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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 often similar, and there is considerable overlap. The actual combination of symptoms will determine the diagnosis.
Depression 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 (15% 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 at any given time
  • It is the most common GP diagnosis – and is present in 17% of people who present to general practice in any given year
  • It accounts for 45% of all psychiatric diagnoses
  • Lifetime risk of 15%
  • Up to 60% of cases will not have had any interaction with medical services in the last 4 months
  • In those with diagnosed depression, lifetime risk of suicide is 6%
  • Mean age of onset is 27
  • 40% of cases present before the age of 20
  • 40% of patients will have a relapse within one year
  • 50% of patients also suffer from anxiety
Differentials – for low mood

Investigations

At the time of a first / new presentation, the following investigations may be considered to rule out an underlying case

  • 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!

Diagnosis

It is recommended that depression be diagnosed in line with the DSM-V diagnostic criteria for depression.

DSM-V Diagnostic criteria

Diagnosing depression requires a relative short history of at least 2 weeks.

At least FIVE of the following almost every day for the last 2 weeks. Numbers ONE and TWO are essential.

  1. Depressed mood
  2. Loss of interest or pleasure in previously enjoyed activities
  3. Change in weight (>5% in <1 month) OR change in appetite
  4. Changes in sleep – insomnia or hypersomnia
  5. Psychomotor agitation (e.g. symptoms of anxiety) or retardation
  6. Fatigue or low energy
  7. Feelings of worthlessness or guilt
  8. Reduced concentration or decisiveness
  9. Suicidal ideation or attempt

There may also be:

  • Psychotic symptoms
  • Hallucinations
  • Delusions
An assessment of severity also depends on the impact on normal functioning.

Previously, depression had been thought of in terms of major and minor symptoms. It can still be useful to think in these terms.

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
‘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.

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. 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 of the depression, as well as to assess risk.

History

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
Mental State
  • 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!
  • 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

Assessing suicidal ideation

Although the predictive power of assessing suicide risk is sometimes controversial (evidence is poor that it is possible to truly predict suicidal risk), it is still important to undertake a suicidal risk assessment.

Ask about:

  • Suicidal thoughts
  • A suicide plan
    • g. “I have a rope in my car and when I leave here I’m going to hang myself from the tree in my front garden”
  • Lethality
    • Are they planning on taking 10 paracetamol, or jumping off a cliff?
  • Means
    • Do they have access to firearms? To other dangerous equipment? What medications do they have at home?
  • Past history
    • Previous suicide attempts?
    • What were they?
  • Suicide of a family member or peer

Management

Basic Principles

The basic principles of management are:

  • Psychological interventions
    • This includes lifestyle factors that are known to improve mood – e.g. regular exercise, healthy diet, social interaction
    • Cognitive behavioural therapy – either in person with a trained medical professional (psychologist or GP), or online – both are thought to be equally effective
  • Antidepressant medication therapy
    • Typically used in combination with psychological interventions
    • Regular follow-up to review the effectiveness of psychological and antidepressant interventions
      • The regularity of this depends on the severity of symptoms – it may range from weekly (in the acute or more severe cases) to once every several months (once in remission)
  • ECT – electroconvulsive therpy
    • Typically reserved for the most severe cases in an inpatient setting
Mild Depression
Advise patient about the diagnosis and explain what it means.
Watchful waiting, psychology / CBT (often long waiting lists to see psychologist on NHS), computerised CBT, self-help, exercise, short psychological interventions (e.g. advise about activity scheduling, structured problem solving, negative though channelling), sleep hygiene.
Moderate and severe depression
All of the above, PLUS:
Medication (see below), psychological interventions, consider getting social support
Treatment-resistant, atypical/psychotic depression, those at risk
All of the above, PLUS:
Medication, complex psychological interventions, combined drug treatment
High risk
All the above, plus consider ECT
 

Psychological interventions

  • Psychotherapy – the process of explaining the diagnosis and it’s effects
  • CBT – cognitive behavioural therapy – a type of “talking therapy” which helps the patient to better understand their symptoms, and helps them to recognise negative thought patterns, and how to better manage these thoughts, including teaching new ways of positive thinking.

Drug treatments

  • BEWARE OF USING ANTIDEPRESSANTS IN BIPOLAR DISORDER
    • Ask about possible periods of mani or sub-mania before prescribing, to ensure it is not a case of bipolar disorder presenting with a low mood episode
    • Anti-depressants can worsen bipolar disorder, and these patients are instead treated with mood stabilisers (typically lithium)
  • Medications are particularly useful in moderate to severe depression, as well as depression with features of anxiety
  • Antidepressants are roughly equally as effective as CBT / psychological interventions in treating depression
    • Patients are about 20% more likely to achieve remission than with placebo
    • In severe depression, antidepressants are more effective than psychological interventions, and the likely benefit is greater
  • Assess the effectiveness of antidepressants at 6-8 weeks
    • If no benefit is felt by 6 weeks, then it is likely the current drug is not suitable for the current patient
    • Consider an alternative medication
    • Typically a “washout period” of days to weeks should be used between antidepressants if medications are changed
  • The aim of treatment is to induce remission
SSRI’s1st line. E.g. fluoxetine, citalopram, sertraline, paroxetine. 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
  • See the article on SSRIs for more information

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

  • SNRI – serotonin-noradreline reuptake inhibitors – e.g. venlafaxine. May be superior to SNRI in severe depression
  • Tricyclic antidepressants
  • MAOI – monoamine oxidase inhibitors
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.

General effects of drug treatment

  • Increased monoamine levels in the brain
  • Reversed damaged intracellular signalling pathways
  • Reduced CRF production
  • Inhibition of NMDA release
  • BEWARE of serotonin syndrome – which is more likely if more than one drug with serotonerigc effects are given concurrently

Continuation of drug treatments

  • If medication is successful, and remission is achieved, it is recommended to continue medication for at least 12 months
  • If there are subsequent further episodes – continue treatment for 2-3 years when it is restarted
  • Risk factors for relapse include:
    • More than 2 episodes int he last 5 years
    • More than 3 previous episodes in total
    • History of severe or prolonged depression
    • Co-morbid medical problems
    • Life stressors

Summary of drug treatments

Drug
Mechanism
Effect
Tricyclic antidepressants
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
Complimentary medicines
  • The evidence for the effectiveness of any other agents (e.g. St John’s Wort, or other herbal treatments) is lacking
  • However – up to 50% of the general population have taken an alternative medication int he last 12 months
  • Public perception differ substantially from the evidence:
    • 80% of people believe that complimentary therapies are likely to help with depression
    • Only 30% of people believe that antidepressants are effective for depression

ECT – electroconvulsive therapy

Still sometimes controversial, ECT has been proven in several studies to be more effective than antidepressant medication.
  • Generally considered safe although can cause some short and long-term memory impairment
  • Should only be performs under psychiatrist supervision
  • Typically in an inpatient setting
  • A typical regimen might include 1-3 sessions per week for 8-12 weeks

Indications include:

  • Depression not responsive to medications and psychotherapy
  • Depression with psychotic features
  • Severe psychomotor depression – e.g. refusal to eat, severe personal neglect
  • It may also be used in:
    • Schizophrenia with severe depressive symptoms
    • Schizophrenia with Clouding of consciousness
    • Mania when drug treatments (both neuroleptics and lithium) have been ineffective
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).
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.
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:
    • Cerebral haemorrhage
    • Bleeding of peptic ulcer

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

Theories of Pathology Depression

The pathology of depression is not well understood. However, one way of thinking about depression is with the stress vulnerability model. This states that individuals have a genetically defined level at which excessive stress will result in a mood disorder (i.e. depression). Subject any given individual to enough stress, and they will surpass this threshold, and begin to suffer from a mood disorder.

At a cellular level, prolonged “stress” results in neuron cell death via two pathways:

  • Mitochondrial dropout
    • Increased glucocorticoids (i.e. cortisol) in response to stress leads to excessive mitochondrial activity, leading to “burnout” of the mitochondria, and subsequent neuronal death
  • Glional dropout
    • Brain-derived neurotrophin factor (BDNF) is a protein in the brain that protects neurons from damage
    • The neurotransmitter serotonin, noradrenalines, and to a lesser extent dopamine all cause increased synthesis of BDNF
    • In depression, there are reduced levels of BDNF and this leads to neuronal cell death
  • The end result of these factors is decreased brain activity in the prefrontal cortex, and increased activity in the limbic system
  • Microscopically, the brains of those with chronic depression can be seed to have neuronal cell death
  • Macroscopially, on MRI, there may be seen up a 1/3 reduction in side of the hippocampus
  • Therefore – real and significant physical brain changes can be seen in depression – it is not just “all in the mind”
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.

Depression and pregnancy

Depression around the time of pregnancy (“perinatal depression”) is extremely common, and affects about 10% of women during pregnancy, and 15% of women after birth.

It typically starts in the first few weeks, and peaks at about 12 weeks after birth. Particularly common symptoms are anxiety and agitation, mood swings, and other features typical of depression. In very severe cases, the wellbeing of the baby may be at risk – ask about infanticidal ideation and well as suicidal ideation.

Risk factors

  • Previous perinatal depression
  • Previous mental health problems
  • Social or cultural isolation
  • Abusive relationship (past or present)
  • Family history of mental health disorder
  • Other life stressors as for depression at any time

It is recommend to screen every pregnant women for depression, both before and after birth, using the Edinburgh Postnatal depression scale (EPNDS). Explain the process before jumping in and asking the questions. Those with a high score (10+), typically require more regular further screening. Those with a score of 13+ require urgent psychological or psychiatric referral. SSRIs can be used in pregnancy, but specialist advice should be sought.

Management

Is typically the same as major depression – a combination of basic lifestyle factors, psychological therapies and medication.

Medications most likely used in the perinatal periods include:

  • SSRIs – sertraline, paroxetine
  • Other – amitriptyline, nortriptyline

Postnatal blues  is a milder form of low mood, that typically 80% of new mothers, typically in the first two weeks after giving birth, and lasts <2 weeks.

Typical features include:

  • Feeling down or depressed
  • Mood swings
  • Irritability
  • Feeling emotional
  • Feeling inadequate
  • Tiredness
  • Muscle aches and pains
  • Headaches

Management

  • Reassurance
  • Get as much rest as possible – ovoid over-tiredness
  • Accept help around the house
  • Share the workload of a new baby with your partner
  • If symptoms last >14 days – consider post-natal depression

Depression in children and adolescents

Depression is common in teenagers, and probably under-diagnose in younger childhood age groups. In children, it is more likely to manifest as irritability and loss of interest in usual activities. Suicidal ideation and attempt is rare before adolescence.

Assessing for depression and other mental health disorders in teenagers can be difficult. Try not to be judgemental. An curious, non-intrusive approach is best.

A useful framework for history taking is the HEADS-ED assessment tool:

  • H – Home
    • How does your family get along with each other?
  • E – Educations / employment
    • How are you doing at school?
    • Do you have a lot of school friends?
    • Are you working?
  • A – Activities and peers
    • What do you do in your spare time?
    • How are your relationships with friends?
  • D – Drugs and alcohol
    • Do you drink alcohol?
    • Do you take any drugs?
  • S – Suicidality
    • Do you have any thoughts of wanting to kill yourself?
  • E – Emotions, behaviours and thought disturbance
    • How have you been feeling lately?
  • Discharge plan
    • Do you have any help? Do you want any help? Are you on a waiting list to see somebody (e.g. psychologist) ?

 

Depression in the elderly

Depression in the elderly is extremely common and often underdiagnosed. It is also often confused with, and associated with dementia.

Symptoms of depression in the elderly can be different to other age groups, and it more commonly associated with psychosis. It also commonly causes a change in sleep pattern.

Elderly patients are less likely to respond to medical therapies.

 

Adjustment disorder

Adjustment disorder is a less severe type of depression, with depressed mood which doesn’t meet the DSM-V criteria, and typically occurs in response to a major life stressor – such as losing your job, or death of a close friend or relative. It typically lasts <6 months, and is not a chronic relapsing and remitting disorder – unlike depression. If symptoms do not resolve within the time frame, then the likely true diagnosis is depression

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