Newer Psychotropic Drugs

1
Newer Psychotropic Drugs

• Guy Brookes
• Leeds PFT

2
Content

• Antipsychotic Medication
• Antidepressant Medication
• Mood Stabilisers
• What does the Evidence mean?

3
Antipsychotic Medication

• The baseline
• Symptom clusters Positive, Negative (1, 2),
  Affect, Cognitive, Disorganised
• Efficacy No difference for positive symptoms
• Effectiveness and Limitations
• Action of antipsychotics
• Dopamine (D2)- Pathways

4
Newer Antipsychotics

• Atypical antipsychotics
• Serotonin / Dopamine antagonists
• Risperidone
• Olanzapine
• Amisulpiride
• Quetiapine
• Aripiprazole

5
Clozapine

• 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
Risperidone

• 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
Olanzapine

• Very similar to Clozapine
• Key side effects
• Weight gain
• Sedation
• Start 10mg. Up to 20mg.
• Single night dose
• Safe
• Low incidence EPSE, 2Neg, ?Prolactin,
• Velotabs and IM
• Not if risk of stroke
• Mood stabiliser, Treatment Resistant depression,
  Anxiety

8
Quetiapine

• 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
Amisulpiride

• 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
Aripiprazole

• 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
• Peoples favourite?

11
EPSE Weight gain Sedation Cognitive Impair Sexual Dysf
Haloperidol
Risperidone
Olanzapine
Quetiapine
Amisulpiride
Aripiprazole
12
Antidepressants

• Baseline
• Depressive illness vs unhappiness
• Effect size severity, trial, placebo
• Practical difficulties
• Comparator bias
• Action
• Serotonin / Noradrenalin / both

13
New Antidepressants

• SSRIs latest developments
• Mirtazepine
• Duloxetine
• Escitalopram

14
The trouble with.SSRIs

• 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
Mirtazepine

• 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
Duloxetine

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

17
Escitalopram

• 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
Outcome

• Efficacy
• Antidepressants no more effective than placebo
  for mild depression.
• Primary care no difference
• Secondary care Venlafaxine, ?Escitalopram gt
  SSRI
• Inpatient TCA gt 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
Mood Stabilisers

• Effects
• Prophylactic, Mania, Depression
• Anti-epileptic
• Valproate, CBZ, Lamotrigine, Gabapentin,
  Topiramate
• Lithium
• Antipsychotic
• Olanzapine, Quetiapine, Aripiprazole

20
Lamotrigine

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

21
Depakote

• Licensed for Mania

22
Other Mood Stabilisers

• 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