Depression

Original article by Tom Leach | Last updated on 16/5/2014
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Introduction

Depression is one of a group of disorders known as the affective mood disorders, and the internalising disorders – other examples include:
The symptoms of these conditions are very similar, and there is considerable overlap. The actual combination of symptoms will determine the diagnosis.
 
Depression
This can occur as a single episode, or as ongoing condition with periods of ‘relapse’ and ‘remission’.
Depressed patients have a decreased quality of life, as well as increased mortality.
 

Aetiology

  • Genetic susceptibility
  • Life factors –i.e. social situation – e.g. single mums
  • Alcohol/drug dependence
  • Abuse (sexual or not) – particularly in childhood
  • Unemployed
  • Previous psychiatric diagnosis
  • Chronic disease
  • Lack of a confiding relationship
  • Urban population
  • Post natal (10% of all women who give birth!)
 

Epidemiology

  • 10-16% of men, and 20-24% of women will have some symptoms of depression
  • 2-4% of men and 7-8& of women will have actual depression
  • It is the most common GP diagnosis – and accounts for about 12% of all new illnesses
  • It accounts for 45% of all psychiatric diagnoses
 
Differentials – for low mood
 

Investigations

  • FBC
  • U+E’s
  • Haemotinics – folate and B12
  • LFT’s– for alcohol / drugs / cancer
  • CXRto look for chronic infection (e.g. TB)
  • ECG – can show up metabolic disturbances
  • Mental state
  • FULL HISTORY!
 

Major Symptoms

The three core symptoms
  • Low mood
  • Anhedonia – does not take any pleasure from any activities (or reduced pleasure from normal activities). Patients will often withdraw from social activities.
  • Low energy levels
 
We say depression is present when 2 or more of these symptoms exist for more than 2 weeks. ‘more than 2 weeks’ means that the patient would have experienced the symptoms for at least part of the day on everyday for the last two weeks.
 

Minor symptoms

Cognitive
  • Feelings of guilt, uselessness, worthlessness
  • Thoughts of SUICIDE
  • Always ask if they say they are having suicidal thoughts if they have acted upon any of these thoughts – e.g. have they started to ‘stock up’ on paracetomol.
  • Poor concentration

Functional

  • Sleep
    • Difficulty getting to sleep
    • Waking up several times during the night
    • Early Waking - This is significant if the patient regularly wakes up 2 hours before ‘normal’
  • Weight loss - This will be because the patient is eating less, either because they take no pleasure in eating and/or because they feel nauseous
  • Weight gain can also occur
    • Patients may ‘comfort eat’
    • Make sure you ask if the weight loss/gain is intentional!
    • Weight change of >5% is significant.
  • Loss of libido.
  • Psychomotor retardation – the patient can be very ‘slow’ both in their thoughts and actions, to a degree that is noticeable by others.
  • Agitated and fidgety – this can be both in their thoughts and physically. Patients may keep going over and over the same thoughts in their mind, or they may e.g. stand up and sit down constantly.
  • Memory problems – people may complain of memory problems, but it is probably not their memory that is the issue. If you test them on memory things you may notice they do not concentrate when the information is first given, thus the information is not processed, and so they are not able to recall it – however it is the information processing and not the memory recall that is at fault.
 
Other clinical characteristics
  • Diurnal variation of symptoms is common. Generally, symptoms are worse early in the morning and late at night than at other times in the day.
  • Hallucinations and delusions – these may be present, and are generally congruent to the current mood.
  • Schneider’s positive symptoms can occur in severe depression.
 
Some patients may experience melancholia – this is where the patient feels unable to experience any emotions at all – emotional numbness.
 

Diagnosis

The diagnosis of severity not only depends on the symptoms below, but also on the impact on normal functioning. An example of functioning for each level of depression is given in green.  
Mild depression – 1 core symptom, and 3 other symptoms for at least 2 weeks
  • Reduced ability to perform at work, reduced willingness to socialise

Moderate Depression - 1 core symptom and 4-7 other symptoms (major or minor), for at least 2 weeks
Severe depression - 1 core symptoms and 7+ other symptoms (major or minor), for at least 2 weeks. There may also be:

  • Psychotic symptoms
  • Hallucinations
  • Delusions
The diagnosis of severity also depends on the impact on normal functioning.
 

Screening Tools

In general practice, screening tools are often used to assess if a patient is suffering from depression, as well as to track the course of the condition over time. Two examples of screening tools are:

Other variations may be used. Patients may complete these as questionnaires on paper, or they may complete them on the computer. The second method is more widely used, as you are able to easily and quickly compare progress over time.
These methods are able to give a rough guide to the severity f the depression, as well as to assess risk.

 

Questions to ask when taking a history

  • Have you felt ‘low’ or miserable recently?
  • Have you lost your emotions?
  • Does it happen everyday?
  • Does anything seem to have brought it on?
  • Have you lost interest in things you usually enjoy? - Do you still see your friends often?
  • Does your current mood/experience interfere with your normal life?
    • Sleep
    • Weight (loss)
    • feelings of guilt
    • feelings of worthlessness
 
  • Appearance and behaviour – poor self care, lack of eye contact, does not ‘engage’ in conversation, little movement, OR lots of fidgeting
  • Speech – monotone, hesitant, slow
 
DEAD SWAMP – depression history taking made easy!
If you can remember this, and ask all these questions, you are unlikely to miss any major Points:
  • D – Depressions
  • E – Energy levels
  • A – Anhedonia
  • D – Death – thoughts about death and self harm – i.e. Risk!
 
  • S – Sleep pattern
  • W – Worthlessness, guilt
  • A – Appetite
  • M – Mentation – decreased ability to think and concentrate
  • P – psychomotor agitation and retardation

 

Post natal depression

Post natal blues – occurs 3-4 days after birth

Post natal depression – occurs about 1 year after baby
Post natal psychosis – can occur at any time, and involves delusions/hallucinations

ECT works particularly well for these patients
Electro-convulsive therapy
 

Treatment

Mild Depression
Watchful waiting, CBT (not usually practical on the NHS due to long waiting lists), computerised CBT, self-help, exercise, short psychological interventions
Moderate and severe depression
Medication (see below), psychological interventions, consider getting social support
Treatment-resistant, atypical/psychotic depression, those at risk
Medication, complex psychological interventions, combined rugs treatment
High risk
All the above, plus consider ECT
 
Drug treatments
There are details about mechanisms and side effects of medications in the Psychiatric medications article
SSRI’s1st line. E.g. fluoxetine, citalopram. Side effects include:
  • Nausea
  • Vomiting
  • Abdominal pain
  • Sexual dysfunction
  • Allow 4-6 weeks for beneficial effects
  • Patient’s may describe how low feelings are not as pronounced, but the drugs do not increase’ happy’ feelings.
  • If one SSRI is not successful, attempt another SSRI, before trying other drugs
 

If these are unsuccessful you can consider the following types of medication:

 
Medications are effective 70% of patients – but you need to trial them for at least 4-6 weeks. If this is unsuccessful try another drug in the same class, before trying a drug in a different class. 
 
Cocktail phenomenon –Anecdotally, doctors report that the antidepressive effect is greatest when you  mix the medications together – although it’s not in the nice guidelines. However! Be aware that you should not use MAOI’s in conjunction with other anti-depressants as they can cause a serotonin syndrome. It is also recommended not to use anoth anti-depressant within 2 weeks of stopping an MAOI inhibitor.
 
 

Theories of Pathology Depression

The Monoamine theory
This is widely accepted, although it isn’t without its flaws.
It states that depression results from underactivity of monoamine transmitters, and conversely, that mania results from overactivity of monoamine transmitters. The main transmitter involved is serotonin although it is thought that noradrenaline is also involved.
  • Most serotonergic neurons arise in the Raphe area of the midbrain, and project to the limbic system and cerebral cortex.
  • Most noradrenalin neurons are found in the locus cereleus and lateral tegumental areas of the brainstem.
  • There are considerable links between Raphe and locus cereleus areas.
 
Evidence for the theory comes from the fact that:
  • There are reduced levels of 5-HT in the brains of depressed people
  • There are increased number of 5-HT receptors in the brains of suicidal patients
The theory is also generally supported by the medications used to treat the condition, although there are some anomalies. In clinical practice, both noradrenaline and 5-HT treatments are equally effective, although some people will respond better to some types of drugs than others.
 
It is also worth noting that when patients take medications the level of the NT in the brain is altered very quickly, but the clinical effect takes weeks to appear. This tells us that there is some secondary adaptive changes in the brain which are responsible for the condition, and not just the actual level of NT present. These changes probably involve the downregulation of receptors.
There are also probably altered signalling pathways in response to 5-HT in depressed patients – basically G-coupling may no longer function properly.
 
Hypothalamic Involvement
Hypothalamic neurons receive 5-HT input, which alters their output (in this case it looks like 5-HT is inhibitory of these neurons). In turn, they release CRH (corticotropic releasing hormone), which controls ACTH, and ultimately, steroid levels. In depressed patients, cortisol levels are often high, because the hypothalamic neurons are not suppressed as much as normal, and just like in Cushing’s, these patients will fail to be suppressed by the dexamethasone suppression test.
Even more interesting is that CRH itself in excess quantities actually causes some of the symptoms of depression – such as anxiety, loss of appetite, reduced activity etc. and CRH levels are also usually raised in depression.
 
Neuroplasticity and Hypotrophy
In depressed patients, there is often neuron loss in the hippocampus and prefrontal cortex. Also, many of the therapies used to treat depression, and thus ultimately 5-HT itself actually promote neurogenesis.
  • ECT (electroconvulsive therapy) also promotes neurogenesis
  • Many of the studies for this have so far only been conducted in animals, and thus it is still only a hypothesis.
 
 

Treatment of Depression

Summary
Drug
Mechanism
Effect
Block NA and 5-HT re-uptake
↑Mood
MAO inhibitors
Increase stores of NA and 5-HT
↑Mood
Reserpine
Increase NA and 5-HT storage
↑Mood
α Methotyrosie
Inhibits NA synthesis
↓Mood*
Methyldopa
Inhibits NA synthesis
↓Mood*
ECT
Increases CNS responsiveness to 5-HT and NA
↑Mood
Tryptophan
Increases 5-HT synthesis
↑Mood
*used to help calm manic patients
 

General effects of drug treatment

  • Increased monoamine levels in the brain
  • Reversed damaged intracellular signalling pathways
  • Reduced CRF production
  • Inhibition of NMDA release
There are details about mechanisms and side effects of medications in the Psychiatric medications article
 

ECT – electroconvulsive therapy

Still controversial, ECT has been proven in several studies to be more effective than antidepressant medications!
 
Mechanism
It is thought that it induces grand mal type seizures, and that these are necessary for anti-depressant effect. It is also thought that seizures that originate in lower brain areas are less effective than seizures that originate in higher brain areas at reducing depression.
Using a high electrical current increases the therapeutic effect, but increases the risk of memory loss and confusion.
  • Unilateral treatment to the non-dominant hemisphere also reduces the risk of confusion and memory loss, but again has reduced efficacy. Patients who undergo this type of ECT require 2-4 more sessions than other individuals.
  • Sub-seizure’ currents do not have therapeutic benefit.
 
ECT increases the activity of 5-HT cell, and increases the number of post-synaptic 5-HT receptors. It also enhances dopamine activity, and has similar effects on noradrenaline to anti-depressant drugs (particularly reduction in β receptors).
 
Clinical use
ECT is mainly used in severe depression. It is mostly reserved for depression that fails to respond to drug intervention.  It is particularly effective in illness that has:
  • Psychomotor retardation
  • Early-morning wakening
  • Psychotic features
  • Severe weight loss
 
It is also used controversially in:
  • Schizophrenia with severe depressive symptoms
  • Schizophrenia with Clouding of consciousness
  • Mania; when drug treatments (both neuroleptics and lithium) have been ineffective
 
Practicalities
It is given under a short acting general anaesthetic. Patients are also given a muscle relaxant to reduce the risk of injury. Patients are usually starved from at least midnight the night before. They are also given Atropine (anticholinergic) to reduce salivary and bronchial secretions, and to prevent bradycardia.
Before the treatment begins, patients are ventilated with 100% O2. This has been proven to reduce amnesia. Electrodes are placed:
  • Unilateral – one on temporal region, one near vertex
  • Bilateral – on each temporal region
They are moistened to allow good contact with the skin. Almost all patients have bilateral ECT.
 
Regimen
  • 2x per week until improvement is seen
  • This is usually after 6-8 treatments
 
Unwanted effects
ECT is relatively safe, but there is a mortality associated with it (1 in 20,000). However, this is extremely low, roughly equal to that of a minor procedure involving a short-acting general anaesthetic (e.g. some dental treatments). 
 
Physical complications
General physiological effects include; increase in BP, massive increase in cerebral bloodflow, altered pulse rate. This means that ECT is contraindicated in patients with previous MI, arryhtmias, aneutysms, previous cerebral haemorrhage and raised ICP.
 
Although rare, serious physical complications can include:
  • MI
  • Cardiac arrhythmias
  • PE
  • Pneumonia
  • Dislocations and fracturesin cases where the muscle relaxant was not administered correctly or was ineffective
  • Increased BP during treatment can cause:
 

Psychological side effects

  • Mania – results from 5% of cases of ECT. This is a similar risk to anti-depressants, and occurs in those at risk of bipolar disorder
  • Confusional state – occurs in almost all patients, but only lasts about ½ an hour. May be associated with headache
  • Memory loss – there is usually both retrograde amnesia (can’t remember what happened just prior to treatment) as well as anterograde amnesia (unable to lay down new memories for a short time after the procedure. Some patients may report difficulty recalling previously well-known materal – e.g. telephone numbers, although in objective tests, there is no obvious problems. Factors that increase the risk of memory loss include:
    • Bilateral shock, shock to dominant hemisphere
    • >12 treatments
    • >3 treatments per week, with <48 hours between treatments
    • Not giving O2 before treatment
    • Using large current
 
ECT is useful in the short-term, but does not give an indication as to what treatments might be useful in the longer term.
TMS – transcranial magnetic stimulation – this does not provide proven benefit in depression, nor does electrical stimulation of the vagus nerve.
 
Risk
Managing risk is important in depression. The risk to others is usually low, but risk of self-harm is increased. You need to specifically ask about thoughts of self harm and suicide.As well as active self harm, many depressed patients suffer self neglect, secondary to the core symptoms of depression (loss of interest in normal activities). In many cases, this can be managed with carers and home support, but in severe cases, where the patient’s physical well-being is at risk, then inpatient care may be necessary.
 

Prognosis

Prognosis for depression is very good. Most patients will make a good recovery. The greatest risk is usually death from suicide before treatment has had time to take effect.
Outcome and timescales are very varied, but many patients on anti-depressant drugs will be symptom free within just 4-6 weeks. However, treatment should be continued for a minimum of 9 months, otherwise there is an 80% risk of relapse. Even despite this, recurrence is common, especially in those with previous depressive episodes in the last 5 years. Clinicians have to make decisions on an individual basis as to whether or not to continue treatment beyond the 9 month period.
 
 Factors that point to a good outcome are:
  • Large loss event precipitating the depression
  • Normal pre-morbid personality