Bipolar Affective Disorder, Depression and Suicide

Psychiatry

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

ElevatedIrritable

Mood

Risks

Pressured speech

Racing thoughtsGrandiosity

Distractible

Core Symptoms of Mania

SocialDisinihibition

Self confident

Making Plans

Aggression

Psychosis

Impulsivity

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

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

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

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 ?

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!!!

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)

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)

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

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

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

Depressed Mood

Anhedonia

Self Depreciation

Hopelessness

Suicidal ideas/ plans

Loss of Interest

Guilt

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.

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

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

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)

Treatment: Physical• Anti-depressant drugs:

-monoamine uptake inhibitors: tricyclics, SSRIs, NARI, SNRI-Monoamine oxidase inhibitors (MAOIs)-Others: mirtazapine (alpha2 NA antagonist)

• ECTTreatment: Psychological• Cognitive Behavioural Therapy• Interpersonal Therapy*** for the future, not for severe cases in the immediate

setting. More preventative.

• 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.

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.

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.

Organic Causes of Depression• Neurological: stroke, Alzheimers, Parkinsons, Huntingtons,

MS, epilepsy, intracranial tumours• Endocrine: Cushing’s, Addisons, hypothyroidism,

hyperparathyroidism• Metabolic: Iron deficiency, B12/folate deficiency,

hypercalcaemia, hypomagnesaemia• Infective: influenza, infectious mononucleosis, hepatitis,

HIV/AIDS• Neoplastic: systemic effects of cancer• Drugs: L-dopa, steroids, Bblockers, digoxin, cocaine,

amphetamines, opioids, alcohol.

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

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

Main Medications

• Anti-depressants• Antipsychotics• Antidementia drugs• Benzodiazipines• Mood stabilisers

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

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

SSRIs• Safe in OD• No significant cardiac A/Es• A/Es: weight loss, nausea, headache, agitation, sexual difficulties• Non-sedative• Examples: citalopram (cipramil) , escitalopram (cipralex),

fluoxetine (prozac) , fluvoxamine (faverin) , paroxetine (seroxat) , sertraline (lustral)

• Indications: • depressive illnesses• Social phobia• PTSD• Anxiety disorders

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

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)

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

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”

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

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.

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

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!

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?