The prevalence of depression in community settings has been estimated to be between 0.4% and 2.5% in children and 0.4% and 8.3% in adolescents [1
]. However, in a more recent community study of children without depression who were initially assessed between the ages of 9 and 13 years, more than 7% of boys and almost 12% of girls developed a depressive disorder by the age of 16 [2
While the diagnosis of major depressive disorder (MDD) in younger patients generally follows the criteria set forth in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) [3
], the treatment of pediatric depression presents many challenges. Not only do children with MDD have multiple co-morbid disorders [4
], psychosocial and academic problems, and are at increased risk for suicide attempts, self-harm, and substance abuse [1
], treatment options are often limited and ineffective, poorly tolerated, and generally present long delays in delivering a therapeutic benefit [11
One of the few antidepressants approved for use in children is the selective serotonin reuptake inhibitor (SSRI) fluoxetine [15
]. The first study that demonstrated the positive effects of using fluoxetine to treat depression in child and adolescent patients was published in 1997 [16
], following a small trial in which no difference was observed between fluoxetine treatment and placebo [17
]. Overall, five clinical trials have been conducted which show the positive effects of using fluoxetine to treat pediatric depression [16
]. In addition, the improvement response rate on the Clinical Global Impressions (CGI) for antidepressant use was found to be between 52% and 61% for fluoxetine patients versus 33% to 37% for patients treated with placebo [22
]. The CGI measures whether or not depressive symptoms have improved after treatment.
Despite being one of the most popular treatments for pediatric patients, in 2004 the use of prescription medication such as fluoxetine as well as other antidepressant medications declined by approximately 20% in the United States [23
]. This shift in prescription patterns is likely due to warnings issued by regulatory agencies, initially in the United Kingdom [24
] and later in the United States [25
], against the use of SSRIs to treat depression in pediatric populations due to the possible link between antidepressant usage and an increased incidence of suicidal ideations or attempts. Subsequently, there is a compelling need for better understanding of the pathophysiology of MDD as well as the development of novel treatment methods that can be used to improve the current clinical management of pediatric depression.
Nutrients like vitamin C (ascorbic acid) have become of interest in adjuvant therapy settings for the management of depressive symptoms due to the fact that psychological abnormalities are among the characteristics of vitamin C deficiency [26
]. A recent population-based survey revealed that 60% of the patients in the acute medical wards of a Montreal teaching hospital were vitamin C deficient, while this deficiency was only detected in 16% of people attending the hospital’s outpatient center [30
]. There is also preliminary evidence that the administration of vitamin C may be able to reduce the severity of MDD in both children [31
] and adults [32
], as well as improve mood in healthy individuals [33
]. In addition, a recent study reported a 35% reduction in average mood disturbance in hospitalized patients following treatment with vitamin C (1000 mg/day) [36
]. In one particular study that investigated mood, patients who were acutely hospitalized were either treated with vitamin C or vitamin D as a deficiency in both of these vitamins has been associated with psychological abnormalities [32
]. The results showed that only vitamin C led to an improved mood. More specifically, treating the vitamin C deficiency led to a decrease in mood disturbance while vitamin D supplementation had no effect on mood. Similar findings were observed in non-critically ill hospitalized patients who were treated with vitamin C for hypovitaminosis C [36
]. Moreover, an animal study showed that the co-administration of vitamin C was found to potentiate the action of subeffective doses of fluoxetine (1 mg/kg) [37
]. This synergistic antidepressant effect of vitamin C and fluoxetine suggests that this vitamin could be helpful in improving conventional pharmacotherapy for pediatric MDD and potentially reduce side effects.
This study would be the first to examine the efficacy of vitamin C as an adjunct to SSRIs in the treatment of pediatric depression. In addition, the low potential toxicity, inexpensiveness, and over-the-counter availability, we sought to investigate whether oral supplementation of vitamin C would improve clinical depressive symptoms. Therefore, the present study was designed to measure the effect of vitamin C on the Children’s Depression Rating Scale (CDRS), the Children’s Depression Inventory (CDI), and the CGI scores in pediatric patients with depression taking fluoxetine.