The cognitive neuropsychological model of antidepressant response

• Antidepressants affect negative affective bias in depression early in treatment.
• Changes in negative affective bias with antidepressants predict later clinical response.
• Neuroimaging shows antidepressants correct imbalance in fronto-limbic circuits in depression.
• Emotional processing measures could detect early clinical response and efficacy of novel treatments.

It has been hypothesised that, at a neuropsychological level, the direct action of antidepressants is to remediate negative biases in affective processing and that these actions occur early in treatment prior to an improvement in mood. Here we discuss the latest evidence for the cognitive neuropsychological model of antidepressant response as well as the clinical applications and limitations of the model. The majority of research has been conducted using antidepressants predominantly affecting serotonin or noradrenaline activity. Future research must focus on replicating these effects in larger samples with antidepressants influencing different neurotransmitter systems, such as dopamine and glutamate.