Understanding Major Depressive Disorder


Major Depressive Disorder (MDD), also known as 'depression', is a profound mental health condition that affects a substantial portion of the global population. An article by The World Health Organization (WHO) in March 2023 stated that approximately 280 million people worldwide have depression. MDD can affect individuals across various demographic groups, but specific trends have been observed and discussed below.

You might be interested in our article "What is Major Depressive Disorder".

Definition of MDD

Depression and its definition can sometimes be confusing. Generally, depression is a syndrome that comprises multiple symptoms and signs that may include a state of persistent low mood or depressed mood indicated by feelings of sadness, despair, anxiety, emptiness, discouragement, guilt, and hopelessness. Individuals with depression also described the symptoms as having no sense of emotion or feeling tearful. 

Additionally, a state of emotional distress such as bipolar disorder, schizophrenia, substance or medication-induced depressive disorder, or depressive disorder related to other general medical conditions may indicate an alternative psychopathological syndrome of depression. 

According to the National Institute of Mental Health, research statistics in 2021 show that 8.3%, or 21 million adults aged 18 or older in the United States, had at least one major depressive episode. 

It is also mentioned in the statistics that adult females have a higher prevalence (10.3%) of major depressive episodes compared to males (6.2%). There is also a higher chance of having MDD among individuals aged 18–25% up to 18.6% compared to adults aged 26–49 years old and above 50 years old. United States citizens with a report of having multiple races (two or more races) also have a prevalence of MDD up to 13.9%.

Diagnosing major depressive disorder

Clinically, Major Depressive Disorder is diagnosed using The Diagnostic and Statistical Manual of Mental Illnesses, or DSM-5. It is positive when there are ≥5 symptoms from DSM-5 Criteria for Major Depressive Disorder occurring during the same two-week period. 

  • Depressed Mood
  • Loss of interest or pleasure
  • Weight loss or gain.
  • Insomnia or hypersomnia
  • Psychomotor agitation (pacing, anxiety) or psychomotor retardation (slowed movement or speech)
  • Fatigue
  • Worthless or guilty feeling
  • Attention/Memory Deficit
  • Suicidal thoughts or self-harm behaviour, or thinking

Risk of major depressive disorder

According to the NHS website, a few causes and risk factors could lead to MDD. MDD could be multifactorial, and these are a few reasons or triggers that could lead a person to have MDD:

  • Stressful life events - Include financial issues, relationship troubles, grief, divorce, illness, traumatic delivery experiences, and added responsibility.
  • Family history - A family history of bipolar disorder, schizophrenia, depression, anxiety, suicide, hallucinations, and psychosis in the past increases the chances of someone having MDD. However, having a family history of mental illness does not always mean an individual will develop MDD.
  • Alcohol and drugs - Research has shown a significant link between alcohol abuse or dependence and major depression. Studies have found that alcohol use can lead to mood symptoms and depression, with some studies suggesting that alcohol detoxification can also impact anxiety and depressive symptoms.
  • Hormonal - Women who are pregnant and just delivered a baby and menopausal women are vulnerable and susceptible to depression due to hormonal changes. This is what is called antenatal, postnatal or postmenopausal depression.
  • Personality - Certain personality traits, such as low self-esteem and being too hard on yourself, enhance the possibility of depression.
  • Loneliness - Having too little human interaction could also generate depression. When loneliness causes depression, it could lead to a cycle of avoiding and cutting off friend and family members, which in turn make the depression symptoms worsen.
  • Illness - General medical conditions such as thyroid issues, diseases causing chronic pain and fatigue, cancer or chronic disease could cause depression.

Impact of depression on individual

Disturbed sleep cycle

An individual experiencing depression or MDD could either experience insomnia or lack of sleep or could have been sleeping too much. Both symptoms could be due to a lack of motivation or being overwhelmed with feelings that they are experiencing.

Weight gain or loss

Depression could increase or suppress appetite, eventually leading to weight gain or loss. A study on depression and weight-related shows that depression increases appetite and is associated with hyperactivation of putative mesocorticolimbic reward circuitry. 

On the other hand, depression-related appetite loss is related to the hypoactivation of insular regions that support monitoring the body's physiological state.1

Chronic pain or fatigue

Individuals with depression, even without chronic disease, usually complain of unexplained persistent fatigue, body aches or pain and headaches.

Decreased libido

A prospective study done in 2018 noted that after treatment with escitalopram in patients with mild to moderate grades of depression, there was an increase in libido and reduced sexual dysfunction with the improvement of depression symptoms in their lives.2

Worsening health conditions

A depressed individual with chronic diseases such as inflammatory bowel disease or IBD or cardiovascular diseases such as Hypertension and at the same time experiencing depression can worsen their health and well-being. Depression could increase blood pressure and heart rate, increasing cardiovascular disease risk. 

Chronic pain is further exacerbated by chronic fatigue in patients with depression. A depressed individual also has no motivation for exercise with a poorly controlled diet and sleeping pattern, leading to a sedentary lifestyle and implications of it. 

Impaired cognitive function

Studies have shown that depression, especially during the acute phase of illness, could lead to cognitive impairment that affects various other issues such as attention deficit, memory deficit, psychomotor speed and executive functioning. No wonder MDD has significant implications for daily functioning and impacts an individual's socioeconomic status.3

Tools and assessment for major depressive disorder

Major Depressive Disorder is mainly diagnosed by clinical history extracted from patients and examination of their mental state. Doctors or healthcare practitioners will also enquire about their family history, underlying medical illness, social and relationship history, past trauma and substance use history and counter the information gained from friends and family members.

It is also essential to run routine examinations such as routine blood investigations (blood counts with their differentials, thyroid function test / TFT, Vitamin D and urinalysis and toxicology to rule out any organic cause first, such as thyroid issue (hyper or hypothyroidism); infections such as meningoencephalitis, HIV, syphilis and a case of brain tumour or cancer.

Depressed individuals are usually presented first to the primary care practitioner with the complaints originating from the signs of depression. They will be asked first to complete a standardised depression rating scale named Patient Health Questionnaire - 9 (PHQ), scoring 0 to 27 scores, which uses nine items that correspond to the criteria of DSM-5. PHQ-9 is for screening, diagnosing, and monitoring responses for treatment for MDD. In the hospital settings, the Hamilton Rating Scale for Depression (HAM-D) is used.5 


There are few modalities for the treatment of MDD. MDD could be treated with lifestyle modifications and psychotherapeutic and pharmacological use. Initially, treating MDD could be a combination of medications and psychotherapy. Lifestyle modifications involve medications, cognitive behavioural therapy, exercise or yoga, counselling, and sleep cycle regulation. 

Initiation or stopping of medications or oral antidepressants is based on clinical judgment by healthcare practitioners. These include starting the medicines with the lowest dose and titrating until symptoms are optimised. 

Antidepressants might take one to two weeks before the benefits are fully seen. One cannot immediately withdraw from taking the medications abruptly but rather taper it slowly (by reducing the dose within up to six weeks before entirely off the medicines). There are several medications or antidepressants to start for major depressive disorder. These include:5

  • SSRI / Selective Serotonin Reuptake Inhibitors
  • SNRI / Selective - Norepinephrine Reuptake Inhibitors
  • TCA / Tricyclic Antidepressant
  • MAOIs / Monoamine Oxidase Inhibitors
  • Serotonin modulators

While having the proper diagnosis for MDD is essential for the right treatment, it is crucial to seek holistic evaluation to ensure the appropriate approach is taken for effective management. 

Differential diagnosis compared with Major Depressive Disorder that could take a whole new turn for its treatment could be:

  • Substance or medication-induced depressive disorder
  • Adjustment disorder with depressed mood
  • Bipolar disorder
  • Schizoaffective disorder
  • Schizophrenia
  • Anxiety disorder
  • Eating disorder
  • Secondary causes of depressive symptoms include neurological, endocrinopathies, metabolic disturbances, infectious diseases, and malignancies.

Support and coping strategies for MDD

Despite having MDD and being started with antidepressants by healthcare professionals, individuals with MDD could still have an everyday healthy life until they no longer depend on medications. 

However, MDD could relapse when a sequence of events or multiple external stressors occur towards the individual. Individuals with MDD cope best with the following:

Support peers - having some close friends or family members who are reliable with whom you can share all the ugly and uncomfortable side of depression works the best, especially when they can check on you if they do not hear from you. 

A depressed individual tends to be anti-social and become lonely, which overall worsens the symptoms of depression. Hence, having this support from peers is helpful, and it is vital to stay in touch, especially on your good days. 

Be active - There is evidence of a link between exercise and good mood. Exercise is a mood booster through the release of natural endorphins. The variance of exercise can start first if one is inactive, like yoga, brisk walking, swimming, or even walking your dog.

Healthy diet - Avoid alcohol and maintain a balanced diet of carbohydrates, proteins, legumes, fruits, and vegetables. Some individuals will experience suppression of appetite, while others could gain weight. Hence, it is crucial to have a balanced, healthy diet so as not to develop other health issues such as anorexia or obesity.

Have a routine - A structured day or a routine is another way to combat the relapse of depression. A depressed individual usually feels overwhelmed, or sometimes a sense of things is out of their control. Hence, a routine could make them feel like they have control over something and can focus on other essential things. A routine also helps individuals focus better as it is something they automatically do every day.

However, it is vital to seek help if symptoms of depression persist after two weeks despite your attempt at self-help. Individuals can find talking therapy services via their hotline, some available at no cost and some paid service. Visiting a primary care practitioner or counsellor service can also be the first step towards seeking help for depression.


Major Depressive Disorder (MDD), also commonly known as depression, is a severe mental health condition affecting millions worldwide. MDD could be presented with persistent low mood, anxiety, guilt, overwhelming and other symptoms.

With over 280 million individuals affected globally, MDD was initially screened with Patient Health Questionnaire - 9 (PHQ-9) and could be diagnosed with DSM-5 criteria. Routine blood investigations and medical examinations are essential to rule out organic pathology. MDD is multifactorial, which includes stress, family history, substance abuse, underlying medical conditions and hormonal changes. MDD could impact individuals' sleeping patterns, appetite, and cognitive function, exacerbate chronic pain, and worsen underlying health conditions. 

MDD treatment comprises lifestyle changes, peer support,  psychotherapy, and medications such as antidepression from different classes. It is also essential to seek professional help if symptoms persist. 


  1. Simmons WK, Burrows K, Avery JA, Kerr KL, Bodurka J, Savage CR, et al. Depression-related increases and decreases in appetite: dissociable patterns of aberrant activity in reward and interoceptive neurocircuitry. AJP [Internet]. 2016 Apr [cited 2023 Aug 29];173(4):418–28.
  2. Available from: http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2015.15020162
  3. Thakurdesai A, Sawant N. A prospective study on sexual dysfunctions in depressed males and the response to treatment. Indian J Psychiatry [Internet]. 2018 [cited 2023 Aug 29];60(4):472. Available from: https://journals.lww.com/10.4103/psychiatry.IndianJPsychiatry_386_17
  4. Hammar Å. Cognitive functioning in major depression – a summary. Front Hum Neurosci [Internet]. 2009 [cited 2023 Aug 29];3. Available from: http://journal.frontiersin.org/article/10.3389/neuro.09.026.2009/abstract
  5. Bains N, Abdijadid S. Major depressive disorder. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Sep 1]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK559078/
  6. Schuch FB, Vasconcelos-Moreno MP, Borowsky C, Zimmermann AB, Rocha NS, Fleck MP. Exercise and severe major depression: Effect on symptom severity and quality of life at discharge in an inpatient cohort. Journal of Psychiatric Research [Internet]. 2015 Feb 1 [cited 2023 Sep 1];61:25–32.  Available from: https://www.sciencedirect.com/science/article/pii/S0022395614003148
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Nureen Izyani Binti Hashim

Doctor of Medicine, MD (Russia), MSc Public Health, Anglia Ruskin University, Essex

Dr. Izyani Hashim is a Malaysian medical doctor with several years of experience and passion for palliative and primary care and health communications. Having completed her medical degree in Russia and served as a medical doctor in Malaysia, rotating into different fields of medicine, she has gained invaluable experience in clinical care and patient interactions, enabling her to bridge the gap between complex medical information and everyday readers.

She is pursuing a Master’s in Public Health in the United Kingdom. With a mission to empower individuals with reliable health information, Dr. Izyani's articles aim to inspire healthier lives with informed choices. Her articles aim to empower populations with reliable health information, ultimately contributing to improved healthcare and well-being nationwide.

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