TARGETING INFLAMMATION TO TREAT DEPRESSION –A NEWER SCIENTIFIC APPROACH: A REVIEW

 

About Authors:
Mr. Satyanand Tyagi*, Patel Chirag J1, Asheesh Singh2
*President, Tyagi Pharmacy Association & Scientific Writer (pharmacy), Chattarpur, New Delhi, India-110074.
Prof. Satyanand Tyagi is a life time member of various pharmacy professional bodies like IPA, APTI and IPGA. He has published various research papers and review articles. His academic works include 52 Publications (44 Review Articles and 08 Research Articles of Pharmaceutical, Medicinal and Clinical Importance, published in standard and reputed National and International Pharmacy journals; Out of 52 publications, 11 are International Publications).
He has published his papers almost in different specialization of Pharmacy field...His research topics of interest are neurodegenerative disorders, diabetes mellitus, cancer, rare genetic disorders,
psycho-pharmacological agents as well as epilepsy.
1Department of Pharmaceutics, Maharishi Arvind Institute of Pharmacy, Mansarovar, Jaipur, Rajasthan, India-302020.
2Research Associate, Center for Research and Development, Ipca Laboratories Ltd Ratlam, Madhya Pradesh, India-457114.
*sntyagi9 @yahoo.com, +91-9871111375 / 9582025220

ABSTRACT:
Prior studies have suggested that depressed people with evidence of high inflammation are less likely to respond to traditional treatments for the disorder, including anti-depressant medications and psychotherapy. This study was designed to see whether blocking inflammation would be a useful treatment for either a wide range of people with difficult-to-treat depression or only those with high levels of inflammation. The study employed infliximab, one of the new biologic drugs used to treat autoimmune and inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. A biologic drug copies the effects of substances naturally made by the body's immune system. In this case, the drug was an antibody that blocks tumour necrosis factor (TNF), a key molecule in inflammation that has been shown to be elevated in some depressed individuals. Study participants all had major depression and were moderately resistant to conventional antidepressant treatment. Each participant was assigned either to infliximab or to a non-active placebo treatment. When investigators looked at the results for the group as a whole, no significant differences were found in the improvement of depression symptoms between the drug and placebo groups. However, when the subjects with high inflammation were examined separately, they exhibited a much better response to infliximab than to placebo.

Reference Id: PHARMATUTOR-ART-1493

INTRODUCTION
Inflammation is a protective tissue response to injury or destruction of tissues, which serves to destroy, dilute, or wall off both the injurious agent and the injured tissues. Inflammation may be acute or chronic. Its cardinal signs are redness (rubor), heat (calor), swelling (tumor), and pain (dolor), often accompanied by loss of function. The process begins with a transitory vasoconstriction, and then is followed by a brief increase in vascular permeability. The second stage is prolonged and consists of sustained increase in vascular permeability, exudation of fluids from the vessels, clustering of leukocytes along the vessel walls, phagocytosis of microorganisms, deposition of fibrin in the vessel, disposal of the accumulated debris by macrophages, and finally migration of fibroblasts to the area and development of new, normal cells. The severity, timing, and local character of any particular inflammatory response depend on the cause, the area affected, and the condition of the host. Histamine, kinins, and various other substances mediate the inflammatory process. Defining inflammation according to clinical signs and symptoms has major limitations, as in most cases the cellular processes and signals that underlie the cardinal signs occur at a sub clinical level and do not give rise to any heat, redness, swelling, or pain [1]. For example, the inflammation of delayed onset muscular soreness may cause tenderness on palpation or mild discomfort [2], but no redness or swelling. Broadening the definition of inflammation to include one or a subset of the cardinal signs is not a solution, as areas of swelling, pain, and tenderness may have a wide variety of non-inflammatory causes. For example, regions of muscle spasm (sometimes called “myositis”) and many cases of tendinosis (often called “tendinitis”[3]) are often confused with inflammation, because of the local pain and swollen nature of the tissue.Depression is a medical illness that causes a persistent feeling of sadness and loss of interest.

Depression can cause physical symptoms, too. Also called major depression, major depressive disorder and clinical depression, it affects how person feel, think and behave. Depression can lead to a variety of emotional and physical problems. Person may have trouble doing normal day-to-day activities, and depression may make feel as if life isn't worth living. Depression is an extremely common psychiatric condition, about which a variety of neurochemical theories exist, and for which a corresponding variety of different types of drug are used in treatment.

It is a field in which therapeutic empiricism has led the way, with mechanistic understanding tending to lag behind, part of the difficulty being that animal models cannot address the mood change that defines the human condition. Depression is a state of low mood and aversion to activity that can have a negative effect on a person's thoughts, behavior, feelings, world view and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, worried, helpless, worthless, guilty, irritable, hurt, or restless. They may lose interest in activities that once were pleasurable; experience loss of appetite or overeating; have problems concentrating, remembering details, or making decisions; and may contemplate or attempt suicide. Insomnia, excessive sleeping, fatigue, loss of energy, or aches, pains or digestive problems that are resistant to treatment may be present [4]. Depressed mood is not necessarily a psychiatric disorder. It is a normal reaction to certain life events, a symptom of some medical conditions, and a side effect of some medical treatments. Depressed mood is also a primary or associated feature of certain psychiatric syndromes such as clinical depression. Depression is the most common of the affective disorders (defined as disorders of mood rather than disturbances of thought or cognition); it may range from a very mild condition, bordering on normality, to severe (psychotic) depression accompanied by hallucinations and delusions. Worldwide, depression is a major cause of disability and premature death. In addition to the significant suicide risk, depressed individuals are more likely to die from other causes, such as heart disease or cancer. The symptoms of depression include emotional and biological components.

SYMPTOMS OF DEPRESSION

Emotional symptoms:
* misery, apathy and pessimism
* low self-esteem: feelings of guilt, inadequacy and ugliness
* Indecisiveness, loss of motivation.

Biological symptoms:
*retardation of thought and action
* loss of libido
* sleep disturbance and loss of appetite.

A number of psychiatric syndromes feature depressed mood as a main symptom. The mood disorders are a group of disorders considered to be primary disturbances of mood. These include major depressive disorder (MDD, commonly called major depression or clinical depression) where a person has at least two weeks of depressed mood or a loss of interest or pleasure in nearly all activities; and dysthymia, a state of chronic depressed mood, the symptoms of which do not meet the severity of a major depressive episode. Another mood disorder, bipolar disorder, features one or more episodes of abnormally elevated energy levels, cognition and mood, but may also involve one or more depressive episodes [5]. When the course of depressive episodes follows a seasonal pattern, the disorder (major depressive disorder, bipolar disorder, etc) may be described as a seasonal affective disorder. Outside the mood disorders: borderline personality disorder commonly features depressed mood; adjustment disorder with depressed mood is a mood disturbance appearing as a psychological response to an identifiable event or stressor, in which the resulting emotional or behavioral symptoms are significant but do not meet the criteria for a major depressive episode [6]; and posttraumatic stress disorder, an anxiety disorder that sometimes follows trauma, is commonly accompanied by depressed mood [7].

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