Depression

Depression is classically divided into endogenous depression and reactive depression, although the validity of this classification is doubtful.

Endogenous depression – principle criteria:

• Pervasive and unresponsive depression
• Early morning waking
• Diurnal variation of mood (worse in the morning)
• Profoundly depressive ideas (e.g. guilt, suicidal feelings)
• The lack of an obvious precipitating cause
• A stable pre-morbid personality

Reactive depression – principle causes:

• A fluctuating depression responsive to environmental change
• Self-pity rather than self-blame
• A clear precipitating cause
• A vulnerable or predisposed personality
• Absence of the criteria of endogenous depression

Aetiology:

Genetic:

• 10-15% of first-degree relatives have an affective disorder (risk in general population is 1-2%)
• 68% of monozygotic twins are concordant for manic-depressive disorder

Biochemical:

• Imbalance in NTs (e.g. monoamine NTs are depleted in depression
• Loss of diurnal rhythm of plasma cortisol
• Hormonal factors (e.g. depression more common after child-birth and post-hysterectomy)

Psychological:

• Maternal deprivation
• Learned helplessness

Social:

• Stressful events (e.g. bereavement, loss of a job)
• Vulnerability factors (e.g. lack of a confiding, intimate relationship)

Clinical features of depression:

Mood Depressed, miserable, unhappy

Talk Impoverished, slow, monotonous, incomplete

Energy Lacking, retarded, apathetic

Ideation feelings of futility, guilt, unworthiness, suicidal thoughts

Cognition Verbal memory impaired, pseudo-dementia in elderly patients

Physical Early waking, weight loss, loss of libido, fatigue, impotence

Behaviour Retardation or agitation, poverty of movement/expression

Hallucinations Auditory – often abusive, hostile, critical

Differential diagnosis of depression:

Systemic physical illness:

• Malignancy
• Hypothyroidism
• Hyperparathyroidism
• Cushing’s syndrome
• Infection and post-infection
• CCF
• Cerebral ischaemia

Drug-induced depression:

• Corticosteroids

Hormones:

• Oestrogen
• Progesterone

Hypotensive agents:

• Reserpine
• Methyldopa
• Clonidine

Anti-parkinsonian drugs:

• Levodopa
• Amantidine hydrochloride

Anti-cancer drugs:

• Vincristine

Psychiatric disorders:

• Schizophrenia
• Alcohol abuse
• Drug abuse
• Anxiety neurosis
• Dementia

Drug therapy in the treatment of depression:

• Tricyclic antidepressants (TCAs)
• Selective serotonin reuptake inhibitors (SSRIs)
• Monoamine oxidase inhibitors (MAOIs)

Tricyclic antidepressants (TCAs):

• e.g. Imipramine, amitryptyline
• The 2 above drugs are given by mouth in initial doses of 25-75mg daily, building up over a week to 150-200mg daily
• Full therapeutic effects can take up to 2-3 weeks to occur
• Act by potentiating the action of monoamines, serotonin and noradrenaline by inhibiting their reuptake into nerve terminals

Side-effects:

• Anticholinergic effects:
• Dry mouth
• Constipation
• Tremor
• Blurred vision
• Urinary retention
• Postural hypotension

• Cardiac effects:
• ECG changes
• Arrhythmias
• Convulsant activity:
• Lowered seizure threshold
• Other effects:
• Weight gain
• Sedation
• Mania

Selective serotonin reuptake inhibitors (SSRIs):

E.g. Fluoxetine (Prozac)

Fewer side-effects than TCAs

Faster onset

Only increase concentrations of serotonin

Common side-effects:

• Nausea
• Headache
• Insomnia
• Diarrhoea

Monoamine oxidase inhibitors (MAOIs):

• E.g. phenelzine (30-60mg daily)
• Act by inhibiting the intracellular enzymes monoamine oxidase A and B, leading to an increase of NA, DA and 5-HT in the brain
• Onset of action is within 24-48 hours

Side-effects:

• Increased appetite/weight gain
• Insomnia

MAOIs also produce a hypertensive crisis with foods containing tyramine or dopamine (therefore, the diet needs to be restricted):

• Tyramine is present in cheese, marmite and red wine
• Dopa is present in broad beans
• The tyramine reaction is treated with IV phentolamine (α-adrenoceptor antagonist)

Electroconvulsive therapy (ECT) for depression:

This is the most rapidly acting of the available physical treatments of depression. It is treatment of first choice in those cases where:

• The patient is dangerously suicidal
• A delay in treatment represents a serious risk to health
• The patient is refusing food and drink
• The patient is in a depressive stupor

The treatment involves the passage of an electric current (usually 80V for a duration of 100-300ms) across 2 electrodes applied to the anterior temporal areas of the scalp:

• Patient is anaesthetized (usually with thiopentone 125-150mg)
• Patient receives a muscle relaxant (usually suxamethonium 30-50mg)
• A course of 6-8 treatments over 3 weeks has been shown to be beneficial

ECT is controversial but it must be stated that it is extremely safe with very few long-term side-effects

Course and prognosis:

• 65-75% of patients admitted to hospital with a major depressive illness will suffer at least 1 relapse requiring hospital admission
• Estimated that 15-20% of depressives never fully recover