Antidepressant Controlled Trial for Negative Symptoms in Schizophrenia (ACTIONS)

Individually Randomised, Placebo-controlled, Parallel Arm RCT With 12-month Follow-up to Establish the Clinical and Cost Effectiveness of the Antidepressant Citalopram in the Management of Negative Symptoms of Schizophrenia

The aim of this double-blind, placebo-controlled trial is to establish the clinical and cost effectiveness of an SSRI antidepressant, citalopram, in the management of persistent negative symptoms of schizophrenia over a year.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Citalopram; Drug: Placebo

Detailed Description

The negative symptoms of schizophrenia represent an important dimension of psychopathology, and reflect the absence or diminution of normal behaviours and functions. They include deficiencies in emotional responsiveness, drive, and emotional and social engagement. Persistent negative symptoms are held to account for much of the long-term morbidity and poor functional outcome in patients with established schizophrenia, but if they prove resistant to antipsychotic medication there is a very limited evidence base regarding specific treatments. The aim of this double-blind, placebo-controlled trial is to establish the clinical and cost effectiveness of an SSRI antidepressant, citalopram, in the management of negative symptoms of schizophrenia over a year. The study sample will be adults with a diagnosis of schizophrenia, clinically stable for 3 months with a consistent antipsychotic regimen, and characterised by persistent negative symptoms to a criterion level of severity.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Bristol, United Kingdom
    • Avon and Wiltshire mental health partnership
  • Derby, United Kingdom
    • Derbyshire Healthcare NHS Foundation Trust
  • Lincoln, United Kingdom
    • Lincolnshire Partnership NHS Foundation Trust
  • London, United Kingdom
    • Central and North West London NHS Foundation Trust
  • London, United Kingdom, W6 8RP
    • West London Mental Health Trust
  • London, United Kingdom
    • Camden and Islington NHS foundation trust
  • London, United Kingdom
    • Oxleas NHS Foundation Trust
  • London, United Kingdom
    • South London and the Maudsley
  • Manchester, United Kingdom
    • Manchester health and social care trust
  • Newcastle, United Kingdom
    • Northumberland, Tyne and Wear NHS foundation trust
  • Oxford, United Kingdom
    • Oxfordshire and Buckinghamshire NHS foundation trust
  • Sheffield, United Kingdom
    • Sheffield social care foundation trust
  • Southampton, United Kingdom, SO14 0YG
    • Southern Health
  • Stafford, United Kingdom
    • South Staffordshire and Shropshire NHS foundation trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• An OPCRIT (Operational Criteria Checklist for Psychosis: 57) diagnosis of schizophrenia, schizophreniform, schizoaffective disorder or psychosis NOS as defined by DSM-IV.
• A negative subscale score of 20 or more on the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). At least three of the seven items on the negative symptom subscale should be rated 3 or more.
• Age 18-75 years, inclusive
• Clinically stable for the last 3 months with a consistent antipsychotic regimen.
• Competent and willing to provide written, informed consent.

Exclusion criteria:

• Any medical contraindications to an SSRI antidepressant.
• Currently receiving antidepressant or clinician wants to treat with an antidepressant;
• Taking any medications that risk interacting with citalopram
• Known congenital long QT syndrome, congestive heart failure, bradyarrhythmias
• QT limit above the upper limit of normal as determined by an electrocardiogram (ECG)
• Serum potassium and/or magnesium levels below the lower limits of normal
• Currently fulfil criteria for major depressive disorder; alcohol/substance hazardous use or dependence in past 3 months
• Treated with ECT in the last 8 weeks.
• Pregnant or planning to become pregnant
• Cognitive or language difficulties that would preclude subjects providing informed consent or compromise participation in study procedures.
• Lack of consent, as judged by the patient's psychiatrist

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Treatment with citalopram will be initiated at 20mg/day for the first 4 weeks (or one placebo capsule), followed by the option to increase the dose to 40mg per day (or two placebo capsules) for the remainder of the study period.
Active Comparator: Citalopram; An SSRI antidepressant	Drug: Citalopram; Treatment with citalopram will be initiated at 20mg/day for the first 4 weeks (or one placebo capsule), followed by the option to increase the dose to 40mg per day (or two placebo capsules) for the remainder of the study period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PANSS Negative Symptom Score	The Positive and Negative Syndrome Scale (PANSS) is a semi-structured interview to elicit symptom ratings for 30 symptoms of psychosis, each scored between 1-7. The negative symptoms subscale uses the individual items in the PANSS that Marder identified as negative symptom (blunted affect, emotional withdrawal, poor rapport, passive/ apathetic social withdrawal, motor retardation, active social avoidance and lack of spontaneity/flow of conversation). Scores on these individual items are summed to create the subscale score. The subscale has a range of 7 to 49, with higher scores indicate greater psychopathology	12 weeks
Heinrich's Quality of Life Scale Score	The Heinrichs Quality of Life scale is a 21-item scale based on a semi-structured interview designed to assess deficit symptoms. Each items is scored from 0-6 and the total score is the sum of all item responses. The total score has a range of 0 to 126, with higher scores indicating better functioning.	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Depression assessed using the Calgary Depression Rating Scale for Schizophrenia.	3 months

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: King's College London; University College, London; University of Oxford; University of Southampton; University of Bristol; University of Manchester
• Investigators: Principal Investigator: Thomas R Barnes, MD, Imperial College London

Publications and helpful links

General Publications

• Barnes TR, Leeson VC, Paton C, Costelloe C, Simon J, Kiss N, Osborn D, Killaspy H, Craig TK, Lewis S, Keown P, Ismail S, Crawford M, Baldwin D, Lewis G, Geddes J, Kumar M, Pathak R, Taylor S. Antidepressant Controlled Trial For Negative Symptoms In Schizophrenia (ACTIONS): a double-blind, placebo-controlled, randomised clinical trial. Health Technol Assess. 2016 Apr;20(29):1-46. doi: 10.3310/hta20290.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: August 4, 2009
• First Submitted That Met QC Criteria: December 14, 2009
• First Posted (Estimated): December 15, 2009

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Schizophrenia; Negative symptoms; SSRI antidepressant
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Selective Serotonin Reuptake Inhibitors; Citalopram
• Other Study ID Numbers: CRO 1250; 2009-009235-30 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO