The temporal restoration of brain monoamines in the synaptic cleft due to MAO inhibition or by blocking catecholamine reuptake is only the the first step on the way to recovery from depression. The second and crucial step represents the feedback system, which can provide the continuous restoration of brain monoamines in the context of free search behavior. This feedback system on the one hand helps to overcome depression and on the other hand causes the hyposensitivity of the postsynaptic catecholamine (CA) receptors, due to the increased activity of the brain CA system. According to the search activity concept, REM sleep in the healthy subject, being a part of the same feedback system, restores brain monoamines. The mechanism of REM sleep deprivation in the treatment of depression is discussed in the context of this feedback system.