Module 1.4.2 (Management of Bipolar) Flashcards
How is medication treatment for bipolar disorder split into 2 parts?
- Treating a current episode (acute) of mania, hypomania or depression
- Preventing the long term recurrence of mania, hypomania and depression (prophylaxis) –> mood stabiliser
For the types of medications used for bipolar disorder, what are the examples of each class of drug:
A) mood stabilisers
B) antidepressants
C) antipsychotics
D) bzd
A)
- Lithium carbonate
- Sodium valproate
- Carbamazepine
- Lamotrigine
B)
- SSRIs (e.g. citalopram, fluoxetine)
- SNRIs (e.g. venlafaxine)
- Mirtazapine
C)
- Olanzapine
- Risperidone/Paliperidone
- Quietapine
- Asenapine
D)
- Diazepam
- Lorazepam
- Temazepam
What are the management aims for BPAD?
- Resolution of acute symptoms
- Prevention of relapse (Individualise treatment)
- Minimise ADRs
- Encourage adherence
- Patient education
- Non-pharmacological interventions
Why do relapses often occur in BPAD that leads to acute mania?
Relapses often due to poor medication compliance, substance abuse, antidepressants or stressful life events
What is used for primary treatment of elevated mood in acute mania?
- Lithium
- Sodium valproate
- Atypical antispychotic
mood stabiliser with/without antipsychotic
What is used for short-term management of associated behavioural disturbance in acute mania?
Benzodiazepines
Atypical antipsychotics
Classical antipsychotics (only if other options have failed)
Withdraw ocne settld
What combination of drugs is used for acutely manic patients?
Mood stabilsier + antipsychotic
What are the 2 steps in treating acute mania?
- Stop antidepressant (if taking)
- Commence mood stabiliser
> if already on mood stabilsier:
- check level
- increase the dose
- switch agents
Mood stabilisers have delayed of onset of action of around 1 week. What medication is used to calm/sedate the patient as an interim measure?
Use an antipsychotic and/or benzodiazapine for short term treatment
- Antipsychotics used for up to 6 months. May also be used as mood stabiliser
- Benzodiazepines used for days-weeks
What to use if patient has poor sleep in mania for short term treatment?
Temazepam 10-20mg nocte
What to use if ongoing agitation/elevated mood in short term treatment of mania?
- Clonazepam –> long half-life
- Diazepam –> prone to abuse
- Lorazepam –> preferred BZD
What are the 2 options of treatment of acute depression in BPAD? What is a precaution?
- Antidepressants –> DONT USE ANTIDEPRESSANTS ALONE IN TREATMENT OF BPAD
- SSRIs. SNRIs, Mirtazapine = 1st line
- mood stabiliser/atypical antipsychotic = lithium, olanzapine, quietapine, lamotrigine good choices
-
Quietapine 300-600mg/day
* monotherapy less commonly used than antidepressant/mood stabiliser combination
What are some other drugs that can be used in bipolar depression?
- Fluoxetine + olanzapine
- Lithium monotherapy and lithium + antidepressant
- Lamotrigine
- Lurasidone (2 trials with good effect)
What to do if there still no response to acute depression? What can antidepressants precipitate? When are they withdrawn?
- Change antidepressant and/or mood stabiliser
- Medication + psychological therapies (e.g. CBT)
- Electroconvulsive therapy (ECT)
Antidepressants may precipitate manic episodes in the acute situation or provoke a rapid cycling pattern
> Ideally withdrawn within 1-2 months of successful resolution of symptoms –> long term if depressive symptoms prominent
What is a mood stabiliser? What does it decreases the chances of? How long does it take to work?
- A medication that has anti-depressant and anti-manic properties, that is effective for the acute treatment of mania and/or bipolar depression.
- Decreases the chances of having further episodes of mania or depression n
- Delay in onset of 1 week+
- Goal is to obtain and maintain remission
What is lithium carbonate inididcated for? what effects does it have?
Indicated for bipolar affective disorder (BPAD) - Also used in schizoaffective disorder, chronic schizophrenia and augmentation for treatment-resistant depression
- Antisuicidal effect
What is used more often and more tolerable than lithium?
Sodium valproate
What is the therapeutic range of lithium dosing for
A) acute mania
B) prophylaxis
A)
Therapeutic range = 0.5-1.2 mmol/L
B)
Therapeutic range = 0.4-1.0 mmol/L
small therapeutic window
Toxicity experience at levels just outside therapeutic range
Many drug interactions which can increase/decrease level
What are the precautions of lithium?
Acute hyponatraemia - increased risk of toxicity
Dehydration - increased risk of toxicity
Renal impairment - increased risk of toxicity
Elderly patients - age-related renal function decline and more sensitive to toxic effects
Psoriasis, acne - can be worsened
Common, infrequent and rare adverse effects of lithium
Common
- Headache, Fatigue, Vertigo, Acne, Psoriasis, Hypothyroidism, weight gain, thirst, polyuria, metallic taste, gi upset
Infrequent
- Diabetes insipidus, memory impairment, hair loss, hyperparathyroidism
Rare
- Cardiac arrythmias
- Hyperthyroidism
For lithium drug interactions, what increases lithium levels?
- Loop diuretics §
- Thiazide diuretics §
- NSAIDs §
- ACE inhibitors §
- Sartans §
- Theophylline §
- Topiramate (high doses)
For lithium drug interactions, what decreases lithium levels?
- Urinary alkalinisers (e.g. Ural sachets)
- Potassium citrate § Antacids (with high sodium content)
What are signs of severe toxicity where lithium level is 2.5-3 or greater mmol/L?
- Stupor - Seizures
- Spontaneous attacks of hyperextension of extremities
- Choreothetosis
What are some considerations for preventing lithium toxicity?
- Avoid dehydration – regular salt and fluid intake. Take care with major dietary changes
- Do not change sodium intake
- Avoid drinking large amounts of caffeinated drinks
- Take extra care in hot weather and during activities causing you to sweat heavily ie. hot baths, saunas & exercise
- Infection or illness that causes heavy sweating, vomiting or diarrhoea
- Some patients experience toxic symptoms within normal range
How to monitor effects of lithium toxicity? What tests needs to be done when lithium is commenced? What other tests are required?
Patients should be aware that regular blood tests are important during treatment with lithium
- Patients commencing lithium - U+E, TFT,PTH, ECG and pregnancy test
Li can cause hypothyroidism. If this occurs, often treated with Levothyroxine
- Monitor serum lithium levels 5 to 7 days after starting or changing dose
- Monitor lithium levels, U+E and TFT every 3-6 months and when clinically indicated
- Blood samples for lithium serum levels should be taken 12 hours post dose (withhold morning dose of lithium if any until blood taken)
What is some counselling information for lithium?
- Take with food to minimise gastric upset
- Regular blood tests are required
- Avoid dehydration. Drink extra fluids on hot days, after exercise (sweating), spa/sauna or after vomiting/diarrhoea
- Educate patient on symptoms of toxicity. Advise doctor if symptoms of toxicity arise (e.g. tremor, increased nausea)
- Many drug interactions. Always advise doctor/pharmacist you are taking lithium
Why is sodium valproate given in BAD? What are some side effects?
sodium valpoate = antiepileptic
Most commonly used mood stabiliser –> lithium has narrow TI and can be toxic. Also used to treat aggressive behaviours.
- take with food to reduce stomach upset
- weight gain can be problematic
What is sodium valproate used as first line in?
Generally used first line in bipolar maintenance as more tolerable than lithium
- Evidence for acute mania, maintenance, and acute depression in combination with antidepressant
Which patients should sodium valproate be avoided in?
Avoid if possible in women of childbearing potential
- Human teratogen
- If necessary, active contraception must be used (i.e contraceptive pill, injection, implant or IUD)
What are some precautions for soium valproate?
Hepatic impairment - avoid use
Surgery - check platelet count and INR before having any surgery
Pregnancy – do not use. increased risk of congenital malformations.
- Women of childbearing age must be on contraception
Lactation - safe to use at low dose
Common, infrequent and rare adverse effects of sodium valproate
common
- GI upset
- Increased appetite
- weight gain
- tremor
- numbness
- drowsiness, ataxia
- elevated liver enymes
infrequent
- thinning or hair loss
- rash
- Menstrual Irregularities (polycystic ovaries)
- Abnormal Bleeding Time
rare
- hepatic failure
- pancreatitis
- decreased white cells
- decresed platelets
- peripheral oedema
- extrapyramidal sydnrome
How to monitor for sodium valproate? What tests to do when commencing?
Patients commencing sodium valproate - FBC, LFT and pregnancy test
- A minimum of 6-monthly thereafter
Monitor serum levels 3-5 days after each dose increase
Blood samples for serum levels should be trough levels (withhold morning dose if any until blood taken)
What is the therapeutic range of sodium valproate?
Therapeutic range 50-100mg/L
- In BPAD generally aim for this level
- Can be used to monitor compliance
- Toxicity generally >125mg/L
How does lamotrigine interact with sodium valproate?
Lamotrigine
- Valproate increases lamotrigine levels, increasing the risk of potentially dangerous rashes
- If currently on valproate, start lamotrigine even more slowly
What decreases sodium valproate levels?
Carbamezepine and phenytoin
What increases sodium valproate levels?
Aspirin increases valproate levels (doses <300mg do not interact);
- Combination also increases risk of bleeding
When is carbamezepeine used?
Used when lithium/valproate is ineffective or if unpleasant side-effects are experienced
- Some evidence in rapid cycling bipolar (4 episodes of mania, depression or a combination in one year)
- not commonly used in BPAD
How to monitor for carbamezepine?
- Therapeutic range 4-12mg/L (epilepsy)
- Trough level (immediately before morning dose)
- Baseline: U&Es, FBP, LFTs, pregnancy
What are the AE of carbamazepine?
- Dizziness, diplopia, drowsiness, ataxia, nausea, headaches
- Hyponatraemia
- Rash – more common in some people Chinese, Thai origin
- Low WBC – do not use with clozapine
What are some interactions for carbamezepine?
Carbamazepine induces enzyme cytochrome P450 3A4, therefore many interactions
- Most antidepressants
- Most antipsychotics
- Benzodiazepines
- Oral contraceptive pills – increased risk of pregnancy
- Induces it’s own metabolism, dose increase required after a few weeks
- Increased risk of hyponatraemia with diuretics
- Clozapine – increased risk of agranulocytosis
When is lamotrigine used?
(expensive)
One of the few agents effective for bipolar depression
- Consider if depression a prominent feature
- Used when there has been inadequate response to existing medications
What is the AE of lamotrigine?
- Including (rarely) Stevens-Johnson syndrome
- Rashes minimised by very slow up-titration of dose
- Risk of serious rash is associated with high initial doses and exceeding dose escalations
- If a skin reaction occurs stop treatment immediately
For antipsychotics that have PBS approvals in BPAD, what do each of the following do:
A) Asenapine (sublingual wafers)
B) Olanzapine (tablets, wafers)
C) Risperidone (liquid, tablets, consta)
D) Quetiapine (immediate release and XR tabs)
E) Zisprasidone
A)
- Acute mania or mixed episode associated with bipolar I disorder, for up to 6 months treatment
- Maintenance treatment of bipolar I disorder as monotherapy
B)
- Maintenance treatment of bipolar I disorder
- Injection not indicated
C)
- Adjunctive therapy to mood stabilisers for up to 6 months, of an episode of acute mania associated with bipolar I disorder (oral)
- Maintenance treatment, in combination with lithium or sodium valproate, of treatment refractory bipolar I disorder (Constaâ)
- Can be used on its own also
D)
- Monotherapy, for up to 6 months, of an episode of acute mania associated with bipolar I disorder
- Maintenance treatment of bipolar I disorder
E)
- Monotherapy, for up to 6 months, of an episode of acute mania or mixed episodes associated with bipolar I disorder.
What to do when there is failure to respond to treatment?
- Check blood level (if applicable)
- Increase dose if required
- Assess adherence with medication
- Check for substance abuse
- Implement psychological therapies
- Combine treatments
When is combination therapy done in BPAD?
- May be beneficial when there is poor response to monotherapy n
- Lithium + valproate more effective than either agent alone n
- Sodium valproate and carbamazepine combination is associated with high rates of adverse effects n
- Lithium/valproate + antipsychotic increasing in practice n
Limited clinical trial evidence
- Halve dose of lamotrigine if combining with sodium valproate to reduce risk of rash
What are the general principles in mood stabiliser therapy?
- Everyone responds differently regarding efficacy and adverse effects
- Not a cure
- Monitor for side effects
- Monitor for signs of toxicity, reminding patients how to avoid toxicity
- Ongoing monitoring of blood levels/tests & signs of relapse
