Summary by Emily L. Dennis, Ph.D
Depression is a common long-term consequence of brain injury, and occurs in up to three-quarters of patients. Some studies have even found that patients can become depressed decades after their injury. Major depressive disorder (MDD) is defined by the DSM (Diagnostic and Statistical Manual of Mental Disorders) as depressed mood or loss of interest in daily activities nearly every day for at least 2 weeks. Symptoms include depressed mood or irritability, change in sleep, change in activity, change in weight, decreased interest in activities, loss of energy, feelings of worthlessness, lack of concentration, and thoughts of suicide.
Depression can make patients less able to take part in rehabilitative efforts post-injury, and increases a patient’s disability. While there are many options for treating depression, prevention may be more effective. With this goal in mind, Jorge et al. studied whether sertraline, a commonly used anti-depressant drug, could prevent depression in patients with TBI. Sertraline is a type of drug in the SSRI-category (selective serotonin reuptake inhibitor). They increase the amount of the neurotransmitter serotonin available to the brain.
This study was conducted at the University of Iowa, over a 4-year period, and included patients between 18-85 years old, with mild, moderate, and severe TBI. This was a double-blind, placebo-controlled study. 94 participants took part and were randomly assigned to two groups: one took sertraline, and the other took placebo every day for 24 weeks. Researchers contacted participants 7 times over the 24 weeks to determine:
- whether a patient became depressed, and
- how soon post-injury they became depressed.
The study used “number needed to treat” or NNT to assess their treatment. The NNT is the average number of patients needed to be treated to have an impact on one person. For NNT, smaller numbers indicate a bigger impact on risk reduction. Treatment with sertraline resulted in an NNT of 5.9 over 24 weeks. This means that we would need to treat 6 TBI patients in order to prevent one of them developing depression.
Sertraline and similar classes of drugs may enhance neuroplasticity in the brain, meaning they may lead to new cells and new connections being made. Given this possibility, the researchers also looked into whether patients treated with sertraline had improved cognitive function. They did not find that sertraline had any impact on cognitive recovery.
These results suggest that preventative treatment with sertraline during the first 6 months post-injury helps prevent patients from developing depression. Prior studies of depression in TBI found that depression usually develops in the first 6 months after injury, so targeting patients up to 6 months is likely to be bring most benefit. These data are also exciting because the dosage amount was small. This study is also important because previous studies had shown that treating depression once it has developed after TBI is probably more difficult.
A limit of this study is that it was relatively small (<100 participants). Also, participants who had psychiatric problems or alcohol or drug addictions at the time of injury were excluded. This means the results may not apply to all those with head injuries, particularly participants of different ages, ethnicities and with other medical conditions.
Overall, this paper is the first trial showing a benefit of preventative anti-depressants after TBI. For this potential treatment to be validated and accepted, additional studies are needed across sites. These results have the potential to have a profound impact on the disability caused by TBI.