Affective Disorders (NM) (DONE) Flashcards
Depression
Leading cause of disability in developed countries
Approximately 1 in 7 people will suffer a depressive episode at some point in their life
More common in women than men
Strong association with suicide
Characteristics of depression
Low mood
Loss of interest/pleasure from normally pleasurable activities
Reduced energy (fatigue)
Low self esteem, feelings of guilt, inability to concentrate, altered psychomotor activity, sleep disturbance, altered appetite, suicidal thoughts
Two core symptoms plus two or more of the others present for most of the day and on most days for at least two weeks
Diagnosis of depression
The symptoms are not attributable to physical illness, alcohol, medication or illicit drugs
There has never been a manic episode, or a hypomanic episode
Aetiology of depression
Biological: genetic factors, monoamine hypothesis, alterations in the hypothalamic-pituitary axis and immune system
Environmental/psychological: early life adversity, personality traits (anxiety, impulsivity, obsessionality), stressful life events, physical illness
Psychopharmacology of depression
A reduction in monoamine (serotonin, noradrenaline, dopamine) neurotransmission (depletion of neurotransmitters and change in receptor function)
Tryptophan depletion which reduces 5HT synthesis can lead to depressive symptoms
Increased activity in the subgenual cingulate cortex- antidepressants and deep brain stimulation reduce the activity of this area
Prognosis of depression
Episodes tend to last for 3-6 months
Approximately 50-80% of patients who have one episode of major depression will go on to have a second
80-90% of those having a second episode will have a third episode
Significant risk of suicide
Risk of recurrence increased by family history, female gender, social factors, co-morbid psychiatric illness, longer duration of episode, co-morbid medical illness
Treatment of depression
Assessment and accurate diagnosis
Psychological- CBT, behavioural activation, interpersonal psychotherapy, problem solving therapy
Social- identifying stressors and working on strategies/signposting to other supporting organisations
Biological- antidepressant medication or antidepressants and antipsychotics in psychotic depression
Antidepressants
Usually divided according to mechanism of action
All potentiate neurotransmission and are effective but with different side effect profiles
All can cause hyponatraemia (caution in elderly)
Tricyclic antidepressants
Amitriptyline, nortriptyline, dosulepin
5HT and NA transporter blockade
Side effects: short lasting sedation, confusion and incoordination in both normal and depressed patients, antimuscarinic effects
Potentiation of the effects of alcohol
SSRIs
Fluoxetine, paroxetine, citalopram (escitalopram), sertraline
Inhibits 5HT transporter
Side effects: nausea, anorexia, insomnia, loss of sexual function
Less anticholinergic side effects and less dangerous in overdose than TCAs
Interactions: NSAIDs, anticoagulants, triptans
SNRIs
Venlafaxine and duloxetine
Inhibits 5HT and NA transporter
Side effects: withdrawal effects
Interactions: NSAIDs, anticoagulants
MAOIs
Irreversible- tranylcypromine
Reversible- moclobemide
Inhibits monoamine oxidase, non-selective (MAO-A and B)
Side effects: anti-muscarinic effects, restlessness as a result of CNS excitation
Interactions: food/drug interactions- cheese effects
Atypical antidepressants
Mirtazapine
a2 autoreceptor antagonism, 5HT receptor blockade
Side effects: sedation, weight gain, increased appetite, blood disorders, withdrawal
Interactions: alcohol
Other antidepressants
Trazodone- weak reuptake inhibitor and 5HT antagonist
Mianserin- 5HT histamine and NA a2 receptor antagonist
Agomelatine- melatonin receptor agonist
Reboxetine- noradrenaline reuptake inhibitor
Tryptophan- serotonin precursor
Treatment approach for depression
Mild symptoms: psychological therapy
Persistent mild symptoms or moderate to severe symptoms: antidepressant and psychological therapy
First line drug treatment usually SSRI
Second line switch to alternate SSRI
Third line switch to an agent from a different class
Practical issues
Initiating an antidepressant can increase feelings of anxiety; consider co-prescribing a short course of BZDs
First few weeks of treatment can have worsening suicidal thoughts with improved motivation
Consider prescribing limited supply of medication
Side effects often transient and improve with time
Caution when switching antidepressants
Serotonin symdrome
Rare but potentially life threatening adverse drug reaction as a result of excessive stimulation of CNS and peripheral serotonin receptors
Antidepressants, analgesics, anti-emetics, recreational
Triad of:autonomic hyperactivity (hypertension, tachycardia, hyperthermia), neuromuscular abnormality (tremor, clonus, hypertonicity), mental status changes
Further depression therapy
If no response to 3 antidepressants then check concordance, review diagnosis and consider if social problems are maintaining depression
Consider augmentation: mirtazapine, quetiapine, aripiprazole, lithium, lamotrigine, ECT
Antidepressant efficacy
Generally the more severe the symptoms, the more effective the antidepressant (compared to placebo)
Usually used for moderate- severe illness
20% recover with no treatment
30% respond to placebo
50% respond to antidepressant
Response to antidepressants
2-4 weeks to see response (longer in elderly patients)
Improvement greatest during weeks 1-2
If no response during that period consider switching to alternative
Extending duration of treatment trial will lead to additional benefit in some
Preventing relapse
Relapse rate 3-6 months post remission is 50% with no drug treatment
A/D treatment reduces absolute risk of relapse by about 50%
After first episode continue for 6-9 months
After second episode continue for 12 months
After third episode continue for 2 years
Novel treatment options
Repetitive transcranial magnet stimulation (rTMS)
Vagal nerve stimulation
Light therapy- useful in seasonal affective disarder
Modulation of glutamate neurotransmission
Ketamine
Electroconvulsive therapy
Used in severe treatment resistant depression or treatment resistant mania. Can also be used to treat catatonia and severe postnatal depression.
Up to 70% efficacy, most effective in older people with depression or people with psychotic depression
Patient is given anaesthetic and muscle relaxant and electric current passed through the brain to cause seizure
Usually given twice weekly and response seen within first few weeks
Risks- associated with general anaesthesia, can cause memory loss, usually short term
Bipolar disorder
Chronic, severe mental illness affecting 0.5% population, more common in women
Characterised by two or more episodes where the patient’s mood and activity is disturbed
Disturbance may be elevation of mood with increased energy and activity, or low mood with decreased energy/activity
Episodes are separated by a period of euthymia or a switch to the opposite symptom type
Manic episode
Elevated mood out of keeping from person’s circumstance
Characterised by: increased energy/activity, pressure of speech, flight of ideas, reduced sleep, distractability, inflated self esteem, loss of inhibitions, reckless/risk taking behaviour
Aetiology of bipolar
Usually presents in young adulthood
Causes include:
Genetic- stronger inheritance than any other psychiatric disorder (10% risk in first degree relatives)
Less evidence for environmental factors/life events
Possible role of the hypothalamic pituitary adrenal axis
Psychopharmacology of bipolar
Mania: increased dopamine activity- amphetamine can induce a manic state; antipsychotics are effective antimanic agents; lithium withdrawal can precipitate mania, with only an indirect effect on dopamine
Depression: serotonin may play a part- SSRIs can be used to treat bipolar depression; tryptophan depletion does not induce symptoms; noradrenaline may also play a role
Prognosis of bipolar
A chronic disorder which may have an episodic course- periods of mania/depression separated by euthymia
Chronic symptoms especially depression may persist
Suicide is common- 15%
Treatment of bipolar disorder
Short term treatments: used to manage acute episodes of mania or depression, subsequently discontinued
Long term treatments: used to prevent relapse, continued indefinitely
Treatment of mania
Antipsychotic or sodium valproate: olanzapine may be superior to valproate, may be more susceptible to adverse effects, usually treat for 2-3 months then maintenance
Usually BZD, either as required or regular for a short period to provide sedation
If patient is prescribed an antidepressant this should be discontinued
Lithium is effective, but difficult to initiate in a manic patient
Treatment of bipolar depression
CBT for mild symptoms SSRI or other antidepressant Lamotrigine Lithium Antipsychotics
Lithium
Effect on neurotransmitters and second messenger systems
Effectiveness if closely associated with treatment continuation- discontinuation gives high risk of relapse
Risk of suicide in bipolar is 15%, lithium reduces risk by 80%
Side effects of lithium
Rapidly absorbed from GI tract, excreted unchanged via kidney
Narrow therapeutic range 0.4-1.0mmol/L
Signs of toxicity: nausea, diarrhoea, ataxia, confusion, coarse tremor, seizures, loss of consciousness
Long term increases risk of: hypothyroidism, hyperparathyroidism, renal impairment
Lithium counselling
Lithium card
Prior checks on renal, thyroid and cardiac function
Keeping appointments for regular monitoring
OTC NSAIDs
Seek medical attention if they develop diarrhoea and or vomiting
Maintain fluid intake
Seek advice about stopping lithium for up to 7 days if they become severely ill
Valproate
NICE recommends as first line for mania, with antidepressant for depression and prophylaxis of BPD
As effective as lithium
Lithium non-responders may respond to valproate
Available in different formulations
Lamotrigine
Voltage dependent Na+ channel blocker, reduces glutamate release
Considered effective for treating bipolar depression and for prophylaxis (as effective as citalopram)
Dose: slow increase very important
Carbamazepine
Blocks voltage dependent Na+ channels, reduces glutamate release and transmitter turnover
Not recommended first line by NICE for mania, may be useful fro bipolar and unipolar depression
Less effective than Li+ for prophylaxis
RCT showed 40% relapse per year
Narrow therapeutic range
Hepatic enzyme inducer
Antiepileptic adverse events
Minor but common: fever, flu-like symptoms, drowsiness
Serious but rare: blood disorders, liver disorders, pancreatitis
Weight gain
Teratogenicity
Rash in lamotrigine
Hyponatraemia
