Management of Bipolar Disorders

&
Mood Dysregulation

Dr Adi Sharma MRCPsych MD

PhD
Clinical Senior Lecturer in Child
and Adolescent Psychiatry

1
Conflicts
(Past 3 years)

Organisation Funding for

BAP and ACAMH Speaker honoraria and
travel expenses
NIHR Research
Lundbeck Unrestricted medical
educational grant

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 • Bipolar Disorder & Disruptive Mood
Dysregulation Disorder (DMDD)
• Treatment considerations when
choosing a psychopharmacological
agent
• Pharmacological management of
Manic (Hypomanic) Episodes
Talk • Pharmacological management of
Bipolar Depression
• Pharmacological management
during euthymia: maintenance
• Comorbid ADHD
• Treatment of DMDD
• Adverse events and monitoring
• Non Pharmacological Management

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A Recap of diagnostic criteria 4
Bipolar Disorder

Mania
A mood disorder characterised Hypomania
by episodes of: Depression
Mixed episodes

For mania and hypomania disturbance can be persistent

elevation or irritability in mood

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 Bipolar Disorder ICD-
ICD -11

• Classified as Bipolar I and II Disorder

• Used for clinical diagnosis in the UK
• Diagnosis can now be made on the basis of 1 manic/mixed
episode

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Bipolar Disorder: DSM-
DSM-5

• Used in USA and for research

• Bipolar I Disorder

• Bipolar II Disorder: no manic

episodes

• Bipolar Disorder NOS: vast

majority of youth (USA) receive
this diagnosis (NIMH, 2001)

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DSM-
DSM-5 Changes

• Bipolar Disorder and Depressive

Disorders are different sections

• Criterion A for manic and hypomanic

episodes now includes an emphasis on
changes in activity and energy as well as
mood

• No ‘mixed episodes’ and instead a new

specifier, “with mixed features,”
introduced

• Anxious Distress Specifier introduced

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 NICE Bipolar Guidelines

• Diagnosis and assessment

• 1.11.4
• Diagnosis of bipolar disorder in children or young people should be
made only after a period of intensive, prospective longitudinal
monitoring by a healthcare professional or multidisciplinary team
trained and experienced in the assessment, diagnosis and
management of bipolar disorder in children and young people,
and in collaboration with the child or young person's parents or carers.

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 • Longitudinal prospective
assessment
NICE
Bipolar • Drug treatment
Guidelines • Caution with diagnosis of Bipolar II

• Focus on assessment of carer

needs

10
Bipolar Disorder in under 18s

How frequent are the manifestations of mania in preadolescents

Differences in clinical manifestations of BD by age eg

grandiosity?

Should there be a modification in criteria eg number of

symptoms

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Narrow Phenotype in Paediatric Bipolar
Disorder

Manic/hypomanic episodes only diagnosed in the context of

elevated mood

Irritability on its own (particularly in prepubertal children) not

enough

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Trends Over Time

National trends in visits with a diagnosis of bipolar

disorder as a percentage of total office-based visits by
youth (aged 0-19 years) and adults (aged ≥ 20 yrs).
(Moreno et al., 2007)

13 Copyright © 2015 American Medical Association.

All rights reserved.
 Challenges

Recent exponential rise in rates of BD in children and

adolescents (mostly in the USA)

BD is 4th leading cause of disability among adolescents aged

15-19 years

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 Challenges
Limited evidence of pharmacological efficacy

Dramatic increase in the use of medication for early onset

Bipolar Disorder

Early age at onset predicts a longer time to first

pharmacological treatment

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Disruptive Mood
Dysregulation Disorder

• 1. Severe recurrent temper outbursts

manifested verbally (e.g., verbal rages) and/or
behaviorally (e.g., physical aggression toward
people or property) that are grossly out of
proportion in intensity or duration to the situation
or provocation.
• 2. The temper outbursts are inconsistent with
developmental level (e.g., the child is older than
you would expect to be having a temper tantrum).
• 3. The temper outbursts occur, on average,
three or more times per week.
• 4. The mood between temper outbursts is
persistently irritable or angry most of the day,
nearly every day, and is observable by others
(e.g., parents, teachers, friends).

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Disruptive Mood
Dysregulation Disorder

• 5. The above criteria have been present for 1

year or more, without a relief period of longer than
3 months. The above criteria must also be present
in two or more settings (e.g., at home and school),
and are severe in at least one of these settings.
• 6. The diagnosis should not be made for the first
time before age 6 years or after age 18. Age of
onset of these symptoms must be before 10 years
old.
• 7. There has never been a distinct period lasting
more than 1 day during which the full symptom
criteria, except duration, for a manic or hypomanic
episode have been met.
• 8. The behaviors do not occur exclusively during
an episode of major depressive disorder and are
not better explained by another mental disorder.

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 • Longer term follow up shows high
DMDD rates of depression and anxiety
disorders and not Bipolar Disorder

• DMDD is part of depressive

disorders section

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 Comorbidity or
Differential Diagnoses
Diagnoses?
agnoses?

19
 Comorbidity

The norm and not the Neurodevelopmental Mental health disorders: Substance use
exception disorders (ADHD, ASD) Anxiety

Emerging Personality Assess for these and Do not ‘double count’

Disorder i.e. EUPD also treat symptoms

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 THE ROLE OF CAMHS OFFER CHOICE

Collaborative CLINICIANS: EXPERT VS

EXPERTISE

decision
making

ENCOURAGE AUTONOMY REDUCE RELIANCE ON

SERVICES

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22
 Na
Agent Quetiapine Aripiprazole Risperidone Lithium Lamotrigine
Valproate
Gender M+F M+F M+F M+F(?) M M+F
Causes sedation +++ +/- ++ - +/- -
Causes weight gain +++ ++ ++ ++ + -
Can increase blood
++ + ++ +/- +/- -
sugar
Cause
++ - +++ - - -
hyperprolactinaemia
Help improve anxiety ++ +/- - - +
Frequency of blood 6 monthly in year 1 6 monthly in year 1 6 monthly in year 1
3 monthly Annually None
tests then annually then annually then annually
Renal dysfunction +/- +/- +/- +++ +/- -
Thyroid dysfunction ++ + ++ +++ - -
Lipid dysfunction ++ + ++ + + -
Cause Steven
+ + + + + +++
Johnson

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 24

Pharmacology on its own:

never enough

Psychotherapeutic
interventions crucial as in
any good CAMHS
management plan
Pharmacological
Management:
Bipolar Disorder

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 Patient and family approach

Evidence base for efficacy of agent

General Phase of illness

Principles

Agents side effects spectrum and safety

Presence of confounding symptoms (rapid

cycling, psychotic symptoms)

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General Principles

Patients history of medication response

Co-morbid conditions: anxiety, OCD, ADHD, ASD etc

History of treatment response in parents may predict response in

offspring (particularly Lithium)

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 ANTIPSYCHOTICS MOOD
STABILISERS
General
Principles

ANTIDEPRESSANTS
Pharmacological Management:
Manic (Hypomanic) Episodes

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 Atypical Antipsychotics
(Quetiapine, Aripiprazole,
Risperidone)

First Line Lithium

Treatment

Anticonvulsants (Valproate
… boys only)

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 Atypicals (Olanzapine,
Clozapine)

Second Line
Treatment

Anticonvulsants (CBZ)

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 • Quetiapine

• Antimanic efficacy
• Mood Stabilising efficacy
• Anti (bipolar) depressant efficacy (?)
• Weight gain
• Prolactin
• Sedation: needs gradual increase

• BNF Indication

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 Aripiprazole
• Novel action on Dopamine receptor
• Anti-manic efficacy
• Mood stabilising efficacy
• Anti (bipolar) depressant efficacy
• EPSE: akathisia
• Prolactin: can lower
• Impact on weight
• Interaction with SSRIs

• BNF Indication

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 Risperidone
• Antimanic efficacy
• Mood stabilising efficacy
• Weight gain
• Prolactin
• Sedation
• SSRI interaction
• Depot available (?Paliperidone)

• BNF Indication

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Lithium

35
Lithium:
preparations and
BNF Indications

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 Comparative
efficacy of
Antipsychotics
versus Traditional
Mood Stabilisers

• Examined all double

blind placebo controlled
trials for adults (n=23)
and youth (n=9)
• Reported significant
differences in Effect
Sizes favouring
Antipsychotics when
compared with classic
mood stabilisers in youth
(ES=0.65) but not adults
(ES=0.2)

37
Meta-analysis
of response
rates in
randomised
placebo
controlled
studies

38 Liu et al 2011
 Pharmacological
Management:
Bipolar
Depression

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Bipolar depression (40% of time) is
primary source of symptomatic
burden amongst youth

Episodes are more frequent and

longer in duration

Depressive episodes are most

common form of recurrence (59.5%
vs 20.9% hypomania, 14.8% manic
and 4.8% mixed) after recovery

Often not diagnosed

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Bipolar Depression

Paucity of psychopharmacological
studies assessing efficacy

Competing concerns Risk of suicide

Exacerbating or
re antidepressants: inducing mania

Psychological therapies?

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Anti-
Anti -depressants

Very limited data Watch for switch Minimal duration

possible

SSRIs Fluoxetine vs SSRIs hold no

Sertraline BNF indication

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 Several case reports
describe successful use
of adjunctive lamotrigine

Lamotrigine

Benefit during
maintenance phase in
preventing depression

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 Single open label 6 week
study in 12-18 year old
inpatients

Lithium Large ES of 1.7 with 50%

drop in depressive scores

No double blind placebo

controlled trial
 Lurasidone

• New antipsychotic

• Antimanic efficacy

• Antidepressant efficacy

• used in patients with Cognitive Impairment

• Metabolically neutral

• EPSEs

• No BNF indication

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 • If choosing an antipsychotic,
choose agents that have minimal
impact on:
• Appetite (weight gain)
• Prolactin (sexual side effects)
Remember…
• Lipids and blood sugar
(metabolic syndrome)
• Can benefit ADHD symptoms
but unlicensed for this
indication
 Carbamazepine

Sodium Valproate … avoid

Anti-
Anti - in females of child bearing
age, polycystic ovarian
convulsants: disease and congenital
anomalies

Lamotrigine … Watch for

skin rash (Toxic Epidermal
Necrolysis)

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 Pharmacological
Management:

Euthymia Maintenance

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 • How long do we treat?
• Collaborative decision
making
• Limited evidence base
• No mood episodes for at
least 18-24 months
Euthymia
• Watch for increase in
Maintenance motivation as symptoms
improve
• Agents:
• Atypicals,
• Conventional mood
stabilisers
• Avoid polypharmacy

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 Agent Indications and max dose
Treatment and Recurrence Prevention of mania (12-18years of age)
Aripiprazole
Max dose 30 mg

Monotherapy and combination therapy in mania (ages 12-18 years)

Olanzapine
Maximum 20 mg daily

Treatment of mania in Bipolar Disorder

Quetiapine (ages 12-18 years)
usual dose 400-600 mg

Short Term mono therapy of mania in bipolar disorder (12-18 years of age)
Risperidone
Max 6 mg daily

Treatment and prophylaxis of mania, bipolar disorder (12-18 years)

Lithium
Target serum range 0.4-1 mmol/litre

BNF Indications

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 • Treat BD first then assess for residual
features of ADHD

Management • If needed, use ADHD medication

of Comorbid dependent on profile to treat the ADHD
symptoms
ADHD and
Bipolar • All forms of Methylphenidate and
Disorder atomoxetine are contra-indicated in
patients with a diagnosis or history of
severe and episodic (Type I) Bipolar
(affective) Disorder (poorly controlled)

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 Limited evidence base

Reported to have high rates of comorbidity with ADHD, ODD,

Aggressive Behaviours and Conduct Disorder

Target comorbid behaviours

DMDD Atypical Antipsychotics (Risperidone)

Lithium

Na Valproate

Psychosocial interventions (including parenting interventions)

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Adverse Event Monitoring

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 Weight gain

Glucose Intolerance

Thyroid

Adverse
Effects
Prolactin

Lipid Dyscontrol

Cardiac Problems

54
 Extra Pyramidal Side Effects

Tardive Dyskinesia

Adverse
effects
Sedation

Sexual side effects

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Weight gain & Hyperglycemia

REGULAR EXERCISE TRY NOVEL EXERCISE I.E. CALORIE CONTROLLED CONSIDER SWITCHING
ZUMBA; BELLY DANCING DIET

ORAL
HYPOGLYCEMICS??

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 Enquire re: gynaecomastia,
galactorrhoea, sexual side
effects

Monitor for asymptomatic

hyperprolactinemia

Hyperprolactinemia

Reduce to minimum
effective dose

Aripiprazole (?)

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 NICE Guidelines suggest to offer:

An evidence-
evidence -based psychological intervention specifically
for Bipolar Disorder i.e. Family Focussed Treatment for
Adolescents with Bipolar Disorder (FFTA-UK)

High-
High-intensity psychological intervention in line with
depression guidelines i.e. Cognitive Behavioural Therapy
Psychological or Interpersonal Therapy

Interventions Psychological therapists should have experience of

working with YP with bipolar disorder.

Family / systemic approach

Ongoing relapse planning and mood monitoring

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Family Focussed Treatment for
Adolescents with
Bipolar Disorder

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 • 16 outpatient sessions over 6
months
• Weekly, biweekly, and
monthly sessions
• Engagement phase
• Psychoeducation (symptoms,
early recognition, etiology,
FFT-A UK treatment, self-management)
version • Communication enhancement
training (behavioral rehearsal of
effective speaking and listening
strategies)
• Problem-solving skills training
 • Parents
• Siblings
• Carers
• Educational settings
i.e. teachers,
SENCOs
• Community / ward /
local service
professionals

Working with the System

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 • Structure and routine is
essential!

• Boundaries and consistency

• Positive risk taking – offers

young person trust and
responsibility!

• Collaborative therapeutic
assessment and management

• Consistent and effective

communication between team
members and external teams!

• Balanced cautious feedback

with therapeutic optimism –
remember it can be scary to
think about being well!

Things to
Consider

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 Wellness Recovery Action
Plan (WRAP)

WRAP is a self designed prevention and wellness tool, focused on Client Decision Making
and Relapse Prevention.

WRAP focuses on 5 areas:

Daily Plan- what does well look like for you, and how do you maintain this?

Early Warning Signs- what subtle signs let you know you may be becoming unwell?

When Things are Breaking Down- What signs let you know that you are feeling much worse?

Crisis Plan- When do others know that its time to take over? What helps you to feel better?
What should others try not to do when you are unwell?

Wellness Toolbox- A list of resources and items to use when you begin to feel unwell. This
can include relaxation techniques, journal prompts, herbal tea, photos or face masks.

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Managing Crises out of hours
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Explore

Why now?

Triggers at
home/education/peer group

Substance misuse (use

toxicology if needed)

Check compliance

Self harm: the function it

serves

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 If patient manic use
Aripiprazole/Risperidone
If you need to
start
medication in
outpatient DO NOT USE:
setting Olanzapine, SSRIs,
Benzodiazepines (if
essential use long acting
ones)

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https://www.bap.org.uk/pdfs/BAP_Position_Statement_Off-
label.pdf

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To Conclude

• Bipolar Disorder diagnosis in children & adolescents is

infrequent
•

• More than 1 in 5 adults with BD reported onset of

symptoms before age 19 years

• Age of onset between 13 and 16 years

• Research suggests an unacceptable (~8 year) delay

between onset of symptoms and start of treatment

• Consider the diagnosis and assess in robust manner

• Seek a second opinion if felt necessary

 Thank
You!
Aditya.Sharma@ncl.ac.uk

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