None listed
Conditions
Brief summary
Psychotic illnesses usually first emerge in young people and result in widespread suffering, protracted disability, premature death, and a huge economic burden. Early intervention represents a vital strategy to reduce this burden. Psychotic disorders are preceded by a prodromal period of distress, impaired functioning and subthreshold psychosis. Although the evidence from 11 Randomised Controlled Trials indicates that interventions can reduce the risk of transition to psychotic disorders by more than 50%, clinicians remain unclear how to select the best sequence of treatments to prevent progression and maximize recovery. This research will conduct a sequential multistage randomized clinical trial to build individualised “adaptive” treatment strategies to reduce the risks for a range of outcomes. Ultra high risk of psychosis participants will be recruited from Orygen Youth Health and four ‘headspace’ youth mental health services. The ‘headspace’ youth mental health service has already delivered care to over 100,000 young people with emerging mental disorders, of whom 40% are considered as having an ultra high risk of developing psychosis. Orygen is Australia’s largest mental health research facility, and specialises in early intervention in young people. The main aim of this study’s sequential multi-stage design is intended to produce evidence to guide a stepwise clinical approach to treatment of ultra high risk of psychosis patients and reduction of risk for psychosis and other deleterious clinical and/or functional outcomes.
Interventions
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
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.
Sponsors
Orygen Youth Health
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
12 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
1. Age 12 -25 years (inclusive) at entry 2. Ability to speak adequate English (for assessment purposes) 3. Ability to provide informed consent. Where participants are minors (i.e. have not reached the age of eighteen), consent will also be obtained from one of the participant’s parents or legal guardian. Both the parent/legal guardian and participant will be required to sign a consent form in such a case. It will be the investigator’s responsibility to determine whether a participant who is a mature minor has the capacity and competence to consent to the study. 4. Meeting one or more UHR for psychosis groups: Vulnerability (Trait and State Risk Factor) Group: Individuals with a combination of a trait risk factor (schizotypal personality disorder or a family history of psychotic disorder in a first degree relative) and a significant deterioration in mental state and/or functioning or sustained low functioning during the past year. Attenuated Psychotic Symptoms (APS) Group: Individuals with subthreshold (intensity or frequency) positive psychotic symptoms. The symptoms must have been present during the past year and be associated with a significant reduction in or sustained low functioning. Brief Limited Intermittent Psychotic Symptoms Group (BLIPS): Individuals with a recent history of frank psychotic symptoms that resolved spontaneously (without antipsychotic medication) within one week. The symptoms must have been present during the past year and be associated with a significant reduction in or sustained low functioning.
Exclusion criteria
1. Past history of a psychotic episode of one week or longer, whether treated with antipsychotic medications or not. 2. Attenuated psychotic symptoms only present during acute intoxication. 3. Organic brain disease known to cause psychotic symptoms, e.g. temporal lobe epilepsy. 4. Any metabolic, endocrine or other physical illness, e.g. thyroid disease, with known neuropsychiatric consequences. 5. Diagnosis of a serious developmental disorder, e.g. Severe Autism Spectrum Disorder. 6. Premorbid IQ<70 and a documented history of developmental delay or intellectual disability. 7. Previous or current SCID diagnosis of Bipolar I.
Outcome results
None listed