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Depressive disorder is a mental health condition characterized by cognitive, behavioral, somatic, emotional, and cognitive symptoms. In 2017, the National Institute of Mental Health (NIMH) conducted a survey that showed that approximately 17.3 million Americans were suffering from certain types of major depressive disorders (MDD) (Almohammed et al., 2022, p. 1). Individuals suffering from chronic diseases such as Cancer also have a higher chance of developing MDD. This is usually associated with a change in mood, leading to a sad life, poor concentration, and lack of interest. Patients suffering from MDD require intervention such as antidepressant, which is believed to improve their quality of life (Teng et al., 2022). Treating MDD among adolescents and children has been challenging for ages. However, antidepressants have changed the face of MDD in children and adolescents. In pediatrics, antidepressants are administered when they are experiencing severe cases of the disorder. They are administered based on the clinical guidelines regarding mood disorders. It is associated with improving the health condition of the individuals that utilize it to improve their depressive lifestyle.
Individuals suffering from Major Depressive Disorder (MDD) utilize antidepressants as the primary intervention method. However, there is a controversy surrounding the efficacy of the antidepressants used. The variation in efficacy is majorly dependent on the age group of individuals utilizing the intervention, including adults, children, and adolescents. The controversy significantly affects the young population. This is because antidepressants are believed to cause poor quality of life and severe consequences in education and social performance. Furthermore, they have been associated with suicidal thoughts, making individuals who use them commit suicide or self-harm because of the extra energy they provide to the patients. The controversy surrounding antidepressants affects how they are perceived by the public, researchers, and their administration in the clinical setup as it provides a different view on their efficacy and suicidality.
Antidepressants treat several mental health conditions in children, adolescents, and adults (Boaden et al., 2020). They are usually licensed based on the type of mood disorder specifically designed to treat. The group supporting antidepressant efficacy argues based on the legality check by organizations such as Food and Drug Administration (FDA). The FDA approved several antidepressants to treat MDD (Boaden et al., 2020). For example, clomipramine, sertraline, fluoxetine, and fluvoxamine for obsessive-compulsive disorder (OCD). Bipolar depression uses a combination of fluoxetine and olanzapine. Duloxetine is licensed to be used for generalized anxiety disorder (GAD) (Boaden et al., 2020). In the United Kingdom, sertraline and fluvoxamine are approved to treat OCD. Fluoxetine is certified for MDD, and imipramine for involuntary urination, mostly at night. However, there are antidepressants used by clinicians, although they have not been certified. This includes imipramine used in attention-deficit/hyperactivity disorder (ADHD) and amitriptyline individuals with damaged nervous systems.
Most researchers have focused on meta-analysis and randomized controlled design to argue the controversy surrounding antidepressants. Masi (2022) used a different analysis to explain the controversy surrounding antidepressants’ efficacy. The researcher focused on the reports analyzed by the FDA regarding the acceptability of antidepressant drugs. Based on the FDA reviews, which make them license a given drug or not, the efficacy of antidepressants varies significantly (Masi, 2022). For instance, the FDA recommended using venlafaxine in treating depression because it had the most significant effect, which is supported by the high evidence load among all the antidepressant drugs analyzed.
Multiple researchers and organizations have checked the efficacy of antidepressants such as fluoxetine, sertraline, paroxetine, bupropion, and others. According to Boaden et al. (2020), fluoxetine has a high efficacy with an average effect when used to treat severe symptoms of depression such as MDD. Based on Boaden et al. (2020) study, other drugs that have proven effective include paroxetine and fluvoxamine, which are effective in relieving severe symptoms of Stress Response Syndrome. In the treatment of OCD, sertraline and fluoxetine proved effective. Desipramine and bupropion improve the clinical symptoms of ADHD and has a large confidence interval. Tianeptine and clomipramine effectively deal with persistent symptoms of autism spectrum disorder (ASD). Teng et al. (2022) research show that using antidepressant is helpful among adolescents and children with MDD despite not portraying positive effects in improving their quality of life. This indicates that only escitalopram, fluoxetine, and nefazodone are helpful in the handling of symptoms of depression in children.
Additionally, the supporting group argues that antidepressants are more effective than a placebo in treating depressive symptoms. Cipriani et al. (2018) argue that antidepressants effectively handle MDD among adults. Among them that show high response with low dropout rates include paroxetine, sertraline, escitalopram, agomelatine, and mirtazapine. Cipriani et al. (2018) show that most antidepressants are not helpful in children and adolescents. However, fluoxetine has proven to be effective in reducing depression symptoms. Cipriani et al. (2018) also argue that the variation in the efficacy of antidepressants among children, adolescents, and adults is because of the small number of research conducted in the area and the methodology used. This leads to the notion that antidepressants are ineffective among children and adolescents. Additionally, for antidepressants to be effective, individuals need to use them for several weeks. Those that halt utilizing it at the beginning are the ones that tend to experience poor responses.
In the identification of antidepressant efficacy, placebo comparison is usually used by researchers. Qin et al. (2018) investigated the effectiveness of the antidepressant by grouping the interventions into placebo, TCAs, SSRIs, Trazadone, and SNRIs. Efficacy was measured based on the mean variation of the symptoms of depression. Their acceptability and tolerance were analyzed using patients on antidepressant treatment and later discontinued because of adverse effects arising from the drugs (Qin et al., 2018). The implications of the research were derived from the rate of discontinuation, which imply that the efficacy of the antidepressant is minimal. Three antidepressants, paroxetine, doxepin, and nortriptyline, were effective compared to the placebo. However, the acceptability rate varied significantly as the doxepin rate was higher than that of paroxetine. Qin et al. (2018) concluded that doxepin has the highest efficacy because of overall tolerability and acceptability. The clinical implication is that paroxetine effectively treats poststroke depression (PSD) as it balances tolerability, effectiveness, and acceptability. Additionally, it is safe, making it fruitful when treating depression.
Despite antidepressants portraying positive results, ketamine has been associated with adverse outcomes such as side effects, including confusion, high blood pressure, and dissociation. Although these effects are usually considered mild, the clinical use of antidepressants is restricted by abuse liability and psychomimetic side effects (Kryst et al., 201d 9). However, the ketamine efficacy is accepted in the short term. The side effects include hypoesthesia, vomiting, dizziness, high blood pressure, lethargy, sedation, anxiety, vertigo, drunkness, and nausea. During the short-term administration of ketamine, adverse events tend to change from mild to moderate (Kryst et al., 2019). The chronic outcome of the serum involved painful urination, liver injury, and ulcerative cystitis (Kryst et al., 2019). Because of the above side effects, the drug can be administered by the physician in a healthcare setting which allows monitoring of the patient adverse effects.
Ketamine efficacy varies among researchers and studies depending on the methodology used. McMullen et al. (2021) studies show that repeat-dose ketamine monotherapy portrays significant effectiveness among individuals with treatment-resistant depression (TRD) who previously responded to IV ketamine. Furthermore, when combined with other interventions, such as electroconvulsive therapy (ECT) and cognitive behavioral therapy (CBT), it shows efficacy evidence (McMullen et al., 2021). Other oral agents did not portray positive results when used in adults having TRD. Repeat-dose IV ketamine is supported with preliminary evidence, such as RCT, which shows its effectiveness in TRD treatment. Despite the result showing short-term efficacy, the finding leaves behind a controversial issue concerning ketamine.
Identifying the (R, S) ketamine for individuals suffering from depressive symptoms was a significant breakthrough. This has led to the development of an esketamine nasal spray currently being used in Europe and the USA despite the efficacy issue surrounding its side effects (Wei et al., 2020). R-ketamine lacks a therapeutic option, and research is still concerning its efficacy. Although R-ketamine research has not been completed, its safety characteristics in humans are better than s-ketamine and (R, S)-ketamine. Wei et al. (2020) study shows that R-ketamine has a long-lasting effect and potency compared to S-ketamine and (R, S)-ketamine. Wei et al. (2020) argue that the safest antidepressant can be R-ketamine, although it requires further research concerning its use in depressed patients. Despite researchers condemning the use of ketamine have failed to produce robust evidence regarding ketamine effects in depression patients. Patients with TSD have improved depression symptoms after using esketamine nasal spray. The development of oral antidepressants such as esketamine is expected to bring change in the mechanism of action to meet the medical need of patients. Esketamine nasal spray is helpful in patients with TSD because of its rapid action.
However, in treating post-traumatic stress disorder (PTSD), none of the antidepressants proved helpful. For instance, venlafaxine, imipramine, and duloxetine also proved ineffective for use by young people suffering from acute major depression. There was no significant difference in treating stress response syndrome (SRS) and ADHD (Boaden et al., 2020). Children who have ASD portrayed a significant challenge tolerating citalopram and tianeptine. Children and adolescents faced a risk of committing suicide or having suicidal thoughts when administered venlafaxine. Antidepressants with low efficacy and high dropout rates comprise trazodone, reboxetine, and fluvoxamine.
A person suffering from severe mental illnesses (SMIs) like MDD may commit suicide. The contributing factors to such risk include substance use disorder, high anxiety levels, severe neuropsychiatric disorder, personality, and substance abuse disorder. Individuals supporting the notion that antidepressants lead to suicidality thoughts argue that it results from improper treatment when using antidepressants involving psychosocial and physical treatment. According to Fornaro et al. (2019), patients exposed to Selective Serotonin Reuptake Inhibitors (SSRIs) had a high suicidal behavior. This made the Food and Drug Administration (FDA) warn about the resulting black box warning on antidepressants. The warning was effective in 2005; in 2006, it was extended to individuals aged 25 (Fornaro et al., 2019). This resulted in media reports concerning the link between suicide and antidepressant drugs. Blackbox warning created an alarm on the effects of antidepressant drugs in causing suicidal risks and thoughts.
Consumption of antidepressants varies significantly with countries and the level of economic development. The opposing group also believes that increased use of antidepressants has promoted suicidal risks and thoughts. Australia is among the top countries that consume significant levels of antidepressants. In the period 2000 to 2015, it was ranked second after Iceland (Whitely et al., 2020, p. 7). Australia majorly consumes SSRI antidepressants, and in 1999/2000, the country consumed 58% of the antidepressants through Pharmaceutical Benefits Scheme (PBS). In 2009/2010 and 2018/2019, the consumption was 45% (Whitely et al., 2020, p. 7). The two periods show significant use of antidepressants which is also linked to suicidal behaviour.
Using time series in the analysis of suicide data has proved effective. The suicide statistics using the three-year moving average show that individuals under 24 experienced an increased rate of 5% in suicide from 2003 to 2005 compared to 2007 to 2009 (Whitely et al., 2020, p. 8). From 2008 to 2009, the suicide rate expanded by 2.9%; from 2017 to 2018, it rose by 4.8% (Whitely et al., 2020, p. 8). The increase from 2017 to 2018 is attributed to the surge in the prescription of antidepressants by 66%, and in the same period, the per capita suicide rate rose by 49% (Whitely et al., 2020, p. 8). The researcher links antidepressant increased prescription and suicide rate. Based on the randomized controlled trials, antidepressants prove to be effective compared to a placebo because of their high response rates. According to Masi (2022), age significantly determines the suicidal risk when using antidepressants. Adolescents and young adults have a higher suicide risk.
On the other hand, other people believe that antidepressant does not lead to suicidal ideation because no clinical trials have been conducted to provide a variation between antidepressant-induced suicide and other underlying conditions. This makes it challenging to accurately represent the active suicide thoughts caused by using antidepressants and with a true frequency of antidepressant-induced suicidal ideation and behavior (AISIB) (Witt-Doerring & Mathew, 2019). When using an active group to report AISIB, the risks include individuals that ended up being suicidal even with other treatment, patients that were suicidal after because of AISIB, and the number of those that were not suicidal after utilizing other treatment models (Witt-Doerring & Mathew, 2019). Giving actual numbers on these cases has become a problem, making it inaccurate to argue suicidal thoughts and behavior induced by antidepressants without concrete evidence.
Additionally, protocols such as the suicide rating scale can provide information concerning drug which causes suicidality; it can only be done by using the clinician’s judgment. This also supports the fact that there is not enough evidence to associate suicidality thoughts and behavior with the use of antidepressant treatment and prescription (Witt-Doerring & Mathew, 2019). Other mechanisms developed, such as scales to detect suicidal thoughts in children, adolescents, and adults, are hypothetically based on detecting activation syndrome. All these developments are coherently dependent on a true or false hypothesis, making the findings inaccurate (Witt-Doerring & Mathew, 2019). A generalized ratio of patients using antidepressants daily to outshine the treatment’s benefits does not provide a significant population representation. In most industrial, clinical trials, the patients who provide data on suicidal thoughts are usually not experiencing AISIB and are taking other mental health medication or psychiatric comorbidities (Witt-Doerring & Mathew, 2019). Additionally, the environment in which they are subjected to collect suicidal data is far more different than clinical trials.
For example, they used antidepressant suicidality data, where children and adolescents form a significant part of the study. According to Witt-Doerring and Mathew (2019), a 36-week clinical trial was conducted to check suicidality thoughts and monitor individuals undergoing outpatient with major depressive disorders. The study excluded the youths because of the high risk of suicide, as they were associated with historical suicide ideation among the group. The study also incorporated individuals undergoing treatment for other psychiatric disorders, and the experiment was randomized and double-blinded in the first 12 weeks (Witt-Doerring & Mathew, 2019). The research findings show that antidepressants and placebo vary significantly in suicidal ideation. The results also showed that individuals taking an antidepressant had increased suicidal thoughts compared to their counterparts. The findings portray an increased risk than that of FDA backbox warning. This makes the finding uncertain because the risk-to-benefit ratio can change significantly when the environment is changed to clinical.
The arguments surrounding the antidepressant controversy help provide theoretical and clinical implications. The effect size and evidence load are crucial for clinicians when selecting a given antidepressant. Despite the conclusion that second-generation drugs are effective in treating depression, multiple studies have opposing views on the issue. Antidepressant controversy is astonishing for most clinicians because of the relevance linked to antidepressants. Regarding evidence-based medicine and clinicians, it is necessary to adapt to questions from individuals and groups outside the professional community. These questions help guide the clinical efficacy of antidepressants and how they are administered to patients. In daily clinical practice, the effectiveness of antidepressants is key, especially when the patients have never been treated or partially used them. It is necessary to check the lethal consequences of antidepressants.
The efficacy of antidepressants in reducing and preventing the chances of suicide is a key public question. This makes the clinicians focus intensively on finding the solution to the question and providing clarification on the matter surrounding antidepressant efficacy. The induced suicidality effects are gaining ground daily, which may outweigh the benefits of using antidepressants in the clinical environment. The discussion does not stop physicians from administering and prescribing antidepressants. It strengthens the care in clinical setup and when providing antidepressant prescriptions to patients between 0 and 24 years. The controversy gives clinicians insight into potential risks to prevent issues such as suicides and other adverse side effects.
Decision-making in the clinical environment is usually complex, especially when it needs the identification of therapy that is controversial. Identifying the right therapy for groups such as children, adolescents, and adults is challenging. The challenge arises when the intervention required has been criticized by the public despite being known by the clinician as beneficial to patients. Making a list of correct diagnoses is shaped by the controversial view, making the clinician identify subtypes of depression known to be resistant to antidepressants before making a treatment decision. For example, when diagnosing a patient with treatment resistance, a clinician must check the psychiatry comorbidity as it may explain the connection. Several patients tend to have treatment-resistant depression, especially after pre-treatment. This is highlighted by comorbid psychiatric disorders and is shaped by the controversy surrounding the efficacy of antidepressants.
The selection of antidepressants for use has also been a subject of controversy, which has made clinicians face challenges. When antidepressants are used in randomized controlled trials, they appear to be similar. This has made the American psychological association revise guidelines on treating MDD by concluding that most approved antidepressants are effective (Monden et al., 2018). This decision was made based on the argument that antidepressants’ efficacy is achieved by various compounds that work the same way resulting in similar effects (Monden et al., 2018). To identify the difference in effectiveness among antidepressants, the focus has to be placed beyond the estimated effect size and incorporate evidence load (Monden et al., 2018). The evidence load focuses on the available efficacy information on the antidepressant. This provides data that favors the strength of the estimated efficacy. Despite having new-generation antidepressants for treating depression and anxiety, it can be noted that they are not perfect as they have several side effects, some detrimental to the patient’s health.
Understanding the controversy surrounding mental health treatment using an antidepressant is essential. Monitoring a mental health patient is a question of suitable clinical practice, specifically during treatment and prescription, to avoid risks associated with antidepressants. For example, when a patient portrays symptoms such as sleep disturbances, agitation, and other side effects, one should consider administering comedication, which will induce sleep in the patient. This is because the side effect may cause suicidality thought in the patient. Substantial support is also essential and should be considered. One should note that suicidal thoughts and depressive symptoms may occur in both the short term and long term hence the need for careful analysis before allowing it on an outpatient basis. Inpatient provides a clinician with more time to monitor the patient and provides an environment for using Ads keeping in mind the controversy surrounding antidepressants in case the situation worsens to suicidality.
In conclusion, antidepressants face controversy regarding their efficacy and effects in inducing suicidality thoughts and behavior. Various researchers, individuals, and groups have opposing views on the issues. On antidepressant efficacy, the proposing groups base their argument on FDA licensing the use of multiple antidepressants despite various studies portraying varying efficacy. They also argue that studies have shown that they are more effective than a placebo in reducing severe depressive symptoms in patients suffering from MDD. (R, S) ketamine is a breakthrough in antidepressants because of its potency and more prolonged effects than a placebo. The opposing view on antidepressant efficacy is based on the minor and chronic side effects. This includes high blood pressure, nausea, feeling drunk, and hypoesthesia, among others.
Antidepressants have also been associated with suicidality thoughts and behavior. Those supporting this view argue that the suicide rate increased significantly with the expanded consumption of antidepressants. On the other hand, the opposing group argues that there is no concrete evidence to support the link between antidepressants and suicidality behavior since correlation does not always mean causality. Additionally, the protocols designed to measure suicidality ideation and behavior are hypothesis based. They cannot provide a correct figure on the number of deaths that resulted from consuming antidepressants in patients.
The controversy has a significant effect on clinical application. It shapes how clinicians handle patients using antidepressants and when treating and prescribing the drug. It makes the clinicians question the efficacy of the antidepressants hence checking necessary risks when they are being administered. It has also changed the clinical environment’s decision-making, leading to increased care when handling antidepressants. Understanding the controversy helps one always to implement good clinical practices to avoid risks. One becomes cautious when handling patients with significant depressive symptoms, primarily inpatients.
References
Almohammed, O., Alsalem, A., Almangour, A., Alotaibi, L., Al Yami, M., & Lai, L. (2022). Antidepressants and health-related quality of life (HRQoL) for patients with depression: Analysis of the medical expenditure panel survey from the United States. PLOS ONE, 17(4), e0265928. Web.
Boaden, K., Tomlinson, A., Cortese, S., & Cipriani, A. (2020). Antidepressants in children and adolescents: Meta-Review of efficacy, tolerability and suicidality in acute treatment. Frontiers In Psychiatry, 11, 1-8. Web.
Cipriani, A., Furukawa, T., Salanti, G., Chaimani, A., Atkinson, L., & Ogawa, Y. et al. (2018). Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: A systematic review and network meta-analysis. The Lancet, 391(10128), 1357-1366. Web.
Fornaro, M., Anastasia, A., Valchera, A., Carano, A., Orsolini, L., & Vellante, F. et al. (2019). The FDA “Black Box” warning on antidepressant suicide risk in young adults: More harm than benefits?Frontiers in Psychiatry, 10, 1-6. Web.
Kryst, J., Kawalec, P., & Pilc, A. (2019). Efficacy and safety of intranasal esketamine for the treatment of major depressive disorder. Expert Opinion on Pharmacotherapy, 21(1), 9-20. Web.
Masi, G. (2022). Controversies in the pharmacotherapy of adolescent depression. Current Pharmaceutical Design, 28(24), 1975-1984. Web.
McMullen, E., Lee, Y., Lipsitz, O., Lui, L., Vinberg, M., & Ho, R. et al. (2021). Strategies to prolong ketamine’s efficacy in adults with treatment-resistant depression. Advances in Therapy, 38(6), 2795-2820. Web.
Monden, R., Roest, A., van Ravenzwaaij, D., Wagenmakers, E., Morey, R., Wardenaar, K., & de Jonge, P. (2018). The comparative evidence basis for the efficacy of second-generation antidepressants in the treatment of depression in the US: A Bayesian meta-analysis of food and drug administration reviews. Journal of Affective Disorders, 235, 393-398. Web.
Qin, B., Chen, H., Gao, W., Zhao, L., Zhao, M., & Qin, H. et al. (2018). Efficacy, acceptability, and tolerability of antidepressant treatments for patients with post-stroke depression: A network meta-analysis. Brazilian Journal of Medical and Biological Research, 51(7), 1-10. Web.
Teng, T., Zhang, Z., Yin, B., Guo, T., Wang, X., & Hu, J. et al. (2022). Effect of antidepressants on functioning and quality of life outcomes in children and adolescents with major depressive disorder: A systematic review and meta-analysis. Translational Psychiatry, 12(1), 1-13. Web.
Wei, Y., Chang, L., & Hashimoto, K. (2020). A historical review of antidepressant effects of ketamine and its enantiomers. Pharmacology Biochemistry and Behavior, 190, 1-17. Web.
Whitely, M., Raven, M., & Jureidini, J. (2020). Antidepressant prescribing and suicide/self-harm by young Australians: Regulatory warnings, contradictory advice, and long-term trends. Frontiers In Psychiatry, 11, 1-10. Web.
Witt-Doerring, J., & Mathew, S. (2019). Antidepressants and suicidality—controversies and possible mechanisms. Neurobiology Of Depression, 301-313. Web.
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