Bipolar Disorder, Psychosis NOS, Schizoaffective Disorder, Schizophrenia, Schizophreniform Disorder
Conditions
Keywords
Adolescence, Adult, Antipsychotic Agents, Female, Human, Male, Risperidone, Omega-3, Schizophrenia, Schizophreniform, Schizoaffective, Schizophrenia -- *drug therapy
Brief summary
This 16-week placebo-control study looks to investigate whether patients with schizophrenia for two years or less may benefit from omega-3 supplements.
Detailed description
This study looks to investigate whether patients with schizophrenia for 2 years or less may benefit from omega-3 supplements. The main hypothesis to be tested in this study is that white matter integrity assessed with diffusion tensor imaging (DTI) and erythrocyte membrane omega-3 concentration may provide the means for identifying patients most likely to derive clinical benefit from omega-3 supplementation. To test this hypothesis the investigators will enroll 58 patients with recent-onset schizophrenia into a 16-week long randomized double blind placebo-controlled study of risperidone versus risperidone plus omega-3 supplementation. Study assessments after consent will include a baseline MRI and an MRI at the final visit, blood-work, clinical interviews to assess symptoms, and medical assessments for side effects. DTI exams and peripheral omega-3 concentration will be obtained prior to the initiation of treatment and the primary outcome measure will be the total Brief Psychiatric Rating Scale Score. Specific aims are: * To examine the efficacy of omega-3 fatty acids as an adjuvant agent in the treatment of patients with recent-onset schizophrenia. The investigators hypothesize that patients treated with omega-3 fatty acids will demonstrate greater Brief Psychiatric Rating Scale (BPRS) reductions compared to the placebo group. * To identify whether pre-treatment fractional anisotropy (FA) assessed by DTI predicts which patients will derive clinical benefit from omega-3 fatty acids. The investigators hypothesize that patients with lower fractional anisotropy will derive greater clinical benefit from omega-3 fatty acid supplementation. * To identify whether pre-treatment peripheral omega-3 fatty acid concentrations predict which patients will derive clinical benefit from omega-3 fatty acids. The investigators hypothesize that patients with lower peripheral omega-3 fatty acid concentrations will derive greater clinical benefit from omega-3 fatty acid supplementation.
Interventions
DRUGPlacebo
The total daily dose for subjects assigned to placebo will be 2000 mg. This dose will start on day 1 and stay the same dose until study completion.
DRUGRisperidone
The dosage for risperidone will be 1 mg to 6 mg per day. The dose of the risperidone will be based on the participant's clinical improvement and side effects.
DRUGOmega-3 capsules
The total daily dose for omega-3 subjects will be 740 mg of eicosapentanoic acid (EPA)and 400 mg of docosahexaenoic acid(DHA). This dose will start on day 1 and stay the same dose until study completion.
Sponsors
National Institute of Mental Health (NIMH)
National Alliance for Research on Schizophrenia and Depression
Delbert Robinson
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
15 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Current DSM-IV-defined diagnosis of schizophrenia, schizophreniform, schizoaffective disorder, psychosis NOS or Bipolar I as assessed using the Structured Clinical Interview for Axis I DSM-IV Disorders; * Does not DSM-IV criteria for a current substance-induced psychotic disorder, a psychotic disorder due to a general medical condition, delusional disorder, brief psychotic disorder, shared psychotic disorder, or a mood disorder with psychotic features; * current positive symptoms rated more than 4 (moderate) on one of these BPRS items: conceptual disorganization, grandiosity, hallucinatory behavior, and unusual thought content; * is in a early phase of illness as defined by having taken antipsychotic medications for a cumulative lifetime period of 2 years or less; * age 15 to 40; * competent and willing to sign informed consent; and * for women, negative pregnancy test and agreement to use a medically accepted birth control method.
Exclusion criteria
* serious neurological or endocrine disorder or any medical condition or treatment known to affect the brain; * any medical condition which requires treatment with a medication with psychotropic effects; * significant risk of suicidal or homicidal behavior; * cognitive or language limitations, or any other factor that would preclude subjects providing informed consent; * medical contraindications to treatment with risperidone (e.g. neuroleptic malignant syndrome with prior risperidone exposure), omega-3 supplements (e.g. bleeding disorder, seafood allergies) or placebo capsules (e.g. allergies to capsule components); * contraindications to MRI imaging (e.g. presence of a pacemaker); * lack of response to a prior adequate trial of risperidone; * taking omega-3 supplements within the past 8 weeks, and * requires treatment with an antidepressant or mood stabilizing medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Response | 16 weeks | The primary outcome measure will be the total Brief Psychiatric Rating Scale Score. The range of the BPRS is 0 to 126 with higher scores indicated more psychological symptoms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omega-3 Capsules & Risperidone Subjects will take 1 capsule in the morning and 1 capsule in the evening. Each capsule contains 370 mg EPA and 200 mg DHA as well as 2 mg/g tocopherol. The study dose will start on day 1 and remain the same throughout the study.
Risperidone: The dosage for risperidone will be 1 mg to 6 mg per day. The dose of the risperidone will be based on the participant's clinical improvement and side effects.
Omega-3 capsules: The total daily dose for omega-3 subjects will be 740 mg of eicosapentanoic acid (EPA)and 400 mg of docosahexaenoic acid(DHA). This dose will start on day 1 and stay the same dose until study completion. | 25 |
| Placebo & Risperidone Subjects will take 1 capsule in the morning and 1 capsule in the evening.The placebo is a soybean/corn blend (each capsule contains 1000 mg). The study dose will start on day 1 and remain the same throughout the study.
Risperidone: The dosage for risperidone will be 1 mg to 6 mg per day. The dose of the risperidone will be based on the participant's clinical improvement and side effects.
Placebo: The total daily dose for subjects assigned to placebo will be 2000 mg. This dose will start on day 1 and stay the same dose until study completion. | 25 |
| Total | 50 |
Baseline characteristics
| Characteristic | Omega-3 Capsules & Risperidone | Placebo & Risperidone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 24 Participants | 49 Participants |
| Region of Enrollment United States | 25 participants | 25 participants | 50 participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 18 Participants | 18 Participants | 36 Participants |
| Structured Clinical interview for DMS-IV (SCID) Bipolar 1 Disorder | 2 participants | 2 participants | 4 participants |
| Structured Clinical interview for DMS-IV (SCID) Psychosis NOS | 0 participants | 1 participants | 1 participants |
| Structured Clinical interview for DMS-IV (SCID) Schizoaffective Disorder | 1 participants | 0 participants | 1 participants |
| Structured Clinical interview for DMS-IV (SCID) Schizophrenia | 17 participants | 17 participants | 34 participants |
| Structured Clinical interview for DMS-IV (SCID) Schizophreriform | 5 participants | 5 participants | 10 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 25 | 0 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 |
Outcome results
Primary
Treatment Response
The primary outcome measure will be the total Brief Psychiatric Rating Scale Score. The range of the BPRS is 0 to 126 with higher scores indicated more psychological symptoms.
Time frame: 16 weeks
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Omega-3 Capsules & Risperidone | Treatment Response | Baseline BPRS Score | 41.64 units on a scale | Standard Error 1.44 |
| Omega-3 Capsules & Risperidone | Treatment Response | Week 16 BPRS Score | 22.5868 units on a scale | Standard Error 2.1744 |
| Placebo & Risperidone | Treatment Response | Week 16 BPRS Score | 27.2235 units on a scale | Standard Error 2.4397 |
| Placebo & Risperidone | Treatment Response | Baseline BPRS Score | 42.38 units on a scale | Standard Error 1.56 |
p-value: 0.0493Mixed Models Analysis