Week 8- treatment of bipolar disorder + lithium

Question 1

what is the non-pharmacotherpay for bipolar?

Answer 1

Psychological Therapies • Psychological treatments i.e. talking therapies such as psychotherapy, CBT and family therapy can be useful for some people, especially early on in treatment, when used with medicines and
perhaps in people with difficult-to-treat symptoms
• Overall CBT doesn’t seem to help to stop highs or lows in Bipolar Disorder
• Psychosocial interventions may have an important part to play. Reduces stress and helps manage
symptoms
• Psychotherapy and CBT are recommended by NICE, which takes the view that because these may help Unipolar Depression they must help Bipolar Depression too
Self-help:
• Mania is susceptible to stresses e.g. changes in time zone, irregular sleep, substance misuse

Question 2

what are some types of pharmacotherapy for bipolar, acute mania and mood stabilisation?

Answer 2

-Mood stabilisation
and relapse
prevention= aims for  Reduction in the
frequency and/or
severity of manic,
depressive and/or
mixed episodes.
-Acute hypomania/mania= aims for  Management and
harm-reduction in
manic or hypomanic
episodes
-bipolar depression= Management of acute bipolar depression.

Question 3

what are the general prescribing princles for mania?

Answer 3

• discountiue any manigenics e.g. antidepressants and stimulants
• stablise any medical conditions
• start non-specific calming medications e.g. benzodiazepines, antipsychotics
• start specific mood-stabiliser or relapse prevenation agents
• hypnotic/sedative use should be consdiered appropriate as a nigh of sleep derivation is likely to escalate any manic patient to a higher degree of mania
• substance misuse should managed

Question 4

what is quetiapine? status

Answer 4

-only drug licenced for acute bipolar depression.
 Licensed as monotherapy for
acute mania and relapse
prevention, acute bipolar
depression and relapse
prevention
  Also acute mania and relapse
prevention in people who
respond in acute state over 2
years 
 Doses and titration varies for
different indications.

Question 5

what are some base-line monitoring for quetiapine?

Answer 5

 Weight/BMI 
 Pulse
 BP
 HbA1c 
 Lipids 
 ECG if at risk

Question 6

what are the ongoing monitoring of quetiapine?

Answer 6

 Pulse & BP after each dose
change
 Weight/BMI weekly for first 6
weeks, then at 12 weeks
 Blood glucose or HbA1c 
 Blood lipid profile at 12 weeks
 Response to treatment 
 Side effects 
 Emergence of movement
disorders
 Adherence

Question 7

what are the examples of dosing for quetiapine?

Answer 7

•Mania:
•Quetiapine XL:
•300 mg on day one
•600 mg on day two
•800 mg/d thereafter, effective at
400–800 mg/d from day four 

•Depression: 
•Quetiapine XL in in bipolar
depression:
•Day 1: 50mg at bedtime
•Day 2: 100mg at bedtime
•Day 3: 200mg at bedtime
•Day 4 onwards 300mg at bedtime
•Onset of action is within one week

Question 8

what are side effects of quetiapine?

Answer 8

•Very common: 
oSleepiness oDizziness
 oDry mouth oWeight gain oPostural hypotension
•Common: 
oHeadache 
oAkathisia 
oAnticholinergic side effects

Question 9

what prescribing advice for quetiapine?

Answer 9

 Initial dose titration must be slow
due to the risk of postural
hypotension in about 10% people
•Although highly sedative at low
doses (e.g. 25mg) the sedation is not
proportional to dose
•Quetiapine XL vs Plain tabletsDependent on Trust and Patient

Question 10

whats the status for olanzapine?

Answer 10

 Licensed for mania and
relapse prevention in
people who have
responded to it acutely
and are lithium or
valproate non-responders
• Widely used as an
antimanic and as a mood
stabiliser

Question 11

what is the monitoring for olazapine?

Answer 11

 Weight/BMI 
 Pulse
 BP
 HbA1c 
 Lipids 
 ECG if at risk

Question 12

what is the formulation olanzapine comes in?

Answer 12

 Available as tablets, shortacting IM injection and
orodispersible tablet and
Depot (restricted use).
• In USA olanzapine is
available as a combination
product with fluoxetine
(Symbyax®) for bipolar
depression but not for UK

Question 13

what are the adverse effectof olanzapine?

Answer 13

• Very common:  Sedation (antihistaminic effect)  Weight gain
• Common:  Postural hypotension  Dry mouth  Constipation  Peripheral oedema  Diabetes  Long-term effects may include
weight gain, metabolic
syndrome (e.g. diabetes, plus
raised lipids and cholesterol)

Question 14

what are some interactions of olanzapine?

Answer 14

• Smoking

Question 15

what are some prescribing advice for olanzapine?

Answer 15

 Starting dose in acute mania is 15
mg/d as monotherapy or 10 mg/d
as an adjunct  Do not give benzodiazepines
within an hour of short-acting IM
olanzapine use (reports of deaths)

Question 16

hat is it the status of ariprprazole?

Answer 16

 Licensed for acute
mania and manic
relapse prevention
in people who have
responded acutely
including in
adolescents aged
13 years or older

Question 17

whats the monitoring for aripiprazole?

Answer 17

 Pulse & BP after each dose
change
 Weight/BMI weekly for first 6
weeks, then at 12 weeks
 Blood glucose or HbA1c 
 Blood lipid profile at 12 weeks
 Response to treatment 
 Side effects 
 Emergence of movement
disorders
 Adherence

Question 18

what formulations does aripiprazoe come in?

Answer 18

 Available as tablets,
orodispersible,
liquid and injection
(plus long-acting
depot injection)

Question 19

what are some adverse effects of arpiprazole?

Answer 19

•Very common: Akathisia (which can be counter-productive in
mania/hypomania)  Insomnia
 Stomach upset Constipation
Blurred vision •Common: Movement disorders (extra-pyramidal side effects) Postural hypotension Palpitations

Question 20

what are some prescribing advice for aripiprazole?

Answer 20

 For mania can start at 15mg, and increase to 30mg/d
•Relapse prevention dose can be 15-30mg/d•Due to aripiprazole’s partial agonism, start aripiprazole at 5mg/d if the person has had another antipsychotic in the
system

Question 21

what is the status of lamotrigine?

Answer 21

Licensed for prevention of relapse of
bipolar depression
No efficacy in mania, mixed, rapidcycling or unipolar depression nor acute
bipolar depression (long titration)

Question 22

what are the adverse effects of lamotrigine?

Answer 22

•Most common: Drowsiness and dizziness Headache Nausea Blurred vision •Rare but serious side effects: Oedema Bone marrow suppression
 Symptoms of unexpected bruising,
infections, and anaemia  Skin rashes- LIFE THREATENING
 Stevens-Johnson syndrome (SJS) or
Toxic Epidermal Necrolysis (TEN). Red rashes across the face and body,
blisters and inflammation in the nose,
mouth and eyes - looks a bit like
serious burning or sunburn

Question 23

what are some prescribing points for lamotrigine?

Answer 23

 Lamotrigine titration must be“by the
book”
•Starting dose must be low and slowly
titrated as per BNF
•25mg/d for 2/52,50mg/d for 2/52 ,then increase by 50-100mg/d every 1-2 weeks
•Half this if used with valproate (e.g.
25mg alternate days for 2/52, taking 6/52 to reach 200mg/d)
•This almost abolishes the risk of the
potentially rapidly fatal Stevens-Johnson Syndrome and Toxic Epidermal
Necrolysis

Question 24

what is the status for valproate?

Answer 24

 Licensed for mania and
relapse prevention  Depakote® and Episenta® are licensed for bipolar
disorder  Epilim is available in
tablets, Prolonged release
tablets and liquid

Question 25

what are the monitoring for valproate?

Answer 25

• Baseline:  Height, weight, FBCs, LFTs  Blood cell count, including platelet count, bleeding time and coagulation before treatment starts then during first 6 months  LFTs before starting, then over next 6/12 • On-going Monitoring:  LFTs and FBCs at 6 months

Question 26

what are the formulations and dosing of valproate?

Answer 26

```  Oral loading doses are of valproate are more rapidly effective in mania, e.g. 20 mg/kg/d may give a rapid response, often within three days  Maintenance dose not established  Epilim is available in tablets, Prolonged release tablets and liquid ```

Question 27

what are the adverse effects of valproate?

Answer 27

• Very common:  Increase in appetite and weight gain • Common  Gastric irritation, diarrhoea  Hair loss –  Nausea • Uncommon  Sleepiness  Impaired liver function • Rare but serious:  Thrombocytopenia and impaired platelet function  Hepatic dysfunction – in first 6/12  Pancreatitis - abdominal pain, nausea, vomiting  PCOS

Question 28

what are some interactions of valproate?

Answer 28

Carbapenem antibiotics (reduced valproate levels) Lamotrigine (variable effect): 34% have a > 25% increase in valproate levels 14% have an increase of > 50% in valproate levels. 5% have a > 25% decrease in valproate levels

Question 29

what are some patient and carer advice for valproate?

Answer 29

• Valproate use by women and girls • Pregnancy Protection Programme ( next slide) • The MHRA advises women and girls should not stop taking valproate without first discussing it with their doctor. • Blood or hepatic disorders • Recognise signs and symptoms of blood or liver disorders and advised to seek immediate medical attention • Pancreatitis • recognise signs and symptoms of pancreatitis and advised to seek immediate medical attention

Question 30

what is the main caution for valporate use?

Answer 30

-The UK has now imposed a ban on prescribing valproate for any female of childbearing potential UNLESS there is no alternative and the woman is on the UK “Pregnancy Protection Programme” (PPP)

Question 31

what are the consequences if valproate is prescribed to someone of childbearing age?

Answer 31

If Valproate is taken during Pregnancy • up to 4 in 10 babies are at risk of developmental disorders • approximately 1 in 10 babies are at risk of birth defects • An increased risk of autistic spectrum disorder (approximately three-fold) and childhood autism (approximately five-fold) • Delayed development, such as talking and walking, low intellectual abilities, poor language skills, and memory problems.

Question 32

what are the options for managment for Women Of Childbearing Potential and Prescribed Valproate?

Answer 32

1.Stop valproate, gradually 2.Switch to another medicine 3.Continue valproate and become part of the “Valproate Pregnancy Prevention Programme”, but only if valproate is for epilepsy, and there is no alternative

Question 33

what must women Prescribed Valproate do?

Answer 33

 Discuss with a doctor or family planning clinic to get professional information and advice on effective contraception• Rapidly consult Dr if a pregnancy is planned or is confirmed  Have a Valproate Annual Risk Acknowledgement Form, where everything should be explained, with a signed document. • Get a Patient Guide from the prescriber• Carry a Patient warning card

Question 34

what are some treatments that can be used ?

Answer 34

``` • The use of antidepressants in bipolar depression is common and logical (based on the symptoms) but lacks an evidence base: • There is a potential for switching to mania • If used, antidepressants can be safeif combined with a mood stabiliser • Accelerated episode frequency is considered possible ``` * Carbamazepine * Haloperidol * Risperidone * Benzodiazepines