Major depressive disorder has a prevalence of 5-10% in the
general population and up to 20% in medical patients. It is a major cause of
disability and of suicide. If comorbid with a medical condition, depression
magnifies disability, diminishes adherence to medical treatment and
rehabilitation, and may even shorten life expectancy.
Aetiology
There is a genetic predisposition to depression, especially
when of early onset, although the number and identity of the specific genes are
unknown. Adverse experiences and emotional deprivation early in life also
predispose to depression. Depressive episodes are often but not always
triggered by adverse life events (especially those that involve loss),
including medical illnesses. Associated biological factors include hypofunction
of monoamine neurotransmitter systems (5-HT and noradrenaline (norepinephrine))
and abnormal hypothalamo-pituitary-adrenal axis (HPA) regulation, which results
in elevated cortisol levels that do not suppress with dexamethasone.
Management and prognosis
There is good evidence for the efficacy of both drug and
psychological treatments for depression, and in practice the choice is
determined by patient preference and local availability. Severe depression
complicated by psychosis, risk of starvation or intractable suicide risk may
require ECT.
Drug treatment
Antidepressant drugs are effective in patients whose
depression is a complication of medical illness as well as in those where it is
the primary problem. These agents are all effective in moderate and
severe degrees of depression.
• Tricyclic antidepressants (TCAs). These have
well-established efficacy and are the most effective antidepressants for
treating chronic pain. They inhibit the re-uptake of the amines noradrenaline
(norepinephrine) and 5-HT at synaptic clefts. There is a delay of 2-3 weeks
between the start of treatment and the onset of therapeutic effect.
Side-effects can be particularly troublesome during this period; they include
anticholinergic effects, postural hypotension, lowering of the seizure
threshold and cardiotoxicity. TCAs may be dangerous in overdose and in people
who have coexisting medical conditions, such as heart disease, glaucoma and
prostatism.
• Selective serotonin re-uptake inhibitors (SSRIs). Less
cardiotoxic, less sedative and with fewer anticholinergic effects than
tricyclics, these can still cause headache, nausea, anorexia and sexual
dysfunction.
• Newer antidepressants. A variety are available, including
venlafaxine, mirtazapine, reboxetine and duloxetine. They have different
profiles of action and adverse effects but none has been shown to be more
effective than the more established agents listed above.
• Monoamine oxidase inhibitors (MAOIs). These increase the
availability of neurotransmitters at synaptic clefts by inhibiting metabolism
of noradrenaline (norepinephrine) and 5-HT. They are now rarely prescribed in
the UK, but it is still important to know of their dangerous interactions with
drugs such as amphetamines, and foods rich in tyramine such as cheese and red
wine. Amines accumulate in the systemic circulation causing a potentially fatal
hypertensive crisis.
