1. Guy Brookes Leeds PFT

2.  Antipsychotic Medication  Antidepressant Medication  Mood Stabilisers  What does the Evidence mean?

3.  The baseline ◦ Symptom clusters – Positive, Negative (1⁰, 2⁰), Affect, Cognitive, Disorganised ◦ Efficacy – No difference for positive symptoms ◦ Effectiveness and Limitations  Action of antipsychotics ◦ Dopamine (D 2 )- Pathways

4.  Atypical antipsychotics ◦ Serotonin / Dopamine antagonists  Risperidone  Olanzapine  Amisulpiride  Quetiapine  Aripiprazole

5.  Prototype for Atypicals  Only Antipsychotic with greater efficacy for Positive symptoms and good evidence for Negative symptoms  Neutropenia  Sedation, Weight gain, Hypersalivation, Fits  Specific indications  NICE Guidance

6.  “Atypical” at lower doses  Key side effects ◦ EPSE, Prolactin (relative) ◦ Sexual side effects  Start 2mg increase to c.4/6mg (max. 16mg) ◦ Single night dose  Less weight gain  Not if risk of stroke  Velotabs, Depot,  Not if risk of stroke

7.  Very similar to Clozapine  Key side effects ◦ Weight gain ◦ Sedation  Start 10mg. Up to 20mg. ◦ Single night dose  Safe  Low incidence: EPSE, 2⁰Neg, ↑Prolactin,  Velotabs and IM  Not if risk of stroke  Mood stabiliser, Treatment Resistant depression, Anxiety

8.  Similar to Clozapine  Dose: Titrate from 25mg to c. 600mg (max 750mg)  Very low EPSE or Prolactin change  Some sedation – problematic as bd dosing  Less weight gain than other atypicals  Titration over several days  Less effective at low/mid doses ◦ For schizophrenia need 600mg per day  Also for BPAD

9.  Not really atypical. Little serotonergic effect  Sedation generally low  Negative symptoms at low dose  Key side effects ◦ EPSE, Raised Prolactin  Little weight gain  Dose 200mg bd to 400mg bd (max 1200mg)

10.  Partial Agonist – NB Frontal lobe  Newest  Little sedation, EPSE, weight gain  Key side effects ◦ Agitation ◦ Nausea  Theoretically effective for Negative symptoms  Start 10mg od. Up to 30mg  People’s favourite?

11. EPSEWeight gain SedationCognitive Impair Sexual Dysf Haloperidol++++++++++++ Risperidone++ Olanzapine+++++ Quetiapine+++ Amisulpiride+++ Aripiprazole+

12.  Baseline ◦ Depressive illness v’s unhappiness ◦ Effect size – severity, trial, placebo ◦ Practical difficulties ◦ Comparator bias  Action ◦ Serotonin / Noradrenalin / both

13.  SSRIs – latest developments  Mirtazepine  Duloxetine  Escitalopram

14.  Effectiveness and Efficacy ◦ Depressive illness – definition ◦ Mild depression / adjustment ◦ Efficacy increases with severity and duration of trial ◦ Publication bias, Placebo increasing with time. ◦ Study design – ITT, Rating scale, duration, age  Suicidality ◦ Agitation / Akathisia  Anxiety, Sexual dysfunction……..  Overuse / social changes

15.  Dual acting  NICE – no greater efficacy  Start 30mg (15mg). Up to 45mg  Key side effects ◦ Sedation (greater at low dose) ◦ Weight gain  Generally well tolerated, safe.  Also for anxiety disorders

16.  Dual acting  Dose 30 – 60mg. Single dose  Key side effects ◦ GI symptoms, anxiety, agitation  Stress incontinence  No evident greater effcicacy

17.  Theoretically should produce fewer side effects – Serotonergic.  Generally no fewer drop-outs in studies.  No clear clinical benefit over SSRIs  Start 10mg – can increase though evidence unclear (max. 20mg)

18.  Efficacy ◦ Antidepressants no more effective than placebo for mild depression. ◦ Primary care – no difference ◦ Secondary care – Venlafaxine, ?Escitalopram > SSRI ◦ Inpatient – TCA > SSRI ◦ SSRIs more likely to be prescribed at therapeutic dose for therapeutic period ◦ Structured interventions around prescribing more effctive  Side effects ◦ Newer antidepressants may be better tolerated than TCAs ◦ Different ◦ Concordance

19.  Effects ◦ Prophylactic, Mania, Depression  Anti-epileptic ◦ Valproate, CBZ, Lamotrigine, Gabapentin, Topiramate  Lithium  Antipsychotic ◦ Olanzapine, Quetiapine, Aripiprazole

20.  Probably prevents depressive more than manic episodes  Generally up to 200mg day  Slow titration upwards – Stevens Johnson Synd.  NICE – not first line treatment

21.  Licensed for Mania

22.  Gabapentin ◦ No efficacy in BP Depression ◦ Inferior to Placebo in Mania ◦ Not recommended by NICE  Topiramate ◦ No evidence of efficacy ◦ Not recommended by NICE  Antipsychotics ◦ Olanzapine, Quetiapine, Aripiprazole