

There are also reports indicating that OCD with poor insight is associated with a higher nonresponse rate to treatment and poorer prognosis.^29,30 One possible explanation for these discrepant findings is that there is a subset of OCD with poor insight and poor prognosis which is part of the schizophrenia spectrum.²³ In support of this hypothesis, patients with poor insight and associated schizotypal personality disorder were more likely to maintain poor insight after treatment with SSRIs than those without schizotypal personality disorder.²⁸ Lack of treatment response in patients with poor insight was also associated with the presence of schizophrenia-spectrum disorders in their first-degree relatives.²⁹

Overall, it is plausible that OCD with poor insight and schizotypal personality disorder represents a subgroup characterized by distinct clinical features, poor treatment response and prognosis, and by a relationship to the schizophrenia spectrum. Controlled pharmacological trials of SRIs both with and without adjunctive antipsychotics are needed to further validate the existence of a subtype of OCD with poor insight and comorbid schizotypal personality disorder.

Compelling evidence indicates that patients with a primary diagnosis of schizophrenia have a substantially higher rate of OCD than the general population.³¹ Certain clinical characteristics have emerged from recent studies evaluating obsessive-compulsive phenomena in schizophrenia.³²Obsessive-compulsive symptoms in schizophrenia were similar in content, severity, and course to pure OCD. In roughly half of patients with schizophrenia-OCD, the onset of obsessive-compulsive symptoms preceded the onset of schizophrenia, thereby complicating the primary diagnosis of schizophrenia. Obsessive-compulsive symptoms seem to progress in severity with the course of illness, worsening the prognosis of schizophrenia.

In addition, increasing evidence points to a heterogeneity of the schizo-obsessive clinical phenotype.^32,33 Subthreshold obsessive-compulsive symptoms, as well as typical obsessive-compulsive symptoms with full or partial insight and independence from psychosis, were identified. An alternative clinical phenotype is characterized by the combination of classic obsessive-compulsive symptoms and those related to delusional and/or hallucinatory content.

Data regarding pharmacotherapy of schizophrenia with obsessive-compulsive symptoms/OCD is scarce and is based on case reports and small, mostly uncontrolled clinical trials. There is a general consensus that compared with non-OCD schizophrenia, schizo-obsessive disorder is difficult to treat. Conventional antipsychotic agents are generally ineffective in schizophrenia with OCD, presumably because of their limited serotonergic properties.³⁴ The role of atypical antipsychotics in patients with schizo-obsessive disorder remains controversial, with reports indicating that clozapine, olanzapine(Drug information on olanzapine), and risperidone(Drug information on risperidone) may induce de novo or aggravate preexisting obsessive-compulsive symptoms of OCD in patients with schizophrenia.³⁵ At the same time, preliminary evidence indicates that clozapine(Drug information on clozapine) and olanzapine, either alone or in combination with SSRIs, may alleviate both schizophrenic and obsessive-compulsive symptoms in some patients who have OCD with comorbid schizophrenia.^31,36

Well-designed, large-scale, placebo-controlled studies of schizophrenia-OCD are still lacking. In the absence of evidence-based data, my colleagues and I summarize our recommendations for the therapeutic management of schizo-obsessive disorder in the Table.³¹

Obsessive-compulsive symptoms in schizophrenia should be considered a target for therapeutic intervention only when their severity is of clinical significance. SSRIs or clomipramine for the treatment of obsessive-compulsive symptoms should be initiated only in neuroleptic-stabilized patients. In addition, patients with schizo-obsessive disorder and a history of impulsivity and aggressiveness may be at higher risk for psychotic exacerbation when taking adjunctive SSRIs. Careful evaluation of the potential risks and benefits of adjunc-tive pharmacotherapy in patients with schizo-obsessive disorder is a prerequisite for successful pharmacotherapy.

Delineation of phenomenologically distinct subtypes of OCD may facilitate a search for their effective management. Subtypes of OCD, namely OCD-schizotypal, OCD with poor insight, hoarding OCD and the schizo-obsessive subtype, may be placed on a putative schizophrenia-OCD axis, whereas tic-related OCD most likely represents a pathophysiologically distinct subgroup. It seems that these OCD subtypes share diminished response to standard pharmacological interventions, a putative therapeutic efficacy of antipsychotic augmentation and, most probably, an involvement of the dopamine(Drug information on dopamine)rgic system. Patients from the described subgroups may benefit from consultation in specialized centers for diagnostic reevaluation and intensive combined therapy.