Definition: - Low mood (mood = patients sustained, subjectively experienced emotional state over a period of time), anhedonia,
anergia plus cognitive, biological, psychotic, suicidal & severe motor symptoms as identified byICD-10.
Epidemiology Lifetime risk of recurrent depressive disorder (10-25% women) (5-12% men). Sex- female 2 : male 1, average age of
onset of recurrent depressive disorder is late 20s
Risk Factors: Low socio-economic class, adverse life events, female, family history, living in retirement home
Female risk factors: loss of mother before age 11, lack of confidante, having three children under the age of 14, living at home & not
working, post-partum (50% feel down, 10% get post-partum depression, ~0.2% get post-partum depressive psychosis)
Aetiology and pathogenesis: Monoamine hypothesis (flawed)- depression is due to a lack of serotonin, noradrenaline, dopamine in
the CNS. Other neurotransmitters like vasopressin, GABA may be involved. Studies have shown reduced noradrenaline-mediated
growth hormone release, reduced tryptophan, reduced TSH response to TRH, altered cerebral bloodflow on PET scan in depressed
patients. Genetics: have a first degree relative affected increased chances by 2-4 times. Monozygotic twin concordance is about 40%,
dizygotic concordance is about 20%.
Clinical Features/ Presentation:
It is crucial to ask about suicidality- if have thought about it, made a plan, written a note, tried it in the past, anyone in their family has
Appearance- self neglect, possible evidence of weight loss, blunted affect.
Behaviour and psychomotor: possible psychomotor agitation/ retardation, poor eye contact,
Cognition- reduced concentration can cause depressive pseudodementia
Speech- may have poverty of speech,
Thought- Beck’s cognitive triad- negative view of self (guilt in reference to the past), negative view of the world (negative
interpretation of day-to-day events), hopeless view of the future. May have mood-congruent delusions eg nihilistic delusions,
delusions of poverty.
Insight- normally intact, unless psychotic form.
Perception- may have mood congruent hallucinations
ICD-10: organic, drug, psychotic causes and normal bereavement reaction must be ruled out. Symptoms must be present for at least 2
Requires 2 out of three core: anhedonia, sustained low mood, anergia. Other ICD-10 features: sleep disturbance (typically early
morning wakening), recurrent thoughts of death, recurrent thoughts of guilt/ low self esteem, episode of self harm, loss of appetite or
loss/gain of weight, lack of hope for the future, psychomotor retardation/ agitation, reduced concentration
Dysthymia- <4 ICD-10 features (may be longer lasting).
4 fts- mild depression. 5-6 fts- moderate depression.
Severe depression-7 or more, plus all three core/ presence of psychosis. Depression with psychotic features is always considered
severe and may require admission. Another severe manifestation is the depressive stupor- patient becomes oblivious to their
surroundings with extreme psychomotor retardation.
Atypical depression differs by causing increased sleeping, increased eating with possible weight gain, and mood worse at the end
rather than the start of the day.
Other depressive features. Social withdrawal, reduced libido, constipation,
Investigations: FBC (risk of agranulocytosis), U&E (SSRI’s may cause hyponatremia), B1/B12/Folate, TFT, ECG (before starting
venlafaxine), dexamethasone suppression test (for Cushing’s. 50% of severely depressed produce false positives), drug screen,
syphilis, HIV screen if appropriate.
Eliminate possible causative therapies. Drugs-Tricyclic antidepressants, Selective serotonin inhibitors, Monoamine oxidase inhibitors
all have roughly the same efficacy- approx 60-80%. Drug therapy is not recommended for mild depression. Only specialists are
supposed to prescribe for childhood depression Treatment should last at least 6 months (indefinite if patient older than 50 or has had a
suicide attempt) and finish by being reduced gradually. Premature termination of therapy can drive patients into a worse depression
than they were in originally. Abrupt ending of therapy can cause discontinuation syndrome- GI and somatic distress, sleep
disturbances. Drugs may require 4-6 weeks to produce any effect. If there is no effect after four weeks, it is important to check
compliance and use of drugs. If patient is compliant, the options are increasing the dose, augmenting it with other drugs (avoid
seratonin syndrome) such as lithium, referring to a psychiatrist, reconsidering the diagnosis.
TCA’s eg imipramine, amitriptyline. Work by blocking reuptake of neurotransmitters noradrenaline and serotonin. Side effects:
blocks histamine receptor (weight gain, drowsiness), blocks muscarinic receptor (dry mouth, urinary retention, blurred vision,
constipation), blocks alpha receptor (postural hypotension). Can also cause prolonged QT interval leading to arrhythmias, ST
elevation, impotence, delayed ejaculation, agranulocytosis, thrombocytopenia, eosinophilia and hyponatremia and are dangerous in
overdose (beware suicide risk, lofepramine is safest in OD) causing convulsions and respiratory failure. Contraindicated by recent MI,
arrhythmias, severe liver disease, mania. Other uses: anxiety, chronic pain, nocturnal enuresis (imipramine)
SSRI’s eg citalopram, sertraline, fluoxetine, paroxetine. First line antidepressant drug, reduces 5-HT reuptake. Side effects- sweating,
insomnia, possible increased risk of suicidal ideation, anxiety early in course, diarrhoea, vomiting, nausea, weight loss, reduced
appetite, hyponatremia via SIADH, impotence, anorgasmia, delayed ejaculation, seratonin syndrome. Contraindicated by mania.
Other uses: anxiety, bulimia nervosa.
Seratonin syndrome is a potentially lethal interaction between SSRI’s, MAOI’s, some TCA’s and opiates, due to an excess of
seratonin, manifest by agitation, hyperthermia, rigidity, myoclonus, arrhythmias (similar to neuroleptic malignant syndrome). Hence,
there has to be a 2 week gap after stopping a MAOI before starting another antidepressant, 3 weeks for clomipramine or imipramine,
5 weeks for fluoxetine. Likewise there is a mandatory 2 week wait before starting MAOI’s after stopping other antidepressants.
MAO inhibitors- irreversible forms eg phenelzine, rarely caused the “cheese reaction” because they were irreversible inhibitors.
Patients eating tyramine-rich foods were vulnerable to dangerous hypertensive crises when tyramine displaced noradrenaline from
presynaptic vesicles which was released and not broken down. Other side effects: postural hypotension, drowsiness, increased
appetite, weight gain, anorgasmia, hepatotoxicity. Risk of seratonin syndrome. Reversible forms eg maclobemide are said to be safer,
may be recommended for atypical depression.
Contraindications: mania, hepatic impairment, cerebrovascular disease, phaeochromocytoma.
SNRI (Seratonin and noradrenaline reuptake inhibitors)- eg venlafaxine- second-line drug due to risk of QT prolongation. No
muscarinic, histaminergic, alpha adrenergic effects. Contraindicated by hepatic impairment, mania, phaeochromocytoma,
Noradrenergic-seratonergic antidepressants eg mirtazepine. Works by presynaptic alpha2 block (prevents negative feedback),
therefore increased levels of NA and 5-HT released.
Atypicals (don’t appear to work via monoamine hypothesis) eg mianserin- serotonin antagonist
Antidepressants may be augmented with lithium and ECT.
ECT: proven in treatment of severe depression, especially depressive stupor, drug-resistance, high risk of suicide, severe depressive
self-neglect (eg dehydration), prolonged/severe mania, puerperal psychosis. Antidepressants and neuroleptics decrease the seizure
threshold, and ECT induces a seizure, under general anaesthetic. Requires informed consent or a second opinion if this is impossible,
under section 58 of MHA
Risks- same anaesthetic risks as minor surgery, short-term memory loss, headache. Relative contraindications: heart disease, increased
intracerebral pressure, risk of cerebral bleed.
Psychiatric referral is required for drug-resistant depression, depression associated with other illness, child and adolescent depression,
self harm risk, depression in pregnancy, uncertain diagnosis, postnatal depression with risk to child.
Reasons for admission: danger to self/others, distressing hallucinations/ delusions, self-neglect.
Psychological- CBT has been shown to be as effective in mild-moderate depression as drug therapy. Other forms- psychoanalysis,
cognitive analytical therapy, group therapy, family therapy.
Social- housing support, benefits, child protection intervention, voluntary work, training schemes, day centeres. Paid/voluntary work
is believed by many to be beneficial because it gives sensory stimulation, a possible social network, structured time, monetary benfits.
Prognosis: Depression is self-limiting in most cases and without treatment it disappears within a year. However, it is very likely to
recur- 25% within 1 yr, 75% within 10 years. More serious forms of depression have a suicide risk of 15%. Worse prognosis with
concurrent substance abuse, adverse life events Depression secondary to conditions like stroke, rheumatoid arthritis, dementia, HIV
can often be missed.
Differential diagnosis: Organic- dementia, frontal stroke, malignancy, Cushing’s, hypopituitarism hyper/pothyoidism, Addison’s,
hyper/poparathyroidism, B12/B6/folate deficiency, chronic infection, chronic inflammatory illness, ME, MS, menstrual, HIV,
syphilis, chronic pain syndromes.
Drug- alcohol abuse, barbiturates, come-down from stimulants, depressogenic medication: interferon, tetrabenazine, beta blockers,
calcium channel blockers…
Psychiatric: schizoaffective disorder, schizophrenia (eg with predominantly symptoms), dysthymia, cyclothymia, bipolar affective
disorder, seasonal affective disorder, anxiety…
Complications: Self harm, job loss, marital breakdown, increased risk of developing dementia in long-term depression…