Evidence-Based Pharmacology: Major Depression

Introduction

Millions of people may regularly experience a feeling of hopelessness. Today, this condition is known as major depression or unipolar depressive disorder that is usually characterized by a lack of energy and interest in something. At the end of the 20th century, several researchers and writers came to the same conclusion that it was impossible to prevent the onset of clinical depression (Muñoz, Beardslee, & Leykin, 2012). However, because of this mental disorder’s frequency that is about 8-12% among the U.S. population and 16-17% among the European population (Flint & Kendler, 2014), depression has become one of the main topics for investigations and discussions.

Numerous attempts to prevent this disease have been already made relying on its genomic issues and pathophysiology. The peculiar feature of this disorder is that patients usually have a normal appearance, and its severe symptoms may be recognized with time. The main symptoms are irritation, a loss of interest and pleasure, appetite or weight changes, retardation, and even suicidal thoughts. In this paper, a certain attention to different treatment approaches that can be offered to patients with depression will be paid, including the evaluation of age implications, follow-ups, and referrals as a part of a care plan.

Pathophysiology

Pathophysiology of major depression is a topic that undergoes considerable discussions and doubts. There is no definite thought about what happens to a person with depression from a pathophysiological point of view. In many investigations, this information is missing, and people cannot find one certain source to rely on. Still, there is an idea that the progression of this disorder is based on an interaction between several pathophysiological mechanisms.

Verduijn et al. (2015) introduce four main mechanisms that are involved in etiology but cannot be associated with clinical progression: inflammation, HPA (hypothalamic-pituitary-adrenal)-axis, neurotrophic growth, and vitamin D. Inflammation, as a pathophysiological mechanism, is also supported by Müller (2014). Lam, Kennedy, McIntyre, and Khullar (2014) underline neural mechanisms’ importance, including cognitive dysfunction, psychological limitations, and work. For example, certain abnormalities are observed in the work of the brain the part of which is responsible for mood regulation. Therefore, depression is usually associated with behavioral changes. The reduction of the grey-matter volume is observed and leads to the decline of the hippocampal function that is closely connected to the HPA axis (Müller, 2014). A high level of corticosteroids determines the hippocampus as well. The work of the dopamine system is also important in the pathophysiology of depression. The brain is responsible for evoking appropriate reactions to food, people, and events. However, the changes in the ventral tegmental area lead to new or inappropriate reactions and attitudes.

Inflammation is a mechanism that is based on the production of serotonin or tryptophan. These compounds may be toxic to the brain and cause inflammation (Verduijn et al., 2015). Inflammation may also be caused by a high level of cytokine interleukin and C-reactive protein. Neurotrophic growth changes are observed through a low level of the brain-derived neurotrophic factor (BDNF). BDNF is a molecular regulator that promotes the survival of neurons in the brain. As soon as some changes occur in this area, the level of depression is increased, and the ability to adapt to something new is decreased. Finally, the role of hormones has to be discussed. Estrogen, thyroid, and vasopressin are the hormones that influence human behaviors and mood and promote the development of a depressive disorder through stress and isolation.

Genomic Issues

The genetic contribution to depression susceptibility remains to be an urgent issue for discussion in terms of which it is possible to understand its main biological underpinnings. On the one hand, it is possible to believe in the connection between depression and genes and investigate the development of this disorder among family members. On the other hand, genomic issues should not be defined as the only contributing factor, and the recognition of the environmental changes and other outside effects is required. Though genetic effects may be an insignificant disease risk, they cannot be neglected.

The chosen bipolar disorder is characterized by a strong genetic influence. Family history may increase the risk of depression in a patient. Regarding ordinary genetic calculations, if one of the parents suffers from depression or has some depression symptoms, a child is likely to have a 25% chance to develop similar symptoms. If both parents have this disorder, the chance increases by up to 50%. Flint and Kendler (2014) develop a thought that the genetic effects of depression differ between males and females, proving the correlation between sexes in about +0.60. Genome-wide association studies are developed in two stages, discovery and replication, to evaluate the combination of genotypes at different levels.

There were several attempts to prove the existence of a special depression gene (Müller, 2014). Still, researchers believe that it is early to establish the link between one particular gene and depression vulnerability. At this moment, the location of depression loci at 12q22-q23.2, 15q25.2-q26.2, and 17q11.2 with such genes as SLC6A4, APOE, and GNB3 have been proved (Flint & Kendler, 2014). The analysis of depression among twins proves that it is wrong to believe that one gene is responsible for depression. Identical twins share the same genetic code. However, if one of the twins becomes depressed, there is only a 19% chance of observing similar symptoms in another twin.

Data Collection

This evidence-based pharmacological paper depends on how well sources can be found, chosen, and used. In addition to the fact that all articles have to be up-to-date (within the last seven years publication) and credible (only peer-reviews articles are allowed), it is necessary to make sure that full texts of all sources are available. It is not enough to read abstracts or summaries to make correct conclusions and find out interesting details for the analysis. Therefore, in addition to the local library and the university library website, it is possible to address such research databases as Medscape, ProQuest, and NCBI using GoogleScholar as an available search engine where publication dates can be established. In terms of this evidence-based research project, the following keywords will be appropriate: “depression”, “major depressive disorder”, “mental disorder”, “genetics of depression”, “pathophysiology of depression”, and “depression treatment”.

To meet the grading criteria of this assignment, it is necessary to focus on the available clinical guidelines related to the chosen disease. The article by Gautam, Jain, Gautam, Vahia, and Grover (2017) contains a clear and up-to-date guideline on how to assess, evaluate, develop and manage a treatment plan, and consider all safety issues among patients. Also, the latest edition of a practice guideline for the treatment of patients with depression developed by the American Psychiatry Association (2010) was used. These sources helped to understand the peculiarities of treatment that had to be offered to patients with depression.

Literature Review: Disease and Treatment

To succeed in the development of an effective treatment plan, it is necessary to investigate the chosen disorder from different perspectives, discussing its major definitions, symptoms, and the experiences of different people. The term ‘depression’ is defined as “a passing mood or emotional state with elements of sadness and demoralization” (Muñoz et al., 2012). It is a common condition that is characterized by a high rate of recurrence and chronicity, as well as the growth of disabilities in the workplace and at home (Lam et al., 2014). As a rule, patients address doctors as soon as they observe such symptoms as regular, unexplainable fatigue, the inability to be involved in the required routine affairs, weight loss, and restlessness.

No age-dependent clinical presentations of depression are identified, and the age of the patient does not determine the age of onset, as well as its symptoms and a treatment course (Wilkowska-Chmielewska, Szelenberger, & Wojnar, 2013). To prevent depression or, at least, to reduce its frequency among the population, Muñoz et al. (2012) offer to keep depressive symptoms below a clinical threshold. If this requirement is taken into consideration, there is a possibility to reduce the duration of the disease and the avoidance of serious complications.

In recent studies, much attention is paid to risk factors for depression to identify the population that may be exposed to frequent cases of depression. For example, Muñoz et al. (2012) discuss specific and nonspecific risk factors. Specific factors include a family history of depression and a prior major depressive disorder. In these cases, the prevention of depression is an integral point of care. Such factors as poverty, violence exposure, posttraumatic stress disorder, or sexual abuse are defined as nonspecific and lead to high rates of depression as well (Muñoz et al., 2012). Taking into consideration these factors and evaluating the symptoms, doctors usually take several tests (Patient Health Questionnaire-9 or Beck Depression Inventory) to diagnose a patient and start developing a treatment plan.

Major depression treatment may be developed pharmacologically and non-pharmacologically. In both cases, doctors understand the threats and benefits of offered care. Pharmacotherapy is commonly recommended in 20-25% of cases (Kosteniuk, Morgan, & D’Arcy, 2012). Counseling is the most frequent form of non-pharmacological treatment that is chosen by about 15-16% of doctors (Kosteniuk et al., 2012). Anyway, antidepressants help to stabilize the condition of patients and reduce the growth of depressive mood and suicidal thoughts. Still, these medications alone can hardly help the patient to deal with depression. Therefore, the combination of approaches is supported by many researchers from different parts of the world (Kosteniuk et al., 2012; Lam et al., 2014; Verduijn et al., 2015). Still, it is necessary to remember that depression may be a separate disorder that bothers people and a symptom of other diseases. Therefore, close attention to all symptoms, and patient history is an integral step in clinical care.

Clinical Guidelines

Major depression bothers millions of people around the whole world. Therefore, it is not a difficult task to find some clinical guidelines and use them with certain patients. For example, much recognition deserves the guidelines developed by the American Psychiatry Association (2010). There are five main phases of treatment that can help patients deal with depression. First, there is psychiatric management in terms of which numerous interventions and activities for psychiatrists and patients are offered. It is necessary to establish a kind of alliance between a doctor and a patient to gather enough information about the past and present illnesses and complaints (American Psychiatry Association, 2010). Then, the time for a psychiatric assessment comes.

The promotion of safety, as well as the establishment of appropriate settings for treatment, is a requirement that cannot be ignored. As soon as the quality of life is evaluated, a patient has to be coordinated and be monitored in case new symptoms or complications occur. According to these guidelines, education to patients and their families have to be provided on the language they comprehend. An acute phase includes the choice of treatment and the identification of the approach that is appropriate for a patient and a facility. During a continuation phase, monitoring and evaluations are required to reduce the risk of having complications and obtaining ineffective treatment. Finally, the maintenance phase and the discontinuation of treatment, conclusions are made, and follow-ups with referrals are given to achieve the best results with the chosen care process (American Psychiatry Association, 2010). In this guideline, it is mentioned that women and men can receive different treatments because of the possibility to develop different reactions to the same events.

Gautman et al. (2017) use the recommendations given by the American Psychiatry Association to develop their clinical practice guidelines and contribute to treatment by recognizing difficulties in role transitions and functioning. Yoga and meditation is a common technique that is supported by different phases. Though these guidelines do not impose doctors and patients to follow one particular order of treatment, their hints and suggestions are based on cooperation and integration of different methods to achieve positive results.

Major Depression Treatment

Pharmacological Approaches

Pharmacological treatments have several benefits due to which many doctors and patients prefer this kind of approach. In many cases, patients recognize their problems and understand that some changes have to be made in their everyday lives. However, health problems and physical unpreparedness deprive people of an opportunity to follow their needs and demands. Therefore, doctors decide to provide their patients with pharmacotherapy that is based on taking such drugs as various antidepressants, serotonin reuptake inhibitors (SSRIs and MRIs), and monoamine oxidase inhibitors (Gartlehner et al., 2017). Paroxetine, citalopram, doxepin, and nefazodone are common drugs that have to be taken regarding the dosage established in the guidelines. A treatment period usually lasts about 10-14 days. Antidepressants help to deal with a deficit in neurocognitive domains and improve the functions of the brain (Lam et al., 2014). Neuropsychological tests are used to prove the effectiveness of antidepressants.

Taking medications during depression may be characterized by certain adverse effects. Therefore, patients have to be properly informed by their doctors and nurses and ready for health changes reports. For example, antidepressants may cause dry mouth, nausea, and a headache. Diarrhea, sleep disturbance, and tachycardia are also on this list. If these effects cause pain or are incompatible with high-quality life, medications have to be changed, and new assessments and evaluations should be developed.

Non-Pharmacological Approaches

Depression is one of the diseases where non-pharmacological treatment is as effective and helpful as pharmacological approaches are. Evidence shows that people who suffer from depression prefer to use non-pharmacological interventions and expect positive outcomes being achieved during the first step of treatment (Gartlehner et al., 2017; Kosteniuk et al., 2012; Müller, 2014). There are more than 100 possible, and doctors, as well as patients, have to evaluate all aspects of the disease development to make the right choice. Sometimes, clinicians are challenged by the existing variety of options for the treatment of depression (Gartlehner et al., 2017). Non-pharmacological treatment may be organized in hospitals, other specific facilities, and at patients’ homes.

For example, it is possible to use interpersonal therapy as a part of integrative therapy for adult patients (Gartlehner et al., 2017). Problem-solving interventions through communication and counseling with a psychiatrist can be offered. Behavioral therapies are usually used for treating young patients who have mild depression. ECT (electroconvulsive therapy) is another option for patients who fail to succeed with drug therapies or who show a positive response to previous cases of therapies. Acupuncture, meditation, and yoga can be rather helpful as well (Gautman et al., 2017). Transcranial magnetic stimulation is an approved non-pharmacological method that can be used to treat severe cases of depression when other methods cannot help.

Final Treatment Approach

The choice of treatment depends on the condition of a patient and the reactions to different approaches. If there are no definite precautions and limitations, one of the best treatment approaches is a mix of pharmacological and non-pharmacological interventions. First, a patient has to be assessed to define the level of depression. Then, one medication has to be chosen. For example, inhibitors may be used to reduce the threat of inflammation and stabilize the condition of a patient with middle depression (Gartlehner et al., 2017; Müller, 2017). Also, professional counseling should be used so that a patient may discuss personal problems and concerns with an expert and be sure to find some solution. Finally, yoga has to be included in a care plan because this activity helps to relax physically and emotionally. During this mixed approach, nurses have to promote education and explanations of how to deal with depression, what this disease’s main complications and consequences, and why it is better to address doctors as soon as some symptoms are notices. Communication between nurses and depressive patients is a key point in treatment.

Plan for Follow-up and Referral

Depression is a type of mental disorder where follow-ups play a very important role. Kosteniuk et al. (2012) identify that a two weeks period is an optimal solution for follow-up that can be suggested to MDE patients. A psychologist and a general therapist are the two referrals in the case of a depressive patient. If new symptoms are mentioned, it is necessary to address a doctor of a specific area. In the majority of cases, general therapists offer to visit specialists. However, patients are also welcome to make their independent decision. Sometimes, patients may want to cooperate with a nutritionist and a professional physical coach to learn enough information and have good experience for the promotion of a healthy lifestyle.

References

American Psychiatry Association. (2010). Practice guideline for the treatment of patients with major depressive disorder (3rd ed.). Web.

Flint, J., & Kendler, K.S. (2014). The genetics of major depression. Neuron, 81(3), 484-503.

Gartlehner, G., Wagner, G., Matyas, N., Titscher, V., Greimel, J., Lux, L.,… Lohr, K. N. (2017). Pharmacological and non-pharmacological treatments for major depressive disorder: Review of systematic reviews. BMJ Open, 7(6). Web.

Gautam, S., Jain, A., Gautam, M., Vahia, V.N., & Grover, S. (2017). Clinical practice guidelines for the management of depression. Indian Journal of Psychiatry, 59(1), 34-50.

Kosteniuk, J., Morgan, D., & D’Arcy, C. (2012). Treatment and follow-up of anxiety and depression in clinical-scenario patients. Canadian Family Physician, 58(3), 152-158.

Lam, R. W., Kennedy, S. H., McIntyre, R. S., & Khullar, A. (2014). Cognitive dysfunction in major depressive disorder: Effects on psychosocial functioning and implications for treatment. The Canadian Journal of Psychiatry, 59(12), 649-654.

Müller, N. (2014). Immunology of major depression. Neuroimmunomodulation, 21(2-3), 123-130.

Muñoz, R. F., Beardslee, W. R., & Leykin, Y. (2012). Major depression can be prevented. American Psychologist, 67(4), 285-295.

Verduijn, J., Milaneschi, Y., Schoevers, R.A., van Hemert, A.M., Beekman, A.T.F., & Penninx, B.W.J.H. (2015). Pathophysiology of major depressive disorder: Mechanisms involved in etiology are not associated with clinical progression. Translational Psychiatry, 5(9). Web.

Wilkowska-Chmielewska, J., Szelenberger, W., & Wojnar, M. (2013). Age-dependent symptomatology of depression in hospitalized patients and its implications for DSM-5. Journal of Affective Disorders, 150(1), 142-145.

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