Management of bipolar affective disorder (mood stabilisers, anticonvulsants) Flashcards
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?
- poor medication compliance
- substance abuse
- antidepressants
- stressful life events
What is used for primary treatment of elevated mood in acute mania?
- lithium
- sodium valproate
- atypical antipsychotic- SGA
What is used for short-term management of associated behavioural disturbance in acute mania?
- BZD
- Atypical antipsychotics
- Classical antipsychotics (only if other options have failed)
- withdraw once settled
Which drugs to use?
- 1 – Olanzapine or risperidone
- 2 – haloperidol, aripiprazole, asenapine, paliperidone, quetiapine, ziprasidone, lithium, valproate, carbamazepine
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?
- antipsychotic and/or benzodiazapine for short term treatment
- Antipsychotics used for up to 6 months. May also be used as mood stabilisers
- Benzodiazepines used for days-weeks
What do we use if a patient has poor sleep in mania for short term treatment?
- temazepam 10-20mg nocte
- If ongoing agitation/elevated mood, consider benzodiazepine use short term:
- Clonazepam
- Diazepam
- Lorazepam
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 When are they withdrawn?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?
- meds that have an anti-depressant & anti-mantic properties
- effective for acute treatment of manic and/or bipolar depression
- decreases chances of having further episodes of mania or depression
- delay in onset of 1 week +
- goal is to obtain and maintain remission
What is lithium carbonate used for? what effects does it have?
- BPAD
- schizoaffective disorder
- chronic schizophrenia
- augmentation for treatment-resistant depression
- has anti suicidal effect
What is used more often and more tolerable than lithium?
- sodium valproate
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
Which drugs interact with lithium & increase lithium level… so you get toxicity?
- Loop diuretics
- Thiazide diuretics
- NSAIDs
- ACE inhibitors
- Sartans
- Theophylline
- Topiramate (high doses)
What drugs interact with lithium & decrease lithium levels… so reduce efficacy?
- Urinary alkalinisers (e.g. Ural sachets)
- Potassium citrate
- Antacids (with high sodium content)
How do we prevent 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 should we counsel lithium?
- Take with food to minimise gastric upset
- Regular blood tests are required
- Avoid dehydration- rink 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
How do we monitor effects of lithium toxicity?
- 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)
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
- used to treat aggressive behaviours
- considered 2nd line for prophylaxis but widely used
What is sodium valproate used as in 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
What are some common ADV of sodium valproate?
- GI upset
- Increased appetite
- weight gain
- tremor
- numbness
- drowsiness, ataxia
- elevated liver enymes
- thinning or hair loss
- rash
- Menstrual Irregularities (polycystic ovaries)
How do we monitor for sodium valproate? What tests do we need 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?
- 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
- phenytoin
What increases sodium valproate levels?
- Aspirin doses above 300mg increases valproate levels
- Combination also increases risk of bleeding
When is carbamezepeine 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 do we monitor for carbamezepine?
- Therapeutic range 4-12mg/L (epilepsy)
- trough level (immediately before morning dose)
- Baseline: U&Es, FBP, LFTs, pregnancy
What some ADVE 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 drug 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
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
- Sodium valproate and carbamazepine combination is associated with high rates of adverse effects
- Lithium/valproate + antipsychotic increasing in practice
- Limited clinical trial evidence
- Halve dose of lamotrigine if combining with sodium valproate to reduce risk of rash
What do you do when there is failure in response to treatment?
- Check blood level (if applicable)
- Increase dose if required
- Assess adherence with medication
- Check for substance abuse
- Implement psychological therapies
- Combine treatments
For antipsychotics that have PBS approvals for BPAD, what do each of the following do:
Asenapine (sublingual wafers)
Olanzapine (tablets, wafers)
Risperidone (liquid, tablets, consta)
Quetiapine (immediate release and XR tabs)
Zisprasidone
- Asenapine (sublingual wafers)
- Acute mania or mixed episode associated with bipolar I disorder, for up to 6 months tx
- Maintenance treatment of bipolar I disorder as monotherapy
- Olanzapine (tablets, wafers)
- Maintenance treatment of bipolar I disorder
- Injection not indicated
- Risperidone (liquid, tablets, consta)
- 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)
- Quetiapine (immediate release and XR tabs)
- Monotherapy, for up to 6 months, of an episode of acute mania associated with bipolar I disorder
- Maintenance treatment of bipolar I disorder
- Zisprasidone
- Monotherapy, for up to 6 months, of an episode of acute mania or mixed episodes associated with bipolar I disorder
