Amminger GP, Schäfer MR, Schlögelhofer M, Klier CM, McGorry PD. Longer-term outcome in the prevention of psychotic disorders by the Vienna omega-3 study. Nat Commun. 2015;6:7934.
Long-term follow-up of a randomized, double-blind, placebo-controlled trial
Eighty-one treatment-seeking individuals were enrolled in the trial; 41 were assigned to the experimental PUFA group and 40 to a placebo group. At the start of the initial trial, participants were 13 to 25 years old (average age 16.4) and met criteria for one or more of the 3 groups of risk factors for psychosis: “attenuated positive psychotic symptoms; transient psychosis; and/or genetic risk plus a decrease in functioning.” Both treatment groups were comparable for age, sex, body mass index (BMI), study entry criteria, illicit drug use, psychiatric symptoms and functioning, and erythrocyte fatty acid levels. Patients were blinded, randomized and assessed at 4, 8, and 12 weeks and then followed up after the 12-week treatment at 6 months, 12 months, and 7 years after baseline.
Study Medication and Dosage
Fish oil capsules containing 700 mg of eicosapentaenoic acid (EPA) and 480 mg of docosahexaenoic acid (DHA) per day for 12 weeks versus placebo.
Primary outcome was conversion to psychotic disorder. Secondary outcomes were measures of psychosocial functioning.
The Positive and Negative Syndrome Scale (PANNS) and the Montgomery-Asberg Depression Rating scale were used to examine psychiatric symptoms. The Global Assessment of Functioning (GAF) score was used as a measure of functioning, and the DSM-IV-TR Axis I Disorders (SCID-I/P) was used to ascertain psychiatric diagnoses. The primary endpoint in the trial was conversion to psychiatric disorder with sustained symptoms for at least a week. The exit criteria marked the threshold at which treatment with antipsychotic medications was initiated.
This data has been previously published. That publication showed that during the initial 12-month follow-up, there was a reduction in the risk of progression to psychotic disorder in study participants receiving fish oil. This current report comes at a median of 6.7 years after the initial intervention.
Seventy-one (87.7%) individuals were successfully followed up with at the 7-year mark post baseline. The cumulative conversion rate to psychosis at the longer-term follow-up was 9.8% (4/41 in the omega-3 group) and 40% (16/40 in the placebo group.) The difference between the groups in the cumulative risk of progression was 30.2% (95% confidence interval).
Psychosocial function was measured as a secondary outcome, independent of conversion to psychosis. In 69 individuals (85.2%, 69/81), a GAF score could be determined as a measure of function when exiting the trial. The omega-3 group had significantly higher functioning when compared to the placebo group, as measured in the long-term follow-up visits.
Understanding the complexity of diagnosis, treatment, and prevention of psychotic disorders continues to challenge medical professionals. Early intervention has been linked to better outcomes, in both at-risk populations and in those with a new diagnosis. Previous studies of neuroanatomical changes observed in at-risk individuals who progress to psychotic states demonstrates an active biological process that raises the possibility for understanding the critical role of intervention therapies, specifically the role of nutrition, in preventing psychotic symptoms.
More than 40% of all people diagnosed with schizophrenia end up in supervised group housing, nursing homes, or hospitals.
Despite the fact that schizophrenia only affects about 1% of the US population—roughly 3 times the number of people who suffer from Parkinson’s disease—the economic burden of this disease is considerable: an estimated $60 billion a year.1 This is in large part because it is a condition that typically manifests in adolescence or early adulthood. More than 40% of all people diagnosed with schizophrenia end up in supervised group housing, nursing homes, or hospitals. Another 6% end up in jail, and an equal proportion end up living on the streets.
Schizophrenia is characterized by hallucinations, delusions, and cognitive problems. While the majority of affected individuals experience a slow or gradual onset of clinically significant symptoms, some experience abrupt onset. In addition to having their mental health affected, individuals with schizophrenia often die more than a decade earlier than the general population from complications due in large part to cardiometabolic conditions.2
Because the use of antipsychotic medications for the prevention of psychotic disorders is controversial at best, clinicians continue to search for and explore novel therapeutics. Despite early treatment strategies being linked to better outcomes, current treatments focus on controlling symptoms with pharmaceuticals, rather than avoiding their development. A recent meta analysis of 2,502 individuals who were at risk found that the cumulative rate of transition to psychosis increased over time, with 18%, 22%, 29%, and 36% developing a psychotic disorder at 6 months, 1, 2, and 3 years, respectively, making early intervention critically important.3
In the past 2 decades, clinicians and researchers have worked tirelessly to identify people presenting with prodromal symptoms of psychosis. This clinical syndrome has been coined an “at-risk mental state,” and “ultra-high risk” criteria have been developed to help identify young people who are at high risk of developing psychosis. Current research strategies are focusing on at-risk individuals who often develop psychosis after the first 24 months of initial presentation, when the risk of transition to a psychotic state is maximal. It is during this window that nutrition intervention may be the key to prevention.
This is not the first time we have seen data from this cohort. The initial report on this trial of omega-3 fatty acids compared to placebo in a 12-week intervention study4 demonstrated a reduced risk of progression to psychotic disorders in young people with sub-threshold psychotic states for a 12-month period. The positive clinical effect of polyunsaturated fatty acids (PUFAs) is assumed to be through a correction to a deficiency. It has been shown that the cell membrane levels of both omega-3 and omega-6 PUFAs are reduced in patients with schizophrenia compared to a healthy population.
Because antipsychotic medication can be used to assess the severity of psychotic phenomena, this study investigated the proportion of individuals in the study who needed to be prescribed medication. The percentages of individuals who needed antipsychotics at follow-up were 29.4% (10/34) in the omega-3 group, and 54.3% (19/35) in the placebo group. Only 2 individuals in the omega-3 group reported continuance of fish oil capsules for longer than 1 month during the follow-up period, suggesting that early nutritional intervention, rather than continuance of treatment, is key to success of treatment. The initial 12-week intervention played a significant role in the prevention of transition to full-threshold psychotic disorder and further led to a sustained symptomatic and functional improvement.
This study, as well as previous studies of omega 3s and psychosis, demonstrates the potential of long-chain PUFAs as a safe and efficacious strategy for the prevention of psychotic states in at-risk individuals. Considering omega-3 PUFAs have no clinically significant side effects and are considered generally beneficial to health, supplementation with omega 3s should be considered as an ideal early nutritional intervention.
- What is schizophrenia? National Institute of Mental Health website. http://www.nimh.nih.gov/health/topics/schizophrenia/index.shtml. Accessed November 2, 2015.
- Correll CU, Robinson DG, Schooler NR, et al. Cardiometabolic risk in patients with first-episode schizophrenia spectrum disorders: baseline results from the RAISE-ETP study. JAMA Psychiatry. 2014;71(12):1350-1363.
- Fusar-Poli P, Bonoldi I, Yung AR, et al. Predicting psychosis: meta-analysis of transition outcomes in individuals at high clinical risk. Arch Gen Psychiatry. 2012;69(3):220-229.
- Amminger GP, Schäfer MR, Papageorgiou K, et al. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry. 2010;67(2):146-154.