What is depression?

Depression has become a popular term to describe negative human emotions. But this can mean anything from unhappiness and grief to profound sadness. The later may be a medical condition called clinical depression or major depression (major depressive disorder DSM V). Not all sadness is a diagnosable medical condition and different people experience sadness differently. People often make the mistake of equating their experience of sadness with another person’s clinical depression thus failing to empathise with the other. Attempting to encourage a depressed person to do more may lead to potential negative consequences such as hopelessness or suicide. Hence it is important to know what constitutes depression. A commonly used guide to diagnosis is Diagnostic and statistical manual of mental disorders (DSM) 5th Edition. According to DSM-V: Depression is characterised by the presence of 5 or more of these depressive symptoms in a 2-week period, which represent a change from previous functioning:

  • Depressed mood most of the day, nearly every day
  • Markedly diminished interest or pleasure in all, or almost all, activities every day
  • Significant weight loss
  • Insomnia
  • Constant restlessness or slowing of movements.
  • Fatigue
  • Feelings of worthlessness or excessive or inappropriate guilt.
  • Diminished ability to think or concentrate, or indecisiveness
  • Recurrent thoughts of death

It should be noted that depression is not just sadness but is a clinical syndrome which not only affects ones mood but also physical activity (fatigue), biological functioning (sleep, appetite) and thinking (attention, memory, problem solving).

How common is depression?

On average, 1 in 6 people – 1 in 5 women and 1 in 8 men – will experience depression at some stage of their lives. Only 1 in 3 Australians with anxiety and depression access treatment with men seeking help less often than women (1). Such data indicates that although depression is a common problem, our experience of it may be influenced by societal expectations, gender roles and cultural background among others.

What causes depression?

Our brain is a complex system with emergent characteristics such as consciousness. The experience of mood is not any different; this may also be conceptualised as a product of complex interaction of various systems in our body. Scientists have looked for answers to the problem of sadness by studying our brain and our genes.

Studies have replicated the finding that our brain is able to switch modes based on the task at hand. It works in its active mode when we are focused on a task, otherwise works on its default mode. The later allows us to reflect on our actions, ruminate about the past or think about the future. Although, it seems to serve a useful purpose for many, it is likely to negatively affect those with history of childhoodsexual abuse, children of mothers with depression or history of childhood mood disorder. Functional imaging (fMRI) scans have allowed us to detect the reason for this phenomenon, which is abnormal hyper-connectivity of certain brain circuits (3). Amygdala is one such region of the brain that is critical for response to negative emotional stimuli. Whereas the anterior cingulate and Insula help to dampen the amygdala’s sensitivity to negative emotional processing, the posterior cingulate and precuneus increase this sensitivity (3). Based on how ones brain works in its resting and active modes and which of these centres and circuits gets activated, one may feel a wide range emotions or thoughts. This can also potentially lead to increased production of the stress hormone cortisol, through its connection with the hypothalamic-pituitary axis (HPA)(2).

The role of genetic factors in depression is slowly unraveling. A meta-analysis of twin research data shows that the heritability rate for depression is 37% (95% CI: 31%−42%), and data from family studies show a two- to threefold increase in the risk of depression in first-degree offspring of patients with depression. However, researchers efforts to identify specific causal genes in individuals with depression, has not yet been consistently replicated. It is widely believed that depression is a result of multiple genes interacting with each other (2). It is likely that these genes might also be functionally modified by lesser known gene-environment interactions such as epigenetics, hormonal (cortisol) and immunological changes (inflammation). Not surprisingly, environmental stress factors such as work, finances, relationship and physical illness can potentially share the causal pathway for depression.

How is depression diagnosed?

Your general practitioner or psychiatrist may diagnose depression using clinical examination (mental state examination). Scans or laboratory tests are not necessary to diagnose depression.

Treatment of Depression: Do you need anti-depressants?

Some forms of sadness can be managed using self-help tools. Check out the tools available on www.cci.health.wa.gov.au. Mild to moderate forms of depression may be treated using psychotherapy/counselling, although depression of any severity will respond to medications. Depression pills called Anti-depressants are usually reserved for moderate to severe depression to balance the clinical benefits with side effects.

Depression is a heterogeneous disorder and hence not everyone responds to the same medicines. Nevertheless, 1in 3 people treated with anti-depressants will show response (6).

Anti-depressants Vs. placebo

Anti-depressants are clearly superior to placebo but the difference is less evident in those with milder forms of depression. It is now known that anti-depressant placebo difference in clinical trials seems to have diminished over the past decades due to methodological changes in those trials(7). fMRI studies showed that 8 weeks of anti-depressant treatment is associated with reversal of the abnormal activation of brain centers such as amygdala and related cortico-limbic circuits. These findings have been replicated in similar studies (3,4).

What are the types of anti-depressants:

The popular ones are called SSRI’s- they include Zoloft, Prozac and Lexapro.

The other classes of medicines include SNRI- Effexor, Pristiq, Cymbalta and NASSA- Avanza, Tricyclics- Amitriptyline, Imipramine, Dothiepin etc

What to do if your depression pills did not work for you?

Studies have shown that some people may need a trial of more than one anti-depressant to get adequate clinical response (8). There is evidence that pharmacogenomic testing may be a useful tool in predicting anti-depressant treatment response (5). You might need a review by a psychiatrist to decide on future course of treatment. Newer and effective treatments such as repetitive trans cranial magnetic stimulation (rTMS) also offer hope to those who failed multiple anti-depressant trials.


  1. Australian Bureau of Statistics. (2008). National Survey of Mental Health and Wellbeing: Summary of Results, 2007. Cat. no. (4326.0). Canberra: ABS.
  2. Shadrina, M., Bondarenko, E. A., & Slominsky, P. A. (2018). Genetics Factors in Major Depression Disease. Frontiers in Psychiatry, 9, 334.
  3. Cullen, K. R., Klimes-Dougan, B., Vu, D. P., Westlund Schreiner, M., Mueller, B. A., Eberly, L. E., Lim, K. O. (2016). Neural Correlates of Antidepressant Treatment Response in Adolescents with Major Depressive Disorder. Journal of Child and Adolescent Psychopharmacology, 26(8), 705–712.
  4. Natalia Jaworska, Xiao-Ru Yang, Verner Knott & Glenda MacQueen (2015) A review of fMRI studies during visual emotive processing in major depressive disorder, The World Journal of Biological Psychiatry, 16:7, 448-471.
  5. The effect of pharmacogenomic testing on response and remission rates in the acute treatment of major depressive disorder: A meta-analysis. Rosenblat, Joshua D. et al.Journal of Affective Disorders , Volume 241 , 484 – 491
  6. Anderson IM et al.Evidence based guidelines for treating depressive disorders with anti-depressants:A revision of the 2000 British Association for Psychopharmacology guidelines.J Psychopharmacol 2008;22:343-396
  7. Khan A et al.Why has the anti-depressant-placebo difference in anti-depressant clinical trials diminished over the past three decades? CNS Neurosci Ther 2010;16:217-226.
  8. Rush AJ et al.Bupropion SR, sertraline or Venlafaxine-XR after failure of SSRIs for depression.N Eng J Med 2006;354:1231-1242.

Author: Dr Anjith Divakaran MD FRANZCP

Psychiatrist at Mindoc Psychiatry Clinic , Glen Waverley VIC