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CNS lectures (Bal) > Module 1.4.2 (Management of Bipolar) > Flashcards

Module 1.4.2 (Management of Bipolar) Flashcards

1
Q

How is medication treatment for bipolar disorder split into 2 parts?

A
  • Treating a current episode (acute) of mania, hypomania or depression
  • Preventing the long term recurrence of mania, hypomania and depression (prophylaxis) –> mood stabiliser
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2
Q

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

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
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3
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
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4
Q

Why do relapses often occur in BPAD that leads to acute mania?

A

Relapses often due to poor medication compliance, substance abuse, antidepressants or stressful life events

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5
Q

What is used for primary treatment of elevated mood in acute mania?

A
  • Lithium
  • Sodium valproate
  • Atypical antispychotic

mood stabiliser with/without antipsychotic

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6
Q

What is used for short-term management of associated behavioural disturbance in acute mania?

A

Benzodiazepines

Atypical antipsychotics

Classical antipsychotics (only if other options have failed)

Withdraw ocne settld

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7
Q

What combination of drugs is used for acutely manic patients?

A

Mood stabilsier + antipsychotic

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8
Q

What are the 2 steps in treating acute mania?

A
  1. Stop antidepressant (if taking)
  2. Commence mood stabiliser

> if already on mood stabilsier:

  • check level
  • increase the dose
  • switch agents
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9
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

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
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10
Q

What to use if patient has poor sleep in mania for short term treatment?

A

Temazepam 10-20mg nocte

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11
Q

What to use if ongoing agitation/elevated mood in short term treatment of mania?

A
  • Clonazepam –> long half-life
  • Diazepam –> prone to abuse
  • Lorazepam –> preferred BZD
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12
Q

What are the 2 options of treatment of acute depression in BPAD? What is a precaution?

A
  1. Antidepressants –> DONT USE ANTIDEPRESSANTS ALONE IN TREATMENT OF BPAD
  • SSRIs. SNRIs, Mirtazapine = 1st line
    • mood stabiliser/atypical antipsychotic = lithium, olanzapine, quietapine, lamotrigine good choices
  1. Quietapine 300-600mg/day
    * monotherapy less commonly used than antidepressant/mood stabiliser combination
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13
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)
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14
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

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15
Q

What is a mood stabiliser? What does it decreases the chances of? How long does it take to work?

A
  • 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
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16
Q

What is lithium carbonate inididcated for? what effects does it have?

A

Indicated for bipolar affective disorder (BPAD) - Also used in schizoaffective disorder, chronic schizophrenia and augmentation for treatment-resistant depression

  • Antisuicidal effect
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17
Q

What is used more often and more tolerable than lithium?

A

Sodium valproate

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18
Q

What is the therapeutic range of lithium dosing for

A) acute mania

B) prophylaxis

A

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

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19
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

20
Q

Common, infrequent and rare adverse effects of lithium

A

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
21
Q

For lithium drug interactions, what increases lithium levels?

A
  • Loop diuretics §
  • Thiazide diuretics §
  • NSAIDs §
  • ACE inhibitors §
  • Sartans §
  • Theophylline §
  • Topiramate (high doses)
22
Q

For lithium drug interactions, what decreases lithium levels?

A
  • Urinary alkalinisers (e.g. Ural sachets)
  • Potassium citrate § Antacids (with high sodium content)
23
Q

What are signs of severe toxicity where lithium level is 2.5-3 or greater mmol/L?

A
  • Stupor - Seizures
  • Spontaneous attacks of hyperextension of extremities
  • Choreothetosis
24
Q

What are some considerations for preventing 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
25
Q

How to monitor effects of lithium toxicity? What tests needs to be done when lithium is commenced? What other tests are required?

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)
26
Q

What is some counselling information for lithium?

A
  • 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
27
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
28
Q

What is sodium valproate used as 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
29
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)
30
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

31
Q

Common, infrequent and rare adverse effects of sodium valproate

A

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
32
Q

How to monitor for sodium valproate? What tests to do when commencing?

A

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)

33
Q

What is the therapeutic range of sodium valproate?

A

Therapeutic range 50-100mg/L

  • In BPAD generally aim for this level
  • Can be used to monitor compliance
  • Toxicity generally >125mg/L
34
Q

How does lamotrigine interact with sodium valproate?

A

Lamotrigine

  • Valproate increases lamotrigine levels, increasing the risk of potentially dangerous rashes
  • If currently on valproate, start lamotrigine even more slowly
35
Q

What decreases sodium valproate levels?

A

Carbamezepine and phenytoin

36
Q

What increases sodium valproate levels?

A

Aspirin increases­ valproate levels (doses <300mg do not interact);

  • Combination also increases risk of bleeding
37
Q

When is carbamezepeine used?

A

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
38
Q

How to monitor for carbamezepine?

A
  • Therapeutic range 4-12mg/L (epilepsy)
  • Trough level (immediately before morning dose)
  • Baseline: U&Es, FBP, LFTs, pregnancy
39
Q

What are the AE of carbamazepine?

A
  • Dizziness, diplopia, drowsiness, ataxia, nausea, headaches
  • Hyponatraemia
  • Rash – more common in some people Chinese, Thai origin
  • Low WBC – do not use with clozapine
40
Q

What are some interactions for carbamezepine?

A

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
41
Q

When is lamotrigine used?

(expensive)

A

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
42
Q

What is the AE of lamotrigine?

A
  • 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
43
Q

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

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.
44
Q

What to do when there is failure to respond to treatment?

A
  • Check blood level (if applicable)
  • Increase dose if required
  • Assess adherence with medication
  • Check for substance abuse
  • Implement psychological therapies
  • Combine treatments
45
Q

When is combination therapy done in BPAD?

A
  • 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
46
Q

What are the general principles in mood stabiliser therapy?

A
  • 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

CNS lectures (Bal) (29 decks)

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