Depression Trials In Melbourne

Depression is a common illness affecting both body and mind and characterised by painful sadness, listless apathy, and exaggerated pessimism. The experience of depression, according to David Foster Wallace, is a “nausea of the cells and soul”, where all potential choices appear “not just unpleasant but literally horrible”.

The precise cause and mechanism of depression remains unknown. The predominant theories involve biological, psychological and social elements, and the reality is likely a complex network of factors pervading all these domains.

How these factors interact is also complex and varies between individuals, but we can at least outline a general pattern: an external trigger acts on internal vulnerabilities to produce a biologically-programmed response. That response is called depression.

External triggers that set an episode of depression in motion can be divided into biological and psychosocial categories.

Common biological triggers are:

• Medical illness, such as anaemia or an overactive thyroid gland.
• Alcohol
• Recreational Drugs
• Medications, such as beta-blockers or benzodiazepines

Common psychosocial triggers are:

• Loss of a loved one
• Relationship problems
• Work problems

One of the most powerful triggers is another mental illness, such as post-traumatic disorder. Like depression itself, other mental illnesses are a mix of biological and psychosocial elements.

Again these factors may be divided into biological and psychosocial categories. For example:

Biological:

• Genetics (depression often runs in families)
• Brain injuries (such as multiple concussions from contact sport)
• Neurological conditions e.g. Epilepsy, Parkinson’s disease

Psychosocial:

• Childhood trauma
• Personality disorders
• Social isolation
• Unemployment

One factor that makes depression more likely is depression itself.

Depression tends to deepen life’s problems, for example, making work and relationships harder, and also sensitises the brain by reinforcing neural circuits that underpin negative thinking. Depression, therefore, smooths the path to its own recurrence.

On the other hand, depression may also increase resilience by provoking positive life changes and summoning inner resources that can insulate a person against future attacks. Which direction the illness goes depends largely on the treatment patients receive and the choices they make.

Some people have known vulnerabilities to depression. Yet from our shared nature as human beings, depression can affect anyone.

Depression has been observed in all cultures and all known periods of history. Depression-like behaviour has also been observed across the animal kingdom, even in species as far down the evolutionary tree as crustaceans.

The pattern is so common and widespread that some researchers see depression not as a disease, like cancer, but as an innate response, like fainting.

We all have the inbuilt machinery that produces depression, but for some people, their trigger-system is more sensitive than others.

The sensitivity could be a collection of genes, which is why family history is a risk factor. The sensitivity could also come from adverse experiences in early life, such as the death of a parent.

Later in life, other elements may arrive to weaken defences, such as alcohol, drugs, or medical illnesses. Then come the manifold stresses of life, any of which can form the tipping point.

Depressed mood or Anhedonia plus 4 or more of:

• Weight change
• Sluggishness (psychomotor retardation)
• Energy loss
• Guilt / Worthlessness
• Concentration loss
• Suicidality
• Insomnia – not a DSM criterion, but very common

Depression is categorised as mild, moderate, or severe. The severity of depression is classed by the number and intensity of symptoms, and impairment they produce. As a general guide:

• mild depression is five or fewer symptoms, where the patient can still work and socialise
• moderate depression is five or six symptoms, with impaired function
• severe depression has at least seven symptoms (or fewer symptoms that are especially intense), along with almost no usual function and the risk of self-harm

Clinicians often use standardised questionnaires to quantify the severity of depression and track it over time.

Depression can be broadly divided into biological and psychological types, although most cases will be a mix of the two.

Biological depression features predominantly biological symptoms, namely:

• weight loss
• morning trough (waking early with mood at its worst)
• physical agitation or sluggishness (called ‘psychomotor’ changes)
• loss of all pleasure and interest (called ‘anhedonia’)

Meanwhile features suggesting psychological depression are:

• a clear life trigger
• mood worsening throughout the day
• prominent anxiety, worry, stress and avoidance
• excessive sleep

Identifying the type of depression can help guide treatment. Biological depression needs biological treatment, such as medication or neurostimulation.

Psychological depression, especially if mild, may depart with psychological therapy and lifestyle changes alone.

Treatment of depression has three general aims:

1. Remove symptoms
2. Restore function
3. Enhance resilience

In other words, treating depression is not simply about removing pain – although blunting the worst of depression’s distress is a vital early step.

Also crucial is a person achieving their optimal level of function, or in the words of Freud, the ability “to love and to work”.

Closely related is producing a buffer against depression’s return, which involves targeting each domain through which depression appeared in the first place: the biological, the psychological, and the social.

There are several simple measures that can benefit anyone with depression, whatever the cause:

• Gradually ceasing medications known to lower mood
• Ceasing alcohol (at least at first) and recreational drugs (permanently)
• Sleep hygiene
• Regular exercise
• Healthy diet
• Addressing other addictive behaviour e.g. social media, pornography, gambling

1. Psychology

Several types of psychological therapy have excellent evidence for treating depression. The most common is cognitive behavioural therapy (CBT); others include interpersonal therapy (IPT) and acceptance and commitment therapy (ACT).

Psychology is the preferred initial treatment for mild depression, and is added to medication in moderate depression.

2. Medication

An antidepressant is preferred for moderate depression, or if psychology is unavailable. The most commonly used are selective-serotonin reuptake inhibitors (SSRIs) or serotonin-noradrenaline reuptake inhibitors (SNRIs). Others include those taken at night, such as mirtazapine or agomelatine.

3. Neurostimulation

The traditional form of neurostimulation is electroconvulsive therapy (ECT), which remains the preferred treatment for very severe depression.

A newer, less-invasive form of neurostimulation is transmagnetic stimulation (TMS), which is used for treatment-resistant depression, and increasingly as a first-line treatment.

4. Esketamine

Esketamine is derived from ketamine. At much higher doses, ketamine is used as an intravenous anaesthetic. Esketamine is a new treatment that comes as a nasal spray, and is used for selected patients as a single dose.

The advantages of esketamine are the rapid resolution of depressive symptoms and suicidal thoughts in many patients.

After diagnosing depression, a doctor will assess the best place for treatment. Mostly this will be outside hospital, but sometimes the severity or circumstances of depression mean that safe treatment at home is not possible.

Examples of when admission to hospital is required include:

• Imminent risk of self-harm
• Mania
• Psychotic depression
• Severe substance abuse
• Danger to physical health (e.g. dehydration)