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Augmentation of Serotonin Reuptake Inhibitors in Refractory Obsessive-Compulsive Disorder Using Adjunctive Olanzapine: A Placebo-Controlled Trial
Abstract
BACKGROUND: The purpose of this study was to explore the efficacy of adding an atypical antipsychotic, olanzapine, to a serotonin reuptake inhibitor (SRI) in treatment-refractory obsessive-compulsive disorder (OCD). METHOD: Twenty-six patients aged between 18 and 65 (mean = 41.2, SD = 11.9) years meeting DSM-IV criteria for OCD, who had not responded to SRIs, were treated for 6 weeks in a double-blind, placebo-controlled augmentation study with either olanzapine (up to 20 mg/day) or placebo. Severity of illness was assessed biweekly by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Analysis of covariance with baseline Y-BOCS score included as a covariate was used to compare improvement in Y-BOCS scores in the 2 groups. Response was defined as a 25% or greater improvement in Y-BOCS score. Data were collected between April 2001 and May 2003. RESULTS: Outcome was assessed for all patients using the last observation carried forward. Subjects in the olanzapine group had a mean decrease of 4.2 (SD = 7.9) in Y-BOCS score compared with a mean increase in score of 0.54 (SD = 1.31) for subjects in the placebo group (F = 4.85, df = 2,23; p =.04). Six (46%) of 13 subjects in the olanzapine group showed a 25% or greater improvement in Y-BOCS score compared with none in the placebo group. The final mean dose of olanzapine was 11.2 (SD = 6.5) mg/day. Medication was well tolerated. Only 2 (15%) of 13 subjects who received olanzapine discontinued because of side effects: sedation (N = 1) or weight gain (N = 1). CONCLUSION: These results provide preliminary evidence that adding olanzapine to SRIs is potentially efficacious and well tolerated in the short-term treatment of patients with refractory OCD. Controlled studies with larger sample sizes are necessary to more definitively address this treatment strategy.
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“Recently, second-generation antipsychotic agents have shown benefit, either alone or as adjunctive therapy. Specifically, high-dose olanzapine [522], quetiapine [523], and risperidone [524] have all shown at least minimal clinical benefit relative to placebo treatment [525].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [522]
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BackgroundInfluentialEvidence-based pharmacotherapy of obsessive-compulsive disorder
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“Unauthorized reproduction of this article is prohibited. augmentation with amisulpride (Metin et al., 2003), olanzapine (Koran et al., 2000; Bystritsky et al., 2004; Marazziti et al., 2005), risperidone (Ravizza et al., 1996; Pfanner et al., 2000) and quetiapine (Denys et al., 2004; Bogan et al.,…”
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“Specific drugs in this class have demonstrated antidepressant efficacy when used to augment SSRI action in certain anxiety disorders, including obsessive compulsive disorder [47-49] and post-traumatic stress disorder [50-52].”
BackgroundAugmentation of olanzapine in treatment-resistant schizophrenia
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InfluentialHow to grade categories of evidence
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“In DBPC studies, the combination of the atypical antipsychotics quetiapine, olanzapine and risperidone with an SSRI was more effective than SSRI monotherapy (Bystritsky et al. 2004; Denys et al. 2004a; Erzegovesi et al. 2005; Hollander et al. 2003b; McDougle et al. 2000; Shapira et al. 2004)(B).”
BackgroundClinical Pharmacology of Comorbid Obsessive–Compulsive Disorder in Tourette Syndrome
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“benefits of dopaminergic blockers (McDougle et al. 1994; Sasson and Zohar 1996; Saxena et al. 1996; Hollander et al. 2003; Bystritsky et al. 2004; Carey et al. 2005; Komossa et al. 2010) and an exacerbation of OCD symptoms during administration of amphetamine or cocaine to OCD patients (Insel et al.”
BackgroundAripiprazole as an adjunctive treatment for refractory unipolar depression
Hellerstein, D. J., Batchelder, S. T., Hyler, S. E., Arnaout, B., Corpuz, V., Coram, L., & Weiss, G. (2007) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2007.11.024 · Cited by 25
“Augmentation strategies using atypical antipsychotics, such as risperidone, ziprasidone, quetiapine, and olanzapine (Shelton et al., 2001; Klein et al., 2004) have been reported to be successful for treatment-resistant depression, and for obsessive compulsive disorder (Bystritsky et al., 2004).”
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Lamotrigine-induced obsessional symptoms in a patient with bipolar II disorder: a case report
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Metadata
- Authors
- Bystritsky, A., Ackerman, D. L., Rosen, R. M., Vapnik, T., Gorbis, E., Maidment, K. M., & Saxena, S.
- Affiliations
- University of California, Los Angeles (US)
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2004-04-15
- Volume
- 65
- Issue
- 4
- Pages
- 565-568
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W1988849721
- Cited by
- 220
- References
- 0
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 5 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 8 · 2018: 3 · 2017: 7 · 2016: 6 · 2015: 11 · 2014: 11 · 2013: 8 · 2012: 41
- FWCI
- 23.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- obsessive-compulsive disorder, treatment-refractory OCD, olanzapine, serotonin reuptake inhibitors, drug augmentation, atypical antipsychotics, Yale-Brown Obsessive Compulsive Scale, drug tolerability
- MeSH terms
- Olanzapine, Adult, Benzodiazepines, Double-Blind Method, Drug Administration Schedule, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Obsessive-Compulsive Disorder, Placebos, Psychiatric Status Rating Scales, Severity of Illness Index, Antipsychotic Agents, Treatment Outcome, Selective Serotonin Reuptake Inhibitors
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