Post-traumatic stress disorder (PTSD) is an anxiety disorder that can develop after experiencing or witnessing a life-threatening event, such as accident, disaster, war trauma, violence or abuse (family, sexual, physical, and/or psychological), or any situation that seriously threatens the integrity of a person. The disorder, however, does not develop in every person exposed to traumatic experience. Stress results from an interaction between the mind and the body. The brain is the organ that determines reaction to stress as it decides on what is stressful and controls biological and physiological responses to stress. These responses vary from one person to another due to differences in their biological, genetic, environmental, and psychological characteristics, as well as their personal history.

Stress causes neuroanatomical and neurochemical changes in the brain. Early traumatic experience (eg, abuse or severe neglect in childhood) may affect the brain structures and functions so as to make a person vulnerable to negative stressful events and more prone to later development of PTSD or other anxiety-related disorders. A particular genetic profile also plays a role in vulnerability or resilience to stress. For example, individuals with a short ss allele of serotonin transporter are more vulnerable to depression and PTSD, especially if they had early traumatic experience. A long-term dysregulation of cortisol and noradrenalin, the main stress mediators, favors the development of different anxiety disorders, including PTSD. Stress-induced changes in hippocampus (atrophy), amygdales (volume reduction), and prefrontal cortex are also frequent findings in patients with these disorders.

The neurobiological changes in the brain, which result from dysregulation of noradrenergic, serotoninergic, dopaminergic, and other neurotransmitter systems, provide the basis for psychophar-macologic treatment of patients with PTSD. The evaluation of different biomarkers might facilitate a goal of the modern medicine, a proper treatment for an individual patient at a given stage of disease. This is especially important in PTSD, a disorder with complex clinical picture, diverse symptoms, and different comorbidities.

PTSD was officially proposed as separate diagnosis in DSM-III, although the clinical consequences of trauma were recognized since ancient times. After its identification in DSM-III, the neurobiology of chronic PTSD has been area of increasing investigation. Earlier the psychoanalytic model of explanation and treatment mostly prevailed. Epidemiological studies show high prevalence of PTSD in general population and specific groups exposed to the traumatic events (survivors of war trauma, natural disasters, terrorist attacks, etc.). Trauma and its consequences affect significantly individual health and functioning, and whole society. The diagnosis of PTSD may have several subtypes, including psychotic symptoms, depending upon pre-existing psychiatric disorder, trauma severity and duration, comorbidity, post-trauma social environment, etc. The role of trauma as an etiological factor in other psychiatric disorders and symptoms remains to be clarified.

Complex neurobiological changes triggered by such a traumatic and stressful experience may explain a wide range of PTSD symptoms and provide the rationale for psychopharmacological treatment. Selective serotonin-reuptake inhibitors make the firstline treatment of PTSD. Clinical experience has shown that they are more effective than noradrenalin-reuptake inhibitors or tricyclic antidepressants. Antipsychotic drugs, especially atypical ones, have been shown effective in PTSD patients with psychotic characteristics or refractoriness to other treatments. Mood stabilizers seem to reduce mostly autonomous overreactions to stress, whereas the evidence for effectiveness of monoamine oxidase inhibitors is largely inconclusive. Other groups of medications, such as serotonin agonists and antagonists, new antidepressants, dual inhibitors of serotonin- and noradrenalin-reuptake, anticon-vulsants, and opiate antagonists are also sometimes used in PTSD treatment. However, as shown in the present article, most clinical studies performed to date to investigate the effectiveness of different psychopharmacological agents in the therapy of PTSD have serious limitations in terms of small sample size, lack of blinding and randomization, and small effect size. More rigorously designed, comparative studies are needed to determine the usefulness, efficacy, tolerability, and safety of particular psychopharma-ceutical drugs in the treatment of this therapeutically and functionally challenging disorder.

One group of medications is often not enough for the treatment of all the PTSD symptoms, especially in cases where PTSD is comorbid with depression, alcoholism, borderline personality disorder, or psychotic, panic, or other disorders. Irrespective of the different mechanisms of action of drugs used in the treatment of PTSD, the final goal is always the same – to reduce distress, reinforce the psychological defense system, and restore the functioning of the person. However, evidence from controlled clinical trials showing the effectiveness of pharmacotherapy in PTSD is still unsatisfactory.