INTRODUCTION:

A. Post-traumatic stress disorder (PTSD):

Posttraumatic stress disorder (PTSD) is a severe, chronic, and disabling anxiety disorder that can develop as a result of witnessing a traumatic event¹. Post-traumatic stress disorder (PTSD) is a mental health condition caused by witnessing or experiencing a terrifying event².

A traumatic event is defined by its ability to elicit fear, helplessness, or horror in response to the threat of injury or death. People who witness such events are more likely to develop PTSD, as well as major depression, panic disorder, generalised anxiety disorder, and substance abuse³.

This disorder may disrupt how individuals and families function, leading to serious medical, financial, and social issues⁴. The anxiety disorder known as post-traumatic stress disorder (PTSD) is very common and has been linked to a higher risk of hypertension and cardiovascular disease^5,6.

Types of PTSD:

Not everyone experiences the same symptoms or responds to traumatic events in the same way. Everyone responds differently. Both PTSD and stress disorders can present similarly and share symptoms. However, there are some variations in how each type is handled⁷.

1. Normal Stress Response:

Prior to the onset of PTSD, a normal stress response takes place. It does not always result in the full-blown disorder, though. things like

· Accidents,

· Injuries,

· Illnesses,

· Surgeries and

· Other sources of unreasonable amounts of tension and stress can all lead to this response⁸.

2. Acute Stress Disorder:

Even though it's not the same as PTSD, acute stress disorder can happen to people who have experienced something that is or feels life-threatening.

· Natural disasters,

· Loss of loved ones,

· Loss of a job or

· Risk of death

All stressors trigger acute stress disorder. If left untreated, acute stress disorder may actually develop into PTSD

3. Uncomplicated PTSD:

The simplest form of PTSD to treat, uncomplicated PTSD is caused by a single, significant traumatic event as opposed to multiple events. Uncomplicated PTSD signs and symptoms include:

· Avoidance of trauma reminders,

· Nightmares,

· Flashbacks to the event,

· Irritability,

· Mood changes and changes in relationships.

4. Complex PTSD:

Uncomplicated PTSD is the antithesis of complex PTSD. It is brought on by numerous traumatic experiences, not just one.

Complex PTSD is frequent in situations involving abuse or domestic violence, repeated exposure to conflict or violent crime, or unexpected loss.

Complex PTSD sufferers may also have dissociative disorders, borderline or antisocial personality disorders, or both.

5. Comorbid PTSD:

Co-occurring disorders are collectively referred as comorbid PTSD. It is used when a person has multiple mental health issues, frequently in conjunction with drug abuse problems. As many people experience multiple conditions simultaneously, comorbid PTSD is very common. The best outcomes come from treating the co-occurring mental health condition and the co-occurring PTSD concurrently⁹.

Etiology:

The proximal or precipitating event can be easily identified, despite the fact that the exact cause of PTSD is unknown¹⁰.

There are many factors that can contribute to someone developing posttraumatic stress disorder. These consist of going through a traumatic experience like,

· Rape

· A near-death experience

· Natural disasters

· Severe illness or injury

· The death of a loved one

· Major Accident¹¹

Pathophysiology:

Increased oxidative stress, dysregulation of the neuroendocrine system, inflammatory response, and hypothalamic-pituitary-adrenal axis are additional characteristics of PTSD that may contribute to cognitive decline (e.g., via increased neuronal death)¹².

Ø Noradrenaline and the biologic response to stress:

The monoamines, which include dopamine (from which noradrenaline is derived), histamine, serotonin, and melatonin, are a larger class of structurally related neurotransmitters that also include noradrenaline¹³. There is evidence that many monoaminergic neurotransmitters may play some part in the pathophysiology or treatment of persistent sequelae following trauma. Monoaminergic neurotransmitters are generally centrally involved in the regulation of both alertness and emotion/mood¹⁴.

The neurotransmitter and neurohormonal functioning are altered in posttraumatic stress disorder, according to the pathophysiology of the condition. Despite their ongoing stress, people with PTSD have been shown to have normal to low cortisol levels and elevated levels of corticotrophin-releasing hormone (CRH). The anterior cingulate cortex releases norepinephrine in response to CRH stimulation, which increases the sympathetic response and causes an increase in heart rate, blood pressure, arousal, and startle response¹⁵.

Ø Hypothalamic–pituitary–adrenal (HPA) axis:

Stress results Impaired in the hypothalamic-pituitary-adrenal (HPA) axis's negative feedback. Additionally, it demonstrates that PTSD patients have altered functioning of other neurotransmitter systems like GABA, glutamate, and serotonin¹⁶.

Fig. 1: The body's primary mechanism for reacting to stress is the hypothalamic-pituitary-adrenal axis. The pituitary gland produces and releases ACTH, which is then transported to the adrenal gland where adrenal hormones like cortisol are produced and released. The hypothalamus secretes CRH, which binds to receptors on pituitary cells. The anterior pituitary and the hypothalamus both experience negative feedback as a result of cortisol release, which also activates sympathetic nervous pathways. Patients with post-traumatic stress disorder appear to have compromised functioning of this negative feedback system. Adrenocorticotropin (ACTH) and corticotropin (CRH) are two related hormones¹⁷.

Your entire life, including your job, your relationships, your health, and the enjoyment of daily activities, can be negatively impacted by post-traumatic stress disorder.

Additionally, having PTSD may increase your risk of developing other mental health issues, such as:

· Anxiety and Depression

· Issues with drugs or alcohol use

· Eating disorders

· Suicidal thoughts and actions¹⁸

SYMPTOMS OF PTSD:

Flashbacks, nightmares, excruciating anxiety, and uncontrollable thoughts about the incident are all possible symptoms.

Indicators that you're re-experiencing include:

· Flashbacks–repeatedly experiencing the trauma, along with accompanying physical signs like a racing heart or sweating

· Bad dreams

· Anxious thoughts

Re-experiencing symptoms can make daily tasks difficult and lead to anxiety and depression. The person's own thoughts and feelings may be the source of the symptoms¹⁹.

Avoidance symptoms include:

· Staying away from places, events, or objects that are reminders of the traumatic experience

· Avoiding thoughts or feelings related to the traumatic event

Avoidance symptoms can be brought on by things that bring back memories of the traumatic event. A person's personal routine may change as a result of these symptoms. A person who typically drives, for instance, might refrain from doing so after a serious auto accident²⁰.

Factors affect the prevalence of the above symptoms:

Table 1: Type of factors with example^21,22

Type of factor	Examples
Pre-traumatic factors	· Personal traits like ethnicity, age, gender, personality, memory, learning style, motivation, and genetic traits. · characteristics of the context, such as availability of socioeconomic resources. · Psychiatric disorder and other medical history. prior contact with traumatic stressors.
Peritraumatic factors	· Increasing physiological responses like elevated blood pressure and fatigue. · Dissociation, such as impaired memory brought on by an excessively emotional reaction to a stressor.
Post-traumatic factors	· Social support · Access to culturally-sensitive and evidence-based treatment options. – Development of coping styles and self-efficacy.

B. Anxiety:

Amygdala activity has been found to be elevated in stress-related affective diseases, such as anxiety disorders, according to functional neuroimaging studies in humans²³. The amygdala is a component of the neural circuitry involved in emotional learning, fear, and anxiety. Currently, it is thought that changes in dendritic and synaptic structure in stress-responsive brain regions mediate the fear and anxiety brought on by traumatic life events^23,24.

People experience fear and anxiety during and after a traumatic event. They might experience physical illness, fear, or stress. The most prevalent or frequently occurring mental disorders are anxiety disorders.

It is a diverse disorder that has an impact on a person's behaviour, physical health, and mood as well as biological, psychological, and environmental factors.

Anxiety disorders can affect a person’s quality of life significantly and are associated with:

· Impaired social and occupational functioning

· Comorbidity with other disorders

· An increased risk of suicide²⁵.

Types of Anxiety:

Table 2: Types of Anxiety Disorders and their clinical symptoms²⁶

Types of Anxiety Disorders	Clinical Features of anxiety
Panic Disorder	It is characterised by abrupt episodes of terror that are frequently accompanied by a racing heart, perspiration, weakness, dizziness, or faintness. People with panic disorder may experience flushing, a chill, tingling or numbness in their hands, nausea, chest pain, and suffocating feelings during these attacks. A sense of unreality, a fear of impending doom, or a fear of losing control are common symptoms of panic attacks.
OCD	Obsessive-compulsive disorder (OCD) is characterised by recurring, distressing thoughts (obsessions) and the use of rituals (compulsions) to manage the anxiety these thoughts cause. The rituals usually have the desired effect of controlling them.

Symptoms of Anxiety:

Depending on who is experiencing it, anxiety can feel different. Feelings can range from stomach aches to a racing heart. There may be a feeling of disconnection between your mind and body that makes you feel out of control.

You may feel anxious and fearful all the time, or you may fear going to a certain location or experiencing a certain thing. You might occasionally have a panic attack²⁷.

Symptoms of anxiety can include:

· Anxious thoughts or beliefs that are difficult to control

· Restlessness

· Trouble concentrating

· Difficulty falling asleep

· Fatigue

· Irritability

· Unexplained aches and pains²⁸

Treatment/Management:

Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are frequently used in the treatment of PTSD and anxiety disorders where pharmacological intervention is recommended. Treatment of sleep disorders, such as sleep apnea (CPAP), nightmares, and insomnia (preferably through psychotherapy), may lessen the symptoms of PTSD and boost mood in anxiety disorders²⁹.

Current drug treatment of PTSD symptoms:

Only two drugs–paroxetine and sertraline–have been approved for the treatment of PTSD over the past 20 years²⁹.

Antidepressants: These drugs can help with depression and anxiety symptoms. They can also aid in enhancing concentration and sleep issues.

The Food and Drug Administration (FDA) has given the medications sertraline (Zoloft), paroxetine (Paxil), and fluoxetine (Fludac) approval for the treatment of PTSD.

Selective serotonin reuptake inhibitors (SSRIs) increase serotonin availability in the synaptic cleft. This action is thought to contribute to the antidepressant and antianxiety effects of the SSRIs³⁰.

Figure 1: Psychological and pharmacological strategies for treatment of PTSD³¹.

Treatment for Anxiety:

These medications can treat severe anxiety and related issues³².

SSRIs may take up to 6 weeks to reach the therapeutic blood level needed for symptoms to be effectively managed when treating PTSD-related anxiety. This prolonged wait is a major factor in subjects leaving research studies, especially. Many PTSD patients may turn to alcohol, drugs, or even suicide during this time in an effort to cope with the agoraphobia, depression, and nightmares that come along with the condition³³.

A benzodiazepine may be necessary to treat acute anxiety. Pharmacotherapy, psychotherapy, or a combination of the two forms of treatment are used to treat chronic anxiety.

Pharmacotherapy:

Selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), benzodiazepines, tricyclic antidepressants, mild tranquilizers, and beta-blockers treat anxiety disorders³⁴.

· All anxiety disorders can be successfully treated with SSRIs (fluoxetine, sertraline, paroxetine, escitalopram, and citalopram), which are regarded as first-line therapy.

· SNRIs (venlafaxine and duloxetine) are regarded as first-line treatments, particularly for generalised anxiety disorder, and are as effective as SSRIs (GAD).

· Amitriptyline, imipramine, and nortriptyline are tricyclic antidepressants that are effective in treating anxiety disorders but have serious side effects³⁴.

· Benzodiazepines (alprazolam, clonazepam, diazepam, and lorazepam) are used to treat anxiety temporarily. They work quickly, providing relief in 30 to 60 minutes. They are efficient at encouraging relaxation, easing tension in the muscles, and minimising other signs of anxiety³⁵.

· Buspirone is a mild tranquillizer that takes about two weeks to start working and has a slower onset of action than benzodiazepines. It benefits from being less sedating, less addictive, and has mild withdrawal symptoms. It helps with GAD.

· Beta-blockers (propranolol and atenolol) reduce the physical signs of anxiety like a racing heart, a trembling voice, sweating, dizziness, and trembling hands. They are especially beneficial for phobias, especially social phobia³⁶.

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Received on 01.04.2023 Modified on 11.07.2023

Asian J. Res. Pharm. Sci. 2023; 13(4):313-317.

DOI: 10.52711/2231-5659.2023.00053