DECIFER: DEpression and Citalopram In First Episode Recovery

Official Title: “Citalopram in First Episode Schizophrenia”

This study seeks to examine the effectiveness of citalopram added to treatment with any oral or injectable second-generation antipsychotic plus standardized psychoeducation in first episode schizophrenia patients. Because depressive symptoms are common in first episode patients, we will test the hypothesis that adding the SSRI citalopram to a pre-established medication regimen will improve quality of life and decrease relapse and suicidality over the course of a 12-month trial.

We propose to conduct a 12-month, placebo-controlled, double-blind, parallel-group trial of citalopram added to treatment with any oral or injectable second-generation antipsychotic plus standardized psychoeducation. Subjects will be 100 patients ages 15-40 with first episode schizophrenia or schizophreniform disorder with onset before age 35 who have received at least 4 weeks and fewer than 16 cumulative weeks of antipsychotic medication, have not been treated with an SSRI within four weeks and do not meet criteria for major depression or significant suicidal ideation. This study will be conducted by the Schizophrenia Program of the Massachusetts General Hospital (MGH) located at the Freedom Trail Clinic and at the Psychiatry Outpatient Clinic of the MGH located in Boston, MA

Upon signing consent, patients will undergo screening procedures to assess eligibility. A diagnosis of schizophrenia or schizophreniform disorder will be determined by the Structured Clinical Interview for DSM IV (SCID) completed by a research clinician using all available clinical data and will be confirmed by consensus diagnosis. A comprehensive medical history and physical exam, including measurement of vital signs, will be performed. A psychiatric history, including diagnosis, treatment history, current medications, and substance use will also be performed. At screening only, a fasting blood sample will be obtained to perform routine laboratory tests including electrolytes, BUN, creatinine, liver function tests, fasting glucose, calcium, phosphate, magnesium, albumin and CBC with differential.

Urinalysis will be performed to identify unstable medical illness. A urine toxicology screen will be performed and a urine pregnancy test will be done for women of child bearing potential. A research assistant will complete the demographics and administer the Calgary Depression Scale for Schizophrenia (CDSS), Scale for the Assessment of Negative Symptoms (SANS) and InterSePT Scale for Suicidal Thinking (ISST) to determine whether inclusion criteria are met.

Subjects who meet study eligibility criteria will complete the baseline assessment which will include the following assessments: Brief Psychiatric Rating Scale (BPRS), SANS, CDSS, ISST, Clinical Global Impression for Severity of Suicidality (CGI-SS), Clinical Global Impression (CGI) and Heinrich Quality of Life Scale (QLS). In addition, side effects will be rated using the Side Effect Checklist (SEC), Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Scale (BAS) and the Simpson Angus Scale for Extrapyramidal Symptoms (SAS).

Assessment of cognitive functioning will be measured by the MATRICS battery.

Subjects will undergo 3 high-resolution MP-RAGE scans: once each at Baseline, 6 months and 12 months. scheduled Participants will be randomized 1:1 to citalopram or placebo. We will follow a standard approach to flexible dosing with citalopram as recommended by the manufacturer, initiating treatment with a dose of 20 mg (two capsules) daily. Clinicians may increase or decrease the dose by one capsule every two weeks to a maximum of 4 capsules and a minimum of one capsule daily.

Beginning at Week 1, participants will receive 16 sessions of weekly, individual psychoeducation and relapse prevention planning followed by 8 monthly sessions.

Participants who score 3 (moderate suicidality) on the CGI-SS or > 7 on the CDSS will be treated with a standard 12 session CBT approach to depression that includes elements targeting suicidality when appropriate. Clinical judgment will be used to determine whether to offer the CBT for depression sessions once or twice weekly. All clinical rating scales and side effect scales with be administered at baseline and then every 4 weeks, with the exception of the QLS which will be administered every 8 weeks. The CDSS, SANS, ISST and SEC will additionally be administered every week for the first 4 weeks, bi-weekly for the next 4 weeks, then monthly for the remainder of the study. The cognitive battery is repeated at week 24 and end of study. Fasting blood samples will be drawn at Baseline, Weeks 4 and 8 and every 8 weeks thereafter for BDNF assay. Blood will also be collected at Baseline for DNA.

Participants who choose to discontinue study drug will be asked if they are willing to continue their scheduled assessments. These subjects will continue to be followed for the entire course of the study but will not receive any study medication. Final study visit will be conducted 1 year post randomization.

The primary outcome measure is change in depression symptoms as measured by the Calgary Depression Scale total score. Secondary outcome measures include a measure of changes in negative symptoms (SANS), relapse rates (BPRS), suicidal ideation (ISST), and quality of life (QOL), measured at various time points during the 12-month trial.

Intervention(s) in this Clinical Trial

• Drug: Citalopram
  • 40 mg by mouth daily for 12 months. Dosing will start at 20mg daily and may be increased after a minimum of one week to the target dose of 40 mg daily. Dose decreases will be made in the presence of side effects. Allowed dose range will be 10 mg daily to 40 mg daily.
• Behavioral: Psychoeducation
  • 16 sessions of weekly, individual psychoeducation and relapse prevention planning followed by 8 monthly sessions
• Behavioral: Cognitive Behavioral Therapy (CBT)
  • Participants who exhibit symptoms of moderate suicidality at any point during the trial will be treated with 12 sessions of CBT, either once or twice weekly based on clinical judgment. Participants who continue to exceed suicidality criteria after 4 weeks of CBT will be dropped from double-blind treatment and may be prescribed openly an SSRI
• Radiation: Functional Magnetic Resonance Imaging (fMRI)
  • 3 1-hour sessions of fMRI brain scanning, assessed at baseline, and weeks 24 and 52.
• Drug: Placebo
  • Placebo by mouth daily for 12 months.
• Behavioral: Psychoeducation
  • 16 sessions of weekly, individual psychoeducation and relapse prevention planning followed by 8 monthly sessions
• Behavioral: Cognitive Behavioral Therapy (CBT)
  • Participants who exhibit symptoms of moderate suicidality at any point during the trial will be treated with 12 sessions of CBT, either once or twice weekly based on clinical judgment. Participants who continue to exceed suicidality criteria after 4 weeks of CBT will be dropped from double-blind treatment and may be prescribed openly an SSRI
• Radiation: Functional Magnetic Resonance Imaging (fMRI)
  • 3 1-hour sessions of fMRI brain scanning, assessed at baseline, and weeks 24 and 52

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Citalopram
  • Participants will receive a daily dose of citalopram, with flexible dosing as determined by clinician, for 12 months.
• Placebo Comparator: Placebo
  • Participants will receive a daily dose of placebo for 12 months.

Primary Measures

• Calgary Depression Scale for Schizophrenia (CDSS)
  • Time Frame: Screening, Weeks 0-4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
    Safety Issue?: No

Secondary Measures

• Scale for the Assessment of Negative Symptoms (SANS)
  • Time Frame: Screening, Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
    Safety Issue?: No
• Brief Psychiatric Rating Scale (BPRS)
  • Time Frame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
    Safety Issue?: No
• InterSePT Scale for Suicidal Thinking (ISST)
  • Time Frame: Screening, Weeks 0-4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
    Safety Issue?: No
• Heinrich Quality of Life Scale (QOL)
  • Time Frame: Weeks 0, 8, 16, 24, 32, 40, 52
    Safety Issue?: No

Inclusion Criteria:

• Male or female
• Ages 15-40 years
• Schizophrenia, any subtype or Schizophreniform disorder
• Treated with any of the following second generation antipsychotics for at least 4 weeks and fewer than 16 weeks: risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, or paliperidone)
• Willing to participate in psychoeducation
• Sufficient proficiency in English to complete assessments

Exclusion Criteria:

• Major depression by DSM-IV criteria
• Clinical Global Assessment of Severity of Suicidality of 3 (moderate) or greater.
• Serious suicide attempt within three years or ANY suicide attempt for subjects age 15-25.
• Active alcohol or other substance abuse or dependence within three months
• Unstable medical illness
• History of SSRI intolerance
• Pregnant or nursing

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 15 Years

Maximum Age for this Clinical Trial: 40 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: National Institute of Mental Health (NIMH) NIH

Overall Clinical Trial Officials and Contacts

Donald C Goff, MD Principal Investigator Massachusetts General Hospital  

Overall Contact: Gail Galendez, BA 617-912-7845 ggalendez@partners.org

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01041274

Study ID Number: 2009-P-001342

ClinicalTrials.gov Identifier: NCT01041274

Health Authority: United States: Federal Government