Depression, Schizophrenia and Bipolar Disorder

What are the core symptoms of depression?

Persistent low mood. Anhedonia. Anergia

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What are the physical symptoms of depression?

Sleep disturbance. Appetite alteration. Lack of concentration. Self-harm. Pain

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Describe the aetiology of depression

Monoamine deficiency hypothesis; proposes that depression is due to a deficiency in one of the three biogenic amines namely serotonin, noradrenaline and/or dopamine

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What is the mechanism of action of all antidepressants?

Increase either: 5HT/NA pre-synaptically by prevention the breakdown of neurotransmitters (MAOI) or prevent the reuptake of neurotransmitters from synaptic cleft (SSRI). Diagram

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Give examples of antidepressants

Sertraline, reboxetine, mirtazapine, citalopram, venlafaxine, paroxetine

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How long does it take for antidepressants to have an effect?

Antidepressants show effects during weeks 1-2 (however full response will be gradual over several weeks and months, 6-9 months)

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What are the types of side effects of antidepressants?

Anticholinergic, cardiac, nausea, sedation, overdose, seizures, sexual dysfunction

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How long do patients take antidepressants?

Only treating symptoms. Taken for 6-9 months. Multiple episodes benefit from maintenance treatment (at least 2 years)

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Which factors need to be considered when stopping antidepressants?

Drug, duration of treatment, speed of stopping, and dose. Consequence of abrupt withdrawal (antidepressant discontinuation syndrome). Symptoms FINISH (flu-like symptoms, insomnia, nausea, instability, sensory disturbance, hyperarousal). Can be self-limiti

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How are antidepressants stopped?

Gradual reduction in dose over a 4 week period (some patients may require longer periods with drugs with a shorter half-life e.g. paroxetine and venlafaxine. Not required for fluoxetine (long half-life)

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What are the key points of antidepressants? (1)

Treat single episodes of depression for 6 – 9 months after remission. Risk of relapse is high and increases with each episode. Chances of staying well are greatly increased by antidepressants.

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What are the key points of antidepressants? (2)

Reassure patients that antidepressants are: Effective, Not addictive, Don’t cause ‘tolerance’ – they stay effective over time, Don’t cause long term side-effects. There are alternatives (don't stop antidepressants abruptly)

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What are the positive symptoms of schizophrenia?

Delusions, hallucinations, thought disorder

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What are the negative symptoms of schizophrenia?

Anhendonia, blunted effect, poverty of speech, avolition, asociality. (social/occupation dysfunction, continuous problems for 6 months)

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The pathophysiology of schizophrenia relates to which theory?

The dopamine theory

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What are the side effects of antipsychotics?

EPS, dose-related EPS, TD, prolactin elevation, agranulocytosis, anticholinergic, AST/ALT elevation, hypotension, sedation, QTc (Torsade de Pointes, fatal) prolongation, weight gain

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What are the types of extrapyramidal side effects? (1)

Dystonia (Oculogyric crisis, Torticollis, onset in hours or years, treat with anticholinergic or switch antipsychotic). Pseudo- parkinsonism (tremor, bradykinesia, onset days-weeks, reduce dose, switch or anticholingeric).

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What are the types of extrapyramidal side effects? (2)

Akathisia (restlessness, onset hours-weeks, for treatment reduce dose, switch or use something unlicensed). Tardive dyskinesia (orofacial dyskinesias, choreiform hand movements, onset months-years, treat by stopping anticholinergic, reduce dose or switch)

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What is the ideal treatment pathway for schizophrenia?

Antipsychotic 1 -> antipsychotic 2 -> clozapine

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Describe features of clozapine (1)

If patient is treatment-resistant. Plasma levels monitored. Aim for 0.35-0.5 mg/L (some patients respond to higher/lower levels). Higher levels (risk of seizures, seizure prophylaxis recommended when levels exceed 0.6 mg/L).

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Describe features of clozapine (2)

Clozapine levels are affected by CYPP450 inducers and inhibitors. CYP1A2 is the major isoenzyme involved in clozapine metabolism (inducers reduce clozapine levels, inhibitors increase clozapine levels)

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Which side effects of clozapine need to be monitored?

Pancytopenia (white blood cells, platelets, neutrophils). Myocarditis, seizures, pneumonia

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What is bipolar disorder?

A mental health condition that causes extreme mood swings (from mania to depression).

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Why do people become toxic to lithium?

Changes in sodium levels. Dehydration. Drug interactions (NSAIDs). Addison's disease. Errors in dosing

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Describe features of brands of lithium

Lithium carbonate 200 mg = 520 mg lithium citrate = 5 mL Priadel liquid. Prescribe by brand name and in milligrams. Not formulation and strength. Look at purple book. First-order kinetics (doubling dose will double serum level). Check patient OTC medicine

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Describe features of using valproate in women of child-bearing age

High risk of developmental disorders (up to 30- 40% of cases) & congenital malformations (10% of cases) in children exposed to valproate in utero. NICE & the MHRA: valproate should not be prescribed in girls, female adolescents, women who are pregnant/chi

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Describe features of bipolar depression

Is not the same as unipolar depression. Is generally more severe. Is associated with a high risk of suicide. Is not as simple to treat as you might hope. NICE guidelines (fluoxetine, olanzapine/quetiapine). Advice will depend on treatment, valproate, lith

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Depression, Schizophrenia and Bipolar Disorder

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