Characterization and Sequential Pharmacotherapy of Severe Mood Dysregulation
Status:
Completed
Trial end date:
2016-06-01
Target enrollment:
Participant gender:
Summary
This project will characterize children and adolescents with severe mood dysregulation (SMD)
and conduct a pilot study of combination pharmacotherapy as a basis for future intervention
trials.
Eligible participants assessed for SMD will have 4 weeks open titration with lisdexamfetamine
(LDX) to optimal dose, followed by double-blind randomization to fluoxetine (N=25) or placebo
(N=25) in combination with optimized LDX for an additional 8 weeks. Participants will be
monitored for clinical response and adverse events.
Specific aims are:
#1: To define youth meeting SMD criteria in terms of psychiatric comorbidity, neurocognitive
functioning, and a potential "bio-signature" derived from electroencephalography (EEG).
Specific hypotheses to be tested include: 1) that SMD participants will differ in comparison
to non-SMD individuals in our pre-existing database on patterns of a) psychiatric
comorbidity, b) symptoms, c) behavioral ratings, and d) neurocognitive functioning, and 2)
that a distinct EEG bio-signature will be confirmed in individuals formally diagnosed with
SMD.
#2: To conduct a preliminary study of sequential pharmacotherapy for SMD with a stimulant
followed by randomized, placebo-controlled selective serotonin re-uptake inhibitor (SSRI)
therapy to evaluate the feasibility of recruitment and enrollment and assess the suitability
of the proposed combination treatment as a basis for future clinical investigations.
Specific hypotheses to be tested include: 1) that significant improvement in Clinical Global
Impression - Improvement -SMD (CGI-I-SMD) scores and other secondary measures are evident
after open-label LDX titration; 2) that participants randomized to fluoxetine will
demonstrate additional significant improvement in CGI-I-SMD scores and other secondary
measures in comparison to participants randomized to placebo; 3) that combination LDX and
SSRI therapy is safe and well tolerated, and 4) that EEG profiles will normalize with
treatment.