Bipolar Flashcards
What is bipolar disorder?
A condition that affects moods, which can swing from one extreme to another.
People with bipolar disorder often have periods or episodes of:
- Depression (feeling very low and lethargic)
- Mania (feeling very high and overactive)
Describe the risk factors for bipolar?
- First degree relative with history of bipolar
- Black and minority ethnic groups
- Psychological factors such as abuse and neglect during childhood
Questionnaires should not be used in primary care to identify bipolar disorder in adults.
True or False?
True
People with bipolar disorder should have a physical health check at least annually. What does this 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 or HbA1c, and blood lipid profile
- Liver function
- Renal and thyroid function, and calcium levels, for people taking long-termlithium.
An ECG should be offered to patients under what circumstance?
- If specified in SPC
- A physical examination has identified a specific cardiovascular risk (such as hypertension)
- A family history of cardiovascular disease, a history of sudden collapse, or other cardiovascular risk factors such as cardiac arrhythmia
- The person is being admitted as an inpatient
What are the four main types of drugs used in bipolar disorder?
- Antidepressants
- Lithium
- Antiepileptics used as mood stabilisers
- Antipsychotics
What is bipolar I?
At least one manic episode with or without history of major depressive episodes
What is bipolar II?
One or more major depressive episodes
At least one hypomanic episode
No evidence of mania
Define:
1. Rapid cycling bipolar
2. Mixed bipolar state
3. Cyclothymia
Rapid cycling bipolar
- four or more episodes of mania, hypomania, depression or mixed states are experienced in a 12-month period
Mixed bipolar state
- symptoms of mania and depression are experienced at the same time
Cyclothymia
- milder form where hypomania is experienced alternating with less severe depression.
Define mania.
How is this different from hypomania?
Distinct period of abnormally and persistently elevated, expansive or irritable mood lasting at least 1 week
- Without treatment, a manic episode may last from three to six months
Severe enough to cause marked impairment in functioning or hospitalisation
Hypomania is similar to mania but less severe and does not affect day-to-day functioning to the same degree
What are the features of mania?
Includes psychotic features
At least 3 additional symptoms - increased energy, incomprehensible speech, disinhibition, extravagant plans, delusions, hallucinations
Describe the management of mania/hypomania.
- Consider stopping any antidepressants
- Can worsen outcomes in mania - Offer an antipsychotic, regardless of
whether the antidepressant is stopped
- risperidone, haloperidol, olanzapine, quetiapine
(Real Housewives Of Quetiapine are manic) - If the first antipsychotic is poorly tolerated at any dose (including rapid weight gain) or ineffective at the maximum licensed dose, offer an alternative
antipsychotic - If still not tolerated/insufficient - add lithium (off-label). If already taking lithium, check levels.
- If lithium ineffective or unsuitable - add valproate (check adherence and increase dose if already taking)
Which antipsychotics are first line in mania?
Risperidone
Haloperidol
Olanzapine
Quetiapine
(Real Housewives Of Quetiapine are manic)
Doses of antipsychotics tend to be higher in mania treatment than doses used to control schizophrenia.
True or False?
True
In addition, antipsychotics can be used in combination with benzodiazepines for severe conditions, particularly if rapid treatment by injection is required
Which anti-epileptic should not be used in mania?
Lamotrigine
What is asenapine?
What are key counselling points?
Asenapine is a second generation antipsychotic licensed for the treatment of moderate to severe manic episodes associated with bipolar disorder
Patients should be counselled in the following points:
- Sublingual tablet that should not be stored anywhere other than in the foil blister pack
- The tablet should not be removed until the patient is ready to take it
- Dry hands should be used when handling the tablet
- The tablet should not be pushed through the pack, but carefully peeled back to remove
- The tablet should be placed under the tongue and allowed to dissolve completely, which should only take a few seconds
- The tablet should not be crushed, chewed or swallowed
- No food or drink should be taken for ten minutes after the tablet has been taken
- If taking any other medicines asenapine should be taken last.
If a patient is unable to take asenapine using this method it may not be a suitable treatment because biovailability when swallowed is less than 2%
Treatment algorithm for mania/hypomania
Treatment for mania should be reviewed after how long?
Within 4 weeks of resolution of symptoms
Discuss whether to continue treatment for mania or start long-term treatment
- If continued, offer it for a further 3 to 6 months, and then review
What is bipolar depression?
Symptoms and diagnosis as with unipolar depression
What must be considered in diagnosis of depression?
If also has bipolar disorder - risk of mania with treatment
Adults who present in primary care with depression should be asked about previous periods of overactivity or disinhibited behaviour.
They should be referred for assessment if these behaviours lasted for how long?
4 days or more
Which antipsychotics are used in acute bipolar depression?
- Olanzapine AND fluoxetine
- Quetiapine
- Olanzapine alone
- Lamotrigine used last line if no response
Describe the acute management of moderate/severe bipolar depression.
Start or maximise dose of mood stabiliser
- Olanzapine AND fluoxetine 1st line / Quetiapine / Olanzapine alone / Lamotrigine used last line if no response
If already taking lithium
- Check their plasma lithium level. If it is inadequate, increase the dose of
lithium
- If lithium is at maximum level, add either fluoxetine combined with olanzapine or quetiapine (or olanzapine alone if preferred)
- If there is no response to adding fluoxetine combined with olanzapine, or adding quetiapine, stop the additional treatment and consider adding lamotrigine to lithium
If already taking valproate:
- Review their treatment including adherence and consider increasing the dose if tolerated
- If at the maximum tolerated dose, or the top of the therapeutic range for valproate, add either fluoxetine combined with olanzapine / quetiapine / olanzapine alone / lamotrigine
- Or change valproate to another treatment
Describe the long term management of moderate/severe bipolar depression.
Consider drugs used effectively in acute episodes
- Discuss with the person whether they prefer to continue this treatment or switch to lithium
Lithium is most effective
If lithium is ineffective, poorly tolerated, or is not suitable (for example, because the person does not agree to routine blood monitoring):
- Consider an antipsychotic (e.g. asenapine, aripiprazole, olanzapine, quetiapine or risperidone)
If the first antipsychotic is poorly tolerated at any dose (including rapid weight gain) or ineffective at the maximum licensed dose, consider an alternative antipsychotic
If an alternative antipsychotic is ineffective, consider a combination of valproate with: an antipsychotic or lithium
What monitoring is required for antipsychotics used in bipolar disorder? (e.g. olanzapine, risperidone, quetiapine)
- Pulse and blood pressure after each dose change
- Weight or BMI weekly for the first 6 weeks, then at 12 weeks
- Fasting blood glucose or HbA1c, and blood lipid profile at 12 weeks
- Response to treatment, including changes in symptoms and behaviour
- Side effects and their impact on physical health and functioning
- The emergence of movement disorders
- Adherence
The secondary care team should maintain responsibility for monitoring the efficacy and tolerability of antipsychotic medication for how long?
At least the first 12 months or until the person’s condition has stabilised, whichever is longer
How are lithium levels monitored?
Measure plasma lithium levels 1 week after starting lithium and 1 week after every dose change, and weekly until the levels are stable
General levels - 0.4 - 0.8mmol/L
- Check 12 hours post-dose
If being prescribed lithium for the first time:
- Aim lithium level between 0.6 and 0.8 mmol/L
If acute mania/had a previous relapse/have subthreshold symptoms with functional impairment
- Consider maintaining plasma lithium levels at 0.8 to 1.0 mmol/L for a trial period of at least 6 months
How often should lithium levels be monitored?
Measure plasma lithium level every 3 months for the first year
After the first year, measure plasma lithium levels every 6 months, or every 3 months for:
- Older people
- People taking drugs that interact with lithium
- People who are at risk of impaired renal or thyroid function, raised calcium levels or other complications
- People who have poor symptom control
- People with poor adherence
- People whose last plasma lithium level was 0.8 mmol/L or higher.
In what conditions is lithium contraindicated?
Addison’s disease, hypothyroidism and cardiac disease
What monitoring must be done for lithium?
U&Es, eGFR, TFTs, Calcium, FBC, BMI
- Every 6 months
- Increased risk of end-stage renal disease, hypothyroidism and hypercalcaemia with lithium
Monitor the person at every appointment for symptoms of neurotoxicity, including
paraesthesia, ataxia, tremor and cognitive impairment, which can occur at therapeutic levels
Name the three brands of lithium.
Are they bioequivalent?
Priadel
Camcolit
Liskonum
They are not bioequivalent. Patients should be advised to continue with the same brand once started
How is lithium cleared?
Renally
Risk of end stage kidney disease
What drugs does lithium interact with?
- NSAIDs
- If prescribed, this should be on a regular (not PRN) and the person should be monitored monthly until a stable lithium level is reached and then every 3 months - Diuretics (specifically thiazide like diuretics)
- ACE inhibitors
Give two side effects of lithium.
Fine tremor
Acneiform eruptions
What are the signs of lithium toxicity?
Coarse tremor
Diarrhoea
Vomiting
CNS disturbances
What counselling should be given to people on lithium?
- Seek medical attention if they develop diarrhoea or vomiting or become acutely ill for any reason (signs of toxicity)
- May cause them to feel thirsty and need to urinate more. Ensure they maintain their fluid intake, particularly after sweating , immobile for long periods or if they develop a chest infection or pneumonia
- May cause weight gain, which could be related to increased consumption of sugary drinks
- Can also cause a metallic taste in the mouth and a fine tremor in the hands
- Talk to their doctor as soon as possible if they become pregnant or are planning a pregnancy
- Not to take OTC NSAIDs
A purple booklet produced by the National Patient Safety Agency (NPSA) should be given to each patient starting lithium. It contains important information about taking lithium, a lithium therapy record book for recording blood plasma levels, and a lithium alert card for patients to carry with them to show healthcare professionals.
Is Lithium suitable for use in pregnancy?
Lithium is teratogenic and carries a 1 in 10 chance of congenital malformations
- Associated with a higher risk of miscarriage and cardiac abnormalities
Some of these risks may be reduced by avoiding lithium during conception and the first trimester of pregnancy, and also by close monitoring
However, these risks need to be balanced against the high risk of relapse and the harm associated with this that could affect both mother and baby . Stopping and starting lithium may worsen disease progression so it is most suitable for patients who are willing, and able, to take it on a long-term basis
How should lithium be stopped?
How long should after stopping should patients be monitored?
Reduce the dose gradually over at least 4 weeks, and
preferably up to 3 months
- Even if the person has started taking another antimanic drug
Monitor for 3 months after lithium treatment is stopped, monitor the person closely for early signs of mania and depression
Which valproate is licensed in mania?
Only semi-sodium valproate (Depakote) licensed in mania
However both sodium valproate and semi-sodium valproate used for treatment of bipolar disorder in clinical practice
Both sodium valproate and semi-sodium are metabolised to valproic acid, otherwise known as valproate, which is the active compound
What are the initial doses of valproate in mania and bipolar disorder?
Depakote (semi-sodium) in mania
- 750mg split in 2-3 divided doses
- Slightly higher dose is required for sodium valproate
Epilim Chrono
- Once daily
- May be better tolerated as lower peak plasma levels are produced compared with enteric-coated forms
- If prescribed for bipolar maintenance treatment, a lower starting dose of 500mg daily can be used and a plasma level of at least 50mg/L should be aimed for
Common side effects of valproate?
Nausea, gastric problems, tremor, anaemia, hair loss with curly regrowth, weight gain and confusion.
Valproate is contraindicated in what conditions?
Hepatic disease and porphyria
What monitoring must be done for valproate?
- Weight/BMI
- FBC
- LFT
Baseline, after 6 months of treatment and repeat
annually
Stop valproate immediately if abnormal liver function or blood dyscrasias
- It is generally accepted that if LFTs persistently
elevated to over 3 times the upper normal limit, continuing to rise or accompanied by clinical symptoms, the suspected drug should be withdrawn
- Raised hepatic enzymes of any magnitude accompanied by reduced albumin or impaired clotting
suggest severe liver disease.
What are some notable interactions with valproate?
- Anticonvulsants (particularly carbamazepine and lamotrigine)
- Olanzapine
- Smoking
What are some key valproate counselling points?
- Look out for signs of liver damage, such as jaundice, tiredness, weight loss and oedema
- ## For women who need to take valproate, highlight the importance of using contraception, treatment should be regularly reviewed, and any thoughts about pregnancy should be deliberated and planned in advance.
Valproate should not be routinely measured. True or False?
True
Unless there is evidence of
ineffectiveness, poor adherence or toxicity
What effects can be seen in a foetus of a woman taking valproate?
- Neural tube defects (Spina bifida)
- Facial dysmorphism
- Cleft lip/palate
- Cardiac, renal and urogenital defects
- Limb defects
The risk is estimated at 10% compared with 2–3% in the general population
What developmental effects can be seen in a child of a woman taking valproate?
- Developmental disorders
- Autistic spectrum disorder
- ADHD
Valproate should only be started in people (male or female) younger than 55 years under what conditions?
- Two specialists independently agree and document that there is no other effective and tolerated treatment or
- Compelling reasons that the reproductive risks do not apply
Ensure the pregnancy prevention programme is
in place if valproate is used in women and girls of childbearing potential.
Folic acid should be given to all women planning pregnancy whilst taking valproate. What is the recommended dose? How long is it continued?
5mg daily until week 12 of pregnancy
Also applies for women with:
- Family history of neural tube defects
- A previous pregnancy affected by a NTD
- If the mother has coeliac disease, diabetes mellitus, sickle-cell anaemia, or is taking antiepileptic medication
Continued past 12 weeks in sickle cell anaemia
If a woman or girl of childbearing potential is already taking valproate, advise her to gradually stop the drug under medical supervision.
True or False?
True
Because of the risk of fetal malformations and adverse neurodevelopmental outcomes
If valproate is to be continued, the lowest possible effective dose should be used, and either a controlled-release form should be prescribed or small doses taken throughout the day to avoid high peak levels
How is bipolar disorder diagnosed in children?
Under 14:
- Refer to CAMHS
14 years and older:
- refer them to a specialist early intervention in psychosis service or a CAMHS team with expertise in the assessment and management of bipolar
disorder
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
- Mania must be present
- Euphoria must be present on most days and for most of the time, for at least 7 days
- Irritability is not a core diagnostic criterion
What antipsychotic is licensed for bipolar disorder in children?
Aripiprazole
For up to 12 weeks of treatment for moderate to severe manic episodes in bipolar I disorder in young people aged 13 and older
Do not offer valproate to children unless there is no other effective and tolerated
treatment
Lithium and valproate should not be started in primary care.
True or False?
True
Only start lithium in primary care if under shared-care arrangements.
People with bipolar disorder managed solely in primary care, should be re-referred to secondary care under what conditions?
Refer to secondary care if:
- There is a poor or partial response to treatment
- The person’s functioning declines significantly
- Treatment adherence is poor
- The person develops intolerable or medically important side effects
- Comorbid alcohol or drug misuse is suspected
- The person is considering stopping any medication after a period of relatively stable mood
- A woman with bipolar disorder is pregnant or planning a pregnancy
What is the only antidepressant effective in bipolar disorder?
Why are antidepressants not generally used in bipolar disorder?
Fluoxetine
But only in combination with olanzapine
Antidepressants are only used to treat episodes of bipolar depression and not as long-term prophylaxis for bipolar disorder because there is a risk of triggering a switch to mania
What is the most effective treatment for bipolar disorder?
Lithium
If stopping treatment, how long should this take?
How long should patients be monitored after stopping?
Reduce the dose gradually over at least 4 weeks to minimise the risk of relapse
Continue monitoring symptoms, mood and mental state for 2 years after medication has stopped entirely
This may be undertaken in primary care
When is lamotrigine licensed in bipolar disorder?
Prevention of depression
What monitoring is required for lamotrigine?
FBCs, U+Es, LFTs
Plasma lamotrigine levels should not be routinely monitored unless there is evidence of ineffectiveness, poor adherence or toxicity
How is lamotrigine dosed? What about if the patient is also taking valproate?
Slow titration
- Starting at 25mg once daily for 14 days, then 50mg daily in 1–2 divided doses for another 14 days, then 100mg daily in 1–2 divided doses for a further 7 days
The usual maintenance dose may be 200mg daily in 1–2 divided doses, up to a maximum of 400mg for monotherapy
If lamotrigine is being used alongside valproate
- Slow initiation
- Starting with 25mg on alternate days for 14 days before 25mg once daily for 14 days and so on, as described above
- The maximum dose if used with valproate would be 200mg daily
Patients should contact their doctor immediately if they develop a rash whilst taking lamotrigine.
True or False?
True
May be a serious life-threatening skin rash such as Stevens-Johnson syndrome or toxic epidermal necrolysis (occurs in 1 in 1,000 patients)
Increased risk if taking alongside valproate, higher initial doses and rapid titration
When is carbamazepine used in bipolar disorder?
What are some key counselling points?
Carbamazepine is licensed for prophylaxis of bipolar disorder that is unresponsive to lithium
The usual dose is 400–600mg daily with plasma levels of between 7–12mg/l (max. 1.6g daily)
- The modified-release forms can be given once or twice daily
Counselling:
- Signs of agranulocytosis
- Serious skin reactions such as Stevens-Johnson syndrome
- Look out for symptoms of fever, sore throat, rash, ulcers in the mouth, bruising or the appearance of red or purple spots. Any of these should be reported to the prescriber immediately
Carbamazepine is contraindicated in what conditions?
Contraindicated in individuals with AV block, a history of bone marrow depression, or a history of hepatic porphyrias
Carbamazepine is metabolised by CYP3A4 and it is also a potent inducer of CYP3A4.
What drugs does this effect?
As an inducer, it reduces effect of:
- antidepressants, antiepileptics and antipsychotics, as well as antivirals, anticoagulants, CCBs, methadone, theophylline, levothyroxine, corticosteroids and oestrogens
- Women taking oral contraceptives should be prescribed products containing 50micrograms or more of oestrogen, or should be advised to use a non-hormonal method of contraceptive
The following drugs can increase carbamazepine levels:
- Antibiotics, some SSRIs, olanzapine, azole antifungals, diltiazem, verapamil and cimetidine
Carbamazepine should be avoided with which antipsychotic? Why?
Clozapine
Combined risk of agranulocytosis
How is carbamazepine managed in pregnancy?
General advice for women taking carbamazepine is similar to that with valproate:
- Inform them of the risks, discuss effective non-hormonal contraception, plan the pregnancy in advance
- Take folic acid supplementation
- Avoid all antiepileptics if it is safe to do so (if not, use monotherapy with the lowest possible dose)
Additionally, give vitamin K1 to the mother in the final weeks of pregnancy and 1mg parenterally to the neonate after delivery
What drug may be preferrable in bipolar disorder in women of child bearing potential?
Lamotrigine
Studies finding lower rates of foetal malformation when used in women with epilepsy compared with valproate
It is a useful maintenance treatment as it is licensed for prophylaxis, does not induce switching to mania or rapid cycling, and causes less weight gain than lithium
NICE recommends antipsychotics in pregnancy under what conditions?
NICE recommends antipsychotics in pregnancy when:
- Pharmacological treatment is indicated for prophylaxis
- Lithium is being stopped
- The patient develops mania
- The patient is planning to breastfeed
People with rapid cycling bipolar disorder should be offered the same interventions as people with other types of bipolar disorder.
True or False?
True
There is currently no strong evidence to suggest that people with rapid cycling bipolar disorder should be treated differently
