The pathophysiology of many diseases, including psychiatric disorders such as depression, can be viewed from several different levels of organization. At the level of the synapse, depression appears to be accompanied by changes in neurotransmitters such as norepinephrine, 5-HT (related to serotonin), and dopamine. On the level of neural pathways, glutamergic and acetycholinergic connects are diminished. The activity of the immune system, especially in response to stress levels, changes during depression. Endocrine processes, such as the hypothalamus-pituitary-adrenal (HPA) axis, are disturbed as well. Finally, the balance in activity between areas of the brain becomes abnormal in the person with major depression (Murck, 2013).
In the synapse, the tiny physical gap between one neuron and another, neurotransmitters move back and forth to ferry excitatory and inhibitory signals along the neural pathways. Biochemical studies of depression have revealed decreases in acetycholinergic and glutamergic activity in the synapse. Other research has shown a functional deficiency in the monoaminergic neurotransmitters norepinephrine, 5-HT, and dopamine. It has been suggested that this represents a depletion in neurotransmitters due to overproduction of the enzymes that degrade them, but healthy volunteers who were depleted of neurotransmitters did not become depressed (Bondy, 2002). However, in depressed individuals the depleted neurotransmitters may be accompanied by changes in their transporters and receptors.
The hypothalamus is a deep brain structure that is the initiator for several pituitary-controlled endocrine processes such as the hypothalamus-pituitary-adrenal (HPA) axis (stress hormones) and the hypothalamus-pituitary-thyroid (HPT) axis (metabolism). Endocrine pathways such as these are often abnormal in the presence of depression; in fact, extended periods of stress and decreased levels of thyroid hormones are associated with depression (Xin & Pang, 2015). Excess stress hormones are known to alter the function of the frontal cortex, the hippocampus, amygdala, and basal ganglia – brain structures that are related to mood and mood disorders. There are a number of other chemical processes in the brain that are believed to affect or to trigger major depression: neuroimmune chemicals such as cytokines, neurotrophic factors, and other modulating factors such as vasopressin, neuropeptide Y, and excitatory amino acids. (Northoff, 2013)
As an episode of depression deepens, the intrinsic activity of the brain at rest shifts from balanced attention to inner and outer stimuli to a focus on the inward focusing task-negative network. This network consists of the medial brain and cortical midline structures (CMS). The task-positive network, which produces environmental perception and other outward thoughts, rests in the lateral prefrontal and parietal cortex. Imaging studies of the brain indicate that during depressed states there is an increase in midline activity and a decrease in lateral activity (Belzung et al., 2015). Behaviorally, this change is accompanied by an increased focus on rumination, self-deprecation, and other facets of the inner self (Northoff, 2013). Perceptions, cognitions, and motivation are primarily focused inward. This results in a feeling of disconnectedness, a loss of emotional connection to the environment. Many depressed individuals feel numb, and because they feel disconnected, they withdraw even more from the outer environment (Northoff 2013).
In New York, the algorithm for assessment, diagnosis, treatment, and patient education begins with the primary care provider who will routinely ask patients if a) they have lost interest in activities they enjoyed or b) they are feeling down, depressed, or hopeless. An answer in the affirmative would be followed for a screening tool for diagnosis and severity. The chosen tool is PHQ-9, which is a nine symptom checklist. The list includes items such as feeling tired or having little energy, poor appetite or overeating, and trouble concentrating, which are graded on a Likert-type scale. Based on the PHQ-9, the PCP determines a tentative diagnosis of major or minor depressive syndrome. Next is an assessment of suicide and/or homicide risk. If the patient is not at risk, the PCP goes on to prescribe treatment (HealthNow New York, 2013). The PCP refers the patient to a mental health professional if there are signs of psychosis, suicide or homicide risk, psychological therapy is needed, or substance abuse is indicated.
Evidence-based pharmacological treatments begin with antidepressant monotherapy, typically selective serotonin reuptake inhibitors (SSRIs), serotonergic noradrenergic reuptake inhibitors (SNRIs), bupropion, or mirtazapine. These drugs have shown similar efficacy in patients who have never been treated before. If the individual partially responds (reduction in PHQ-9 but not to remission level), augmentation with an additional SSRI, SNRI, bupropion, mirtazapine, buspirone, or thyroxine is suggested. If there is no response, monotherapy with a different antidepressant is indicated. This may be augmented as above if required. If the patient still does not respond, combination treatments with two or three of the above drugs, or combinations including tricyclic antidepressants, lithium, or monoamine oxidase inhibitors should be tried. At stage four, a different combination may be tried, or olanzapine, risperidone, or lamotrigine may be added, or electroconvulsive therapy may be indicated. When a medication or combination is successful, is should be continued for six to nine months following remission, then reduced to a maintenance dose (Rogge, 2014).
This algorithm for pharmacologic depression treatment is extensive and, in the first four stages, firmly based on evidence. Fortunately, the number of individuals who have not remitted by stage four is relatively small. At that point the evidence for suggested treatments is less robust. Throughout the pharmacological algorithm, evidence-based psychotherapy and lifestyle interventions are recommended (Rogge, 2014). The algorithm is followed relatively closely in the community, especially in the county clinic. This is required due to Medicaid regulations. Providers in the clinic must show that they are following the state prescribed processes. Private physicians are more able to adjust; however, the algorithm provides a number of alternatives for treatment-resistant patients.
A patient who manages her major depression well has easy, affordable access to both outpatient and inpatient care as needed. She is able to buy her prescriptions or they are provided through Medicaid, insurance, or pharmaceutical company programs. She has transportation to her appointments, which are initially frequent then, as she achieves remission, become farther apart. She is compliant with medication, therapy, and lifestyle changes as suggested by her doctor. Social support, whether from family, friends, support groups, or all three, is extremely important. If she has recurrent depression, she is always able to see her doctor and get new treatments or hospitalization if required. Because of proper management, her disease does not impinge too greatly on her life, and she has a normal life expectancy with positive quality.
According to the World Health Organization (WHO), depression is a common problem around the world, and it is increasing. There is a gap between provision of other types of health care and provision of mental health care in many countries. Therefore, the WHO has devised the Mental Health Gap Action Programme which includes depression as a priority. This programme helps non-specialist health care workers learn to assess, diagnose, and treat depression as well as other mental, neurological, and substance use disorders. The goal is to help people around the world with mental disorders to live normal lives even when there is an absence of mental health specialists (WHO, 2015).
Financial resources, whether private funds, insurance, or public aid (Medicare or Medicaid), are absolutely essential for management of a disease like depression which is typically chronic. Without proper management, the individual will have a poor quality of life, a shortened life expectancy, and may get into trouble with the law. Access to care is also crucial. People living in rural or exurban areas sometimes have difficulty getting to doctors, especially if a specialist is required. Programs that provide transportation to proper medical care as well as pharmacies can mean the difference between life and death (literally). Social support is very important. Withdrawal and isolation are symptoms of depression that also work to keep the person depressed. It is imperative for depressed persons to have some kind of social interaction. Support groups are particularly good because the person feels that other people understand (sometimes families and friends do not understand, and say harmful things unknowingly). Again, people living in isolated areas are likely to have difficulty finding support. If groups can be arranged that they attend when they go for medical appointments, this would help to increase their recovery.
If a person has major depression and does not have the financial resources, the access to care, and the social support required to manage the disease, his depression could last for years and become deeper until he is psychotic, suicidal, and/or homicidal. He may turn to alcohol or drugs to self-medicate. Jails and prisons are full of people with unmanaged depression and other mental illnesses. Psychosis may cause him to believe others are conspiring against him, or that he is actually dead inside, or that he sees and hears frightening images.
The depression process affects patients in life-altering ways. Stigma and lack of understanding of mental disorders can lead to loss of relationships, jobs, and self-respect. Even if family and employers try to understand, the depressed person’s behavior may be such that it is intolerable. For instance, if a man works as a car salesman and becomes depressed, he may fear talking to customers, feel like a failure, and eventually have no sales at all. He may begin to stay at home in bed every day. His employer would be hard pressed to keep him as an employee, no matter how much he tried to understand. The same would be true of a woman who is an executive in a company. Depression would cause her to lose faith in her ability to make decisions, and her indecisiveness would affect others in the company.
Similarly, depression can be devastating to families, especially those whose culture does not included the concept of mental illness. They do not understand what is happening to their family member and they may feel shame about his or her behavior. The financial costs can be considerable if they do not have insurance or public aid. Treatment of any chronic illness can become very expensive over time. Minority populations in my community tend to have less financial resources, and the availability of help is sometimes limited. In particular, there are families who slip through the cracks – they make too much money to qualify for Medicaid, but not enough to be able to buy insurance on their own. These families have difficulty paying for treatment and are especially stressed when inpatient treatment is needed.
Best practices for management of depression in my organization begin with screening individuals for the disorder. Many people put on their “happy face” even around their health care personnel, but in fact they feel like dying inside. Screening can help to find these people so they can be treated. It is important to let them know that depression is an illness just like heart disease – it is based in the brain and dependent on chemicals as well as other properties of the brain. Another best practice is knowledge of resources. Nurses and other personnel, as well as doctors, should be aware of resources available for people who have financial or transportation constraints. It is also important to know about area support groups for depression. Finally, nurses and other caregivers should be knowledgeable about the most-used psychiatric medications and should have written information at hand whenever it is needed.
The first strategy to implement best practices would be to routinely apply the two-question screening about loss of interest in activities and feeling down, depressed, or hopeless. Signs could be posted in each room to encourage this screening. Second, a survey of resources should be conducted and compiled into a brochure to give to patients. Finally, written material about the most commonly-used depression treatments should be developed to give patients (with alternate languages represented), and nurses should be familiar with the SSRIs, SNRIs, bupropion, and mirtazapine. The success of these practices could be evaluated by recording the number of patients identified with depression before and after the screening was invoked, devising a questionnaire to give to patients for feedback about resources, and a similar questionnaire for feedback concerning the pharmacology materials.
- Belzung, C., Willner, P., & Philippot, P. (2015). Depression: from psychopathology to pathophysiology. Current Opinion In Neurobiology, 30(SI: Neuropsychiatry), 24-30. doi:10.1016/j.conb.2014.08.013
- Bondy, B. (2002). Pathophysiology of depression and mechanisms of treatment. Dialogues in clinical neuroscience, 4, 7-20.
- HealthNow New York. (2013). Practice Guidelines for Providers. Retrieved from https://www.bcbswny.com/content/bcbs_prov_guid_depression.pdf
- Murck, H. (2013). Review: Ketamine, magnesium and major depression – From pharmacology to pathophysiology and back. Journal Of Psychiatric Research, 47955-965. doi:10.1016/j.jpsychires.2013.02.015
- Northoff, Georg, M.D., PhD. (2013). Psychopathology and pathophysiology of depression. Psychiatric Times, 30(9), 3-16C,16D,16E. Retrieved from http://vlib.excelsior.edu/login?url=http://search.proquest.com/docview/1442707660?accountid=134966
- Rogge, T. (2014). New York Methodist – Depression. Retrieved from http://nymethodist.adam.com/content.aspx?productId=10&pid=10&gid=000008
- World Health Organization (WHO). (2015). Depression. Retrieved from http://www.who.int/mediacentre/factsheets/fs369/en/
- Xin, D., & Pang, T. Y. (2015). Is dysregulation of the HPA-axis a core pathophysiology mediating co-morbid depression in neurodegenerative diseases?. Frontiers In Psychiatry, 61-33. doi:10.3389/fpsyt.2015.00032
