DECIFER: Depression and Citalopram In First Episode Recovery
Condition: Schizophrenia; Schizophreniform Disorder
MeSH terms: Schizophrenia; Psychotic Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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 16-40 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 NYU Langone Medical Center and at the Psychiatry Outpatient Clinic of Bellevue Hospital
      located in New York, NY

      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), Heinrich Quality of Life Scale (QLS), WHO Quality of Life Scale (WHO-QOL), Scale for
      the Assessment of Positive Symptoms-Delusions (SAPS-D),Birchwood Insight Scale (IS), Brief
      Time Use Survey (BTUS), MIRECC Global Assessment of Functioning (MIRECC GAF), Beck Depression
      Inventory-II (BDI-II), State-Trait Anxiety Inventory (STAI),MacArthur Perceived Coercion
      Scale (PCS), Basis-24, Subject Well-being under Neuroleptic Scale (SWN-S),Subjective Scale to
      Investigate Cognition in Schizophrenia (SSTICS), Brief Adherence Rating Scale (BARS),
      Medication Adherence Rating Scale (MARS), Social Behavior Scale (SBS), WHO Alcohol Smoking
      and Substance Involvement Screening Test (WHO ASSIST), and a Drug Use Survey. In addition,
      side effects will be rated using the Systematic Assessment for Treatment Emergent Events
      (SAFTEE), 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 4 high-resolution MP-RAGE scans: once each at Baseline, 2 months, 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.

      The CDSS, ISST, and CGI-SS will be administered at baseline and then weekly up to week 8,
      then monthly. The SANS, BPRS, and BARS will be administered at baseline, then monthly for the
      duration of the study. The Heinrich's QOL and WHO QOL will be administered at baseline, and
      then monthly until study completion, excepting week 28, week 36, week 44, and week 48. The
      SAPS-D,IS, BTUS, MIRECC GAF, CGI, STAI, PCS, Basis-24, SWN-S, SSTICS, MARS, and SBS will be
      administered at baseline, week 24, and week 52. The BDI-II will be administered at screening,
      baseline, weeks 1-16, then monthly. The WHO-ASSIST will be administered at baseline, week 12,
      week 24, and week 52. The drug use survey will be administered at baseline, week 4, week 8,
      week 12, week 16, week 20, week 24, and week 52.

      A fasting blood sample will be drawn at Baseline, weeks 4 and 8 and every 8 weeks thereafter
      for BDNF assay. Blood samples collected at Baseline, week 24, and week 52 will be assayed for
      prolactin and inflammation markers. Blood samples collected at baseline, week 8, week 24, and
      week 52 will be assayed for C-Reactive Protein. Additionally, a blood sample for DNA will be
      collected at week 4. Saliva will be collected with tongue swabs at Baseline, Week 4, Week 8,
      Week 16, Week 24, Week 36, and Week 52 for cortisol analyses.

      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 name(s): Citalopram; Placebo; Psychoeducation; Cognitive Behavioral Therapy (CBT); Functional Magnetic Resonance Imaging (fMRI)
Intervention type(s): Drug; Drug; Behavioral; Behavioral; Radiation
Intervention description(s): 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.; Placebo by mouth daily for 12 months.; 16 sessions of weekly, individual psychoeducation and relapse prevention planning followed by 8 monthly sessions; 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; 3 1-hour sessions of fMRI brain scanning, assessed at baseline, and weeks 24 and 52
Other intervention name(s): Celexa; Cipramil; Sugar pill; Therapy; Therapy; Neuroimaging
Intervention MeSH terms: Citalopram
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Schizophrenia; Citalopram; First episode; fMRI; Cognitive behavioral therapy; Psychoeducation