The presence of mixed symptoms of anxiety and depression are well known to every clinician. Panic, generalised anxiety and obsessive-compulsive disorder all have considerable overlap with major depressive illness. Factor analysis of anxiety and depression symptoms has sought to predict response to treatment as well as to establish a diagnosis. Sleep disturbances are important concomitants of both syndromes. The analysis of the architecture and phasing of sleep stages has been proposed as a biological marker to separate anxiety and depression. The modification of REM and delta sleep has been correlated with antidepressant action. The earliest studies of trimipramine noted antidepressant, anxiolytic and hypnotic effects. Further observations have shown this drug to have atypical effects on REM sleep. In addition, despite its structural similarity to other tricyclic antidepressants, its pharmacological profile in animals is very different: there is no synaptosomal reuptake of serotonin or noradrenaline, and no desensitisation of beta-adrenoceptors after long term administration. A series of studies was carried out on 99 patients. Admission criteria for the studies specified a minimum score of 20 on the Anxiety Status Inventory as well as the presence of moderate depression. An uncontrolled trial demonstrated the anxiolytic efficacy of trimipramine. Further controlled trials showed superior anxiolytic efficacy of trimipramine to amitriptyline and doxepin with comparable anxiolytic efficacy of trimipramine with maprotiline. All agents had equal antidepressant effects.