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Why Is Depressive Disorder Hard To Treat?

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By Koushani Das, Farooq Ali Khan, Abhishek Kumar, Raamesh Gowri Raghavan, and Sukant Khurana:

Art by Sukant Khurana


Depression is a significant medical illness that adversely affects a person in all ways ranging from how they perceive or feel, how they think and how they act in a given situation. Depression was previously termed as ‘melancholia’, which is currently known as major depression or clinical depression. The 11 th century physician Avicenna first described ‘melancholia’ as a depressive type of mood disorder in which the person may become suspicious or doubtful and develop certain types of phobias.


  • Depressed mood with a lack of interest or pleasure in activities once enjoyed
  • Low self esteem and confidence with loss of energy
  • Changes in appetite generally excessive weight loss
  • Trouble sleeping and thoughts of suicide are frequent. Patients are advised to Call 800-SUICIDE (800–784–2433) or 800–273-TALK (800–273–8255) or the deaf hotline at 800–799–4889 for immediate help.
  • Anxiety/ panic attacks
  • Loss in sexual desire
  • Increase in purposeless physical activity (e.g., hand-wringing or pacing) or slowed movements and speech (actions observable by others)
  • Low concentration and a sudden detachment from the world

When To Detect Depression?

To be diagnosed with depression, the symptoms must be present for at least two weeks.

Types Of Depression

  • Major depressive disorder
  • Persistent depressive disorder (dysthymia)
  • Premenstrual dysphoric disorder : Women have several depression symptoms and feeling of irritability just before their menstruation.
  • Depressive disorder due to another medical condition
  • Substance/medication-induced depressive disorder
  • Psychotic depression: severe depressive illness accompanied by some form of psychosis like a break with reality, hallucinations and delusions
  • Postpartum depression: generally new mothers develop a major depressive disorder within one month after delivery in around 10–15% of women.
  • Seasonal affective disorder ( SAD): caused due to change in seasons. Mainly caused in spring or early summers.
  • Bipolar disorder: unusual shift in mood and energy levels and sudden escape from reality.


  • Racism can be one of the cause of depression
  • With a misuse of buprenorphine (an opioid) and benzodiazepines, several cases of respiratory depression has been observed.
  • Genetic effects: If a member of a family suffered from depression,then there is a maximum likelihood that you may be experiencing a depressive disorder too.
  • Hormonal Changes effects: Changes in hormone states like -menopause, childbirth, thyroid problems can cause depression.
  • Any major changes in life or a trauma can trigger depression.

This may include:

  1. Observing something scary
  2. Childhood abuse or trauma
  3. A serious accident
  4. Diagnosed with a life threatening condition.
  5. Poor academics in college students or failed relationships

Untreated Depression

  • Untreated depression can be a risky factor with a severe drug and alcohol addiction, aggravate relationships, difficult to overcome illness and serious problems at work. Untreated depression or no treatment and lack of use of antidepressant in depressed patients can lead to a hippocampal volume loss.
  • People suffering from depression are unable to cope up with the challenges their illness presents like recovering from a stroke or coronary heart disease.
  • Higher risk of death in first few months after a heart attack.
  • Feeling of hopelessness and helplessness.
  • Sleep that always feels like not “enough”
  • Untreated depression is as costly as heart disease or AIDS to the US economy. Annual cost of untreated depression is more than $43.7 billion in lost productivity, treatment cost and ignorance and absence from work.

Who Is Affected?

  • Older adults suffer more frequently from depression because of the frequent loss of their loved ones or ignorance from their loved ones.
  • Women are about twice as likely as men to develop major depression
  • Published by the Harvard Medical School, this “gender gap” has not been clearly mentioned but men are less likely to talk about feelings or tend to hide their feelings and not seek help for mood problems. Moreover men are most likely to show up depression in forms of substance abuse or violent behaviour.
  • Major depression tend to affect about 6.7% of the U.S. population above age 18, according to the National Institute of Mental Health. Overall, between 20% and 25% of adults may suffer an from major depression at some point during their lifetime.
  • This table shows any mental illness in the past year among adults aged 18 or older, by age and gender (2012) (National Survey on drug use and health)


  • Initial treatment of major depressive disorder in adolescents may include cognitive-behavioral therapy (CBT) or a selective serotonin reuptake inhibitor (SSRI).
  • Fluoxetine alone is a higher-level treatment to CBT alone.The combination of fluoxetine with CBT generally offers the most favorable tradeoff between benefit and risk for adolescents with major depressive disorder
  • Fluoxetine enhances reduction in suicidal thinking.The cost of fluoxetine oral capsule 10 mg is around $13 for a supply of 14 capsules ( by the US pharmacies)
  • Countries with a higher intake of fish oil have reduced depressive disorder.The author has listed a specific omega-3 fatty acid, the ethyl ester of eicosapentaenoic acid ( E-EPA), is used to medicate recurrent unipolar disorder.
  • Self rating depression scale can be used to assess psychiatric disorders.
  • The Zung Self-Rating Depression Scale was designed by W.W. Zung to measure the level of depression for patients diagnosed with depressive disorder. There are 20 items on the scale that rate the four common characteristics of depression: the pervasive effect, the physiological equivalents and other disturbances. ( Zung, WW (1965) A self-rating depression scale. Arch Gen Psychiatry 12, 63–70. )
  • The scores range from 25–100.  25–49 is the Normal Range. 50–59  is Mildly Depressed, 60–69 Moderately Depressed and 70 and above Severely Depressed
  • Herbal therapy : popular depression treatment in Europe, St. John’s Wort is a herbal supplement useful for mild or moderate depression.
  • Taking St. John’s wort along with antidepressant can cause a major side effect. Proper consultation with a doctor is prescribed before consuming this drug. The cost is around $ 23 . The usual dosage for mild depression is 300 mg, 3 times per day and is available in time-release capsules and also as liquid extract or tea.
  • Electroconvulsive therapy (ECTS) : performed under general anesthesia, electric current passed through the brain and quickly reverses the symptoms of any mental illness.
  • Psychotherapy : The very first form of treatment recommended for depression. The patient generally consults a trained psychiatrist or mental health care professional.

Case Studies

Zinc plays a part in modulating the brain and body’s response to stress all along the way. When zinc levels were measured in depressed patients, it showed subsequent low levels while the patients who were discharged from hospital after proper treatment, had a much higher plasma zinc levels.

Decreased dopaminergic transmission has been implicated in the pathophysiology of major depression. Dopaminergic transmission plays an important role in visual contrast sensitivity. When patients with depressionwere asked to detect a gabor target with a slightly elevated luminance contrast , their contrast discrimination performance failed drastically which portrayed an altered dopaminergic neurotransmission.

Two patients A ( a 39-year-old) and B (a 33-year-old) were suffering from depression since 18 months (A) and four years (B) respectively. After treatment with antidepressants like citalopram , Mirtazapine and also electroconvulsive therapy, they showed very little recovery. So scientists discovered that after treatment with low dose infusion of ketamine , patients tend to recover soon within hours (The wholesale cost in the developing world is between US $0.08 and US $0.32 per dose). Both patient showed tremendous recovery with a positive change in their moods.

Published by American College Of Occupational and Environmental Medicines, extensiveness of depression is directly linked with around 104 occupations as measured by the National Institute Of Mental Health’s Diagnostic Interview Schedule.

Online Exposure/Help

  • Anxiety and Depression Association Of America (ADAA) and SAVE is a non profit organisation which is glad to announce the release of a new collaborative Suicide Prevention infographic.They aim towards increase awareness and proper diagnosis for depression. For more information visit this website.
  • Founded in 1844, American Psychiatric Association have reached out to help people with depression. It is an organization with psychiatrists in United States and the largest organization in the world.
  • The Live Love Laugh foundation reaches out to people to counsel them suffering from anxiety,stress and depression.

Current Research And Ongoing Studies

University of Arizona have recently published an article that suggests bouldering, a form of rock climbing, can help build muscle and endurance while reducing stress and depression.

American Academy Of Sleep Medicine (AASM) has published a recent article that depressed patients with insomnia who sleep seven or more hours per night are more likely to benefit from cognitive behavioral therapy(CBT) for insomnia and achieve depression suspension.

Prominent Cases Of Depression In History

Sylvia Plath, a young and an eminent poet who died 40 years ago in London, suffered from major depressive disorder and attempted suicide quite a few times.

Shortly before her psychiatric appointment was due, she was found dead in her own kitchen, with her head in the oven and the gas turned on.

Her last words included :

I should sugar and preserve my days like fruit!

My mirror is clouding over —

A few more breaths, and it will reflect nothing at all.”


  • More than half of those with depression develop a chronic disorder after a first depressive incident and are likely to spend more than 20% of their life-time in a depressed condition.
  • There is no certain way to prevent depression. However, some strategies may help.
  • Multiple group memberships can become the premise of “social cure” which plays an important role in recovering from medical issues.( Haslam et al., 2009 ; Jetten et al., 2012)
  • Increasing literacy about late life depression and enhancing proper dietary supplements with proper exercise.(19)
  • Indulge into taking proper steps control stress, to increase our resilience and boost our self-confidence, to surround oneself with positive people
  • Reach out to family and friends, especially in times of emergency.
  • Getting proper treatment at the earliest sign of a problem to prevent depression from worsening.
  • To consider getting long-term maintenance treatment to help prevent deterioration of symptoms.


Dr. Sukant Khurana runs an academic research lab and several tech companies. He is also a known artist, author, and speaker. You can learn more about Sukant at or and if you wish to work on biomedical research, neuroscience, sustainable development, artificial intelligence or data science projects for public good, you can contact him at

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