depressive illness

Depression: What Is It?

Why Drug Treatment?

A great deal has been written on the subject of defining the medical illness of depression.  That is not a main theme of this website, nor do I profess to be an expert in the classifying of diseases (nosology).  But it is a frequently asked question, so what I will do here is to make some comments and direct readers to quality sources that address such questions.

For more than 100 years comments have appeared in the medical literature bemoaning the fact that the every-day-word used for being ‘down’ mentally is the same as the medical illness of depression. In 1906 there was an article in the ‘Journal of Mental Science’ (1) suggesting that it should not be called ‘melancholia’, as it was then, because that was the word (then) in everyday ‘non-medical’ use for feeling down, but rather it should be called ‘depression’.

Things do not change much, we are now doing the reverse and talking of re-introducing melancholia!

That does not matter much because what we are interested in here is the optimal use of drugs to treat that portion of people suffering from, and sometimes dying from, this condition.  Although there is some difficulty in defining what separates the universal human experiences of stress, distress, and dejection and what distinguishes them from depression as a medical illness, and different and depressive syndromes (because it is certainly not a single and homogenous entity), we can still be confident that there is such an entity as the medical illness of depression, resulting from biological and physical causes.

The ability of doctors to separate drug responsive illnesses from other conditions is still as much of an art as it is a science. There is little doubt that many people treated with so-called antidepressant drugs do not suffer from a depressive illness of the sort that is most appropriately treated by medication.  On the other hand, we know, despite education efforts over the last few decades, that there are still many who suffer serious drug-treatable depression but who do not get effective drug treatment.

That is the great paradox of depressive illness, that it is both over-diagnosed and under-treated.  That can be explained partly by the fact that the illness is difficult to define because none of the symptoms are really patho-gnomonic (i.e. exclusively characteristic of).  There are many symptoms, and the symptoms displayed differ significantly from one patient to another (i.e. it has pleio-morphic, or many-faceted, presentation).

There are several definite good reasons for being very confident that depressive illness does indeed result from both physical and chemical alterations in the way the brain works.

  1. Its occurrence, and the form it takes, is significantly influenced by an individual’s genetic make-up.
  2. It occurs with substantially increased frequency in association with certain specific diseases, Cushing’s syndrome, and neurological diseases in general, particularly Parkinson’s disease.
  3. It is precipitated (and relieved) by drugs that have specific actions on neurotransmitters, the first of these to be observed was reserpine, but there are others including tetrabenazine.
  4. It can be emulated and relieved by damage to, or electrical stimulation of, particular pathways in the brain.

Those observations, among others, are reliable and reproducible and lead to the reasonable supposition that the reverse is also likely to be true; i.e. that both drugs, and other treatments like TMS, ECT, deep brain stimulation, and psychosurgery, may be effective, as indeed they are.

However, the simplistic the notion that seemed to gain a great deal of currency in the last couple of decades, that depression is due to a deficiency of serotonin, is clearly not the answer.  Despite what has been written in the scientific literature there has never been much good evidence to support that idea.  That impression was fostered through the influence of pharmaceutical companies seeking to promote the rationalization and legitimization of the supposed effectiveness of SSRIs like Prozac.  In defence of psycho-pharmacologists, few that I knew found the serotonin deficiency theory satisfactory.

Let me add a brief word of explanation here, because I am sure there are people reading this who are thinking it is wrong because they know they have felt mentally improved after taking SSRIs.  I do not dispute that.  I am sure that SSRIs can have a beneficial effect on mental state of some people.  However, that does not make them antidepressant drugs. Indeed, they were initially developed as anxiety relieving drugs.  They were marketed as antidepressants to distance them from the negative image associated with habit-forming drugs like barbiturates and Librium/Valium etc.

Before we move on to try to illuminate what the features predictive of drug treatable depression are, it is first appropriate to comment on the American ‘Diagnostic and Statistical Manual of Mental Disorders (DSM). I include myself amongst the many psychiatrists and researchers who have always had grave reservations about DSM and especially the way it diagnoses depression (2).  It has blurred the distinction between drug treatable depression and other forms of depression, which in turn has had a significant influence on the types of patients who have been included in drug trials: it has thereby clouded the issue of drug responsiveness (3).

Updating note (2014): since I wrote the initial version of this commentary, quite some time ago, that discontent about DSM has grown greater and greater.

The terms endogenous, biological, melancholic, psychotic, and atypical are used to describe those forms of depressive illness which are likely to be drug responsive.  Ultimately, the most decisive demonstration of whether someone has such an illness is a definite improvement within a short time of initiating drug treatment.  Although that is slightly circular logic it is nevertheless useful and worth remembering.  In medicine any definite response to a treatment with specific indications is used to presumptively confirm a diagnosis; e.g. a rapid response to an anti-biotic confirms it is a bacterial infection, not a virus. Conversely, a failure of such treatment raises a suspicion that the initial diagnosis was incorrect. That is Bayesian logic in operation.

Other predictors include a genetic susceptibility, as revealed by a definite family history in close family members (mother, father, brother, sister). Next come typical symptoms and signs that separate, to a greater or lesser degree, such types of depression from other conditions.

There is a description of the core changes that are the key to distinguish biological illnesses on this website in the following [links] and there are also descriptive quotations from sources in the general literature [Kay Redfield Jamison, John Stuart Mill and William Styron]. Read them; many people find they are helpful in conveying the essence of the illness.

Next, I would direct readers to the useful comments in a very recent editorial in the journal “Bipolar Disorders” (3), which is available free as an online PDF file downloaded directly with this link

Updating note (2014): Well well, no great surprise here. On checking the above link I find the publishers are no longer making it available without payment. But (up yours Wiley – and other publishers), you can get it courtesy of Russian ‘white-hackers’ here

Just put in any ‘DOI’ and you will often get the pdf. Consider giving them a donation, they deserve it.

I quote from it re melancholic features:

“Clinical features: depressed mood, persistent lassitude; felt spiritual abandonment, attitude of depletion; hopelessness, morbid preoccupation; thoughts of perdition ⁄ ruin, anxiety ⁄ panic; middle insomnia, diurnal variation, worse in am; threatening illusions, pervasive anhedonia; loss of usually rewarding solace, wish for release (passively suicidal), paucity of thoughts; psychomotor retardation, non-precipitated mood; perplexity, distinct quality of mood, non-reactive mood, loss of appetite; drained of energy, contesting worth of or whether deserving of treatment, querulous suspicion; hypochondriasis, ambivalent morbid catastrophizing, frozen emotions; suicidal planning, pain complaints; self devaluation, unfamiliar, pathological mood; pathological guilt.”

One excellent concise source of information and well-informed discussion is the material on the “Black Dog Institute” website.

Needless to say there are other sources scattered widely over the Internet. The Black Dog is the best single site that I know of for depression information. Bookmark it, use it.

It is the domain of an eminent urbane polymath Australian professor, Gordon Parker, who is a leading researcher and long-time advocate of the importance of making these distinctions. The following are direct links that will download the relevant free PDFs for you with concise definitions of causes, symptoms and types of depression, including atypical and melancholic depression.

Causes of depression

Symptoms of depression

Types of depression (including atypical depression)

Melancholic Depression


  1. Drapes, T, A Note on Psychiatric Terminology and Classification. BJP, 1906. 52: p. 75-84.
  2. Parker, G, Fink, M, Shorter, E, Taylor, MA, et al., Issues for DSM-5: whither melancholia? The case for its classification as a distinct mood disorder. Am J Psychiatry, 2010. 167(7): p. 745-7.
  3. Carroll, BJ, Bringing back melancholia. Bipolar Disord, 2012. 14(1): p. 1-5.

Keywords: antidepressive agents; serotonin uptake inhibitors; drug combinations; drug–drug interactions;

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