Risperidone in the Treatment of Psychotic-like and Deficit Symptoms of Schizotypal Personality Disorder
Condition: Schizotypal Personality Disorder
MeSH terms: Personality Disorders; Schizotypal Personality Disorder
Study type: Interventional

Summary: 
      The purpose of this study is to determine the efficacy of risperidone compared to placebo in
      the treatment of the psychotic-like and deficit symptoms of schizotypal personality disorder
      (SPD). Treatment with risperidone, a 5HT2 and dopamine D2 blocking agent, holds particular
      promise in the treatment of SPD. Unlike traditional antipsychotics, risperidone targets the
      deficit or negative symptoms of schizophrenia. The deficit-like symptoms of SPD are therefore
      also likely respond to treatment with risperidone. One common complication in the present
      psychopharmacologic treatment of SPD with traditional neuroleptics is the fact that many
      patients discontinue treatment due to the medication-induced dysphoria. Given initial reports
      and the serotonergic component of the risperidone mechanism, risperidone is anticipated to
      produce little or no dysphoria.
    

Detailed description: 
      All patients receive a comprehensive medical evaluation prior to their participation in any
      studies, as part of their normal clinical care. The evaluation includes an extensive medical
      history, physical examination, and laboratory evaluation including SMA-18, CBC with
      differential, TFT's, U/A, stool guaiac, serology, drug screen, chest X-ray (where indicated),
      EKG, and, for women, pregnancy test. [Note: Subjects will have consented to these procedures
      in a separate consent, "Biological Correlates of Personality Disorder- Information for
      Subjects (88244)", before being invited to join this study.] Patients will be interviewed by
      clinical psychology doctoral students trained in the use of structured instruments to assess
      Axis I and Axis II pathology. A rater will independently complete either the Schedule for
      Affective Disorders and Schizophrenia (SADS) (Spitzer & Endicott 1978), modified for
      evaluation of DSM-IV criteria for Axis 1 disorders, or the Structured Clinical Interview for
      DSM-IV Axis I Disorders ( First et al 1996) and the Structured Interview for DSM-III-R
      Personality Disorders (SIDP-R) (Pfohl et al 1989) also modified for the evaluation of DSM-IV
      criteria. When possible, information will be gathered independently from an informant (first
      degree relative or life-long friend) to supplement information obtained from clinical
      interviews and review of past records. The use of structured interviews, and questionnaires
      are not part of standard clinical care.

      PART 1 Part 1 is a single-blind two-week placebo washout. Patients will be seen weekly by a
      research psychiatrist. One week of (placebo) medication will be dispensed at a time by a
      research program physician under the direct supervision of Dr. Koenigsberg. Patients will be
      seen weekly throughout the study. Interviews and assessments are standardized and identical
      throughout all phases of the study. They include the Clinical Global Impression scale (CGI),
      the Scale for the Assessment of Negative Symptoms (SANS), the Positive and Negative Symptom
      Scale (PANSS), and the Hamilton Depression Rating Scale (HDRS), all administered weekly. At
      baseline and after 4- and 9-weeks of treatment, subjects will also receive a series of
      paper-and-pencil and computer-presented cognitive tests (DOT test, Paced Auditory Serial
      Addition Task, Continuous Performance Task-Identical Pairs version, Serial Verbal Learning
      Test and the Wechsler memory Scale-Revised Visual Reproduction test). No medications, other
      than study drug, are allowed during the protocol. If, during this two-week placebo washout
      period, the total SANS score decreases by 35% or greater, patients will not be entered into
      Phase 2. Use of a placebo washout is not part of standard clinical care.

      PART 2 Part 2 is the double blind, 9-week parallel-arm placebo-controlled portion of the
      study. Randomization will be conducted by the Pharmacy. One week of medication (active or
      placebo) will be dispensed at a time by a research program physician under the direct
      supervision of Dr. Koenigsberg. The patient will receive 1 tablet PO QD every day of the
      study. If enrolled in the Active Arm of the study, the patient will receive a .25 mg
      risperidone tablet orally once daily for Days 1 to 7; .5 mg risperidone tablet orally once
      daily for Days 8 to 21; 1 mg risperidone tablet orally once daily for Days 22-35; 1.5 mg
      risperidone tablet orally once daily for days 36-49; and a 2 mgs of risperidone orally once
      daily for days 50 to 63. If the treating psychiatrist believes that a higher dose is
      clinically indicated, the physician may alter the above by increasing the dose to 2 mg per
      day beginning on day 22 and to 4 mg per day beginning on day 50. Weekly visits will include
      standard assessment and review of protocol compliance. Treatment with risperidone is not part
      of current standard clinical care of schizotypal personality disorder and this study is
      designed to establish its usefulness with this population. Similarly use of a double bind
      placebo control is not part of standard clinical care.

      PART 3 Patients who were randomized into the placebo arm of Part 2 will be offered the
      opportunity of participating in an 8 week open label study of risperidone otherwise identical
      to Part 2.

      Data will be analyzed by a repeated measures analysis of variance separately for scores on
      the CGI, SANS, PANSS, and HDSR comparing placebo and active medication.
    

Intervention name(s): Risperidone; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): The dosage of risperidone was titrated upward in a stepwise design, beginning with 0.25 mg/d for the first week, 0.5 mg/d for weeks 2 and 3, 1.0 mg/d for weeks 4 and 5, 1.5 mg/d for weeks 6 and 7, and 2.0 mg/d for the remaining weeks.; placebo match in identical tablets
Intervention MeSH terms: Risperidone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Schizotypal Personality Disorder; Risperidone; Treatment; Cognitive