This is an information service for doctors written by Clinical Assoc. Prof. David Horgan.  Only general information is being provided, not specialist advice for the treatment of individual patients.   Dr. Horgan accepts responsibility only for his own patients in the use of this information.  Questions can be emailed to , indicating that you are a doctor, and a general response will be made, but individual patients tend not to be dealt with.



What is the earliest sign of depression?


I believe that difficulty concentrating is a very early sign of depression, so that the patient does not retain information easily when reading, and may even have trouble watching a TV programme or even following a discussion. High IQ patients may compensate automatically, but will then tell you their memory is not as razor-sharp as usual.


Reduction in normal sexual interest is also very common as an early symptom, but young people may still retain their libido, due to having strong biological drives.   Also, many women lose their libido when their relationship or their life is stressful, without having actually developed depressive illness.



What other conditions may be mistaken for depression?


The standard medical conditions that make people tired are important to exclude, in particular having an under-active thyroid gland, being anaemic, or other general medical illnesses.


Heavy intake of alcohol or marijuana (or other street drugs) give users all the standard symptoms of “depression” (loss of motivation, inability to concentrate, tiredness, sleep disturbance etc.), and indeed it is usually impossible to tell if the patient has both depression and substance abuse, or substance abuse only.   It is only after a few weeks of significant reduction in the use of these substances, that it can be seen if the “depression” clears up spontaneously, or persists.


It is difficult to decide when a normal grief reaction has progressed to causing depression as a complication, but after three months, some lessening of the emotional pain would be expected in normal grief.   If the pain remains unchanged for a prolonged period of time after a tragedy, antidepressant treatment may be necessary to allow normal healing to then take place.


Overshoot of antidepressant medication can be mistaken for ongoing depression.  The main difference is that people with depression are tired, but they are normally not yawning / drowsy, they do not have trouble finding the right word when thinking or talking, and they do not make silly mistakes frequently.



When should an antidepressant start to work?


While traditional teaching and textbooks describe antidepressants as taking 3-6 weeks to work, recent analysis of thousands of patients in innumerable drug trials indicates that some improvement is visible within two weeks, and certainly within three weeks.   Indeed, there is evidence to suggest that lack of improvement within three weeks is highly correlated with almost inevitable failure of that antidepressant.



When should a decision be made about increasing the dose or changing the medication?


Three to four weeks after starting the antidepressants, this decision should be made.   If the patient is doing very well, the antidepressant and its dose would seem to be correct.   If the patient is doing well, but only to a limited extent, increasing the dose is indicated.   If the patient has really made no significant improvement after 3-4 weeks on any particular antidepressant, it is extremely unlikely that prolonged use or dose increase will make any difference, and change of antidepressant is indicated.



What can be done to make antidepressants work better?


Helping the patient to deal with the stresses in their lives, by discussion, by problem-solving options being discussed, and by CBT (Cognitive Behaviour Therapy) are all very useful, and indeed no-one wants depression treated by medication without appropriate counselling or therapy.


Low doses of the new generation atypical antipsychotics (Zyprexa, Seroquel, Abilify, Solian, Risperdal etc.) are often dramatically effective in patients with a wide range of depression symptoms.


Traditional advice has been to add lithium (Lithicarb or Quilonum) to supplement the benefits of antidepressants, but many clinicians are quite disillusioned with the claimed benefits of such an approach.   American psychiatrists are strongly in favour of the addition of thyroid hormone (especially T3 more than T4) but this is not seen as useful by the majority of Australian psychiatrists.   Adding a second antidepressant is often very useful.   This involves increasing the first antidepressant progressively until no further benefit is obtained, reducing the first antidepressant back to the level where it had produced most benefit, and slowly adding progressive doses of a second antidepressant.   This is controversial in Australia, despite research showing 80% of Australian psychiatrists and 66% of GPs have done this.   The rare risk of the Serotonin Syndrome, and the even more rare risk that it would be serious, needs to be discussed with the patient, and duly noted.  Adding Avanza to existing antidepressants is considered very safe, whereas adding anything to MAO inhibitors (Parnate, Nardil, Aurorix etc.) is quite dangerous.   The use of tricyclic antidepressants, especially in combination with other antidepressants, should probably be done only by psychiatrists, or under psychiatrist supervision, especially as some modern antidepressants markedly inhibit the metabolism of tricyclics, causing a risk of tricyclic antidepressant toxicity (such as cardiac arrhythmias and grand mal seizures).


Mixing two types of SSRIs together is  sometimes effective.


N.B. Patients must understand that this approach is fundamentally a clinical experiment, with some risks attached, and it has not been irrefutably proven to be superior treatment, as otherwise combination antidepressant therapy would be standard advice in all text books and journals.



Why do patients who were doing well suddenly deteriorate?


There are two common problems.


Firstly, patients can become resistant to a previously effective antidepressant, apparently due to receptor changes in the central nervous system.   This is described by the Americans as “poop out”!   In a minority of cases, increasing the dose of antidepressant will work, but usually the antidepressant needs to be changed.


Another common issue is that the antidepressant has been “too effective”, and the patient has had all their symptoms eradicated, but continues to be pounded by the highly effective antidepressant.   With no symptoms left to absorb the medication, the patient develops apparent relapse of their symptoms.   This is similar to patients who are highly anxious becoming sedated when their symptoms subside, unless they reduce the dose of their anti-anxiety medication.  This mechanism has been written in our College of Psychiatrists’ Journal by me, under the heading, ‘The YES Syndrome’.  Yawning, expressive dysphasia (intellectual difficulty finding the right word when thinking or talking), and silly mistakes (spelling errors, typing errors or putting things in the wrong place) are the result of the patient being over-medicated in effect as the illness subsides.   Reduction in the dose of the antidepressant will resolve the issue in 48-72 hours usually.  (If in fact the patient was becoming more depressed as a result of poop out of the antidepressant, they will in fact get worse 48-72 hours after reducing the dose).



What about long-term use of antidepressants?


Many patients see depression as similar to an infection, and after a short period of taking antidepressants, feel there is no need to continue them.   Unfortunately, all that antidepressants do in effect is shove the symptoms below the surface, and if not kept submerged long enough, the symptoms will have a high risk of recurring.   


We advise ideally that antidepressants be taken for one year after the first episode of illness, and for two years after a second episode of illness, in the hope of totally eradicating the symptoms, and lessening the risks of recurrence.   However, 50% of depressions will recur after one episode and 75% of depressions will recur after two episodes.   Accordingly, we advise lifelong antidepressant treatment (with various therapies such as CBT) in people who have had three or more episodes of depression, as relapse is considered to be almost statistically inevitable.



Should patients take the same doses of antidepressants all the time?


Treating depression is a fluctuating scenario, as there is an ongoing interaction between the ups and downs of peoples’ lives and fluctuations in their internal biochemistry.   Accordingly, depression often becomes somewhat worse pre-menstrually, at times of stress, or after eight hours, and taking more antidepressant at these times is usually useful.    Similarly, if things are going well in a patient’s life, or the antidepressant has been quite effective, the patient may become over-medicated and develop the YES Syndrome described elsewhere on this page, in which case the dose of antidepressant can be reduced.


It is very useful to teach patients to titrate their antidepressants, taking more or less depending on how they feel, and using their ability to concentrate and remember what they have read or seen on TV as an indicator that their dose is correct.


Increases or decreases in antidepressant doses normally produce clinical changes in 48-72 hours.



When is depression likely to indicate Bipolar illness?


Bipolar illness can only be finally diagnosed when the patient actually has a hypomanic or manic episode, but certain factors increase the index of suspicion.   In particular, rapid onset of depression and especially rapid progress to severe symptoms, is a highly suspicious pattern.   Similarly, rapid response of a severe illness is a significant warning sign.   A family history of Bipolar illness, or a personal history of mild mood swings (especially any indicator of hypomanic swings) are also warning signs.


It is very useful to ask all patients with depression if they have ever had a night or a number of nights in which they did not need much sleep, and felt energetic and fine all the next day.   Having no actual need for sleep, as distinct from not sleeping, is a unique symptom.   This is different to people who cannot sleep for whatever reason, or who choose not to sleep, to socialise or to complete certain tasks; the vast majority of people feel tired the next day as a result of such a decision or inability to sleep.



Many people say they are depressed, when the real issue is they are unhappy and not actually suffering from an illness.   What factors indicate the difference between unhappiness and depression?


This is a common problem.   It is normal of course to be unhappy when things are going wrong.  This state of emotional distress may temporarily benefit from “emotional painkillers” such as Valium etc., but medication is not going to have a significant role to play in such a scenario.   There are a number of useful differential features.

  1. People who are depressed almost always have trouble concentrating or remembering, to a degree worse than usual.   In contrast, people who are unhappy can still concentrate if they are interested in what they are reading or watching on TV.
  2. People who are depressed describe the sensation as being with them continuously, even if it is shoved to the background in pleasant situations or in less stressful situations.   In contrast, people who are unhappy will describe being completely free of symptoms in enjoyable situations, with the symptoms returning in their normal day.   For example, people who are unhappy will describe being completely back to their normal selves, and having no symptoms, when they are in an enjoyable social situation, or when they are on holiday.   Whereas, people who are depressed will say the symptoms are always in the background, even on such enjoyable occasions.
  3. Unhappiness rarely goes on for weeks or months without changing significantly in some ways, whereas depression can go on for a very long time if left untreated.
  4. People with depression will describe their personality as having changed noticeably, and indeed this may have been commented upon by those close to them.   In contrast, people who are unhappy will agree that their personality is essentially the same as always.

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