2. Bipolar Affective Disorder (BAD)
• Common illness affecting 2% pop
• Symptomatic at least 50% of time
• Mood states/phases: mania, hypomania, cyclothymia, euthymia
(normal mood), dysthymia and depression.
• Diagnosis of mania: a period of elevated or irritable mood lasting at
least a week. Severe enough to disrupt work or social activities
completely. 3 of the following:
• Increased activity and restlessness
• Pressure of speech
• Increased speed of thought
• Grandiose ideas
• Increased sleep
• Abnormal distractibility
• Disinhibited behaviour
• Hypomania: milder form where work and social activities are not
completely disrupted
4. Classification of BAD
• Bipolar 1: full manic and depressive episodes. M=F.
• Bipolar 2: 1 hypomanic and 1 full depression. F>M.
• Bipolar 3: depressive episode with antidepressant
induced mania
• Mixed states
• Rapid cycling: avoid Antidepressants. Dual prophylactic
agents. Check THYROID function.
• Bipolar disorder not otherwise specified: bipolar features
that do not meet criteria for any specific bipolar
disorders
5.
6. BAD
• Greatest genetic input of all mental illnesses
• Can have impaired social function even when symptom free
• Life events can precede onset of symptoms
• Higher numbers of manic episodes in early summer
• Increased brain amine activity (amine overactivity hypothesis)
• 50% first bipolar episodes are depressive episodes: considerable
mortality and morbidity. Have a chronic course.
• 80% pts exhibit significant suicidality
• 60% pts with dysmorphic mania exhibit suicidality
• Depressive episodes dominate course of bipolar disorder (x2 time
of mania)
• 25-30% pts diagnosed with unipolar depression subsequently have
a manic or hypomanic episode
• >50% alcohol/drug abuse
• 50% attempt suicide & 15% succeed. Predictors: high impulsivity,
alcohol/substance abuse, depression in MIXED episodes, Hx abuse,
incorrect treatment
7. BAD
• Neurochemistry:
– Increased hyperactivity of monoamines
– “out of tune” circuits
– Depression and mania simultaneously complicates picture
– DOPAMINE, NORADRENALIN, SEROTONIN AND GABA play a role
– ?role of glutamate
• Neurobiology
– Highly heritable: 80% genetic contributin
– Multiple genes
– 16 different chromosomal regions
– Structural and functional brain abnormalities: amygdala, anterior
cingulate and prefrontal cortex, putamen, thalamus/hypothalamus
8. Treatment
• Where – ward, care facility, home
• Voluntary/detained
• Good nursing: deal with aggression, disinhibition, dehydration
• MEDICATION
– Lithium
– Depakote (semi-sodium valproate): FBP, LFT. SAFE DRUG.
– Atypical neuroleptics: olanzapine, risperidone, quetiapine&aripiprazole.
High doses required. Long term A/Es. Weight gain. More tolerable initially.
– Typical neruroleptics: difficult cases. More A/Es.
• Different types/combinations of drugs used for different types of
bipolar and severities
• Acute mania: lithium, depakote, atypical and typical neuroleptics
• Acute depression:
– Mild: prophylactic agents
– Moderate: SSRI, TCA ?, Quetiapine (atypical antipsychotic with unique
antidepressant effect as well as anti manic), CBT ?
9. Lithium
• Therapeutic index 0.6-1.0
• In acute mania maximise plasma levels – 0.8-1.0
• Slow onset, not optimum treatment on its own for an acute episode
• Can be used with neuroleptics
• Uses:
– Bipolar affective disorder prophylaxis
– Acute mania (not alone)
– Augmentation of depressive illness
– Prophylaxis of depressive illness
– Schizoaffective disorder (schiz and BAD)
– Aggression
• 1/1000 pop take lithium, 50% stop within 1 year. 25% more than 25years
• A/Es: renal damage and hypothyroidism. Thirst, polyuria, tremor, weight
gain, (psoriasis and migraines get worse) , arrythmias, nausea, GI upset.
• Toxicity: alopecia, confusion, ataxia, coma, death.
• >1.5 coarse tremor, >2 ataxia and confusion, >2.5 coma&death
• Population estimates, 0.3 might be enough for one pt, 1.2 for another
CHECK TFTs and U&Es,
eGFR. Can increase WBCs
so used with clozapine to
counteract
agranulocytosis!!!
Reduces risk of
suicide!!!
10. Lithium
• Natural occurring salt so kidney can get confused and not be able to
distinguish them so toxic levels can arise
• Inhibits second messenger enzymes (same as ADH and TSH)
• Not so good for rapid cycling or mixed states
• Dose: start at 400mg/day
– 200mg in elderly or renal impairment
– Monitor plasma levels every 5-7days until level 0.6-1.0
– After levels tested every 3-6 months
– All samples taken 12 hours post dose
• Precautions: excreted through kidneys and potentially nephrotoxic. Check
U&E prior to starting. Hypothyroidism in significant proportion. TFT before
starting and every 6months. Thyroxine given if problems arise. TFTs return
to normal on stopping Rx.
• Contra-Indications: pregnancy, breast feeding, renal impairment,
tyroidopathies and sick sinus syndrome (causes arrythmias)
• Interactions: antipsychotics (increased neurotxicity, rare), diuretics (inc
lithium conc), ace inhibitors (toxicity) , NSAIDS (toxicity), alcohol (inc peak
concentration)
11. Anti-epileptic Drugs• Valproate : mania/mixed
– 500mg daily initially, increase to plasma levels 50-100mg/L. Tolerated better than Lithium
– Check baseline renal and hepatic function, then 6monthly and FBC
– Contraindications: pregnancy, breast feeding and hepatic disease
– A/Es: mild sedation, alopecia, N/V, weight gain, headache, pancreatitis, thrombocytopenia
• Carbamazepine /oxcarbazepine : mania/mixed
– Dose: 200mg bd. Slowly increasing to 600-1000mg/day. Target range 8-12mg/L. Monitor
every 2-4 weeks to stable, then 3-6m.
– A/Es: N/V, fatigue, dizziness, tremor, rash, SJS (0.1-0.5%). Drug interactions – Inc conc with
verapamil, cimetidine, erythromycin. Dec conc with phenytoin.
– Serious: early leucopenia (20%) transient but benign, aganulocytosis in 1/20,000. aplastic
anaemia 1/20,000, hepatitis, TEN 1/20,000.
– Toxicity: diplopia, nausea, ataxia and sedation
– Contraindications: pregnancy and breast feeding
• Lamotrigine : BP-D/ rapid cycling
– Uses: BP 1 acute, maintenance of BP and rapid cycling BPII
– 50-200mg/day. Watch for rash. Contraindications: pregnancy& hepatic impairment
– A/Es: rash, ataxia, diplopia, headache and vomiting
• Topiramate : mania/ mixed, esp rapid cycling
– 200-300mg/day. A/E: slow thinking, sedation, N,Diarrhoea, Headache, parasthaesia, tremor,
metabolic acidosis (carbonic anhydrase inhibition), urinary stones, 2o angle closure glaucoma
• Gabapentine/pregabalin : analgesic and anxiolytic effect (?)
– A/Es: dizziness, ataxia, fatigue, thyroiditis, renal impairment (nephrotic Syndrome)
12. Maintenance Rx
• Monotherapy with lithium or valproate
• Newer atypicals as alternatives
• Optimise medications most effective in last episode
• Combination therapy for sub-threshold symptoms or
breakthrough mood episodes
• Avoid antidepressants as monotherapy
• ** manic and give ADs, lead to depression and vice versa
When to stop
•Risk benefits balanced, e.g. Planned pregnancy
•Tapered down over at least 2 weeks
•Abrupt withdrawal of lithium often induces manic episode
•Risk of relapse remains, even after years of remission
Other medications/Approaches
•Atypical anti-psychotic meds e.g. Quetiapine
•Combined meds if difficult to stabilise
•Awareness of relapse signatures, stop it before
it fully develops
•COMPLIANCE
PROPHYLACTIC TREATMENTS
CORNERSTONE OF BAP
MANAGEMENT
ECT may be
required for
severe
depression
13. Summary
• Lifetime risk BAD 0.3-1.5%
• Mean age of onset 21, all races and genders equally affected
• GENETIC factor has a particularly important role
• Mania ?monoamine overactivity
• Frequency and severity of episodes variable
• Cyclothymia: numerous episodes fo mild elation and mild
depressive symptoms
• Hypomania: mood elevated, expansive and irritable but no
psychotic features or social functioning impairment
• Rx determined by pts symptoms
• After first manic episode 90% recur and intervals between get
shorter
14. Depression
• The pathological state of sadness
• 4th leading cause of disease burden worldwide
• Costs massive: drugs, loss of work, economic burden on family and society
• 6% population experience depression or dysthymia (short of depression,
gloomy outlook, more likely to develop depression) at any one time
• Lifetime risk 5-12% males , 9-26% females. Generally F2:1M. Due to many
reasons: genetic predisposition, hormones, social pressures, admission and
reporting.
• Overall prevalence rising
• Highly recurrent: without maintenance medication 50% relapse within 2 years
• Increased Risk of death (1.7) and suicide (19.7)
• Negative view of events e.g. Someone not waving in the street
• ? Brain chemistry gone, then depression OR depression affects brain chemistry
changes.
• Dopamine least important
16. Recognising Depression
• ICD-10 criteria:
-Depressive episode for at least 2 weeks
-No Hx hypomania/mania (BPD)
-Exclude psychoactive substance use or oganic mental disorder
• Range of severity: mild (dealt with by GP) – moderate – severe
(psychiatrist)
• Can be psychotic or non-psychotic (psychotic symptoms: out of
touch with reality. Manifests with delusions, hallucinations and loss
of insight)
• +/- somatic symptoms: loss of appetite, weight loss, decreased
energy levels, pain
• Only 50% depression detected. Of those 70% managed at GP. 1%
admitted to psych unit.
17. Symptoms
• Depressed mood
• Loss of interest/pleasure in activities : apathy
• Decreased energy
• Loss of confidence, self-esteem
• Guilt ( mild – extreme & delusional )
• Recurrent suicidal thoughts
• Poor concentration
• Psychomotor agitation/retardation
• Sleep disturbance: EARLY MORNING WAKENING, >30 mins
before normal, regularly
• Change in appetite and weight
• Psychotic symptoms: usually congruent with mood
18. Somatic Symptoms
• At least 4 of the following
- marked loss of enjoyment in activities
- lack of emotional reactivity (laughing at jokes,
crying at sad tv shows)
- diurnal mood variation
- marked psychomotor changes
-marked loss of appetite
-weight loss of >5% over last month
- marked loss o libido
19. Aetiology
• Multifactorial aetiology, not really understood
• Genes for major depression overlap for anxiety and neuroticism.
• BiPolar in MZ twin: 40% risk BP, 27% unipolar
• Unipolar in MZ: 44% risk uni, 1.5% bipolar
• BIPOLAR: manic depression, sometimes up and sometimes down
• UNIPOLAR: only depressed
• Environment: cumulative childhood disadvantages increases risk:
e.g. Child abuse, violent families, bullying, low economic status
(DEBT)
• Married status a protective factor. Married, single, widowed,
divorced increasingly more likely to be depressed.
• Life events: loss, entrapment, HUMILIATION
• (Kindling hypothesis: onset of recurrent episodes becomes
increasingly autonomous and less related to life events)
20. Treatment: Physical
• Anti-depressant drugs:
-monoamine uptake inhibitors: tricyclics, SSRIs,
NARI, SNRI
-Monoamine oxidase inhibitors (MAOIs)
-Others: mirtazapine (alpha2 NA antagonist)
• ECT
Treatment: Psychological
• Cognitive Behavioural Therapy
• Interpersonal Therapy
*** for the future, not for severe cases in the
immediate setting. More preventative.
21. • Tricyclics: effective anti-depressants, non-selective so many side
effects, often affecting compliance e.g. Anticholinergic. TOXIC IN
OD – especially dothiepin and amitryptiline (can cause death due
to quinidine like effect on heart, slowing it). Used less commonly
today. Hard to get theraputic dose.
• SSRIs: First choice agents. No significant cardiac A/Es. Safe(r) in
OD. Main A/Es: nausea, headache, agitation, sexual difficulties.
• MAOIs: irreversible non-selectiveL Phenelxine. Reversible
selective: moclobemide. A/Es- hypotension, cheese reaction
(thiamine in foods, huge rise in BP), oedema, abnormal LFTs,
agitation, anticholinergic effects. Avoid with other
antidepressants, opiates and sympathomimetics. Not used much.
• ECT: used in life-threatening depression/severe depression
unresponsive to other therapy. Fast response. Main risk is due to
anaesthetic. (1/20,000 death). A/Es: headache, muscle pain, short
term memory loss. DEFINITELY WORKS.
22. Course and Prognosis
• Age of onset is less than bipolar affective disorder (BAD)
• Average length of depressive episode is 6months, though
25% have episodes >1year
• 10-20% chronic, unremitting course despite Rx
• 80% with major depression will have further episodes &
interval between becomes shorter.
• Moderat – severe: 25% do very well, 50% moderate
outcome 25% poor outcome- recurrent/ protracted
episodes/suicide)
• Poor prognostic factors: Illness severity, number of previous
episodes, delay in Rx, duration of episodes, comorbid
anxiety/substance misuse, compliance issues, Rx
insufficient, social & personality factors.
23. Deliberate Self Harm (DSH) and Suicide
In Pts with Depression
• Lifetime suicide risk 6-10% (compared to 1%)
• Need to educate the public on how to
recognise suicidal behaviour and increase help
facilities , restrict availability of paracetamol
etc and introduce occupational health in
stressful jobs to give people a place to go if
they are struggling.
25. Duration Of Rx
• One episode: full dose for 4-6months
• If recurrent: longer term prophylaxis (several
years) should be considered
• Discontinue antidepressants over 1-2 weeks to
avoid withdrawl effects
• Consider multiple drugs in controlling severe
depression
26. Psychotropics
• Often treat symptoms rather than specific
conditions or illnesses
• Sometimes drugs are prescribed to counter A/Es
of other meds
• Drugs have multiple functions: anti-depressants
are also anti-anxiety and pain, some mood
stabilisers also treat epilepsy
• General aim is to increase/decrease the NT that is
low:
• Depression: serotonin & adrenaline
• Psychosis: dopamine
• Dementia: acetylcholine
28. Anti-Depressants
• Tricyclic Antidepressants TCAs
• Monoamine oxidase inhibitors MAOIs
• Selective Serotonin Reuptake Inhibitors SSRIs
• Selective Noradrenaline Reuptake Inhibitors SNRIs (not
used much)
• Others
• Take several weeks to work
• Not addictive
• Choice depends on: A/Es , risk of OD, previous
response, safety regarding age&health
• Usual order of choice = SSRI SNRI TCA
29. TCAs
• Very dangerous in OD because of the effects on
the heart
• E.g.s Amitryptyline, clomipramine, dothiepin,
doxepin, nortryptyline, trimipramine
• A/Es:
– sedation often with hangover
– Postural hypotension
– Tachycardia& arrythmias
– Dry mouth, tremor, headache
– Blurred vision, constipation, urinary retention
– Mania, sexual difficulties, jaundice
– Blood problems, lower epileptic threshold so increased risk of
seizures
31. St Johns Wort
• Unlicensed but may be effective for mild depression
• Can interact with MANY medications causing serious
side effects e.g. Pregnancy when on pill
• Hypericum perforatum plant
• Well tolerated
• A/Es:
• Dry mouth
• Constipation
• Nausea
• Fatigue
• Dizziness
• Headache
• Restlessness
32. Mood Stabilisers
• Used in the treatment of Bipolar disorder to
suppress swings between mania and
depression
• Lab monitoring required for most (lithium,
tegretol and valproic acid)
• Commonly:
• Lithium (priadel)
• Carbamazepine (tegretol)
• Gabapentin (neurontin)
• Valproic Acid (depakote)
33. Anti-Psychotics
• Reduce psychotic symptoms in a manner not
reproduced by any other meds
• Effect independent of any sedative effects
• No clouding of consciousness
• First generation: haloperidol, chlorpromazine
• Second generation: olanzapine, amisulpride,
clozapine, resperidone. A/Es: weight gain & DM
• Uses:
• Psychotic illnesses
• Increase effects of antidepressants
• Phantom limb pain
• Shingles
• Nausea
34. A/Es of Antipsychotics
• Acute dystonias: abnormal movements, alarming, distressing and
dramatic in onset, occur after first few doses. More common in
men and younger patients. Classically “oculogyric crisis” and last
several hours if not treated. Spasms of lips, tongue, face and
throat. Rarely cause jaw dislocation
• Parkinsonism: lack of movement (akinesia), rigidity/increased
muscle tone, tremor of possibly one side only, >3 weeks to appear,
1/3 patients
• Akathisia: up to 50% pts, within a few days or after many weeks,
motor restlessness, agitation, intolerance of inactivity, dysphoria.
Associated with suicide, like restless leg syndrome
• Tardive dyskinesia: 40-50% long term treatment pts, can occur
after short term use. Months-years to appear. W>M. Serious,
disfiguring, often permanent disorder. Classically orofacial and
buccal-lingual involuntary movements. Choreoathetoid
movements of U&L limbs, tics, abnormal posture, hemiballismus,
grunting and distrubed respiration. Rare, severe version exist e.g.
“rabbit syndrome”
35. Maternity Blues and Post Natal Depression
• Maternity Blues
– Minor mood disturbance that occurs in 50% of mothers on the 3rd/4th day
postpartum
– More common in primiparous mothers (first baby)
– Thought to be due to a rapid decline in sex steroids, the psychological stresses
of childbirth and mothering
– Clinical features: tearfulness, irritability and LABILITY of AFFECT
– No specific treatment other than explanation and reassurance
– Resolves spontaneously in a matter of days
• Post Natal Depression
– 10-15% of mothers first month postpartum
– Due to stresses of mothering, feelings of anxiety and guilt about caring for the
baby
– More common if mother has a past psych Hx or lacks social support
– Tiredness, irritability and anxiety more prominent than depressed mood
– Baby may be a t short term risk of neglect and harm
– Treatment: explanation, reassurance, ADs, or psychological Rx. If hosp
required, mother and baby unit so bonding not compromised
http://www.elliothospital.org/_newsite/downloads/EPDSw_self-
referralcriteria.pdf
36. Suicide and DSH
• Risk of suicide: 1/100 (varies in time and location)
• High risk: Drs, anaesthetists, dentists, police... Jobs with high
levels of stress, responsibility, guilt, shift work and MEANS
e.g. Gun/access to drugs
• RISK ASSESSMENT of suicide, DSH or violence:
OSCE EVERY YEAR!!!!!
• 13/100,000 deaths each year in UK
• NI 16/100,000
• Males 2-4: 1 (NI 26/100,000) Females more likely to try but
men more likely to succeed (more violent means)
• Age 20-24, mid-late 40s and >85 high risk groups. Rates
RISING
• DSH: F>M. 0.4% pop/year. 10-20 X higher than suicide rates.
Peak age 15-24. May be a release/control thing.
37. Risk Factors for Suicide
• HAVE THEY TRIED IT BEFORE??? 40-60% suicides have
tried before. Risk 12% in the year following an attempt
• Personal factors: Age, FHx, gender, marital status
(Divorced > widowed > single > married)
• Social class (1&5 riskiest)
• Unemployment
• Occupation
• Social network and supports
• Contact history with Psych services
• Urban Pop (MCQ!!!)
• Stressors
38. Suicide – Risk Factors
• Method of attempt Important for determining how serious
they were.
• Men typically: hanging, drowning, guns. VIOLENT
• Women: OD, cutting
• DSH: OD, cutting
• Psych&Medical RFs:
– Mood disorders : depression and BAD 30X MORE LIKELY
– Schizophrenia: initially when most unstable
– Substance abuse
– Chronic medical illnesses: terminal diseases, DM...
– InPatients and upto 2 weeks post discharge. Especially if depressed.
Severely depressed and want to kill themselves but cant motivate
themselves to do it get slightly better and now can be bothered
and are at home alone after constant care!
39. Risk Assessment In Suicide
• Information about attempt: how, where, why, when...
• Assessment of degree of intent and seriousness: how much
they wanted to complete suicide- 4Ps:
– Planning or impulsive
– Performance (infront of other people)
– Preparations (tell anyone, suicide note, planned funeral)
– Precautions to avoid being discovered
• Current situation:
– Mood and hopelessness: plans for future/protective factors
– Thoughts of self harm
– Plans to self harm: CURRENTLY
– Command hallucinations (voices telling them to do it?)
– Subtance misuse
• REGRETS? HOW DO THEY FEEL NOW? ANGRY FOR PERSON
FINDING THEM?
