A Global Perspective on Mental Health

Critical appraisal of current drug treatments of depression

Introduction

Manifestations of mental illnesses are increasingly being evident in the people. The prevalence of mental health according to the WHO (2019) estimates indicates that one in four people will suffer from mental illness complication at any point in their lifetime. Nearly 450 million people worldwide suffer from mental health disorders. Depression is one of the common forms of mental illness that affect millions of people. The condition affects adults, adolescents and children. Furthermore, the condition of depression can cause disability, among other effects. By definition, depression is a mental health disorder responsible for persistent feeling of sadness and loss of interest.

The clinical manifestation of depression is exhibited through different signs and symptoms such as reduced interest and pleasure in the activities once enjoyed, changes in appetite, unintentional weight loss or gain, agitation and restlessness. Among adolescents and adults, depression can arise from the unpleasant and sad experiences such as loss of job, bereavement, and episodes of depression can last for days, weeks, months or even years. Among children however, postpartum is the common form of depression children face. This study critically analyses the various drug treatment alternatives for depression. To achieve this, 5 most common drug interventions will be explored, followed by a discussion of pertinent issue of drug resistance and side effects associated with drug treatments of depression.

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Pharmacological approach to treatment of depression

Grabowski and Przybylak (2019) point that following the clinical diagnosis of depression there are pharmacological options that can be used in treatment of depression. However, the authors contend that depressive patients are less likely going to cooperate in the medication. Drug interaction following administration of medication to depressive patients varies depending on the type of the drug administered, the severity of the depression condition and the patient’s body immunity level.

In their study, Grabowski and Przybylak (2019) explain that following the administration of drugs to depressive patients, remission after monotherapy is reached in 20-25% of the patients while therapeutic response to treatment during the first pharmacology attempt is observed in a third of the patients examined in their study.

Drug treatments have been to result in rapid improvement of mental state as a mechanism of action against depression. The commonly used drugs for treatment of depression are discussed in this section

Mainserin and Mirtazapine

These drugs have been identified to have different molecule structure but similar drug activity potential due to similar effects and side effects manifested upon administration of the drugs (Grabowski and Przybylak 2019). In this regard, Mainserin and Mirtazapine are strong antidepressants with hypnotic and anxiolytic activity which can potentially appear prior to the target effect treatment, though it rarely manifests during a single dose.

The dosage significantly determines the neuropysiologiocal profile of the drug. Drevets and Li (2018) account that the hypnotic effect appearing at lower doses of mainserin and mirtazapine drugs can be eliminated by increasing the dosage of the drugs resulting in the activation of noradrenergic pathway to ease excessive sedation at low doses drugs.

Following the administration of these drugs in palliative care, patients can have increased appetite, although it has been reported that this effect is largely not physiological. Additionally, mirtazapine has been reported to have antiemetic effect that can improve the patient’s wellbeing at the end of life. However, there are disadvantages associated with mainserin and mirtazapine, common being the difficulty in achieving therapeutic doses occasioning from intense side effects of the drugs such as sedation, restless leg syndrome and potential cause of delirium (Grabowski and Przybylak 2019). There are more complications associated with dosages of mainserina and mirtazapine including neutropenia (bone marrow suppression), oedema, and hypertension (reported in cases of high dosage).

Pregablin

This depression treatment drug is a gamma-ammunobutyric acid analogue whose activity focuses on the calcium channes on the central nervous system of the patient. Upon administration of the drug, it results in rapid reduction of anxiety and improvement of sleep. Grabowski and Przybylak (2019) identify that pregablin can further be used in palliative care to manage analgesia and reduce somatic symptoms of anxiety.

However, much as the drug can be used to reduce signs of anxiety thereby diminishing suicidal thoughts and improving then mood of the patient, there is a risk of addiction to the drug especially when used for long term treatment. Grabowski and Przybylak (2019) explain that due to the nature and activity of the drug, it should be a recommended dose for treating anxiety and due to the possible addiction to the drug, fostered by body tolerance to the drug following long term use the drug should not be used for monotherapy.

Quietiapine

This depression treatment drug has the characteristic of atypical antipsychotic drug whose effect is dependent on the dose- and form of the drug administered. The mechanism of action of quietiapine is manifested through numerous neurotransmission systems of the nervous system (Grabowski and Przybylak 2019). The drug has abilities for dopamine, antihistamine, and cholinolytic blocking as well as hypnotic activity when administered in low doses.

Quietiapine drug has been proposed to be effective in management of anxiety and depression, when significant doses are administered to the patients. Specifically, extended release form in doses of 150 to 300mg of the drugs has been attributed to have effective anxiety and depression management ability. The drug can be used in both monotherapy and polytherapy with high efficacy potential for major depression disorder management.

However, just like the previously discussed drugs, quietiapine is associated with many side effects when administered as depression management drugs. Common side effects include severe decreases in blood pressure, and sedation.

Trazodone

This depression treatment drug is classified as antidepressant whose effect is dependent on the dose administered to the patients. Low doses of trazodone have sedative and hypnotic activity, medium dose have anxiolytic activity, while high doses of 300g and more have antidepressant activity (Grabowski and Przybylak 2019). Upon administration of the drug, patients experience rapid sleep improvement, and anxiety and restlessness reduction.

Trazodone can be administered in two forms as either chronic release (CR) or extended release (XR) form. Grabowski and Przybylak (2019) explain that a combined use of the two forms of the drug can be more effective in managing depression. However, sleep induced by trazodone drug has physiological features. Trazodone drugs have the potential of causing cardiac conduction and rhythm disturbances.

Ketamine

Ketamine drugs have for a long time been used in medical applications especially in the field of anaesthesia. However, recent studies have sought to test its applicability in treatment of depression patients. This drug has an antagonist N-Methyl-D-aspartic acid.

The drug functioning of ketamine allows the patients who respond to the drug may show reduced suicidality and relief from serious symptoms of depression. However, just like other antidepressants, Ketamine side effects vary from one patient to the other depending on the dosage administered to the patient.

Ketamine has also been administered to patients that have exhibited treatment- resistant depression. Two forms of the drug (Racemic and esketsmine) are mainly used in the treatment of these types of depression. Unlike the other discussed drugs, Racemic Ketamine can be administered to the bloodstream through an intravenous infusion often referred to as IV.

However Ketamine is associated with side effects, just like other drugs discussed above. Ketamine side effects include high blood pressure, nausea and vomiting, perceptual disturbances and dissociation.

Domany et al (2019) examined the use of ketamine as an antidepressant to manage depression-resistant conditions. The authors presented that up to 30% of depression patients fail to respond to depression treatment drugs leading thus developing resistance to medication. Ketamine is then administered to treat such patients to manage the condition, often referred to as Treatment-resistant depression.

In their study, Domany et al (2019) explain that intravenous administration of ketamine to patients presents obstacles in the clinical applicability in community setting. When testing the application of ketamine in treatment of treatment-resistant depression, Domany et al (2019) conducted a randomised placebo-controlled proof-of-concept trial for 21 days and a follow-up session at day 28. From this the authors found out that repeated oral administration of ketamine can help in reduction of depression symptoms and can be tolerated in community settings.

Discussion

Mental health illness may have serious complications to patients with its effects potentially lasting for years. Depression, one of the common forms of mental illnesses may have serious impacts on the patients. Drug treatment is one of the common clinical interventions for management of depression. However, regardless of whether the all above discussed depression treatment drugs are administered, there are key issues with the drug treatment methodology for management of depression.

Chamberlain et al (2019) conducted a study to examine the drug resistance to the drug treatment approach in managing depression. In their study, the authors examined the effect of C-reactive protein to depression drug resistance. C-reactive protein is a type of peripheral immune system activation which has been linked to major depressive disorder. Peripheral immune biomarkers have been associated with heterogeneity in response to drug treatment of depression symptoms and one of the contributors to major depressive disorder. Therefore, whereas the above discussed drugs have presented ability to significantly manage depression conditions, existence of peripheral immune system activation affects the drug activity and efficacy of the drug in the treatment of depression (Chamberlain et al 2019). Instead, when the drug fails to manage the immune biomarkers such as C-reactive protein, the patient’s depressive condition may worsen resulting into major depressive disorders.

To support this, Chamberlain et al (2019) examined the effect of C-reactive protein on the drug action against depression. In their study, the authors recruited participants with depression conditions and found out that patients with treatment-resistant depression have the most abnormally increased CRP levels in comparison to treatment responsive or untreated patients. This point to the fact that drug activity against depression is largely inhibited by peripheral immune system activation and thus accounts to the limited effectiveness of the drugs in the management of depression. From the drugs reviewed above, most reviews have placed the effectiveness level of the drug at 30- 50%.

The limited effectiveness of drugs in management of depression raises questions on how well depressions can be managed (Drevets and Li 2018). The above reviewed medications tend to support the fact that effective management of depression using drug treatment depends on the dosage level administered to the patients with high dosage appearing to give better results.

Tirado et al (2018) sought to examine the effectiveness of depression dosage among patients with substance use disorder. The authors identified that clinical diagnosis of mood disorder among substance users is complex depending on a number of factors. However, due to the mood disorders among patients with substance use history, there is a high possibility of dual depression which is manifested through some peculiar features. According to Tirado et al (2018) dual depression is more frequent when substance use disorder is moderate to severe, dual mood disorder is frequently independent than induced, and patients with dual depression have a high prevalence of attempted suicides. However, the authors recommend that depressive episode should be treated even if patients are actively using drugs but conclude that the efficacy of depression treatment drugs is reduced by the use of substances such as alcohol, cocaine and opiates.

Factors influencing the efficacy of anti-depression drugs

It has been clearly identified that depression treatment drugs exhibit multiple functioning potential when administered to patients. There are crucial factors that shape the effectiveness of these ant-depression drugs and are discussed herein.

Age

Studies have sought to examine the body response to depression treatment drugs in respect to age and it can be explained that the efficacy of antidepressants in older adults is slightly lower with these categories of patients taking longer time to recover compared to young adults (Tirado et al 2018). This can be linked to the fact that older people’s body have low functioning ability as well as immunity level compared to younger adults who are generally active and concerned with living a healthy lifestyle.

The severity of depression condition

In the previous section covered in this essay, it has been identified that depression condition can occur and last for days, weeks, months or even years. Therefore, there is a link between the longevity of the depression condition with the medication used. In this case, it may be improper to administer high dosage of anti-depressants to the patients whose depression episode is only days or weeks old but such a dose may be suitable for patients with major depressive disorder (Tirado et al 2018). Additionally, this study has identified that ketamine is largely administered to patients whose depression episodes appear resistant to medication. In this case, it may be improper to administer high dosage of ketamine to patients with mild manifestation of depression (Grabowski et al 2019).

Lifestyle behaviours accompanying depression

Depression condition stem from a number of causal factors and instances including loss of job, traumatic experiences and lifestyle behaviour (Chamberlain et al 2019). These causal factors affect individuals differently and thus, require different clinical approaches to manage the depressive conditions among the patients. For instance, patients who are depressed due to a job loss may not be accorded similar drugs to those with chronic depression stemming from addiction to drugs and substances such as cocaine and alcohol.in an event a common drug is administered to these two different cases, patients whose depression is accompanied with accustomed use and addiction to drugs and substances may show no or little response to the treatment.

From the examination of the 5 drugs in the previous section of this analysis, it is clear that each drug exhibit side effects associated with drug activity and body reactions upon the administration of the drugs to manage depression (Grabowski et al 2019). This study has identified that the side effects of the anti-depression drugs vary in terms of the severity of the side effect in the body. Much as the antidepressants described above have abilities to treat depression and lead in the recovery of the patients, the side effects are quite common. Among the common mild side effects include drowsiness, nausea, tiredness, dry mouth and trouble sleeping, especially hours of weeks after the administration of the drugs (Tirado et al 2018). However, there are other significantly serious side effects whose occurrence may be a cause of alarm and can aggravate the condition. These side effects include blurred vision, anxiety, lower sex drive and weight gain. Prolonged feelings of anxiety following the administration of drugs for instance may aggravate the feelings of depression (Domany et al 2019). This is equally the case to the lower sex drive which is as well a symptom of depression. Weight gain is a precursor of development of obesity, a chronic medical condition that can last for a life time and increases chances of development of cardiovascular and heart complications. Furthermore, the potential addiction to antidepressants hampers the recovery from the depression since the patients will be accustomed to the medication resulting in misuse of the medication and exposure to the side effects associated with the drugs (Chamberlain et al 2019).

Recommendations

Drugs are mainly used in the treatment of depression and its symptoms. The above list of drugs is evidence of the availability of antidepressants that can be applied in managing the depression condition. However, gearing in mind the side effects and the possible low efficacy of these drugs, and the fact that there are factors such as age, drug and substance abuse that inhibit effective functioning of drugs, there are crucial recommendations that can be followed in order to achieve the best results from the drugs. To begin with, it is important that the depressive patients is diagnosed and drugs prescribed by a qualified physicians.

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Qualified physicians have the knowledge of depression management and will recommend the appropriate dosage to patients depending on the severity of their depressive condition (Tirado et al 2018). There might be temptation to buy over the counter drugs which may result into dosage miscalculations and wrong diagnosis. Additionally, there is need to adhere to the dosage prescribed by the physicians. Bearing in mind that, as a result of the depression effect, patients with depressive condition may result medication and taking of the drugs, the family should be involved to ensure that they guide their patients to adhere to the right dosage prescribed by the doctor. However, since the side effects of the drugs are real, and may be severe depending on different factors, it is crucial that the patients be monitored and seeks help from the doctor (Grabowski et al 2019). This will increase the efficiency of managing depression.

Conclusion

Depression is a psychological disease that can cause cognitive impairment and also affect other aspects of life such as socialization, and general physical wellbeing. Depending on the severity of the condition, patients with depression exhibit different reactions to the drugs administered to medicate the pain and aid in their recovery. There are a host of antidepressants that can be administered to manage the depression condition and such drugs have different performance potential depending on the dosage administered to the patients. Ketamine however, compared to the other discussed drugs above, appear to have more effect on more serious depression conditions. However, despite the differences in the drug potential, there are other factors that inhibit the efficiency of the medication and they include age, and the severity of the depression condition as discussed above. These factors account for the heterogeneity in the response to the drugs administered to manage depression. It is also important to note that effective management of depression condition can be achieved through following the recommendations highlighted above including adhering to the right dosage, and seeking help from the doctor in case of the manifestation of the side effects associated with the anti-depression drugs.

References

Chamberlain, S.R., Cavanagh, J., de Boer, P., Mondelli, V., Jones, D.N., Drevets, W.C., Cowen, P.J., Harrison, N.A., Pointon, L., Pariante, C.M. and Bullmore, E.T., 2019. Treatment-resistant depression and peripheral C-reactive protein. The British Journal of Psychiatry, 214(1), pp.11-19.

Domany, Y., Bleich-Cohen, M., Tarrasch, R., Meidan, R., Litvak-Lazar, O., Stoppleman, N., Schreiber, S., Bloch, M., Hendler, T. and Sharon, H., 2019. Repeated oral ketamine for out-patient treatment of resistant depression: randomised, double-blind, placebo-controlled, proof-of-concept study. The British Journal of Psychiatry, 214(1), pp.20-26

Drevets, W.C. and Li, Q.S., Janssen Pharmaceutica NV, 2018. Method for the treatment of depression. U.S. Patent 10,098,854.

Grabowski, J. and Przybylak, M., 2019. Pharmacotherapy of depression in patients with advanced diseases. Palliative Medicine in Practice, 13(2), pp.82-89.

Tirado-Muñoz, J., Farré, A., Mestre-Pintó, J., Szerman, N. and Torrens, M., 2018. Dual diagnosis in Depression: treatment recommendations. adicciones, 30(1).

Annoted Bibliography

Grabowski, J. and Przybylak, M., 2019. Pharmacotherapy of depression in patients with advanced diseases. Palliative Medicine in Practice, 13(2), pp.82-89.

Graboski and Przybylak conducted a study to evaluate the most commonly used drugs in the treatment of depression. From their findings, the listed individual drugs such as Ketamine, Quietiapine and Trazodone, and presented evidence on their efficacy as well as side effects when administered in the body.

Domany, Y., Bleich-Cohen, M., Tarrasch, R., Meidan, R., Litvak-Lazar, O., Stoppleman, N., Schreiber, S., Bloch, M., Hendler, T. and Sharon, H., 2019. Repeated oral ketamine for out-patient treatment of resistant depression: randomised, double-blind, placebo-controlled, proof-of-concept study. The British Journal of Psychiatry, 214(1), pp.20-26

Domany et al (2019) conducted a study to examine the ability of Ketamine in treating patients with resistant depression. The oral doses were administered to sampled participants in a randomized and placebo-controlled setting. From their findings, the authors presented that oral ketamine can be administered to the patients in a community setting and have significant ability to manage resistant depression condition

Chamberlain, S.R., Cavanagh, J., de Boer, P., Mondelli, V., Jones, D.N., Drevets, W.C., Cowen, P.J., Harrison, N.A., Pointon, L., Pariante, C.M. and Bullmore, E.T., 2019. Treatment-resistant depression and peripheral C-reactive protein. The British Journal of Psychiatry, 214(1), pp.11-19 Chamberlain et al (2019) focused their study on evaluating the effect of treatment-resist5ant depression and C - reactive protein on response to drugs administered to manage depression.

After analysis, the authors found that C - reactive protein inhibits the patient’s response to medication and the efficacy of the drug in treating depression in patients with C - reactive protein or resistant-depression is quite low.

Tirado-Muñoz, J., Farré, A., Mestre-Pintó, J., Szerman, N. and Torrens, M., 2018. Dual diagnosis in Depression: treatment recommendations. adicciones, 30(1)

Tirado et al (2018) focused their study on the treatment recommendations on the patients with major depression and at the same time grappling with substance use disorder. The authors found out that patients with substance use disorder such as alcohol, cocaine or cigarette show little response to depression medication drugs and as such, they recommended that they should be accorded medication that tackles depression as well as substance use disorder.

Drevets, W.C. and Li, Q.S., Janssen Pharmaceutica NV, 2018. Method for the treatment of depression. U.S. Patent 10,098,854.

Drevets and Li describe the methods used in the treatment of depression, their report covers the drugs used in treating depression and highlights key issues such as low efficacy and accompanied side effects that affect patients administered with depression management drugs. The author found that different drugs have different efficacy ability when administered to treat depression.

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