Clinical trial NCT01041274
Conditions: Schizophrenia Schizophreniform Disorder
Keywords: Schizophrenia Citalopram First episode fMRI Cognitive behavioral therapy Psychoeducation
Sponsor: NYU Langone Health
Start date: 2010-01-01; Completion date: 2018-03-26
Enrollment: 95 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Arms: arm 1: Participants will receive a daily dose of citalopram, with flexible dosing as determined by clinician, for 12 months. arm 2: Participants will receive a daily dose of placebo for 12 months.
Interventions: intervention 1: Citalopram intervention 2: Placebo intervention 3: Psychoeducation intervention 4: Cognitive Behavioral Therapy (CBT) intervention 5: Functional Magnetic Resonance Imaging (fMRI)
Intervention descriptions: intervention 1: 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. intervention 2: Placebo by mouth daily for 12 months. intervention 3: 16 sessions of weekly, individual psychoeducation and relapse prevention planning followed by 8 monthly sessions intervention 4: 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 intervention 5: 3 1-hour sessions of fMRI brain scanning, assessed at baseline, and weeks 24 and 52

Protocol documents: