Staged Treatment in Early Psychosis (STEP): A sequential multistage randomized clinical trial (SMART) of interventions for Ultra High Risk (UHR) of psychosis patients.

Intervention

Intervention code Behaviour , Treatment: Drugs

The study treatment sequence involves three stages, which are referred to as steps. Each step follows on immediately from the previous step, without any break. Step 1- Support and Problem Solving (SPS) All trial participants receive Support and Problem Solving treatment in Step 1. This therapy will be administered by allied health professionals. Support and Problem Solving therapy involves providing participants with emotional support and help with resolving their problems in day-to-day life. Th .... The study treatment sequence involves three stages, which are referred to as steps. Each step follows on immediately from the previous step, without any break. Step 1- Support and Problem Solving (SPS) All trial participants receive Support and Problem Solving treatment in Step 1. This therapy will be administered by allied health professionals. Support and Problem Solving therapy involves providing participants with emotional support and help with resolving their problems in day-to-day life. This treatment is administered to participants on a one-on-one basis, with each session lasting between 30-50 minutes. Step 1 involves attending between three and six sessions over the six-week period. The Week 4 and Week 6 visits also include an interview to assess their symptoms and mental state. Depending on how they respond to the six-week period of treatment in Step 1, participants are randomly assigned to a new treatment arm at the end of Step 1 as detailed below: Participants who improve with the Support and Problem Solving treatment they receive during Step 1, will be randomised to either continue receiving monthly SPS sessions for up to one year OR to simple monitoring at three-monthly intervals for up to one year. Simple monitoring will consist of the research assistant carrying out a research assessment as well as the clinician making contact with the participant, either by phone or in person. The clinician will monitor the participant's mental state and risk and assess whether there has been any mental health deterioration which would indicate a need for change in clinical management (e.g. referral to a new service or need to reengage with headspace) Participants who do not improve with the Support and Problem Solving treatment they receive during Step 1 will be randomised to continue receiving treatment in one of the two groups in Step 2 as outlined below. Step 2- Support and Problem Solving (SPS) OR Cognitive Behavioural Case Management (CBCM). Both of these therapies will be administered by allied health professionals. In Step 2, participants will receive either Support and Problem Solving OR Cognitive Behavioural Case Management for a period of 18 weeks. The treatment is provided on a one-on-one basis to participants, with the frequency of sessions depending on a combination of clinical need and preference of the participant. The sessions may occur weekly or fortnightly, and there will be at least six sessions provided during Step 2. Cognitive Behavioural Case Management has a number of different elements including: strategies to help with stress management; therapy that targets thinking and behavioural patterns; practical assistance, as well as yoga and mindfulness. Participants who improve with the treatment they receive in Step 2 will be randomised to receive EITHER monthly sessions of Support and Problem Solving for a further six months OR to simple monitoring at three-monthly intervals for a further six months. Participants who do not improve with the treatment they receive in Step 2 will be randomised to one of two treatment groups in Step 3 as outlined below. Step 3 Cognitive Behavioural Case Management plus antidepressant medication OR Cognitive Behavioural Case Management plus placebo medication. Participants assigned to one of the two treatment groups in Step 3 will receive the corresponding treatment over a six-month period. The frequency of these sessions will depend on a combination of clinical judgement and the preferences of the participants, but may occur weekly-fortnightly. Both treatment groups will involve: regular Cognitive Behavioural Case Management sessions; regular review by a clinician, as well as the assigned medication. Participants will undergo regular review (fortnightly-monthly) with a psychiatrist who will monitor their response to the medication. Depending on which group participants are randomised to, they may either receive antidepressant medication OR placebo medication. The medication is used alongside CBCM for the whole six-month period of Step 3. The antidepressant medication used for Step 3 is a Selective Serotonin Reuptake Inhibitor called Fluoxetine. This oral medication will initially be prescribed at 20 mg/day, The dose of Fluoxetine will be titrated at 6 weeks from 20 mg to 40 mg daily (one to two capsules of matching placebo) if there is no response based on clinical judgment of the treating psychiatrist.. If a participant does not improve, or deteriorates by 12 weeks into Step 3, they will be given a choice to: continue with the treatment regime already assigned to them; increase the dosage of their medication, or start a new medication. Upon their choosing, the medication at this stage may either be an antipsychotic medication (Quetiapine or Aripiprazole), OR omega-3 fatty acids ('fish oil'), taken in addition to the other treatment components of this step. Quetiapine will be administered orally at a starting dose of 50 mg/day, and the dosage will be adjusted based on clinical judgment of the treating doctor. Aripiprazole will be administered orally at a starting dose of 10 mg/day, and the dosage will be adjusted based on clinical judgement of the treating doctor. Fish oil will be administered orally with the dosage being 2.8 g/day. During Step 3 participants will be requested to return all unused medication and empty containers to the research assistants at their next visit. The research assistant will count and record the number of tablets and bottles returned. All participant returns will be returned to the dispensing clinical trials pharmacy for accountability purposes. Compliance with medication will also be monitored using a mobile application developed by our group .This mobile phone application will consist of a system that prompts participants every evening to input their medication use (number of capsules taken) over the previous day. A mobile phone message system will also be used to remind participants to take their medication (one message/day), which will assist in increasing compliance rates.
Read more

Comparison

Control group Active

Step 1: All participants will receive Support and Problem Solving. Step 2: Support and Problem Solving will be compared with Cognitive Behavioural Case Management. Step 3: Cognitive Behavioural Case Management PLUS Selective Serotonin Reuptake Inhibitor (SSRI) will be compared with Cognitive Behavioural Case Management PLUS placebo (microcellulose tablet) Participants in these steps of the trial will be compared with participants who respond to Steps 1 and 2 and are randomised to Support and Pro .... Step 1: All participants will receive Support and Problem Solving. Step 2: Support and Problem Solving will be compared with Cognitive Behavioural Case Management. Step 3: Cognitive Behavioural Case Management PLUS Selective Serotonin Reuptake Inhibitor (SSRI) will be compared with Cognitive Behavioural Case Management PLUS placebo (microcellulose tablet) Participants in these steps of the trial will be compared with participants who respond to Steps 1 and 2 and are randomised to Support and Problem Solving or Monitoring.
Read more

Outcomes

Outcome: To test the effect of a sequential treatment approach consisting of Support and Problem Solving/Support and Problem Solving and Support and Problem Solving/Cognitive Behavioural Case Management on functioning levels of Ultra High Risk patients 6 months from baseline (end of Step 2). Functioning will be measured using the Global Functioning: Social and Role Scales assessment tool.
Timepoint: Six months from baseline visit (end of Step 2).