Affective Disorders Flashcards
How common is depression?
Prevalence 2-5%
1/5 will suffer at some point in their lives
Is depression more common in F or M?
2:1 F:M
What is the pathophysiology of depression?
Monoamine (MA) theory - depression associated with reduced noradrenaline or serotonin in brain
Antidepressants inhibit breakdown of MA rapidly but clinical improvements can take weeks
List the monoamine neurotransmitters
Imadazoleamines - histamines
Catecholamines - adrenaline, noradrenaline, dopamine
Indolamines - serotonin, melatonine
What are the core symptoms of depression?
1) Depressed mood for most of the day, every day
- Little variation in mood despite changes in time, circumstances or activity
- Possible diurnal variation (worse in morning and improving throughout day)
2) Anhedonia
3) Fatigue
What are the typical symptoms of depression?
Biological:
1) Poor appetite with marked unintentional weight loss
- >5% in past month
(Rarely inc appetite and weight gain)
2) Disrupted sleep
- Initial insomnia with early waking (3+ hrs)
3) Psychomotor retardation eg sluggish thought processes, limited spontaneous movement or restlessness
4) Decreased libido
5) Inability to concentrate
Plus:
6) Feelings of worthlessness or inappropriate guilt
7) Recurrent thoughts of death, suicidal ideation or suicide attempts
What is needed to diagnose depression?
At least 2 core symptoms + 2/more typical symptoms
Symptoms present every or nearly every day without significant changes throughout the day for over 2 weeks
Must represent a change from normal personality without alcohol/drugs, medical disorders or bereavement
List the ICD-10 categories for mild, moderate, severe depression
When should this be used?
Mild = 2 x core + 2 x typical Moderate = 2 x core + 3(+) typical Severe = 3 x core + 4(+) typical
First episode (further depressive episodes classified as recurrent depressive disorder)
List some ddx for depression
Psych - dysthymia, bipolar disorder, schizophrenia, anorexia nervosa, anxiety
Neuro - dementia, PD, HD, MS, stroke
Metabolic - hypoglycaemia, hypercalcaemia
Haem - anaemia
Inflammatory - SLE
Infections - syphilis, Lyme disease, HIV encephalopathy
Medications - anti-HTN, steroids, H2 blockers, sedatives, antipsychotics
Substance misuse - alcohol, BDZ, opiates
Sleep disorders
What psychotic symptoms may someone with depression suffer from?
Delusions eg poverty, guilt over things which could not be their fault, punishment, nihilism
Hallucinations eg auditory (accusatory, cries for help), olfactory (rotten food, faeces), visual (demons, corpses etc)
What investigations should be done for depression?
Bloods
- FBC: anaemia
- ESR
- B12/ filate
- TFTs
- Glucose
- Calcium
Urine toxicity Syphilis serology HIV Dexamethasone suppression test ACTH stimulation
What is the dexamethasone suppression test?
Dexamethasone reduces ACTH release in normal people
Thus taking dexamethasone should reduce ACTH and lead to decreased cortisol
Cortisol is measured either overnight (more common) or standard (3 days) after administration of dexamethasone
Why may pt with depression present with an abnormal dexamethasone suppression test?
NA inhibits corticotropin releasing factor, thus decreasing ACTH secretion by the pituitary, and in turn, cortisol secretion by the adrenal glands
Deficiency of brain NA can lead to both depressive symptoms and increased cortisol production
Episodes fo cortisol secretion are longer and more frequent in depressed patients, and the circadian rhythm of cortisol release is altered
Dexamethasone does not suppress plasma cortsol levels in pts cvs normal subjects
What is ACTH stimulation?
aka cosyntropin test / syncathen test
Measures the response of adrenal glands to ACTH (should release cortisol)
List some biological causes of depression (7)
1) Genetic serotonin transporter gene (FH++)
2) Abnormal concentrations of serotonin and other NTs
3) Disregulation of the HPA axis
- Inc cortisol in 50%
- Linked to adrenal hypertrophy and failed dexamethosone suppression test
4) Hypothyroidism
5) Postnatal
6) Chronic pain
7) Medications
List some psychological causes of depression (7)
1) Childhood trauma
2) PTSD
3) Low self esteem
4) Stress, lack of coping, lack of resilience
5) Attitudes and beliefs
6) Anxiety and guilt
7) Burden of chronic disease / comorbities
List some social causes of depression (8)
1) Isolation
2) Bereavement
3) Stress
4) Abuse
5) Relationships
6) SES
7) Homelessness
8) Education
List antidepressants which may be used in the management of depression
SSRIs = first line
SNRI - Serotonin noradrenaline re-uptake inhibitors
NARI - Noradrenaline re-uptake inhibitor
TCA - Tricyclics
MAOIs - Monoamine oxidase inhibitors
NASSA - Nonadreneric and specific serotonergic antidepressants
Give some examples of SSRIS
Fluoxetine Citalopram Escitalopram Sertraline Fluvoxamine Paroxetine
In which populations are SSRIs more commonly used?
Elderly
Anxiety
OCD
What are some side effects of SSRIs?
Nausea and vomiting common
Agitation
Sexual dysfunction - 70% affected and difficult to treat
Also dizziness, dry mouth, blurred vision
Which SSRIs prolong the QT interval?
Citalopram
Escitalopram
What is serotonin syndrome?
Acute toxic syndrome due to increased 5HT activity
How does serotonin syndrome present?
Confusion Myoclonic jerks and hyperreflexia Pyrexia and sweating GI symptoms Mood changes and mania Convulsions Death
When can serotonin syndrome occur?
Within a few hours of SSRI dose or dose changes
How is serotonin syndrome managed?
Symptomatic support
Give some examples of TCAs
Amitriptyline
Imipramine
Lofepramine
Dosulepin
How do TCAs work?
5HT and NA reuptake inhibition
Anticholinergic effects
Antihistaminergic effects
What are some side effects of TCAs?
Cardiotoxic:
- QT prolongation
- ST elevation
- AV block
Alpha adrenergic blockade:
- Postural HTN
- Sedation
What are some risks of TCAs?
Increased risk of manic switch in bipolar disorder
In which populations are TCAs less useful?
Elderly
Physically ill
Overdose risk pt
What is the mechanism of action of MAOIs?
Inhibition of MAO-A and MAO-B
MAO-A metabolises NA, 5HT and tyramine
MAO-B metabolises DA and tyramine
Thus increase storage and release of 5HT and NA
Give some examples of MAOIs
Phenelzine
Tranylcypromine
What are some side effects of MAOIs?
Postural HTN Restlessness Oedema Nausea Sexual dysfunction
What interaction is important to note for those taking MAOIs?
Interaction with tyramine containing foods
- Cheese
- Yeast extracts
- Hung game
- Some alcoholic drinks eg red wine
- Pickled herring
What is tyramine?
Naturally occurring monoamine compound and trace amine derived from the amino acid tyrosine
It is a catecholamine releasing agent
Unable to cross BBB thus is can only lead to non-psychoactive peripheral sympathomimetic effects
However a HTN crisis can result from ingestion of tyramine rich foods in conjunction with MAOI
What happens when someone taking MAOIs ingests foods rich in tyramine?
Tyramine is not inactivated by MAO
Tyramine causes catecholaime release = tachycardia, sweating, HTN, arrythmias, stroke, death
What are venlafaxine and duloxetine?
Serotonin and NA reuptake inhibitors
How do SNRIs work?
Dual action reuptake inhibitors
NA reuptake is only seen at higher doses
Which SNRI can cause HTN at higher doses?
Venlafaxine
Compare SNRIs and TCAs
SNRIs = ‘cleaner’ and safer in OD than TCAs
What is mirtazapine?
Noradrenergic and specific serotonergic antedepressant (NASSAs)
How does mirtazazapine work?
Presynaptic alpha 2 autoreceptor antagonist = thus enhances NA transmission
More sedative at LOWER doses due to its antihistaminergic effect predominating over its noradrenergic effects - useful in pt who cannot sleep
What are some side effects of mirtazapine?
Stimulates appetite, causes weight gain (may be useful in some pt), sedation classic (take at night)
LACKS CV and anticholinergic side effects
Less incidence of sexual dysfunction
What is the onset of action of antidepressants?
Myth that they do not exert effects for 2-4wks
ALL antidepressants show a pattern of response where rate of improvement is highest during weeks 1-2 and lowest during weeks 4-6
If no effect by 3-4 weeks, consider switching
What does the term discontinuation symptoms describe? When do they occur?
Used to describe symptoms experienced on stopping prescribed durgs that are not drugs of dependence = NOT WITHDRAWAL
Onset usually within 5 days of stopping treatment
List classic discontinuation symptoms
Flu-like symptoms Insomnia Agitation Irritability Shock-like sensations Vivid dreams
Which drugs most commonly cause discontinuation symptoms?
Drugs with shorter half lives
Eg immediate release venlafaxine, paroxetine
How can discontinuation symptoms be avoided?
Discontinue antidepressant slowly - ie over 4 week period
How should antidepressants be swapped / stopped?
Avoid abrupt withdrawal
Cross-tapering is preferred = old drug is slowly reduced and the new one is slowly increased
- Speed judged by pt tolerability
- Not always necessary eg when switching from one SSRI to another (if you cross-tapered there would be a risk of serotonin syndrome)
- Not appropriate sometimes eg MAOIs to TCAs
What must be warned to pt starting antidepressants?
Motivation improves before mood and this leads to a period of increased risk where people might suddenly have the motivation to act on suicidal ideation
What is the electrolyte risk with antidepressants? Who is more at risk?
Hyponatraemia
Inc risk in older, thin females in the summer with poor renal function
What length of treatment is recommended for antidepressants?
Don’t have to be on it forever
Usually recommended person stays on it for 6-9mnths following recovery
If it is not the first time then consider being on it for 2yrs
Other than antidepressants, what biological treatment options are available for depression?
Augmentation of antidepressants with:
- Lithium
- Other antidepressants (combination therapy)
- Antipsychotics
Thyroxine
ECT
What are the indications for lithium?
Mania - treatment and prophylaxis
Bipolar affective disorder
Recurrent depression
Aggressive or self-mutilating behaviour
What are the pharmacokinetics of lithium?
Clearance is via kidney thus clearance depends on renal function, fluid intake and sodium intake
- Should monitor levels 12hrs after last dose
What baseline investigations should be performed before starting lithium?
Weight U&Es Renal function TFTs Calcium ECG Pregnancy test
How frequently should lithium levels be monitored?
Check 5 days after 1st dose
Then check every week until levels have been stable for 4 weeks
After than check every 3 months
Renal function, U&Es, thyroid and calcium should be checked every 6 months
What are some side effects of lithium?
Early:
- Dry mouth
- Metallic taste
- Nausea
- Fine tremor
- Fatigue
- Polyuria
- Polydipsia
Late:
- Nephrogenic diabetes insipidus
- Kidney damage with long term treatment
- Hypothyroidism
What drug interactions are associated with lithium?
Narrow therapeutic index (0.4-1mmol/L)
Most clinically significant interactions are with drugs that affect sodium handling:
- ACEi
- NSAIDs
- Thiazide diuretic
What is the mechanism of action of lithium?
Only partially understood
Increases synthesis and release of 5HT
Range of effects on CNS
Handled by body in similar way to sodium
May have neuroprotective effects
Takes approx a week to work
What are symptoms of lithium toxicity?
Early:
- Blurred vision
- Anorexia
- N&V&D
- Coarse tremor
- Ataxia
- Dysarthria
Late:
- Confusion
- Renal failure
- Fits
- Delirium
- Death
What is ECT?
Electroconvulsive therapy
Very good evidence base
Electrical currents sent through brain to induce seizures
A short acting GA and muscle relaxant administered
How often is ECT performed?
2 x weekly therapies for 6 weeks
What are some side effects of ECT?
Headache
Nausea
Muscle pain
Memory loss around time of seizure (both retrograde and anterograde)
What are some psychological management options for depression?
Mainly for mild-moderate (medication not indicated):
- Advice on sleep hygiene
- Physical exercise
- CBT
- Self help books
Moderate-severe:
- CBT (8-12 sessions over 2-3 months)
- IPT (interpersonal therapy)
- Combination of psychosocial and biological management
What is IPT? How many sessions are recommended?
Aims to help the person with their relationship with others - how they are interacting with and relating to other people
Brief = 16-20 session
What is CBT?
Based on cognitive behavioural model - it is not the event that causes problems but instead how we respond to it
Tries to spot patterns in behaviour and attitudes that might lead to the symptoms of depression and then try to break these patterns down by changing things that CAN be controlled
- ie your behaviour when you experience a certain trigger
- Try and change the response so that you’re not feeding into the negative pattern of behaviour
List some cognitive biases
1) Catastrophising
2) Jumping to conclusions
3) All or nothing view
4) Personalising (it went wrong and it must have been something I did)
5) Generalising (one bad thing going wrong means everything will go wrong)
What are some social management options for depression?
Friends and family education
Community and voluntary organisations
Selt help
IAPT = Improving access to psychological therapies
What are the tiers of making a referral to secondary care for depression?
Tier 1 - GP
Tier 2 - Primary care mental health worker (PCMHW)
Tier 3 - Community mental health team (CMHT)
Tier 4 - Inpatient or home treatment
Exceptions - risk to self or others, severe functional impairment, indication for specialist treatment
What is the prognosis of depression?
Average depressive episode = 6 months
80% pt have recurrent episodes
Approx 10% have manic episodes and become bipolar
Suicide 13%
What are some medical causes of mania? (14)
Cerebral neoplasms, infarcts Trauma, infection (inc HIV) Cushing's disease Huntington's disease Hyperthyroidism MS Renal failure SLE Temporal lobe epilepsy Vit b12 and niacin deficiency
What are some substances which can cause mania? (11)
1) Amphetamines
2) Anticholinergics
3) Antidepressants
4) Antiviral drugs
5) Antimalarials
6) Captopril (ACEi)
7) Cimetidine
8) Cocaine
9) Corticosteroids
10) Hallucinogens
11) L-dopa
How does mania present? (timeframe)
Usually begins abruptly with 3/more characteristic symptoms of mania lasting for > 1 week
What are some biological symptoms of mania?
Decreased need for sleep
- Usually one of the earliest warning signs
- Can be a few hrs to no sleep
- Not associated with fatigue
Increased energy
- Increased goal directed activity
- When coupled with impaired judgement can lead to reckless behaviour, inc risk taking eg gambling, drugs, sexual encounters
What are some cognitive symptoms of mania?
Elevated mood
- Lability likely
- “Finally seeing things clearly”
- “On top of the world”
Elevated sense of self or grandiosity
- Hypomanic pt may overestimate abilities or social / financial status
Poor concentration
- Can be identified in thought content, thoughts may not be linear and going off on tangents
Accelerated thinking
- When thoughts are associated but expressed rapidly in.a stream of ideas = flight of ideas
- Pressurised speech
Impaired judgement and insight
What are some psychotic symptoms of mania?
Disordered thought form:
- Most commonly circumstantiality = focus of conversation drifting, over-inclusion of details but often coming back to the point
- Tangentiality = initial train of thought is diverted from but does not come back to the point
Secondary delusions = ones that develop in response to another psychopathological state (abnormal mood). It is understandable how the delusion occurred when one examines the pt mental state
- Eg grandiose delusions in pt with elevated mood
Perceptual disturbance
- Things appearing louder = hyperacusis
- Colours seem brighter = visual hyperaesthesia
What is a distinguishing symptom between mania and hypomania?
Psychotic symptoms such as auditory and visual hallucinations
What is hypomania?
A lesser degree of mania with 3 / more symptoms lasting at least 4 days
Not severe enough to interfere with social / occupation or require hospital admission
No psychotic symptoms
Outline MSE findings in someone presenting with mania
A&B
- Bright unusual combination of clothing
- Hyperactive, aggressive, flirtatious or overfamiliar behaviour
Speech
- Pressurised speech, neologisms
Mood
- Euphoric, irritable, labile
Thought form
- Racing, flight of ideas, loosening of associations, tangential
Thought content
- Optimistic, grandiose delusions
Perceptions
- Hallucinations if severe
Cognition
- Intact
- Poor attention and concentration
Insight
- Very poor
What is the biological management of mania?
Compulsory admission
1st line = Lithium
- 80% response rate for mood stabilisation
Antipsychotics
- Olanzapine or respiradone
- Useful in severely agitated pt to allow recovery before starting them on long term mood stabiliser
BDZs
- May stabilise pt without need for antipsychotics
Stop antidepressants
Anticonvulsants eg carbamazepine / valproate
ECT if drug resistance
What is the psychosocial management of mania?
Education to recognise the importance of lifestyle changes
- Avoid triggers
- Sleep well
- Importance of compliance
What is the prognosis of mania?
Average length of manic episode is 4 months
What assessment should be done for someone presenting with mania?
If already on lithium - check blood level for adherence
Bloods - FBC, U&Es, TFT, LFT, Vit B12, folate
CT head and EEG
Urine - dip and drugs screen
Assess risk - suicide, self harm, to others, from others
How common is bipolar affective disorder (BAD)?
Approx 1%
Is BAD more common in M or F?
M=F
How do first episodes of BAD differ in M and F?
M first episode usually manic
F first episode usually depressive
What is the mean age of onset of BAD?
21yrs
>51yrs = more likely to have an organic cause
What is the aetiology of BAD?
Neurochemical abnormalities (monoamine theory)
- Inc levels of NA, DA, 5HT can cause neuronal insults
- Thus cocaine and amphetamines exacerbate mania
- Environemtal stressors and exogenous steroids can affect hormones = thus glucocorticoids may be implicated
Genetics
- First degree relative have 7x risk od developing
- Children of bipolar parents have 50% chance of psychiatric disorder
Seasonal
- More onset in late spring and summer
What is the ICD-10 criteria for BAD?
1) Elevated mood, irritable mood, lability
2) Inc energy levels, over-activity
3) Distractibility, reduced concentration, constant change of plans
4) Perceived reduced NEED for sleep
5) Inflated self-esteem / grandiosity
6) Overfamiliarity / disinhibition
7) Reckless behaviour / overspending
8) Inc in sex drive
9) Flight of ideas
10) Psychotic symptoms
= 2 x episodes of seriously seriously disturbed mood
What is bipolar I and II?
Bipolar I - one or manic episodes with/without one or more depressive episodes
Bipolar II - one or more depressive episodes with AT LEAST ONE manic / hypomanic episode
How long should a manic, hypomanic or depressive episode last in BAD?
Manic = 1 week
Hypomanic = 4 days
Depressive = 2 weeks
NB patients with manic or hypomanic episodes can be diagnosed with BAD even in the absence of depressive episodes
What is a mixed episode in BAD?
Contain both manic / hypomanic and depressive symptoms in a single episode, lasting at least 2 weeks:
- Depression plus overactivity / pressured speech
- Mania plus reduced energy / libido
What is rapid cycling in BAD? More common in F or M?
4 / more episodes in a year
More common in F
What is cyclothymia?
Usually begins in early adulthood and follows a chronic course with intermittent periods of wellness in between
Characterised by instability of mood resulting in alternating periods of mild elation and mild depression that are not severe or long enough to meet criteria for either a hypomanic or depressive episode
What is the management of BAD?
Depends on nature of presenting episode
Mania - antipsychotics to stabilise followed by mood stabiliser
Depressive - antidepressants augmented by a mood stabiliser (use with caution as risk of inducing manic episode and / or rapid cycling)
Follow up 4 weeks after
Psychosocial therapies can help to identify trigger factors for relapse
Psychosocial therapies can help to identify trigger factors for relapse eg CBT
Hospital admission if severe
What is a mood stabiliser?
Term applied to lithium, anticonvulsant drugs and some atypical drugs used to treat BAD
Refers to the ability of a drug to treat one or both poles of bipolar disorder without causing a switch to the other pole
List 4 mood stabilisers
1) Lithium
2) Carbamazepine
3) Sodium valproate
4) Lamotrigine
How does carbamazepine work?
Blocks voltage dependent sodium channels thus inhibiting repetitive neuronal firing
Reduces glutamate release and decreases turnover of DA and NA
Similar structure to TCAs
What interactions does carbamazepine have?
Hepatic enzyme inducer so lots of interactions
Both carbamazepine and clozapine can cause agranulocytosis
What are some side effects of carbamazepine?
Dizziness Diplopia Drowsiness Ataxia Nausea Headaches Blood dycrasias
How does sodium valproate work?
Inhibits catabolism of GABA
When is sodium valproate used?
Effective in treatment of mania and thought to reduce aggression in other psychiatric disorders
What is a benefit of sodium valproate?
No routine plasma level monitoring
What are some side effects of sodium valproate?
Blood dycrasias Weight gain Hair loss with curly regrowth Pancreatitis Sedation Dose related tremor Thrombocytopenia - unusual bleeding / bruising
+ MAJOR human teratogen so not really used in women of childbearing age
What is a risk associated with lamotrigine?
SJS
What is a standard starting and max dose of:
1) Sertraline
2) Citalopram
1) Sertaline - 50mg OD (can increase in 50mg incrrements up to 200mg)
2) Citalopram - 20mg up to max 40mg
Outline the ATHLETICS pneumonic for drugs counselling
Action Timeline Length of treatment Effects (time before felt) Tests Important SE Complications and Contraindications Supplementary advice
Outline ATHLETICS for SSRIs
A - Antidepressants alter the balance of some of the chemicals in the brain (neurotransmitters). SSRI antidepressants mainly affect a neurotransmitter called serotonin. An altered balance of serotonin and other neurotransmitters is thought to play a part in causing depression and other conditions
T - OD
H - Tablet
L - stop 3-6 months after feeling better (taper off)
Effect - 4-6wks
T - none
I - GI (n&v&d), headaches, drowsiness (can take at night), anxiety for 2w, withdrawal, hyponatraemia
C - CI if suicide risk of past psych illness
Caution in pregnancy
S - mind.org.uk
What must be warned for pt starting SSRIs <30yr?
Motivation increases before mood
Increased risk of suicide / impulsive behaviours in first few weeks
Outline ATHLETICS for lithium
A - Mood stabiliser. Exact mechanism unknown.
Thought to enter the cells and interfere with neurotransmitter release and second messenger systems
T - One or twice daily depending on brand
H - Tablet, capsule or syrup
L - lifelong (if works, regular reviews by psychiatrist)
E - 1-2 weeks
T - Before starting = FBC, U&Es, TFTs, beta-HCG, ECG
Check lithium after 5 days, then every week until stable for 4 weeks, then every 3 months
Check TFTs, U&Es, calcium every 6mnths
I - GI (abdo pain, nausea), metallic taste, fine tremor, water symptoms (thirst, polyuria, impaired urinary conc, weight gain, oedema)
- Lithium toxicity = GI (anorexia, d&b), NM (dysarthria, dizziness, ataxia, muscle twitching, tremor), drowziness, apathy, restlessness
C - complications = renal toxicity, nephrogenic diabetes insipidus, hypothyroidism
CI - 1st trimester pregnancy, BF, cardiac disease, significant renal impairment, Addison’s disease, low Na diets, untreated hypothyroidism
S - bipolaruk.org.uk
What are the concerns surrounding SSRIs in pregnancy?
Particularly in third trimester
Can increases risk of persistent pulmonary HTN of newborn
Paroxetine increases risk of congenital malformations
What substances can be added to SSRI therapy to make it more effective?
Lithium
Atypical antipsychotics:
Quetiapine
Risperidone
Ariprprazole
What are some important drug interactions with SSRIs? (12)
1) NSAIDS - give PPI if alternatives not found
2) Warfarin or heparin
3) SSRIs
4) ‘Triptan’ drugs for migraine
5) Monoamine oxidase B inhibitors
- Eg selegiline and rasagiline
6) Theophylline
7) Clozapine
8) Methadone
9) Tizamide
10) Flecainide
11) Propafenone
12) Atomoxetine
What are some side effects of SNRI?
Similar to SSRIs as they block serotonin - weight change, insomnia, appetite changes, drowsiness, dizziness, fatigue, headache
Also inc NA and so can cause additional SE:
- Inc HR
- Inc BP (measure BP before starting and ensure well controlled)
- Anxiety
QT prolongation
