None listed
Conditions
Brief summary
Borderline personality disorder (BPD) affects over 95,000 15-24 year-old Australians and is a leading cause disability and mortality in this age group. Up to half of patients with BPD experience distressing and disabling auditory verbal hallucinations (AVHs) but opinion about their veracity and their treatment is polarised. Second generation antipsychotic medications (SGAs) are prescribed frequently ‘off label’ for BPD, despite limited supporting evidence. Recent studies show that AVHs in BPD and schizophrenia are phenomenologically indistinguishable. However, no randomised controlled trial (RCT) has ever tested whether conventional pharmacotherapy for AVHs in schizophrenia is applicable to AVHs in BPD. This study is a 12-week, single-centre, RCT of aripiprazole versus placebo, with a 27-week follow-up period, for 15-25 year-olds with BPD and AVH. The primary outcome is AVH severity, measured using a standardised scale. Secondary outcomes include BPD severity, general psychopathology, functioning, experience of psychotic symptoms and changes in neurobiological mechanisms underlying AVHs that are associated with treatment. Currently, the NHMRC clinical practice guidelines for BPD recommend against the use of antipsychotic medications as first-line treatment for BPD, which places them in direct conflict with NHMRC clinical practice guidelines for psychotic disorders. This novel study will advance knowledge about treatment for BPD by providing information about the efficacy of antipsychotics in the treatment of AVHs when they co-occur with BPD. It will also extend knowledge about the phenomenology of AVHs, whether AVHs should be considered as part of the symptom profile of BPD and the neurobiological basis of this symptom.
Interventions
Aripiprazole.
Aripiprazole to be administered by oral tablet(s) in accordance with the following schedule: 2mg once daily in Week 1; 5mg once daily in Week 2; 10mg once daily in Week 3; Week 4 to Week 12 increments to 15mg once daily, 20mg once daily then 30mg once daily for participants who have persistent symptoms and can tolerate further dose escalation, at discretion of treating team, with at least a 1-week gap between dose increments. The maximum allowable dose will be 30mg/day; Week 13 to
Aripiprazole. Aripiprazole to be administered by oral tablet(s) in accordance with the following schedule: 2mg once daily in Week 1; 5mg once daily in Week 2; 10mg once daily in Week 3; Week 4 to Week 12 increments to 15mg once daily, 20mg once daily then 30mg once daily for participants who have persistent symptoms and can tolerate further dose escalation, at discretion of treating team, with at least a 1-week gap between dose increments. The maximum allowable dose will be 30mg/day; Week 13 to Week 39 – aripiprazole prescribed at discretion of treating team. At any stage, a dose may be reduced or an increment postponed at the discretion of the treating team, in consultation with the investigator(s). If a break in pharmacotherapy occurs, the participant may be recommenced on the investigational product, with the restarting dose at the discretion of the treating team, in consultation with the investigator(s). Medication adherence will be monitored via capsule counts, recorded in returns to the Pharmacy and with the 10-item self-report Medication Adherence Rating Scale (Thompson, Kulkarni & Sergejew, 2000). At each study visit, participants will be reminded in person to take study medication and to return empty containers. Participants may also be assisted with SMS or phone call reminders. They may be supported to program reminders in their phone calendar, a reminders app, or with a medication-reminder app. Most participants will receive weekly psychosocial treatment in the Helping Young People Early (HYPE) program at Orygen Youth Health, comprising general psychiatric care, clinical case management and may include up to 16 x 50-minute sessions of individual Cognitive Analytic Therapy. Treatment is provided by a multidisciplinary team including psychiatrists, clinical psychologists, social workers and occupational therapists and is delivered at Orygen Youth Health sites and in the community. Some participants might receive multidisciplinary treatment from other Orygen Youth Health programs or they might receive individual or multidisciplinary care from mental health services external to Orygen. The decision to provide treatment in other Orygen Youth Health programs or external services is based on Orygen Youth Health operational protocols. The treatment may include a combination of general psychiatric care, case management and/or individual psychotherapy, as indicated.
Sponsors
Orygen
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
15 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
(1) males and females aged 15-25 years inclusive; (2) ability to give informed consent and adhere to study procedures; (3) sufficient fluency in English; (4) Structured Clinical Interview for Diagnostic and Statistical Manual 5th Edition - Personality Disorders (SCID-5-PD) borderline personality disorder; (5) threshold auditory verbal hallucinations (5 or 6 on severity and 4 or more on frequency) for longer than one week within the past four weeks using ratings on the Comprehensive Assessment of At Risk Mental State (CAARMS: Yung et al, 2005).
Exclusion criteria
(1) DSM-5 schizophreniform disorder, schizophrenia, schizoaffective disorder, psychotic disorder due to another medical condition, catatonia, delusional disorder, bipolar I disorder, or substance/medication induced psychotic disorder; (2) prior sensitivity or allergy to aripiprazole or formulation; (3) antipsychotic treatment for 4 weeks or more at a dose equal to or greater than 200 mg chlorpromazine equivalent within 8 weeks of study entry; (4) pregnancy, lactation, or if sexually active, no effective contraception; (5) clinically significant liver or thyroid function, or haematological findings which in the opinion of the Investigator, may present a safety issue for the participant or confound the trial results; (6) acute or unstable systemic medical disorder; (7) psychiatric condition due to a medical condition; (8) severe disturbance, such that the person is unable to comply with either the requirements of informed consent or the treatment protocol; (9) does not meet the Orygen Youth Health clinical service’s eligibility criteria; (10) for Magnetic Resonance Imaging (MRI) scans: lifetime history of head injury, loss of consciousness for more than 10 mins, seizures, thyroid disorder or other significant medical illness that in the opinion of the Investigator would preclude participation in the study.
Outcome results
None listed