Management of bipolar affective disorder (mood stabilisers, anticonvulsants) Flashcards
1
Q
What are the management aims for BPAD?
A
- Resolution of acute symptoms
- Prevention of relapse (Individualise treatment)
- Minimise ADRs
- Encourage adherence
- Patient education
- Non-pharmacological interventions
2
Q
Why do relapses often occur in BPAD that leads to acute mania?
A
- poor medication compliance
- substance abuse
- antidepressants
- stressful life events
3
Q
What is used for primary treatment of elevated mood in acute mania?
A
- lithium
- sodium valproate
- atypical antipsychotic- SGA
4
Q
What is used for short-term management of associated behavioural disturbance in acute mania?
A
- BZD
- Atypical antipsychotics
- Classical antipsychotics (only if other options have failed)
- withdraw once settled
5
Q
Which drugs to use?
A
- 1 – Olanzapine or risperidone
- 2 – haloperidol, aripiprazole, asenapine, paliperidone, quetiapine, ziprasidone, lithium, valproate, carbamazepine
6
Q
What are the 2 steps in treating acute mania?
A
- Stop antidepressant (if taking)
- Commence mood stabiliser
- if already on mood stabilsier:
- check level
- increase the dose
- switch agents
7
Q
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?
A
- 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
8
Q
What do we use if a patient has poor sleep in mania for short term treatment?
A
- temazepam 10-20mg nocte
- If ongoing agitation/elevated mood, consider benzodiazepine use short term:
- Clonazepam
- Diazepam
- Lorazepam
9
Q
What are the 2 options of treatment of acute depression in BPAD? What is a precaution?
A
- 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
10
Q
What are some other drugs that can be used in bipolar depression?
A
- Fluoxetine + olanzapine
- Lithium monotherapy and lithium + antidepressant
- Lamotrigine
- Lurasidone (2 trials with good effect)
11
Q
What to do if there still no response to acute depression? What can antidepressants precipitate? When are they withdrawn?
A
- 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
12
Q
What is a mood stabiliser?
A
- 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
13
Q
What is lithium carbonate used for? what effects does it have?
A
- BPAD
- schizoaffective disorder
- chronic schizophrenia
- augmentation for treatment-resistant depression
- has anti suicidal effect
14
Q
What is used more often and more tolerable than lithium?
A
- sodium valproate
15
Q
What are the precautions of lithium?
A
- 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
16
Q
Which drugs interact with lithium & increase lithium level… so you get toxicity?
A
- Loop diuretics
- Thiazide diuretics
- NSAIDs
- ACE inhibitors
- Sartans
- Theophylline
- Topiramate (high doses)
17
Q
What drugs interact with lithium & decrease lithium levels… so reduce efficacy?
A
- Urinary alkalinisers (e.g. Ural sachets)
- Potassium citrate
- Antacids (with high sodium content)
18
Q
How do we prevent lithium toxicity?
A
- 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
19
Q
How should we counsel lithium?
A
- 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
20
Q
How do we monitor effects of lithium toxicity?
A
- 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)
21
Q
Why is sodium valproate given in BAD? What are some side effects?
- sodium valpoate = antiepileptic
A
- 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
22
Q
What is sodium valproate used as in first line in?
A
- generally used first line in bipolar maintenance as more tolerable than lithium
- evidence for acute mania, maintenance, and acute depression in combination with antidepressant
23
Q
Which patients should sodium valproate be avoided in?
A
- 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)
24
Q
What are some precautions for soium valproate?
A
- 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
25
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)
26
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)
27
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
28
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
29
What decreases sodium valproate levels?
* Carbamezepine
* phenytoin
30
What increases sodium valproate levels?
* Aspirin doses above 300mg increases valproate levels
* Combination also increases risk of bleeding
31
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
32
How do we monitor for carbamezepine?
* Therapeutic range 4-12mg/L (epilepsy)
* trough level (immediately before morning dose)
* Baseline: U&Es, FBP, LFTs, pregnancy
33
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
34
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
35
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
36
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
37
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
38
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
