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There is a high incidence of psychiatric comorbidity in people with epilepsy (PWE), particularly depression. The manifold adverse consequences of comorbid depression have been more clearly mapped in recent years. Accordingly, considerable efforts have been made to improve detection and diagnosis, with the result that many PWE are treated with antidepressant drugs, medications with the potential to influence both epilepsy and depression. Exposure to older generations of antidepressants (notably tricyclic antidepressants and bupropion) can increase seizure frequency. However, a growing body of evidence suggests that newer ('second generation') antidepressants, such as selective serotonin reuptake inhibitors or serotonin-noradrenaline reuptake inhibitors, have markedly less effect on excitability and may lead to improvements in epilepsy severity. Although a great deal is known about how antidepressants affect excitability on short time scales in experimental models, little is known about the effects of chronic antidepressant exposure on the underlying processes subsumed under the term 'epileptogenesis': the progressive neurobiological processes by which the non-epileptic brain changes so that it generates spontaneous, recurrent seizures. This paper reviews the literature concerning the influences of antidepressants in PWE and in animal models. The second section describes neurobiological mechanisms implicated in both antidepressant actions and in epileptogenesis, highlighting potential substrates that may mediate any effects of antidepressants on the development and progression of epilepsy. Although much indirect evidence suggests the overall clinical effects of antidepressants on epilepsy itself are beneficial, there are reasons for caution and the need for further research, discussed in the concluding section., (© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.)

Mood disturbances, including depression and anxiety disorders, are common and disabling long-term sequelae of traumatic brain injury (TBI). These psychiatric conditions have generally been considered psychosocial consequences of the trauma, but neurobiological alterations and causes have also been implicated. Using a rat model of TBI (lateral fluid-percussion injury), this longitudinal study seeks to assess anxiety and depression-like behaviors following experimental TBI. Male Wistar rats (n = 20) received a severe (approximately 3.5 atmosphere) pressure pulse directed to the right sensorimotor cortex, or sham surgery (n = 15). At 1, 3, and 6 months following injury, all rats underwent four assessments of anxiety and depression-like behaviors: exposure to an open field, elevated plus maze test, the forced swim test, and the sucrose preference test. Injured animals displayed increased anxiety-like behaviors throughout the study, as evidenced by reduced time spent (p = 0.014) and reduced entries (p < 0.001) into the center area of the open field, and reduced proportion of time in the open arms of the plus maze (p = 0.015), compared to sham-injured controls. These striking changes were particularly evident 1 and 3 months after injury. No differences were observed in depression-like behaviors in the forced swim test (a measure of behavioral despair) and the sucrose preference test (a measure of anhedonia). This report provides the first evidence of persistent anxiety-like disturbances in an experimental model of TBI. This finding indicates that the common occurrence of these symptoms in human sufferers is likely to have, at least in part, a neurobiological basis. Studies in this model could provide insight into the mechanisms underlying affective disturbance in brain-injured patients.