Enrico Pessina

8-week, single-blind, randomized trial comparing risperidone versus olanzapine augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive–compulsive disorder

The aim of the present pilot study was to investigate in a single-blind manner, over a period of 8 weeks, the comparative efficacy and tolerability of risperidone versus olanzapine addition in the treatment of OCD patients who did not show a >or=35% decrease in the YBOCS score after 16-week SRI treatment (defined as resistant). The study consisted of two different phases: a 16-week open-label prospective phase to ascertain resistance to SRI treatment and an 8-week single-blind addition phase for resistant subjects only. Ninety-six subjects with DSM-IV OCD (YBOCS>or=16) entered the open-label prospective phase; at the end of the 16-week period, 50 (52%) were judged to be resistant and were randomized to receive risperidone (1 to 3 mg/d) or olanzapine (2.5 to 10 mg/d) addition for 8 weeks. Overall, patients in both groups responded significantly, without differences between the two treatment groups; although no differences emerged for the proportion of patients reporting at least an adverse event, the profiles of adverse experiences differed significantly, being risperidone associated with amenorrhoea and olanzapine with weight gain.

Aripiprazole augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a 12-week open-label preliminary study

One of the most studied and well-documented strategies for treatment-resistant obsessive–compulsive disorder (OCD) is the addition of antipsychotic drugs to the ongoing serotonin reuptake inhibitor (SRI) treatment. To date, there has been a paucity of data regarding the use of aripiprazole in OCD patients who failed to respond to SRIs. The aim of the present pilot study was to investigate the efficacy of flexible doses of aripiprazole as augmenting agent in the treatment of resistant OCD patients. Patients meeting the inclusion criteria of treatment-resistant OCD entered a 12-week, open-label, flexible-dose trial of aripiprazole addition to SRIs. Aripiprazole was started at 5 mg/day and increased up to a maximum of 20 mg/day. Twelve patients fulfilled entry criteria; nine patients took at least one dose of study medication and eight of them completed the study. The mean daily dosage of aripiprazole in completers was 11.2±5.2 mg/day. Patients showed a significant improvement over the 12-week study period (paired t-test for mean Yale-Brown Obsessive Compulsive Scale total score at week 12 as compared with baseline – all patients: t = 4.860, d.f. = 8, P = 0.001). The most common adverse event reported was inner unrest reported by four (44.4%) patients. Our study supports the notion that adding aripiprazole to SRIs could be a valid strategy for treatment-resistant OCD patients, and points towards the need of randomized, double-blind studies.

Early-onset obsessive–compulsive disorder and personality disorders in adulthood

Obsessive-compulsive disorder (OCD) often emerges in childhood or adolescence. The aim of the present study was to evaluate whether adult patients with prepuberal onset differ from subjects with later onset in terms of personality disorder comorbidity. The Structured Clinical Interview for DSM-IV Axis II Disorders was used to assess 148 patients with a principal diagnosis of OCD according to the Structured Clinical Interview for DSM-IV Axis I Disorders. The following two subgroups of subjects were selected according to the age at onset of symptomatology: patients with an early-onset (< or =10 years), and patients with a later onset (> or =17 years). Of the 148 patients screened for the present study, 33 (22.3%) had an early onset and 1369 (46.6%) had a later onset. With regard to personality disorders, early-onset patients showed more OC personality disorders (OCPD) than later onset patients. Our finding suggests that OCD in childhood increases the risk for developing OCPD in adulthood, or that early-onset OCD and OCPD share a common pathogenesis.

Antipsychotics in Obsessive-Compulsive Disorder

Drug treatment of OCD entails serotonin re-uptake inhibitors as first-line interventions. However, many patients with OCD do not benefit from standard treatments with SRIs; this proportion of patients may be approximately estimated between 40 and 50 percent of all subjects who are initially treated with these agents. One of the most studied approaches for treatment-resistant patients is antipsychotic augmentation, which consists in adding to the ongoing SRI an antipsychotic. Good results have been obtained when the augmentation was made with a low-dose first generation antipsychotic (haloperidol, for which a double-blind study exists, and pimozide). Given the side-effects profile of first generation antipsychotics, researchers have, in the last years, tried second generation ones as augmentation drugs. Risperidone, olanzapine and, more recently, quetiapine at low doses have been proved to be effective in a series of open label reports and in double-blind studies. The present paper will review all available studies concerning the use of antipsychotics in OCD, pointing toward benefits and potential side effects of this augmentation strategy. All of the studies that evaluated the addition of an antipsychotic in resistant OCD lasted 6-12 weeks; only a preliminary study lasted 16 weeks. A question that remains unresolved to date is then how long should a clinician maintain the antipsychotic augmentation in patients who responded to this strategy. In other words, is antipsychotic at low doses only necessary in order to elicit a response or is it also necessary in order to maintain it? Another way of looking at the problem is to examine whether the discontinuation of the antipsychotic in patients who responded to this strategy is associated with a worsening of obsessive-compulsive symptoms. We will present data on relapse rates in patients who responded to the addition of the antipsychotic and then discontinued it without discontinuing the SSRI.