Efficacy and tolerability of olanzapine in the treatment of schizotypal personality disorder Matcheri Keshavan * , Mujeeb Shad, Paul Soloff, Nina Schooler University of Pittsburgh Medical Center, Health System-Western Psychiatric Institute and Clinic, Room 984, 3811 O’Hara Street, Pittsburgh, PA 15213, USA Received 15 August 2003; received in revised form 3 December 2003; accepted 10 December 2003 Available online 6 March 2004 Abstract Background: Few treatment studies of schizotypal personality disorder (SPD) have investigated the new, atypical antipsychotic drugs. This study examined the efficacy and tolerability of olanzapine, an atypical antipsychotic drug, in a series of patients with DSM-IV diagnosed schizotypal personality disorder. Method: This was a 26-week, open-label study with flexible dose design in 11 subjects with a diagnosis of schizotypal personality disorder based on Structured Clinical Interview for DSM-IV (SCID) and Personality Disorder Examination (PDE Journal of Psychiatric Disorders 1 (1987) 1). Subjects were treated with a low dose (average 9.32 mg/day) of olanzapine. Psychopathology was assessed at baseline and at the end of the study and analyzed with last observation carried forward analysis. Results: Patients showed significant improvements in psychosis and depression ratings, as well as in overall functioning. Olanzapine was well tolerated, though significant weight gain was observed. Conclusion: This study provides preliminary data regarding olanzapine efficacy and tolerability in schizotypal personality disorder subjects. These data need to be confirmed in larger controlled clinical trials. D 2004 Elsevier B.V. All rights reserved. Keywords: Efficacy; Tolerability; Olanzapine; Schizotypal personality disorder 1. Introduction Schizotypal personality disorder (SPD), which affects 3–5% of population, is characterized by per- vasive social and interpersonal deficits, and subtle, psychotic-like symptoms (Gunderson and Phillips, 1995). Observations that first-degree relatives of sub- jects with SPD have a higher risk for schizophrenia- related disorders (Baron et al., 1985; Siever et al., 1990b) suggests that SPD is a schizophrenia related disorder. Similarly, neurobiological markers such as deficits in prepulse inhibition, P50 suppression, and antisaccade paradigms reported in schizophrenic sub- jects are also observed in subjects with SPD (Caden- head et al., 2002; Siever et al., 1990a). Patients with SPD also show many of the same cognitive deficits as seen in schizophrenia, though such deficits are less severe; deficits are seen in working memory, attention, and executive functioning (Park and McTigue, 1997). Additionally, up to 40% of patients with SPD may go on to develop schizophrenia as compared to about 1% 0920-9964/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2003.12.008 * Corresponding author. Tel.: +1-412-624-2794; fax: +1-412- 624-1459. E-mail address: keshavanms@msx.upmc.edu (M. Keshavan). www.elsevier.com/locate/schres Schizophrenia Research 71 (2004) 97 – 101