1. Introduction

Depression [major depressive disorder (MDD)] is a pathological affective disorder characterized by the presence of various emotional, physical, behavioral, and cognitive symptoms, with variable duration of manifestations, with progressive evolution toward worsening, and with a high frequency of comorbidities [1, 2].

Monoaminergic theory of depression postulates that depressive manifestations are caused by the lack of one or more of the three essential neuro-mediators (serotonin, dopamine, norepinephrine) from the central nervous system synapses. These areas are situated especially in the cortex of the frontal lobe (dorsolateral, prefrontal, and orbitofrontal), the self-processing headquarters. In these areas, regional atrophy and atrophic alterations were observed, following the

New Antidepressant Medication: Benefits Versus Adverse Effects

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• Serotonin deficiency causes in particular: sadness and thoughts with mainly negative

• Noradrenaline deficiency is associated with the diminution of voluntary and involuntary motor behaviors: the patient speaks slowly, in a monotone voice with low intensity, as if his energy is exhausted at each joint; the mimic and the gestures diminish; the posture begins to sketch the defense; the limbs are brought down (the generalized flexion tendency or even the genital posture appears); the patient's mobility decreases; in the beginning, the gestures of social and family significance are not performed; and the patient

• Dopamine deficiency is manifested by anhedonia; the patient can no longer enjoy any of the things that previously used to cause pleasure. From the outset, it should be noted that the therapeutic response appears differently for the three components. Often, the first neuro-mediator involved in the response is norepinephrine. Serotonin responds a little bit later. The patient regains his motor skills, before the ideation has normalized. This situation, in which the patient has the power to practice negative thoughts, appears in the early weeks of antidepressant therapy onset and is responsible for the suicidal accidents that may occur [9]. In conclusion, people with inhibited depression should be closely monitored during the first 3 weeks after the therapy is

A therapeutic response consists of 50% alleviation of the symptoms following administration of the antidepressant medication. A small percentage of people may develop resistance to antidepressants (through lack of synthesis or transport or excess metabolism of one or more monoamines). These patients are recommended to either potentiation of the treatment or electroconvulsive therapy, as a solution for achieving remission of the

In these conditions, the therapeutic targets of currently used antidepressant drugs are aimed at

augmenting the monoaminergic deficiency at the synaptic level.

• The receptor stimulation through neuro-mediator release

• Inhibition of the reuptake pump or inhibition of the metabolism enzyme

stress associated with the hypothalamic-pituitary-adrenal axis [8, 9]. Different types of deficits modulate the characters of depression:

lacks personal hygiene behavior [10, 11].

content [8].

established.

This response can be achieved by: • The action on the receptor level

depression.

According to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, the clinical symptomatology includes a series of manifestations lasting more than 2 weeks: depressed mood, diminishing interest in current activities (home and work), lack of pleasure and energy, permanent fatigue, loss of confidence and self-esteem, feelings of guilt, inability to make decisions, lack of initiative, loss of attention and concentration, sleep disturbances (insomnia or hypersomnia), appetite disturbances, weight gain, modification of psychomotor activity, and recurrent thoughts of death. The symptoms are not caused by a substance or another medical condition [3–5].

To determine the severity of depressive symptoms, a number of depression rating scales are available. Montgomery-Asberg Depression Rating Scale, Hamilton Depression Scale, and Young Mania Rating Scale are clinician-administered scales. In addition, self-administered scales can be useful (Patient Health Questionnaire, Beck Depression Inventory, Zung Self-Rating Depression Scale, and Mood Disorder Questionnaire) [6, 7].

The treatment of MDD is based on pharmacotherapy, which includes numerous drugs with various structures and mechanisms of action.

The aim of this chapter is to review the literature, highlight important aspects regarding the main incriminated theories of depression and the side effects of agents used to treat MDD, and especially point out the most relevant details of the latest antidepressant drugs.

This chapter synthetizes the classic and modern features concerning the MDD pathophysiology and treatment, as well as the information about the newest antidepressants introduced in the therapy (desvenlafaxine, levomilnacipran, vilazodone, and vortioxetine), detailing the mechanism of action, pharmacokinetic aspects, their side effects, and benefits. The first two substances have similar mechanisms of action to existing medications, and the other two compounds are multimodal antidepressants, which combine SSRI activity with additional receptor activity.
