bipolar disorder in practice

Question 1

what is bipolar affective disorder?

Answer 1

A chronic relapsing and remitting disorder
• Abnormally elevated mood or irritability alternates with depressed mood
• In most cases depressive episodes are more frequent than manic ones

Question 2

what is BPAD associated with?

Answer 2

BPAD is associated with poor physical health and drug treatments can add to this

Question 3

what does NICE recommend for a patient with BPAD each year?

Answer 3

NICE recommends a physical health check at least annually for people with bipolar disorder, to include
– weight or BMI
– diet
– nutritional status and level of physical activity;
– cardiovascular status, including pulse and blood pressure;
– metabolic status, including fasting blood glucose, HbA1c, prolactin, blood lipid profile, liver function.
– If prescribed lithium also renal function/TFTs and calcium levels

Question 4

what is done if there is suspected bipolar disorder?

Answer 4

People with suspected bipolar disorder are all
referred to specialist mental health services
• Advice before any medication changes while
awaiting assessment

Question 5

how is treatment determined?

Answer 5

determined by the phase of illness and subtype of disorder
• Individual variation in response to medication will often determine the choice of drug, as will;
– age
– side effects
– interactions and associated cautions
– child-bearing potential
– previous history
– medical comorbidities
– individual preferences

Question 6

how would you manage acute hypomania?

Answer 6

• Assessment of patient
– Triggers, Medication adherence 
• Consider withdrawing any existing
– Antidepressant therapy
– Stimulants
• If not currently prescribed an antipsychotic or mood stabiliser
initiate 
• If already taking lithium, check plasma levels and optimise. 
Consider adding antipsychotic. 
 Short term use of benzodiazepine can be considered for severe agitation ( 
concern over dependence and withdrawal)
• Psychotherapy

Question 7

what antispychotic/ mood stabliser would you give for acute hypomania?

Answer 7

– Haloperidol, olanzapine, quetiapine, risperidone
– If poorly tolerated or ineffective at max licensed dose, select alternative
– If not sufficient consider adding lithium or if not suitable valproate (see
pregnancy prevention programme later in lecture)

Question 8

when should long term treatment for hypomania be discussed?

Answer 8

Long-term treatment should be discussed within 4 weeks of resolution of symptoms following acute treatment.

Question 9

how would you treat long term hypomania?

Answer 9

If appropriate, treatment for acute episodes can continue for a further 3–6 months, and then should be reviewed

Question 10

what are the agents that are NOT recommended for use in mania?

Answer 10

 Antidepressants (induce mania)
 Lamotrigine (bipolar depression)
 Gabapentin, topiramate
 Carbamazepine + antipsychotics metabolized primarily by CYP3A4 (interaction)

Question 11

what treeatment is recommended for bipolar depression?

Answer 11

Antidepressant monotherapy NOT recommended
– NICE recommends fluoxetine + olanzapine
– Atypical antipyschotic e.g. olanzapine,quetiapine
– Consider Lamotrigine if no response to above

Question 12

what should be avoided in the treatment of bipolar depression?

Answer 12

– Tricyclic antidepressants and venlafaxine avoided

Question 13

what should be discussed within 4 weeks of resolution of symptoms of bipolar depression?

Answer 13

iscuss with patient whether to continue psychological or pharmacological treatment for bipolar depression or start long-term treatment
• If continued offer for further 3-6 months then review
– Discontinuation recommended to reduce risk of switching to mania

Question 14

what treatment should be used for long-term management of bipolar depression?

Answer 14

• Prophylaxis indicated
– after manic episode with significant risk
– 2 or more acute episodes bipolar I disorder
– Significant functional impairment or suicide risk
• First line tx lithium, valproate* or olanzapine
• Second line tx
– Lamotrigine (as adjunct) or carbamazepine
• Tx continued at least 2 years after episode
• Reduce treatments gradually on withdrawal

Question 15

what must stay the same when prescribing lithium?

Answer 15

Lithium MUST be prescribed by NAME and BRAND
• Should not be initiated in primary care without specialist advice
Secondary care or shared care

Question 16

how long of a trial is needed for lithium?

Answer 16

at least a 6 month trial to est efficacy

Question 17

what therapeutic effects does lithium have?

Answer 17

– Acute mania
– Prophylactic agent for mania and depression
– Antidepressant properties

Question 18

what is first line to treat bipolar depression to prevent relapse?

Answer 18

lithium

Question 19

how long should lithium monitoring occur?

Answer 19

t least every 6 months during treatment

more frequently in early stages of treatment

Question 20

what do you monitor with lithium?

Answer 20

• Serum electrolytes
• eGFR
• Body-weight/BMI/waist 
circumference/lipids
• Thyroid function 
• Calcium levels
• (Also monitor FBC on initiation plus ECG 
if cardiac risk factors)

Question 21

how often do you monitor lithium?

Answer 21

Therapeutic drug monitoring (lithium levels) at least every 3-6 months
• initially weekly
• Additional tests if concerns e.g. signs of toxicity
• Additional test 5-7 days after every dose change or starting/stopping
interacting drugs

Question 22

when should you take lithium levels?

Answer 22

Take levels 12 hours post dose (10-14 hrs probably OK in practice)

Question 23

what are the lithium levels for initial treatment?

Answer 23

– Lithium levels for initial treatment
• 0.6-0.8 mmol/L
• 0.8–1.0 mmol/L

Question 24

who is the higher range of lithium levels suitable for?

Answer 24

The higher range above suitable for people who have relapsed
previously while taking lithium or who still have sub-threshold
symptoms with functional impairment while receiving lithium

Question 25

what levels indicate lithium toxicity?

Answer 25

toxicicty more common in lithium levels>1.5mmol/L

Question 26

what are the side effects of lithium?

Answer 26

• Fine tremor
• Sedation
• Impaired co-ordination
• GI disturbances
• Polyuria, polydipsia
• QT prolongation
• Longer term effects
– Weight changes
– Thyroid disorders
– Hyperparathyroidism
– Renal impairment

Question 27

what are the signs of lithium toxicity?

Answer 27

• Lack of appetite , diarrhoea and 
vomiting
• Blurred vision
• Marked tremor 
• Unsteadiness , slurred speech 
• Drowsiness and confusion
• At levels > 2mmol/L: 
– muscle twitches 
– more severe drowsiness and 
confusion
– Convulsions 
– unconsciousness

Question 28

what are the main interactions with lithium?

Answer 28

• Generally anything that impacts on renal 
function or sodium levels
–Diuretics
–NSAIDs
–ACE inhibitors
–Antidepressants (serotonin syndrome)
• Carbamazepine
• Haloperidol

Question 29

are lithium tablets are liquid interchangable?

Answer 29

• Liquid and tablets are not interchangeable
• Dose conversion
• Lithium carbonate = tablets
• Lithium citrate = liquid
• 200mg tablets = 509mg liquid
• 204mg tablets = 520mg liquid

Question 30

what should the lithium starter pack entail?

Answer 30

info

booklet, alert card, record book for tracking serum-lithium concentration.

Question 31

how should a patient be counselled on lithium?

Answer 31

Take lithium every day. Try not to miss any doses.
• To carry a lithium card at all times
• Advise patient that each time they collect prescription check the brand is the
same as usual
• Tell pharmacist before buying any OTC products or supermarket medications
• Maintain adequate fluid intake to avoid dehydration
• Avoid dietary changes that reduce or increase sodium intake
• Will need to have regular blood tests- dose may be adjusted
depending on the results of the blood tests.
• Check before taking other medications..–OTC and prescribed
e.g. nonsteroidal anti-inflammatory drugs
• Women of childbearing age should be advised to use reliable
contraception.
• Managing missed doses
• Common side effects, such as dry mouth or metallic taste in
mouth, feeling thirsty, weight gain, fluid retention. Try to drink
low calorie drinks to avoid weight gain.
recogise signs of toxicity
seek medical advise if become dehydrated

Question 32

what are some important practial points for lithium for the pharmacist?

Answer 32

Usually given at night (trough serum lithium level can
be taken in the morning 12 hrs post dose)
• If twice daily dosing- morning dose should be taken
after taking lithium level to avoid high readings
• Patients admitted to hospital on lithium –check bloods
• Ensure additional blood tests if signs of renal
impairment, toxicity etc
• Check lithium book and ensure kept up to date
• Be vigilant for drug interactions and signs of toxicity
• Patient education/supporting adherence

Question 33

what is valporate used for?

Answer 33

–Acute mania

–Prophylactic agent

Question 34

what is valporate available as?

Answer 34

sodium valproate,

valproic acid, semi-sodium valproate.

Question 35

what are semisodium and sodium valporate metabolised to?

Answer 35

valproic acid, which is responsible for

the pharmacological activity of all three preparations

Question 36

what is an important point to tell women of child bearing age when on valporate?

Answer 36

– To be provided with a patient card every time valproate is dispensed
– For valproate to be dispensed with a copy of the PIL , and if repackaged, with a warning on the container supplied as well
– To be reminded of the risks in pregnancy and the need for highly effective contraception, and a reminder of the need for annual specialist review
– To be asked if they have received the patient guide

Question 37

what are the side effects of valporate?

Answer 37

– Weight gain
– GI irritation
– Blood disorders
– Impaired Liver function
– Pancreatitis
– Fatigue, nausea, sedation, hair loss
– Risk of suicidal thoughts
– Tetatogenic

Question 38

what interactions occur with valporate?

Answer 38

Highly protein bound (up to 94%), therefore may be displaced
from albumin precipitating toxicity
• Other less strongly protein-bound drugs (e.g. warfarin) can be
displaced by valproate; this may lead to higher free levels and
increased therapeutic effect or toxicity of the concomitant
drug.
• Valproate is metabolized by the liver, so drugs that inhibit
cytochrome P450 enzymes can increase valproate levels.

Question 39

what is the preferred treatment option for acute mania?

Answer 39

Olanzapine, quetiapine,

aripiprazole

Question 40

what is the longer term effects of atypical antipsychotics?

Answer 40

– Weight gain
– Dyslipidaemia
– Hyperprolactinaemia
• may lead to galactorrhea, amenorrhoea, gynaecomastia, hypogonadism, sexual dysfunction, and an increased risk of osteoporosis. 
– Hypertension
• A small, steady increase in blood pressure over time (may be associated with weight gain), or
• An unpredictable, sharp increase in blood pressure on starting a new drug.
– Reduced seizure threshold
– Impaired glucose tolerance 
– QT interval prolongation
– Stroke risk 
– Venous thromboembolism (VTE)

Question 41

what is lamotrigine licensed in the UK for?

Answer 41

for prevention of depressive disorders in bipolar I disorder but not for treatment of acute manic or depressive episodes

Question 42

what are the side effects of lamotrigine?

Answer 42

– Skin rashes
• Must be promptly evaluated and lamotrigine withdrawn immediately unless the rash is clearly not drug related.
– Headache, dizziness, nausea, drowsiness, insomnia
– Blood disorders (rarely)
– Small risk of suicidal thoughts and behaviours

Question 43

what interactions are there with lamotrigine?

Answer 43

– Plasma concentration of lamotrigine is reduced by phenytoin, primidone, carbamazepine, oestrogens, and progestogens.
• The dose of lamotrigine may need to be increased.
– Plasma concentration of lamotrigine is increased by valproate.

Question 44

what are some non pharmacological interventions for bipolar disorder?

Answer 44

• Patient education
– Coping strategies
• Regular routine & sleep hygiene
• Detecting early warning symptoms
– Concordance with medication & blood monitoring
• Cognitive Behavioural Therapy
– Individual or group
• Psychosocial support
• ECT Therapy
– Limited use
– Severe bipolar unresponsive to multiple medications