Depressive Disorders

Author

Cansun Sahin Cam, MD

MD- Marmara University Faculty of Medicine, Department of Mental Health and Diseases

"Depression extends beyond transient feelings of sadness; it is a health issue that can be addressed through treatment"

What is depression?

A depressed mood and loss of pleasure/interest constitute the primary symptoms of depression. Depression can manifest through a variety of emotional and physical symptoms, significantly affecting a person's overall well-being and functionality. It may create challenges in performing daily tasks and disrupt various areas of life. It is important to note, however, that individuals with depression may not consistently display these observable signs. Some may appear to maintain their social lives seemingly unaffected, yet still experience the internal struggles associated with depression. Depressive symptoms can manifest differently in each person, and outward appearances may not always reflect the emotional challenges they are facing.

Depression is characterized by a range of physical symptoms, often referred as the autonomic nervous system*-related symptoms. Among the most prevalent physical manifestations are fatigue/loss of energy, diminished attention span, insomnia, loss of appetite, decreased sexual desire, and disruptions in the menstrual cycle. It is worth noting that some individuals may experience atypical or reversed autonomic nervous system-related findings, including an increase in appetite and extended sleep duration. These variations highlight the diverse ways in which depression can manifest in individuals, reflecting the complexity of the disorder.

*Autonomic nervous system: Controls all vital basic functions of the body.

Epidemiology of depression

According to World Health Organization (WHO) data, the global prevalence of depressive disorders is reported to be 3.8%, with a higher prevalence in adults at 5% (280 million people). Additionally, it has been noted that depressive disorders are more common in women than in men [1]. The reasons for this discrepancy are multifaceted, encompassing psychological, biological, and social factors. While one explanation suggests that the unequal position of women in many societies might contribute, it has been observed that rates of depression do not necessarily change significantly in societies where women have a more equitable status. Biologically, changes in hormone levels, particularly in women, are also considered potential contributors to the higher prevalence of depression in this demographic.

What are depressive disorders?

Depressive disorders include Major Depressive Disorder (MDD), Dysthymic Disorder (Persistent Depressive Disorder), and Premenstrual Dysphoric Disorder.

How is it diagnosed?

In psychiatry, standardized diagnostic approaches are essential for establishing a mutual understanding worldwide. The predominant diagnostic tools currently utilized include the 'Diagnostic and Statistical Manual of Mental Disorders (DSM-5)' and the 'International Statistical Classification of Diseases and Related Health Problems (ICD-11)' [2, 3].

Diagnosis of MDD

For a diagnosis of MDD according to DSM-5 criteria, a patient must show symptoms for at least two weeks and have at least five of the nine specified symptoms, including at least one of the first two symptoms. The identified symptoms are: 1. Depressed mood, 2. Loss of interest or lack of pleasure in almost all activities, 3. Changes in appetite (either decrease or increase), 4. Insomnia or excessive sleeping, 5. Slowness or agitation in movements, 6. Low energy, 7. Feelings of guilt, 8. Difficulty concentrating or indecisiveness, 9. Thoughts or plans of death/suicide. The diagnosis is further nuanced by considering accompanying symptoms or conditions. For instance, if anxiety is presented, it might be termed depression with anxious distress. If symptoms include loss of pleasure, severe depression, worsening in the mornings, early morning awakening, weight loss, and guilt, it might be labeled as melancholic depression. Depression with seasonal pattern is noted when depressive episodes occur during specific seasons. This comprehensive evaluation allows for a more precise characterization of depressive disorders based on individual symptomatology.

Diagnosis of dysthymic disorder

Dysthymic disorder is characterized by milder symptoms than MDD but follows a chronic course. Many patients report feeling as if they have "always been like this," as the onset typically occurs in adolescence or the 20s. According to DSM-5 criteria, a diagnosis of dysthymic disorder requires symptoms to persist for at least two years. In addition to a depressed mood, the presence of at least two of the following symptoms is necessary: 1. Decrease or increase in appetite, 2. Insomnia or excessive sleeping, 3. Low energy, 4. Low self-confidence, 5. Attention deficit, 6. Feelings of hopelessness. This extended duration and the presence of chronic, albeit less severe, symptoms distinguish dysthymic disorder from major depressive episodes. The persistent nature of these symptoms over an extended period contributes to the chronicity of the disorder.

Correct diagnosis of depression

Given the similarity of symptoms between depressive disorders and various other diseases or conditions, a careful and thorough differential diagnosis becomes imperative.

Many medications are believed to potentially cause depressive symptoms. These include oral contraceptives (birth control pills), certain hypertension medications (reserpine, methyldopa), painkillers (indomethacin), corticosteroids (dexamethasone, prednisone), epilepsy medications (barbiturates, vigabatrin, topiramate), and medications for Parkinson's disease (levodopa, amantadine). Case examples in the literature also highlight the presence of depressive symptoms with medications like flunarazine for migraines, certain drugs used for infections (cycloserine, efavirenz, interferon), and oncological drugs (vincristine, vinblastine) [4]. In a 2019 investigation, commonly used drugs like metoprolol, atenolol, omeprazole, hydrocodone, and gabapentin were identified as being associated with depression [5]. However, it is important to note that there is criticism suggesting that the conditions for which these drugs are prescribed might themselves be linked to depression. This highlights the complex interplay between medications and the health conditions they are intended to treat, making it challenging to establish a direct cause-and-effect relationship. Further research and comprehensive analyses are needed to untangle these intricate associations.

It is well-established that endocrine-metabolic disorders are linked to depressive symptoms. Numerous studies have demonstrated the association between conditions like hypothyroidism, hyperthyroidism, hyperparathyroidism, hypopituitarism, Addison's disease, and diabetes with the development of depression [6].

Depressive symptoms are also commonly observed in various neurological diseases, including Parkinson's Disease, neurocognitive disorders, epilepsy, cerebrovascular (brain vessels related) events (such as stroke), and tumors [7].

Premenstrual dysphoric disorder

Premenstrual Dysphoric Disorder (PMDD) is characterized by symptoms similar to those seen in other depressive disorders. However, what distinguishes PMDD is that these symptoms specifically manifest in the last week before the onset of menstruation and notably improve within a few days after menstruation begins.

Grieving is not depression

The mourning process is an essential consideration in the differential diagnosis of depression. Grief following a significant loss is not categorized as a mental illness, and individuals experiencing normal bereavement are not diagnosed with depressive disorder even if they meet the criteria for it. However, it is worth noting that some individuals may develop MDD during the mourning process. Individuals going through a normal mourning process might still exhibit reactions to their environment and experience positive emotions. Unlike those with depression, they typically do not show a psychomotor retardation, intense feelings of worthlessness or guilt are less frequent, and suicidal thoughts are less common. By carefully observing these distinctions, healthcare professionals can better differentiate between normal grief reactions and depressive disorders.

Course of depression

Untreated depressive episodes tend to last around 6-12 months, but with appropriate treatment, the duration is often reduced to approximately 3 months. The progression of the disease may lead to more frequent and prolonged depressive episodes over time. Positive factors influencing the course of depressive disorders include low disease severity, the absence of other comorbid psychiatric or medical conditions, good treatment adherence, and strong social support. On the flip side, negative factors associated with a more challenging course include the presence of comorbid psychiatric conditions (e.g., anxiety disorder, alcohol or substance use disorder), personality disorders, a history of multiple hospitalizations, and the onset of the disease at an older age [8].

Treatment options

Treatment options mainly include pharmacotherapy and psychotherapy. In addition, neurostimulation methods (vagal nerve stimulation, transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), electroconvulsive therapy (ECT)), and phototherapy (bright light therapy) are among the methods that can be preferred.

Medications

The effectiveness of medications used in depression treatment has been substantiated by numerous studies. Typically, it takes approximately 3-4 weeks for the efficacies of almost all antidepressant drugs to become apparent. It is important to note that deeming drugs ineffective prematurely can be inaccurate. Recommendations often include continuing medication for at least 6 months after it has proven effective. When discontinuing, a gradual reduction of the dose over a few weeks is suggested. Adequate doses and a sufficient duration of use are essential factors in determining their effectiveness. Physicians, considering the severity and frequency of depressive episodes, may recommend the continuation of medications for an extended period to maintain stability and prevent relapse. Individualized treatment plans, including medication management, are crucial for the optimal care of individuals with depression. The choice of antidepressant is carefully made, considering the individual's symptoms, physical condition, and comorbid diseases (a person has more than one disease or condition at the same time).

The most commonly prescribed antidepressant drugs belong to the group called selective serotonin reuptake inhibitors (SSRIs), which include citalopram, escitalopram, sertraline, fluoxetine, and paroxetine. Additional options comprise venlafaxine and duloxetine, categorized as serotonin and norepinephrine reuptake inhibitors (SNRIs). Second-generation antidepressants such as mirtazapine, bupropion, and vortioxetine are also used.

In addition to these, various other psychotropic drugs might be considered as adjuncts to the treatment based on the progression of the disease. The selection and combination of medications are often tailored to the individual's response, tolerability, and the specific features of their condition. This personalized approach ensures a comprehensive and effective strategy for managing depressive disorders.

New drug treatments, such as ketamine, have demonstrated rapid efficacy in addressing depression, often producing effects within 24 hours. Esketamine, administered intranasally (into the nose), has obtained approval from the United States Food and Drug Administration (FDA), and its usage has been sanctioned by the Ministry of Health in Turkey. Given the potential side effects associated with the drug, it necessitates administration under clinician supervision [9].

Psychotherapy methods

Psychotherapy methods include therapy orientations such as cognitive-behavioral therapy (CBT), interpersonal therapy (IPT), psychoanalytic therapy, and family therapy. Among these, CBT and interpersonal therapy have the most research on their effectiveness on depression. Studies indicate that the combination of psychotherapy and pharmacotherapy yields greater effectiveness in the treatment of depression [10].

In the CBT approach, the goal is to assist individuals in shifting towards alternative and more positive thinking patterns by addressing cognitive distortions and dysfunctional behaviors. IPT centers on issues within the realm of relationships, positing that existing relational challenges are the origin of the initiation and persistence of depressive symptoms. In psychoanalytic therapy, the objective extends beyond treatment of the symptoms; it seeks to enhance self-understanding and facilitate change across various domains, including establishing closeness, comprehending and experiencing emotions, and developing coping mechanisms.

In both CBT and IPT, the therapist assumes a more active and directive role. These approaches typically involve setting specific treatment goals, and the duration of treatment tends to be relatively short. In contrast, psychoanalytic therapy involves a less active and directive approach compared to other orientations. It does not specify particular treatment targets, and therapy durations tend to be longer. Selecting the most appropriate psychotherapy method should take into account diverse factors, such as the individual's social and cognitive context, specific concerns, treatment expectations, and living conditions. This personalized approach allows for a better alignment between the chosen therapeutic method and the unique needs and preferences of the individual seeking treatment.

1. (WHO), W.H.O. Depressive disorder (depression). 2023 31.03.2023; Available from: https://www.who.int/news-room/fact-sheets/detail/depression.

2. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders. 5th ed. 2013, Washington, DC.

3. World Health Organization (WHO), International Classification of Diseases, Eleventh Revision (ICD-11). 11th ed. 2019.

4. Celano, C.M., et al., Depressogenic effects of medications: a review. Dialogues Clin Neurosci, 2011. 13(1): p. 109-25. https://www.tandfonline.com/doi/full/10.31887/DCNS.2011.13.1/ccelano

5. Qato, D.M., K. Ozenberger, and M. Olfson, Prevalence of Prescription Medications With Depression as a Potential Adverse Effect Among Adults in the United States. JAMA, 2018. 319(22): p. 2289-2298. https://jamanetwork.com/journals/jama/fullarticle/2684607

6. Gold, P.W., Endocrine Factors in Key Structural and Intracellular Changes in Depression. Trends Endocrinol Metab, 2021. 32(4): p. 212-223. https://www.sciencedirect.com/science/article/abs/pii/S1043276021000199

7. Pagonabarraga, J., et al., Depression in Major Neurodegenerative Diseases and Strokes: A Critical Review of Similarities and Differences among Neurological Disorders. Brain Sci, 2023. 13(2). https://www.mdpi.com/2076-3425/13/2/318

8. Bains, N. and S. Abdijadid, Major Depressive Disorder, in StatPearls. 2023: Treasure Island (FL) ineligible companies. Disclosure: Sara Abdijadid declares no relevant financial relationships with ineligible companies. https://www.ncbi.nlm.nih.gov/books/NBK559078/

9. JM, K.F., et al., Therapeutic Protocols Using Ketamine and Esketamine for Depressive Disorders: A Systematic Review. J Psychoactive Drugs, 2023: p. 1-17. https://www.tandfonline.com/doi/full/10.1080/02791072.2023.2248989

10. Cuijpers, P., et al., A network meta-analysis of the effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression. World Psychiatry, 2020. 19(1): p. 92-107. https://onlinelibrary.wiley.com/doi/10.1002/wps.20701