Citalopram in First Episode Schizophrenia

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.