Toward a Computationally-Informed, Personalized Treatment for Hallucinations
Yale University
Summary
Auditory hallucinations are among the most distressing aspects of psychotic illness, and between 10 and 30% of people with hallucinations do not respond to antipsychotic medications. The authors have used computational modeling of behavior to link brain activity to development of auditory hallucinations in the hope of guiding new treatment development. The proposed studies take the first step toward individualized treatment approaches to hallucinations by attempting causal, pharmacological manipulation of relevant model parameters underlying these phenomena.
Description
Auditory verbal hallucinations (AVH) are present throughout the course of psychotic illness and are among its most distressing symptoms. The presence of hallucinations alone increases risk of suicide in patients with psychosis. While antipsychotic medications often succeed in ameliorating auditory hallucinations, 10-30% of those with hallucinations exhibit little to no response to these treatments. Understanding how the processes underlying auditory perception might go awry to produce auditory hallucinations is a critical next step in the development of new treatments that are more soundly bas…
Eligibility
- Age range
- 18–65 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Age 18-65 * English speaking * Right handedness * Diagnosed with schizophrenia schizoaffective, schizophreniform, schizotypal, or brief psychotic disorder * History of auditory verbal hallucinations occurring at least weekly Exclusion Criteria: * Current substance dependence or active use as determined by drug test. * Any neurological, medical or developmental problem that is known to impair cognition significantly * Contraindications for MR scanning including metallic implants of any kind, pacemakers and history of accidents with metal, claustrophobia * History of sei…
Interventions
- DrugRivastigmine Transdermal System
Rivastigmine doses will be administered transdermally using 9.5 mg/24 hr transdermal patches. Participants will be randomized to two treatments with oral rivastigmine vs. placebo separated by a 15-hour washout period (\>5 half-lives to eliminate any residual effects). This will require three separate visits: a baseline visit, a visit for the first transdermal treatment and a visit for the second transdermal treatment. All visits include fMRI scans. The first transdermal patch will be administered 8-14 hours before the scan. After the washout period, the second transdermal patch will be administered 8-14 hours before the scan. No study team member except for the unblinded team member will know which capsule the participant receives first. Because we are interested in rivastigmine as a probe for a pre-identified computational/physiological abnormality, we will median-split groups post-hoc for the purposes of analysis.
- DrugScopolamine
The authors have chosen to use scopolamine to determine the effects of cholinergic antagonism, as treatment with scopolamine demonstrates a dose-related increase in propensity toward conditioned hallucinations and in doses much higher than those proposed here, can cause spontaneous hallucinations. At the proposed dose, scopolamine has an excellent safety profile and has been used routinely for nearly 20 years for treatment of nausea due to surgery or motion sickness in adults and children. Scopolamine is available in the US only as a 1mg / 72 hours transdermal patch, and peak plasma levels are reached within 24 hours. This standard dosage level is very well tolerated in the general population.
- DrugPlacebo Patch
Participants in Aim 2 will receive a placebo patch versus rivastigmine patch.
Location
- Connecticut Mental Health CenterNew Haven, Connecticut