A Systematic Review of Interventions, Severity Classification, and Diagnostic Tools to Reduce the Gap in Moderate Depressive Disorders

Depressive disorders are one of the highly prevalent multifactorial diseases which are becoming more and more intriguing with the increasing complexity of life on the planet. Depressive disorders are characterized by persistent sadness, loss of interest or pleasure, feelings of guilt or low self-worth, disturbed sleep or appetite, fatigue, and poor concentration1-2. The World Health Organization (WHO) has estimated that by 2030 depressive disorders will be counted as the primary cause of global disease burden. The estimates depict that more than 264 million people worldwide currently suffer from some  form of depression, making it a significant cause of disability worldwide. The global burden of diseases, injuries and risk factor study in 2016 has demonstrated depression to be the fifth largest cause of years lived with disability (YLD)3-4. According to American Psychiatric Association (APA), it has been estimated that one in 15 adults is affected by depressive disorders thereby making the yearly prevalence to be 6.7%. The lifetime prevalence of depressive disorders has been estimated to be 16.6%5. Recent studies suggest that the prevalence may be increasing, particularly among younger populations due to changing social and economic stressors. The growing prevalence of this serious medical illness has raised significant concern among researchers. However, due to a lack of awareness regarding the condition in low and middle-income countries, an estimated 76% -85% of people with depression do not receive any treatment which exacerbates the condition and contributes to its rising prevalence⁶. Being multifactorial, depressive disorders arise from complex interactions between biological, psychological and social factors7. This complexity poses a significant challenge for clinicians in detecting, diagnosing and managing these disorders. In addition, recent genetic studies have identified hundreds of genetic variations linked to depression, enhancing our understanding of its biological underpinnings. Apart from this, the unpredictable course of prognosis and high variability in the response to treatment pose further challenges for clinicians. This systematic review therefore puts forward a consolidated perspective on various types of depression placing particular emphasis on moderate depressive disorders due to their rising prevalence and significant impact on quality of life (QoL). Apart from this, the paper also focuses on various interventions, both medical and psychological that have been reported as effective in reducing the impact of moderate depression. The paper also provides a brief overview of the tools that are majorly cited in the earlier literature to diagnose depressive disorders including the Patient Health Questionnaire-9 (PHQ-9), Hamilton Rating Scale for Depression (HAMD), and Montgomery–Åsberg Depression Rating Scale (MADRS). An attempt to present the bibliometric trends in research and development related to depression and its management has also been undertaken. Thus, the primary aim of this systematic review is to report various aspects of recently published primary literature related to moderate depressive disorders in order to trace and identify the research gaps and develop a vivid outlook for future research.

The current systematic literature review follows the review method proposed by Webster and Watson8 (2002), known as the concept-driven systematic review approach. This method examines the literature from a conceptual perspective synthesizing insights from multiple studies rather than focusing on individual author contributions. Unlike an author-driven approach which analyses multiple concepts across different authors’ works, this method organises research based on themes emerging from prior studies. Given the extensive body of literature on depressive disorders this approach is particularly suitable as it allows for a structured and comprehensive synthesis of relevant research. Moreover, the rising global prevalence of depression has intensified research interest in this area, making depressive disorders a major emerging topic in healthcare research. Thus, this review methodology effectively captures relevant studies in a systematic and concise manner.

Sources:

The process of review was initiated by looking at three major research databases namely SCOPUS, PubMed, and ScienceDirect in order to collect relevant articles. However, a majority of the articles retrieved from PubMed and ScienceDirect were also indexed in the SCOPUS database. Therefore, SCOPUS was chosen as the primary database for data collection. Articles were selected using relevant keywords like “Depression,” “Depressive Disorders,” and “Depression & Interventions”. The retrieved studies were then systematically reviewed and analyzed for further classification and synthesis.

Theme identification:

The themes for the review were identified following a rigorous analysis of the research papers retrieved using the selected keywords. The process began with a title-screening phase ensuring that the selected studies aligned with the primary focus of the review. It was observed that moderate depressive disorder is an underrepresented area of research particularly concerning diagnosis and interventions. Given its increasing prevalence and clinical significance moderate depressive disorder was chosen as the core theme of this review. Additionally, network visualization analysis of depression-related terms in SCOPUS revealed the frequent co-occurrence of specific keywords further reflecting the growing research interest in this domain. Based on this analysis the literature was further categorized into sub-themes derived from selected studies related to the core theme. This categorization facilitated a structured assessment of research contributions, particularly emphasizing moderate depressive disorders.

Data extraction and synthesis:

After determining the core theme, the selected papers were thoroughly reviewed and analysed. To minimize selection bias, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart was employed to define inclusion and exclusion criteria for the selected studies. Furthermore, bibliometric analyses using SCOPUS were conducted to examine research trends and assess the evolving landscape of scholarly contributions related to moderate depressive disorders. This data-driven approach allowed for a comprehensive evaluation of research patterns providing insights into the thematic and methodological evolution of studies in this field.

A total of 7,779 research papers were retrieved through database searches using the aforementioned keywords. After removing duplicates and excluding papers published before 2010, approximately 2,219 papers were found to fit into the core theme (moderate depressive disorder) and thus were finally subjected to title screening for retrieval of the sub-themes. The database search depicted many aspects of moderate depressive disorders which were chosen as the sub-themes. 3 themes identified and reviewed in the current review are stated below:

Theme 1: Assessment tools for depressive disorders. Theme 2: Severity and types of depressive disorders with special emphasis on moderate depressive disorders. Theme 3: Interventions: Medical and Psychological. Following an extensive analysis around 42 papers were finally chosen for the data extraction. The PRISMA scheme depicting the mode of selection of the papers for the current review is represented in Figure 1.

Fig.1: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Scheme for selection of articles for the systematic review

For the data extraction, the key data of the selected papers were screened and analysed on the following set of particulars: details of the authors; year of publication; study size; severity, assessment tools, interventions and tested outcomes, and special highlight in results (if any). These key data sets were summarized in a tabular format to ease further theme-wise analysis further depicted in Table 1.

Table 1: Data extraction and synthesis for selected papers

Fig 2: Prevalence of various depression assessment scales in the literature (SCOPUS database)

Assessment tools for depressive disorders:

The literature review has found the following scales to be quite prevalent and sensitive in measuring depressive disorders:  Diagnostic and Statistical Manual of Mental Disorders (DSM), International Classification for Diseases and Related Disorders (ICD 10), Hamilton Depression Rating Scale (HDRS), Beck Depression Inventory (BDI), Patient

Health Questionnaire (PHQ), Major Depression Inventory (MDI), Center for Epidemiologic Studies Depression Scale (CES-D), Zung Self-Rating Depression Scale (SDS), Geriatric Depression Scale (GDS), Cornell Scale for Depression in Dementia (CSDD), Global Mental Health Assessment tool (GMHAT). Among these, the DSM, HDRS and BDI scales were the most commonly reported in the SCOPUS database (Fig 2).

As discussed in the background section, the DSM is one of the most commonly used and rated tools in terms of its efficiency in screening depressive disorders51. The current version, DSM-V (published in 2013), has been validated for diagnosing depressive disorders in both children and adolescents. It includes 23 questions accessing 13 psychiatric domains over a two-week period. Another widely used diagnostic tool, the ICD-10 is often referenced in literature for measuring depressive disorders. Although it identifies common symptoms of depression, it has a lower threshold for symptom requirements compared to the DSM-V. A comparative analysis of the DSM-V and ICD-10 in terms of symptom assessment and thresholds for severity has been provided in Table 2. Out of many other tools, the Hamilton Depression Rating Scale (HDRS) was the earliest interview-based scale developed to measure depression severity52. It includes 17 core items, with four additional items (18–21) for further categorization. Scores are based on a 3-point or 5-point scale, where a score of 20 or above indicates moderately severe depression. The HDRS focuses more on somatic than cognitive symptoms53.

Similarly, the Beck Depression Inventory (BDI) is a widely used self-rating scale requiring only 5 to 10 minutes to complete. It evaluates 21 items, including somatic, behavioral, and emotional symptoms. These items are generally scored between 0-3 and a score above 30 indicates severe depression while a score of 19 to 29 is indicative of moderate depression while a score between 10 to 18 indicates mild depression. Many studies have reported BDI scale to be extremely specific with a sensitivity of 97% and specificity of 99%54. Furthermore, in terms of sensitivity and specificity, the Patient Health Questionnaire (PHQ) is another effective tool with 80% sensitivity and 92% specificity55. This self-administered tool is known for assessing the frequency of depression and anhedonia for the last 2 weeks. The scoring ranges from 0 to 23. The currently used version of PHQ that is PHQ-9 is effective in distinguishing between severities of depression by demarcating mild depression with PHQ minimum score of 5, moderate depression with PHQ score of 10 and severe depression with a score of 20. Another self-rating scale, the Major Depression Inventory (MDI) has been developed for the measurement of depression in accordance with DCM-IV and ICD-10 scales56. This tool has been set with a cut-off score of 26 for the diagnosis of moderate to severe depression. The sensitivity of the MDI scale has been reported to be 86 to 92% while the specificity is between 82 to 86%57. In terms of large-scale population surveys, a very popular tool that has been reported in the review literature is the Centre for Epidemiologic Studies Depression Scale (CES-D). This scale was published in 1977 with 20 items of which 4 are positively worded and 16 are negatively worded. This scale is effective in the measurement of somatic symptoms of depression with a score ranging from 0 to 6058. Moreover, some other scales such as Zung Self-Rated Depression Scale (SDS) also has been reported to provide quick and inclusive identification of depression54. A score above 70 is indicated as severe depression while a score between 50-60 and 62-70 is indicated as mild and moderate depression respectively. Similarly, Cornell Scale for Depression in Dementia (CSDD) is also an assessment tool used specifically for elderly patients having underlying cognitive issues. The scale has been marked for 93% of sensitivity and 97% of specificity for this specific purpose57. In the same context, another specific depression scale known as Geriatric Depression Scale (GDS) which is a 30-item scale used for older adults has also been reported effective with a sensitivity of 94% and specificity of 81%. Apart from this, another scale that has been gaining popularity in recent times is the Global Mental Health Assessment tool (GMHAT). It is a computerised clinical assessment tool developed for rapid assessment of mental health problems in a range of settings59. This tool has gained popularity during the recent times of COVID-19 due to its computerised far-reaching form.

Types and severity of depressive disorders with emphasis on moderate depressive disorders:

Depressive disorders vary significantly in severity, requiring precise classification for accurate diagnosis and treatment. Several assessment tools, including those mentioned above categorize depression severity. According to the 2004 NICE guidelines, severity classification was based on ICD-10, using symptom count. However, this approach was later deemed ambiguous, leading to its revision in the 2018 NICE guidelines, which now follow the DSM-V. A comparative analysis of DSM-V and ICD-10 in terms of symptoms and classification criteria is provided in Table 2.

Table 2: Comparison of Depression Assessment Tools (DSM-V vs. ICD-10)

Key findings from the literature review suggests that moderate depressive disorders are often merged with mild or severe depression in research studies. While most diagnostic tools distinguish moderate depression, there is limited research focusing on the overlap between mild and severe depression. Figure 3 (Scopus bibliometric analysis) supports this observation, consistent with findings from Wittchen et al. (2011) and Aherne et al. (2017).

Apart from this, a basic trend that could be traced from literature related to moderate depressive disorders indicates another classification for depressive disorders in terms of the presence and absence of somatic symptoms. The somatic symptoms associated with moderate depressive disorders include fatigue and low energy, loss of libido, sleep disturbances, change in appetite, dysphonia, dizziness and palpitations along with general aches and pain (such as headache) and gastrointestinal disorders62. These somatic symptoms are gaining more and more attention in terms of depression research because many authors have suggested that somatic symptoms can be used as tools to identify depressive disorders at a very early stage63-64

Apart from this, the growing prevalence of somatic symptoms is also a point of concern because depression is becoming somatoform in nature, increasing the disability and burden associated with it. The bibliometric trend of research papers in terms of somatic depression is also growing which can be directly seen from the increasing number of publications under this heading (Fig.4)

Interventions: Medical and Psychological:

The literature review identified two primary intervention types for treating moderate depressive disorders. These two interventions are medical interventions and psychological interventions. The medical interventions basically deal with the use of drugs that lead to a decrease in depressive symptoms in the patients. A list of approved drug classes that are used for the treatment of depressive disorders and their prevalence in the existing Scopus database has been mentioned in Table 3.

Table 3: Approved antidepressants for depressive disorder

Among these drug classes, the literature review demonstrates that selective serotonin reuptake inhibitors (SSRIs) are the most commonly used class due to their efficacy and tolerability.

Psychological Interventions:

Fig 5: Trend of publications in the psychological intervention of depression (SCOPUS database)

Psychological therapies, particularly Cognitive Behavioral Therapy (CBT) are gaining prominence due to concerns over antidepressant side effects. Scopus bibliometric analysis (Figure 5) indicates a rise in research on psychological interventions in the last decade. Studies also suggest that combining psychological therapy with pharmacological treatment may reduce required drug dosages, enhancing patient outcomes.

This is due to the fact that most of the drug classes used for treating various levels of depression have been reported with some or the other side effects65. Therefore, clinical research in the field of combined interventions has been given more interest.  Many large-scale randomized trials have proved the efficiency of psychological interventions in enhancing the outcomes of medical interventions66-67. Some studies have also indicated that psychological intervention helps in reducing the dosage size of the drugs that are used for the treatment of these depressive disorders24.

This systematic review conclusively points to the fact that most of the studies relating to moderate depression are considered to overlap with either mild or severe depression. This ambiguity underscores the need for strict adherence to diagnostic guidelines to ensure accurate differentiation of depression severity. The inconsistent classification terminology used in research such as "moderate to severe" or "mild to moderate", further limits focused investigation into moderate depression as a distinct entity. Consequently, the interventions proposed in many studies may not be specifically tailored to moderate depression raising significant concerns about the effectiveness of both pharmacological and psychological treatments in this subgroup. This research gap presents a major opportunity for future studies to develop targeted interventions that specifically address moderate depression, rather than generalizing findings from mild or severe cases. While mixed treatment approaches combining medical and psychological interventions have shown promise, their efficacy for moderate depression requires further validation through controlled studies. Furthermore, the review emphasizes that moderate depressive disorder remains an underexplored area of mental health research. The lack of exclusive data on moderate depression's etiology, symptomatology, and treatment outcomes underscores the urgency for dedicated investigations. Collecting comprehensive patient-specific data will not only enhance clinical understanding but also contribute to the reformation of public health policies and mental healthcare strategies. Establishing clear distinctions between mild, moderate, and severe depression in both research and clinical practice is crucial to ensure that patients receive appropriate and effective treatment rather than being misclassified and treated under a generalized approach. This will help bridge the existing knowledge gap, refine diagnostic protocols, and improve the effectiveness of personalized treatment strategies ultimately enhancing mental health outcomes for individuals affected by moderate depression.

Acknowledgement:

I sincerely acknowledge the support and guidance of my mentors and colleagues. Their invaluable insights and encouragement were instrumental in this work.

Conflict of Interest:

The author(s) do not have any conflict of interest.

Funding Sources:

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Statement of Informed Consent:

Informed consent was not required as this study is a systematic review utilizing previously published data.

Data Availability Statement:

The authors confirm that the data supporting the findings of this study are available within the article.

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