FORCED SWIM MODEL FOR DEPRESSION (MICE) - Pharmacy Project Report Part 1
Introduction:Depression is a mood disorder that is characterized by sadness. Nearly everyone feels sometimes; however, the sad feelings become intense, last for long periods, and keep a person from leading a normal life. This is a common mental disorder that presents with depressed mood, loss of interest or pleasure, feelings of guilt or low self-worth, disturbed sleep or appetite, low energy, changes in weigh, thoughts of death or suicide, and poor concentration. These problems can become chronic or recurrent and lead to substantial impairments in an individual's ability to take care of his or her everyday responsibilities. Depression is classified as major if the person has at least five of these symptoms for two weeks or more. However, there are several types of depressive disorders. Someone with fewer than five of these symptoms who is having difficulty functioning should seek treatment for his or her symptoms. At its worst, depression can lead to suicide, a tragic fatality associated with the loss of about 850 000 lives every year.
Sleep, or insomnia, is one of the major signs of depression. (A small percentage of depressed people, approximately 15%, oversleep, or sleep too much.) Lack of sleep alone cannot cause depression, but it does play a role. Lack of sleep caused by another medical illness or by personal problems can make depression worse. An inability to sleep that lasts over a long period of time is also an important clue that someone may be depressed. Causes of mental disorders are Chemical imbalances in the brain Physical and mental health disorders Environment such as living in a place that is often cloudy and gray. Stress Alcohol or drug abuse Medications Lack of support from family and friends Poor diet.
Depression is diagnosed by doctor, who will take your medical history, and will likely ask you whether anyone in your family has depression or other mental health problems. He or she may also ask you to describe your moods, your appetite and energy, if you feel under stress, and if you have ever thought about suicide. A doctor will also perform a physical examination to determine if the cause of your symptoms is caused by another illness.
Treatment choices for depression depend on how serious the illness is Major depressive disorder is treated with psychotherapy (counseling, or talk therapy with a psychologist, psychiatrist, or licensed counselor), medications, or a combination of the two The most effective treatment for depression is a combination of psychotherapy and medication. Medication tends to work more quickly to decrease symptoms while psychotherapy helps people to learn coping strategies to prevent the onset of future depressive symptoms. Hypnotics are a class of medications for people who cannot sleep. These drugs include Ambien, Sonata, and Restoril. Doctors may sometimes treat depression and insomnia by prescribing SSRIs along with a sedating antidepressant or with a hypnotic medication. However, hypnotic medications can only be taken for a short period of time.
PSYCHOPATHOLOGY:
The most widely accepted theory antidepressant is the monoamine hypothesis, which was developed based on the observation of a high occurrence of depression in patients receiving the antihypertensive drug reserpine. Reserpine depletes catecholamines from postganglionic sympathetic nerves and the adrenal medulla; it also depletes catecholamines and serotonin in the brain. The monoamine hypothesis links the depletion of brain monoamines, specifically nor epinephrine and serotonin, to the development of clinical depression. The monoamine hypothesis of gene expression has become an area of research. This hypothesis describes a pseudo monoamine deficiency in that the signal is blunted due to a deficiency in brain-derived neurotrophic factor (BDNF) in the presence of normal levels of neurotransmitters and normal receptors. In normal circumstances, BDNF permits normal signal transduction. However, under stress the gene for BDNF is suppressed, ultimately resulting in refractory depression. The frequency of depression in patients with a debilitating medical condition ranges from 20-60%.Depression in association with an illness such as cardiovascular disease, acquired immunodeficiency syndrome, or other debilitating conditions may be difficult to evaluate due to multiple factors, specifically, psychosocial stressors. Nevertheless, patients with cardiovascular disease have been found to have a frequency of major depression ranging from 15-23%. The medical history of the patient also plays an important role in the development of depression after a myocardial infarction or other cardiac event, such as a coronary artery bypass graft.] Risk factors for development of depression after myocardial infarction include the presence of other debilitating medical conditions, previous major or minor depression, and type a personality. Depression that follows a myocardial infarction is a cause of increased morbidity and mortality. Multiple cross-sectional and longitudinal trials have shown that patients with heart failure have a higher frequency of major and minor depression than patients without heart failure. It has also been suggested that patients with both heart failure and depression have a higher mortality rate than patients with heart failure alone. Due to the increased frequency of depression among patients with cardiac disease, as well as the increase in morbidity and mortality that depression causes in this patient population, treatment of depression in patients with cardiovascular disease is imperative.
ANTIDEPRESSANT:
An antidepressant is a medication used primarily in the treatment of depression. Depression can occur if some of the chemicals called neurotransmitters in the brain are not functioning effectively. There are three specific chemicals that can affect a person's mood: serotonin, nor epinephrine, or dopamine. Antidepressants affect one or more of these chemicals in different ways to help stabilize the chemical imbalance often seen in depression. Antidepressant drugs are not happy pills, and they are not a panacea. They are prescription-only drugs that come with risks as well as benefits and should only be taken under a doctor's supervision. Because children and adolescents experience depression just as adults do, they are sometimes prescribed antidepressant.
In ancient time the pharmacological agents given to patients with mental disorder were limited to herbal portion that consisted mostly of inactive ingredient. The end of the 19th century saw influence of Sigmund Freud’s psychoanalysis of neurotic disorders, but the treatment of psychotic patients remained crud, and include technique like isolation, restraint, sleep therapy, hydrotherapy insulin shock, electroconvulsive therapy. Little progress was made until early 1950s, when clinical pharmacology made major advance with the introduction of chlorpromazine and reserpine.
Today reserving is not longer used the treatment of psychosis because of its toxicity and the availability of more effective drugs. However chlorpromazine and newer antipsychotic drugs are used for treating patients. The most effective treatment available for the control of mental disorder is drug therapy.
DESCRIPTION:
Antidepressants are medicines used to help people who have depression. Antidepressant medications may be indicated for those children and adolescents with bipolar depression, psychotic depression, depression with severe symptoms that prevent effective psychotherapy or counseling, and depression that do not respond to psychotherapy. However, given the psychosocial dynamics that often coexist with depression, antidepressants are usually insufficient as the only treatment for children who have the disorder. Psychotherapy is often recommended as an adjunct treatment along with the prescribed antidepressant. The use of antidepressants among children has been growing steadily since the late 1980s.
All antidepressant medications have a slow onset of action, typically three to five weeks. Although side effects may be observed as early as the first dose, significant therapeutic improvement is always delayed. Most antidepressants are believed to work by slowing the removal of certain chemicals from the brain. These chemicals are called neurotransmitters, which are needed for normal brain function. Antidepressants help people with depression by making these natural chemicals more available to the brain.
Causes:
We know that depression seems to run in families. This suggests that there's a genetic link to depression. Children, siblings, and parents of people with severe depression are much more likely to suffer from depression than are members of the general population. Multiple genes interacting with one another in special ways probably contribute to the various types of depression that run in families. Yet despite all the evidence of a family link to depression, scientists still have not been able to identify a "depression" gene
NEWER ANTIDEPRESSANTS:
.Early antidepressant medications e.g. tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) are effective because they enhance either noradrenergic or serotonergic mechanisms, or both. Unfortunately, these compounds block cholinergic, histaminergic and alpha-1-adrenergic receptor sites, interact with a number of other medications and bring about numerous undesirable side effects. Several chemically unrelated agents have been developed and introduced in the past decade to supplement the early antidepressants. These include selective inhibitors of the reuptake of serotonin (the selective serotonin reuptake inhibitors (SSRIs)) or noradrenaline (reboxetine) or both (SNRIs: milnacipran and venlafaxine), as well as drugs with distinct neurochemical profiles such as mirtazapine, nefazodone, moclobemide and tianeptine. All these newer compounds are the results of rational developmental strategies to find drugs that were as effective as the TCAs but of higher safety and tolerability profile. In spite of the remarkable structural diversity, most currently introduced antidepressants are monoamin based and modulating monoamine activity as a therapeutic strategy continues to dominate antidepressant research. It must be emphasised, however, that these newer antidepressants are far from the ideal ones, also resulting in undesirable side effects and requiring 2-6 weeks of treatment to produce therapeutic effect. Furthermore, approximately 30% of the population does not respond to current therapies. An important new development has been the emergence of potential novel mechanisms of action beyond the monoaminergic synapse. The results of recent novel developmental approaches have suggested that modulation of N-methyl-D-aspartate (NMDA), neuropeptide (substance P and corticotrophin-releasing factor) receptors and the intracellular messenger system may provide an entirely new set of potential therapeutic targets. This paper discusses the advances from monoamine-based treatment strategies and looks at the future developments in the treatment of depression.