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Treating All Phases of Bipolar for Non-Medical Prescribers

For LPT non-medical prescribers 9 November 2013.
by

Nick Stafford

on 28 July 2014

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Transcript of Treating All Phases of Bipolar for Non-Medical Prescribers

Treating
Bipolar

Conclusions
Dr Nick Stafford
Consultant Psychiatrist
Leicestershire Partnership Trust
I have grants / research support, consulting fees and honoraria from AstraZeneca, GSK, Pfizer, Lundbeck, Otsuka, BMS, Servier, Eli Lilly, Sanofi-Aventis. No shares.

Bipolar UK – Immediate Past Vice Chair

Mental Health Today, Scotsman Newspapers, Doctors.net.uk, others ...
Declarations
Pharmacotherapy of all phases
for non-medical prescribers

Mania
WFSBP Mania Guidelines
Bipolar Depression
Maintenance Treatment
Weaker evidence base
Pure euphoric mania is rare

Typical mania (59%) incl. mixed states

Mixed states poorly defined (DSM-5)

Psychotic mania (27%)

Hypomania – boundary with mania
Mania is not a monolithic state
Mixed States
Guideline Algorithm
Mania Treatments
<10% of acutely manic patients receive monotherapy

Average number medications used = 3

Manifold co-morbidities

<20% screened naturalistic patients fulfill inclusion criteria for RCTs
The 'real world' of treating acute mania
Haloperidol (FGA) in mania
SGAs in mania
SGAs versus Haloperidol in mania
Scherk H et al. (2007), Arch Gen Psychiatry 64(4):442-455
SGA Side Effects
Adjunctive treatment in mania
Strong evidence:
Lithium
Valproate
Carbamazepine
Based on RCTs, the following mood stabilisers have antimanic properties
20 studies since 1954

Only since 1990s of good methodological standard

3 arm (Li, VPA, plac) Bowden et al 1994

Meta-analysis RCTs of Li revealed effect size 0.40 (95%CI 0.28-0.53) NNT 6
Comparator studies showed equivalence with lithium (which can be slower by a few days)
Chlorpromazine
Haloperidol
Olanzapine
Risperidone
Aripiprazole

Target plasma levels in RCTs 0.6 – 1.0
Lithium in mania
Various names / forms:
Valproic acid (crosses BBB)
Sodium valproate
Divalproate
Divaproex sodium

Several RCTs show consistent evidence for efficacy in mania
Similar efficacy in comparator trials to:
Lithium
Carbamazepine
Haloperidol
Olanzapine (in 1 study but not in 2 others)

Dose loading 20-30mg/kg
Plasma levels 75-99mg/L

Birth defects - Guidelines
Valproate for mania
Carbamazepine for mania
First studied Okuma et al. 1973

Two large RCTs Owen 2006
CBZ effective in mania

Particularly in sub-groups:
Incomplete response to lithium
Rapid cycling
Co-morbid organic (neurological) disorders
Schizoaffective disorder
Manifold interactions
Limits use with combination treatments


Mood stabilisers in mania
Antipsychotics
Cipriani A et al. (2006), Cochrane Database of Systemic Reviews (3):CDOO4362
Bipolar depression or MDD?
WFSBP Bipolar Depression Guidelines
WFSBP Combination Guidelines
Older studies give stronger evidence than recent studies

Meta-analyses show lithium is more effective at preventing mania than depression cf. placebo

Lithium’s evidence less clear as antidepressant than as antimanic

Large effect size on reducing suicide risk with longer use
Lithium in Bipolar I Depression
Srisurapanont 1995; Young 2010; Geddes 2004; Smith 2007
Kessing et al, Arch Gen Psych 2005, 62, 860-866
Lamotrigine as monotherapy
Geddes, Calabrese, Goodwin 2009
Quetiapine studies - BOLDER & EMBOLDEN
Lurasidone

Buspirone

Modafinil

Mifepristone

EPA
Other agents (not exclusive)
Divalproex and lithium
Lamotrigine
Quetiapine
Antidepressants
Thyroxine
Clozapine
Carbamazepine
Combinations are order of the day
Rapid cycling
Do antidepresssants increase the risk of suicide in bipolar?
Do antidepresssants increase the risk of suicide in bipolar?
Bipolar or MDD?
Guidelines
Lithium
Lamotrigine
Do antidepressants harm?
Special
cases
Antipsychotics
Detail
Suicide in bipolar - SMR
Contents of
today's talk
Thou shalt always use a mood stabiliser in all phases of the disorder!
What do the treatment guidelines say?
How Lithium Works
Lithium prevents manic relapse
Lithium prevents depressive relapse
Carbemazepine vs. Lithium any pole
Lithium +/- Valproate: BALANCE
Lamotrigine vs. Lithium both ways
Olanzapine vs. Lithium all ways
Aripiprazole in maintenance
Aripiprazole does not prevent depressive relapse
Quetiapine vs. lithium vs. placebo
Quetiapine vs. Lithium both ways
Most studies exclude important comorbidity

Comorbidity has a major impact on illness course and treatment effectiveness

Alcohol abuse
Substance misuse
Anxiety disorders
Personality disorder
Comorbidity in mania
The aim of maintenance treatment should be to fully treat all symptoms, not just hypomania and depression.

Relapse and recurrence are greater with increasing subsyndromal symptoms and comorbidity.
Comorbidity
Lithium
Carbemazepine
Valproate
Lamotrigine
Olanzapine
Aripiprazole
Quetiapine
Ensure early diagnosis and prompt treatment

Many treatment options exist for all phases of bipolar disorder

Aim for full remission of all symptoms

Single agents will minimise side effects

Combination treatments are more efficaceous and more common

Comorbidities worsen outcomes - treat them aggressively

Consider patient needs and special cases
Final Analysis
Plasticity
Local recommendations:

BMI, BP, Umbilical circumference
FBC, U&E, blood lipids, glucose, HBa1C

Initial, 3 months, 6 months, 12 months, yearly
First year by LPT
Subsequent years by GP

All SGAs and other mood stabilisers
Metabolic screening
Minimum work up:
U&E, eGFR, TFTs, ECG, Weight

NPSA guidelines follow up:
3 monthly lithium levels
TFTs every 6 months

GP yearly metabolic screening

Plasma levels (NICE): 0.6 - 1.0
Lithium work up & monitoring
Acknowledgments:

Professor Heinz Grunze, Newcastle. Many of the slides in this presentation relating to research results have been prepared by Professor Grunze and his team in Newcastle.
GOD
Worse prognosis

High degree of anxiety and agitation

Often show mood incongruent psychotic symptoms

High suicide risk

High comorbidity with substance misuse
New treatments for bipolar
Biological Mechanisms
Cognitive impairment

Inflammation

Neurotrophic factors

Oxidative stress
Mifepristone and anti-steroids
WFSBP
NICE
BAP
APA
ISBD Taskforce on Antidepressant
use in Bipolar (AmJPsych 2013)
Controversial
Limited data
No broad statements
Some patients may benefit
SSRIs less switch than TCAs
Mood elevation greater in bipolar I
In bipolar I disorder use a MS
Full transcript