Reducing Weight Gain and Improving Metabolic Function in Children Being Treated With Antipsychotics
Condition: Psychotic Disorders
MeSH terms: Weight Gain; Psychotic Disorders
Intervention: Aripiprazole or Perphenazine; Metformin; Olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetine
Intervention description: Baseline second generation antipsychotic (SGA) treatment will be gradually decreased and discontinued over 8 weeks while treatment with aripiprazole or perphenazine will be increased to effective levels.; Metformin treatment will be added to current SGA treatment, with dosing based on participant weight and increased according to a preset titration schedule unless side effects interfere.; Current antipsychotic medication will be continued throughout the treatment period, with changes in dose only made as clinically indicated
Intervention MeSH terms: Metformin; Olanzapine; Risperidone; Aripiprazole; Quetiapine Fumarate; Paliperidone Palmitate; Ziprasidone; Lurasidone Hydrochloride; Asenapine; Iloperidone; Perphenazine; Fluoxetine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 127.0
Sex: All
Minimum age: 8 Years
Maximum age: 19 Years
Healthy volunteers: No
Keywords: Weight Gain; Obesity; IMPACT; Antipsychotic Treatment; Excessive Weight Gain Associated With Antipsychotic Treatment; Hybrid Efficacy/Effectiveness Design; Reducing Weight Gain; Improving Metabolic Parameters; Aripiprazole; Metformin; Risperdal; Seroquel; Quetiapine; Olanzapine; Zyprexa; Geodon; Risperidone; Abilify; Trilafon; Perphenazine; Glucophage; Paliperidone; Olanzapine/fluoxetine

Summary:

      This study will test the effectiveness of two different treatments for children and
      adolescents who have gained weight on their antipsychotic medications.
    

Eligibility criteria:

        Inclusion Criteria:

          -  DSM diagnoses that have an FDA indication for atypical antipsychotic use for at least
             one agent in the respective pediatric or adult age group. Specifically, primary DSM-IV
             diagnosis of Early Onset Schizophrenia Spectrum (EOSS; schizophrenia, schizoaffective
             disorder, schizophreniform disorder, psychotic disorder NOS); Bipolar Spectrum
             (bipolar I, II and NOS); Major depressive disorder with psychosis; Mood disorder NOS
             corresponding to Leibenluft and colleagues severely mood dysregulated (SMD) broad
             spectrum bipolar disorder; Mood disorder NOS corresponding to irritability associated
             with autism spectrum disorders; or - for adult teen participants aged 18-19 years -
             Major depressive disorder. Diagnoses will be determined by clinical interview,
             Leibenluft's modification of the K-SADS-PL, and the "Aberrant Behavior Checklist"
             (cutoff score of 18, as used by FDA for approval of risperidone and aripiprazole in
             minors).

          -  Clinically stable on current treatment regimen for at least 30 days, as assessed in a
             three-step process

          -  Current SGA treatment with olanzapine, quetiapine, risperidone, ziprasidone
             aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or
             olanzapine/fluoxetine for ≥ 8 weeks

          -  Stable dose of current SGA and psychotropic co-medications for at least 30 days

          -  Body mass index (BMI) at least in the 85th percentile for age and gender

          -  Substantial weight gain over the previous 3 years while taking a SGA, as reflected by
             family and referring physician's judgment. The weight gain did not have to occur on
             the child's current SGA. Weight needs to have remained stable or increased over past
             year.

          -  Agrees to use two effective forms of birth control or to remain abstinent

          -  Has a primary caretaker who has known the child well for at least 6 months before
             study entry

          -  Primary caretaker is able to participate in study appointments as clinically indicated

        Exclusion Criteria:

          -  Treatment with any medication (other than the currently prescribed psychotropic
             medications) that would significantly alter glucose, insulin, or lipid levels.
             Exception: orlistat and amantadine are permitted if the individual has taken the drug
             for at least one year without weight loss.

          -  Major neurological or medical illness that affects weight gain or that would prevent
             participation in physical activities

          -  Fasting glucose levels indicating need for prompt treatment

          -  Pediatrician or pediatric gastroenterologist recommendation to address abnormal
             fasting labs by pursuing more active treatment than those in the 2007 American Medical
             Association guidelines

          -  Diagnosis of anorexia nervosa or bulimia nervosa, as based on current or lifetime
             DSM-IV criteria

          -  Diagnosis of substance dependence disorder (other than tobacco dependence) within the
             past month, as based on DSM-IV criteria

          -  Positive urine toxicology indicating ongoing use of illicit substance

          -  Current treatment with more than one antipsychotic medication

          -  Current treatment with more than 3 total psychotropic medications (i.e., 2
             psychotropics plus SGA), with the exception of subjects taking 2 medications for ADHD
             in which a total of 4 psychotropic medications are allowed.

          -  Known hypersensitivity to metformin

          -  Prior treatment with aripiprazole and perphenazine for more than 2 weeks that was
             stopped for inefficacy or intolerability

          -  Pregnant, breastfeeding, or unwilling to comply with contraceptive requirements of
             study

          -  IQ score less than 55

          -  Significant risk of dangerousness to self or to others that would make study
             participation inadvisable

          -  Language issues that prevent child and/or parent from completing assessments or
             treatment

          -  Ongoing or previously undisclosed child abuse requiring new department of social
             service intervention