Detection and treatment of long-chain omega-3 fatty acid deficiency in adolescents with SSRI-resistant major depressive disorder

Abstract

Residual depressive symptoms are commonly observed in adolescents with major depressive disorder (MDD) following treatment with selective serotonin reuptake inhibitors (SSRIs). This study combined a case-control analysis and an open-label fish oil (FO) trial to investigate the relationship between long-chain omega-3 (LCn-3) fatty acid status and residual depressive symptoms in SSRI-resistant adolescent MDD patients. Baseline erythrocyte docosahexaenoic acid (DHA)(-28%, p=0.0003), but not eicosapentaenoic acid (EPA)(-18%, p=0.2), was significantly lower in patients (n=20) compared with healthy controls (n=20). Patients receiving 10-week low-dose (2.4 g/d, n=7) and high-dose (16.2 g/d, n=7) FO exhibited significant increases in erythrocyte EPA and DHA composition. In the intent-to-treat sample, depressive symptoms decreased significantly in the high-dose group (n=7, -40%, p<0.0001), and there was a trend in the low-dose group (n=10, −20%, p=0.06). Symptom remission was observed in 40% of patients in the low-dose group and 100% of patients in the high-dose group. There were no significant changes in vital signs and adverse events were rated as mild or moderate in severity. These preliminary findings demonstrate that adolescents with SSRI-resistant depression exhibit robust DHA deficits, and suggest that adjunctive FO supplementation is well-tolerated and effective for increasing LCn-3 fatty acid status and augmenting SSRI antidepressant effects.

Dietary DHA during development affects depression-like behaviors and biomarkers that emerge after puberty in adolescent rats

“…In addition, studies by Ferraz et al ( 85 ) and DeMar et al ( 86 ) indicated that feeding male rats diets supplemented with fi sh oil or ␣ -linolenic acid, respectively, after weaning (P21) into adulthood for 6 months decreased data, only trace levels of EPA are found in the brain where upon entry it is rapidly ␤ -oxidized and metabolized ( 97,98 ). Furthermore, erythrocyte DHA, but not EPA, content was shown to be lower in SSRI-resistant depressed adolescents compared with healthy counterparts ( 29 ). Given that DHA, but not EPA, is highly enriched in neural tissue and is essential for brain development, it may play a critical role in the developmental factors that shape the etiology of adolescent depression, a supposition in alignment with the results of our study.…”

“…Indeed, DHA defi ciency throughout development leads to decreased DHA levels in neural tissue and is associated with defi cits in psychomotor development ( 21 ), problem solving ( 22 ), reading skills ( 23 ), visual acuity ( 24 ), and attention ( 25 ). Furthermore, emerging clinical data support a link between suffi cient DHA intake with a reduction in the incidence and/or symptomatic relief of adolescent depression ( 5,(26)(27)(28)(29), and there exists an abundance of clinical evidence supporting a positive role for the omega-3 PUFA EPA in the treatment of adult depression ( 30 ). However, the studies examining the importance of DHA, in particular, are limited in scope and interpretation, and no longitudinal studies have been reported to date.…”

A review of nutrient treatments for paediatric depression

“…For example, in an adolescent population with SSRI-resistant major depressive disorder, erythrocyte DHA, but not EPA, was significantly lower in patients compared with healthy controls (McNamara et al, 2014). In a study by Pottala et al, (2012) levels of red blood cell EPA+DHA were lower in depressed adolescents compared to non-depressed adolescent controls.…”

“…Symptom remission was observed in 40% of patients in the low-dose group and 100% of patients in the high-dose group. Adverse events included mild-to-moderate severity of headache and gastrointestinal symptoms but this did not lead to a discontinuation in treatment (McNamara et al, 2014).…”

“…However, the open-label design used in the study by McNamara et al, (2014) limit the strength of conclusions that can be made from the study. In contrast, the randomised, double-blind, placebo-controlled study design used by Nemets et al, (2006) provides stronger support for the antidepressant benefits of omega-3 supplementation on youths, although this is tempered by the small sample size.…”