A long-term trial of the effectiveness and safety of atypical antipsychotic agents in augmenting SSRI-refractory obsessive-compulsive disorder.
OBJECTIVE
Although atypical antipsychotic agents have been found effective in the augmentation of serotonin reuptake inhibitors (SRIs) for treatment-resistant obsessive-compulsive disorder (OCD) in short-term trials, there are few data on the effectiveness and safety of these agents in clinical settings over the long term.


METHODS
Subjects (N = 46) who responded to selective SRIs (SSRIs) in an initial 12-week trial were continued on SSRI monotherapy plus cognitive-behavioral therapy (CBT) for 1 year. Subjects (N = 44) who failed to respond to SSRIs were randomly assigned to 1 of 3 atypical antipsychotics -- olanzapine, quetiapine, or risperidone -- and were consecutively treated using SSRI + atypical antipsychotics combined with CBT for 1 year. This study was conducted from January 2006 to November 2007 at Osaka City University Graduate School of Medicine Hospital, Japan.


RESULTS
Augmentation with atypical antipsychotics reduced mean +/- SD Yale-Brown Obsessive Compulsive Scale (YBOCS) total scores in SSRI-refractory OCD patients (at initial assessment = 29.3 +/- 9.9, after 1 year = 19.3 +/- 6.8). However, compared to SSRI responders (at initial assessment = 25.8 +/- 11.4, after 1 year = 13.7 +/- 4.6), total YBOCS scores in those who required atypical antipsychotic augmentation were initially higher, and they remained at higher levels than those of SRI responders after 1 year of the treatments.


CONCLUSIONS
Our work does not sufficiently support the long-term effectiveness of the atypical antipsychotics in the augmentation of SSRIs for treatment-resistant OCD patients. Even though this approach seems useful for some types of OCD patients, such as those with symmetry/ordering and hoarding symptoms, these data emphasize the limitations of the current pharmacotherapeutic options in treatment-refractory OCD, and their chronic use raises a number of safety concerns.


BACKGROUND
(ClinicalTrials.gov) Identifier NCT00854919.
Matsunaga
Hisato
H
Department of Neuropsychiatry, Osaka City University Graduate School of Medicine, Osaka, Japan. hisato@msic.med.osaka-cu.ac.jp
Nagata
Toshihiko
T
Hayashida
Kazuhisa
K
Ohya
Kenzo
K
Kiriike
Nobuo
N
Stein
Dan J
DJ
D000328:Adult; D000553:Ambulatory Care; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects; D015992:Body Mass Index; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D003987:Dibenzothiazepines / Q000008:administration & dosage / Q000009:adverse effects; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D016666:Fluvoxamine / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D008134:Long-Term Care; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D000077152:Olanzapine; D017374:Paroxetine / Q000008:administration & dosage / Q000009:adverse effects; D000069348:Quetiapine Fumarate; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D003987:Dibenzothiazepines; D016666:Fluvoxamine; D000077152:Olanzapine; D017374:Paroxetine; D000069348:Quetiapine Fumarate; D018967:Risperidone; D017367:Selective Serotonin Reuptake Inhibitors