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Disclosures
• Oliver Howes is a psychiatrist and clinical academic at the Maudsley Hospital NHS Trust & KCL and ICL, UK
• He has received investigator-initiated research grants from, and/or is on advisory/ speaker bureaux for:• Astra-Zeneca, Autifony, BMS, Eli Lilly, Janssen/J&J,
Leyden-Delta, Lundbeck, Otsuka, Servier, Sunovion, Roche
• Neither Dr Howes nor his family have shares/other investments in or are employed by biopharmaceutical companies
outline
• Treatment resistance: intro
• The problem:
• Meta-analyses
• Clinical guidelines
• Trial reporting
• Trial definitions
Treatment resistance is common
N= 240 first episode
~10 year follow-up33% treatment resistant>15% from onset
Responder
Treatmentresistant
Lally et al 2016
0.008
0.009
0.01
0.011
0.012
0.013
0.014
0.015
0.016
Controls Responders Treatment
resistant
p=0.01
Treatment resistance: biology is different
DA
syn
thes
is
cap
aci
ty/
min
p=0.02;
ES=1.12
Demjaha et al, AJPsych 2012; Mouchlianitis et al Scz Bull 2016
0.6
0.8
1
1.2
1.4
1.6
1.8
2
Glu
tam
ate
/ IU
Responders Resistant
p<0.05,
effect size=0.75
Treatment resistance: needs different therapy
outline
• Treatment resistance: intro
• The problem:
• Meta-analyses
• Clinical guidelines
• Trial reporting
• Trial definitions
1st problem: clinical guidelines
Howes et al AJPsych 2017
2nd problem: study comparisons
Samara et al 2016
But in non-treatment resistant patients…..
Leucht et al 2013
Siskind et al 2016
Favours
clozapine
And clozapine comes out best in another meta-analysis….
Are they comparing like with like?
Systematic review of drug trials in treatment resistant schizophrenia• Search: 1980-2016
• Treatment resistant/ refractory schizophrenia
• Randomised controlled trial
• 2808 reports
• 42 studies met criteria
Howes et al AJPsych 2017
How many defined treatment resistance?
• 50%: no clear definition
• 95%: used different or no
clear definition
Howes et al AJPsych 2017
Variation in criteria
Variation in criteria: including treatment intolerant
No standard definition of treatment resistance
Need consensus on definition and
reporting
Summary
• Clinical guidelines vague
• No consensus on reporting
• Wide variation in criteria used
• Some studies include intolerance as well as resistance
Implication:
• Comparisons are difficult!
• Clinical guidelines impossible!
Howes et al AJPsych 2017
