Treatment for Bipolar

Question 1

What are some of the psychological interventions for bipolar?

Answer 1

This can include psychotherapy, CBT and family therapy for patients early on with treatment or hard to treat symptoms.

Question 2

Are psychological interventions helpful?

Answer 2

Ultimately they do not stop the highs and lows associated with bipolar, but interventions like psychosocial support and talk therapies alongside medication can help to reduce relapse and stress management which mania is susceptible to.

Question 3

What are the three categories for pharmacotherapy for bipolar?

Answer 3

Treatments aimed at:
- Mood stabilisation and relapse prevention
- Acute hypomania/mania
- Bipolar depression

Question 4

Which medications should be stopped if mania occurs?

Answer 4

Discontinue any manicogenic agents such as anti-depressants and psychostimulants

Question 5

What are some important considerations about prescribing in bipolar regarding anti-depressants?

Answer 5

Medications for bipolar should be adjusted specific to the patient and the symptoms which they are experiencing.
For example if they are suffering with severe bipolar depression they must be on a mood stabiliser that either has cover for bipolar depression (Quetiapine) or used a combination of a mood stabiliser such as Olanzapine alongside an antipsychotic.
Also there will be people believed to have unipolar depression that have just never experienced a psychotic episode before.
Additionally if a person develops mania or hypomania and is taking an antidepressant (as defined by the BNF) in combination with a mood stabiliser, consider stopping the antidepressant.

Antidepressants should always be stopped within a stepwise manner and not suddenly.

Question 6

Which medications should be started in mania?

Answer 6

Begin with non-specific calming medications such as benzodiazepines
Start a specific mood stabiliser or relapse prevention agent
Consider hypnotics/sedatives

Question 7

What other considerations should be made if a patient is in acute mania?

Answer 7

Tackle any underlying/stabilise medical conditions and co-morbid substance misuse as recovery is poorer in people with a history of substance misuse.

Question 8

What are the first line medications used for bipolar?

Answer 8

Lithium
Valproate
Olanzapine
Quetiapine
Aripiprazole

Question 9

Which drug is often used first line for bipolar?

Answer 9

Usually Quetiapine as it is the only drug licensed for acute bipolar (mania/hypomania) and relapse prevention in addition to bipolar depression acute and relapse prevention.

It states Lithium is as well but I think is only used as an add on/failure of multiple mood stabilisers.

Question 10

What are the second line medications for bipolar?

Answer 10

Carbamazepine
Risperidone
Asenapine
Benzodiazepines (although can be used acutely? not for long term)
Haloperidol
Lurasidone
Anti-depressants

Apart from Carbamazepine most of these medications have no licensing for bipolar depression and only a few have licensing for acute bipolar so they are used less frequently.

Question 11

When may you consider a combination of fluoxetine and olanzapine?

Answer 11

If a person develops moderate or severe bipolar depression and is not taking a drug to treat their bipolar disorder. However the patient may be able to, if they prefer take Olanzapine on its own. Symbax is licensed within the US but not in the UK.

Question 12

What is the baseline monitoring for Quetiapine?

Answer 12

As a second generation anti-psychotic due to the link with metabolic syndrome the following monitoring is required:

Weight
Pulse
Blood pressure
HbA1c
Lipids
ECG risk (QT prolongation)

Plasma levels of Quetiapine are not required for bipolar

Question 13

What is the ongoing monitoring required for Quetiapine?

Answer 13

After each dose change:
Pulse and Blood pressure after each dose change

Weekly for the first six weeks and then every 12 weeks:
Weight, BMI

At 12 weeks:
Blood glucose, HbA1c
Side effects, emergence of movement disorders - Parkinsonism
Adherence

Question 14

What is an example of dose titrations for Quetiapine?

Answer 14

Quetiapine XL for mania
Day 1: 300mg
Day 2: 600mg
Then 800mg the day thereafter

For depression:
Day 1: 50mg at bedtime
Day 2: 100mg at bedtime
Day 3: 200mg at bedtime
Day 4 onwards: 300mg at bedtime

If used standard release the dosing will be twice daily.

Question 15

What are two key side effects to take into consideration regarding Quetiapine therapy?

Answer 15

The initial dose titration must be slow due to risk of postural hypotension which occurs within 10% of patients.
Furthermore sedation is not proportional to dose.

Question 16

When is Olanzapine used?

Answer 16

In the treatment of mania and relapse prevention (again doesn’t have the bipolar depression cover) for patients who have responded to it acutely and for Valproate and Lithium non-responders.

Question 17

What are the monitoring requirements/side effects of Olanzapine?

Answer 17

As a second generation antipsychotic the monitoring is the same as Quetiapine and similar side effect profile - antagonist at 5-HT, anticholinergic, metabolic disorders etc.

Question 18

What are some key interactions with Olanzapine?

Answer 18

Smoking induces the CYP1A2 enzyme, leading to reduced levels of olanzapine, clozapine, and other drugs metabolized by CYP1A2, if stopped this can lead to toxic levels of Olanzapine accumulating.
Also don’t give a benzodiazepine within one hour of a short acting intramuscular injection as there is an increased risk of death.

Question 19

When is Aripiprazole used?

Answer 19

In acute mania and relapse prevention in people who have responded to it acutely including adolescents aged over 13 years.

Question 20

What is a key side effect associated with Aripiprazole which limits its use in mania/hypomania?

Answer 20

A very common side effect associated with Aripiprazole is akathisia (inability to remain still) which occurs at the beginning and is counter productive within acute mania.

Question 21

Why is it important to take Aripiprazole in the morning?

Answer 21

As it is associated with insomnia and therefore important to take in the morning, as poor sleep can precipitate mania.

Question 22

What are the most common side effects associated with Aripiprazole?

Answer 22

Very common:
Akathisia
Insomnia
GI - constipation, blurred vision, stomach upset

Common:
Movement disorders
Postural hypotension
Palpitations

Question 23

What is an important consideration regarding Aripiprazole if switching anti-psychotic?

Answer 23

Aripiprazole has partial agonism at dopamine receptors so if the patient has just been discontinued on another antipsychotic begin Aripiprazole dose at 5mg/day rather than 15mg as if dopamine is decreased to only 5% of the usual activity, Arirpipirazole will increase this to 30% by displacing other anti-psychotics.

Question 24

What is Lamotrigine licensed for?

Answer 24

Only for the prevention of relapse of bipolar depression, it has no efficacy for other indications within bipolar.

Question 25

What are the most common side effects associated with Lamotrigine?

Answer 25

Drowsiness/Dizziness Headache Nausea Blurred vision Rare but serious side effects: Oedema Bone marrow suppression Steven Johnson syndrome/Toxic epidermal necrolysis Red rash/blisters across the face

Question 26

How is the risk associated with fatal skin rashes mitigated with use of Lamotrigine?

Answer 26

Dosing regimen should be: start low, go slow 25mg/day for two weeks followed by 50mg/day for two weeks then increase by 50-100mg/day every 1-2 weeks

Question 27

If used alongside Valproate how does this change the dosing requirements?

Answer 27

The dosing regimen should be halved - slower and lower dose should be used such as six weeks to reach 600mg/day

Question 28

When is Valproate licensed?

Answer 28

Valproate is only licensed for mania and relapse prevention.

Question 29

What is an important consideration regarding the brands of Valproate?

Answer 29

Only Depakote and Episenta is licensed for bipolar disorder. Depakote which is semi-sodium valproate is only licensed for bipolar and not for epilepsy.

Question 30

What is the baseline monitoring for Valproate?

Answer 30

Height and weights FBC LFTs Clotting screening · including bleeding time and coagulation tests Pregnancy test

Question 31

What is the ongoing monitoring required for Valproate?

Answer 31

LFTs should be continued until stable. Raised liver enzymes are usually transient- lasting only a short time but should be monitored closely At 6 months, then annually Body mass index Full blood count Liver function tests If toxicity is suspected request plasma levels of valproate

Question 32

What is the dosing regimen for Valproate?

Answer 32

Oral loading doses of Valproate is more recommended in mania which is usually 20mg/kg a day with rapid onset, often within 3 days

Question 33

What are some of the very common/common side effects of Valproate?

Answer 33

Weight gain Gastric irritation Diarrhoea Nausea Sleepiness although not very common

Question 34

What are some of the rare but serious side effects associated with Valproate?

Answer 34

Thrombocytopenia, impaired platelet function Hepatic dysfunction which usually occurs within the first six weeks Pancreatitis which presents as abdominal pain, nausea, vomiting PCOS

Question 35

What are the key interactions with Valproate?

Answer 35

Lamotrigine affects Valproate levels and Carbapenems (antibiotics) reduces Valproate levels.

Question 36

What are some of the key counselling advice for Valproate?

Answer 36

Advise on the signs and symptoms of liver toxicity, blood disorders and pancreatitis. Valproate, like with its indication for epilepsy cannot be initiated without being signed by two independent specialist for both men and women under the age of 55 where there is no other effective or tolerated treatment. If of child bearing potential patients should be initiated onto the pregnancy prevention programme- involving highly effective contraception which is either: Copper or Levonorgestrel IUD Progesterone implant Male/female sterilisation Or CHC patch, pill, vaginal ring or medroxyprogesterone injection used alongside a barrier method. A risk acknowledgement form must be signed annually and patients should receive a guide/warning card

Question 37

What is the risks of Valproate use in men?

Answer 37

Infertility, which is reversible upon reduction/withdrawal Testicular toxicity which is greater in males under 55

Question 38

When is Carbamazepine used?

Answer 38

Second line treatment for acute mania and relapse prevention and for bipolar depression in Lithium non-responders but has limited efficacy

Question 39

What are some of the key interactions with Carbamazepine?

Answer 39

It is a CYP 3A4 inducer and therefore has key interactions associated with COC, TCA and Anthramycin Again can cause Steven Johnson syndrome and therefore plasma levels may need to be checked

Question 40

When is Haloperidol often used?

Answer 40

In acute mania or hypomania, frequently used alongside benzodiazepines as it comes in the IM formulation (rapid tranquilisation)

Question 41

When is Risperidone used?

Answer 41

As monotherapy of bipolar mania 1-6mg to be used daily Lack of sedation and slow titration

Question 42

Golden three medications for acute mania?

Answer 42

Anti-psychotics and/or mood stabiliser and benzodiazepines for quicker onset and are more effective short term.

Question 43

Which antipsychotics are mood stabilisers?

Answer 43

Haloperidol FGA Quetiapine SGA Risperidone SGA Olanzapine SGA

Question 44

What is the importance of mood stabilisers?

Answer 44

Reduce the risk of mood switching from depression to mania. They do what their name says they stabilise mood. Think mood stabilisers have the cover of both - cover mania and depression. Anti-depressants only cover depression and therefore there is a risk of mania.

Question 45

Which medications can be used for bipolar depression?

Answer 45

Either: Mood stabilisers alone, Mood stabilisers with anti-depressant or Lamotrigine and anti-depressant Lamotrigine Sodium Valproate Lithium Quetiapine Risperidone Olanzapine Any combination can be used for relapse prevention

Question 46

What is the appropriate amendments for bipolar prescribing in pregnancy?

Answer 46

Mood stabiliser is discontinued, risk of relapse is higher There no mood stabilisers totally safe in pregnancy and therefore there is a risk to the mother, baby or neonate Choice is between the patient and prescriber but Lithium and AEDs have the greatest risk

Question 47

What is the appropriate amendments for prescribing in hepatic impairment?

Answer 47

Majority of anti-psychotics are metabolised by the liver except amasolphadride/solphadride AEDs must be taken into consideration/dose adjustments made

Question 48

What is the appropriate amendments for prescribing in renal impairment?

Answer 48

Avoid Lithium Avoid amasolphadride/solphadride Take care with Lamotrigine

Question 49

When is Lithium indicated?

Answer 49

Prophylaxis against bipolar disorder Management of acute mania/hypomania episodes must have previously responded and symptoms are not too severe Recurrent depression Control of aggressive behaviour/intentional self-harm

Question 50

What are some of the disadvantages associated with Lithium therapy?

Answer 50

Whilst Lithium is actually the most effective treatment option it is not used as frequently due to the extensive blood monitoring which is required. Furthermore in mania there is delayed onset of 5-7 days for the medication and higher levels are required- it is difficult to conduct blood monitoring when the patient is disturbed.

Question 51

What is the mechanism of Lithium?

Answer 51

Although not fully understood it is believed to modify the production and turnover of certain neurotransmitters particularly serotonin, may also block dopamine receptors.

Question 52

Why is it important to maintain the same brand of Lithium?

Answer 52

Different brands and formulations of lithium are not bioequivalent and care must be taken to make sure that the patient receives the same preparation each time a prescription is supplied.

Question 53

What is the Priadel MR tablets and Priadel liquid dose conversion?

Answer 53

Not bioequivalent: For Priadel® liquid: Lithium citrate tetrahydrate 520 mg is equivalent to lithium carbonate 204 mg.

Question 54

What are some of the contraindications to Lithium therapy?

Answer 54

Hypersensivity to Lithium Cardiac disease Cardiac insufficiency (both due to QT prolongation) Severe renal impairment - excretion Untreated hypothyroidism Breastfeeding Patient with low body sodium dehydrated or on a sodium restricted diet) Addison's disease Brugada syndrome which is a hereditary disease or the cardiac sodium channels

Question 55

When is use of Lithium cautioned?

Answer 55

Avoid in pregnancy unless there are exceptional circumstances Renal impairment ECT or other medications that lower epileptic threshold QT prolongation or a patient taking concomitant medications causing QT prolongation

Question 56

Why is use of Lithium advised to be avoided in pregnancy?

Answer 56

Should be avoided particularly within the first trimester due to causing heart defects. Dose requirements increased during the second and third trimesters (but on delivery return abruptly to normal).

Question 57

What is the baseline monitoring for Lithium?

Answer 57

Body weight or Body mass index Cardiac function · especially in patients with cardiovascular disease or at risk who may require ECG. Estimated glomerular filtration rate Full blood count Serum calcium )predispose Lithium toxicty) Thyroid function tests · patients should be euthyroid before initiation Urea and electrolytes

Question 58

What is the ongoing monitoring requirements for Lithium?

Answer 58

At one week; then weekly until levels stable; then every 3 months for first year Lithium levels · take sample just prior to time of next dose (i.e. trough level 12 hours following last dose) Ongoing once stable: Every 3 - 6 months Lithium levels 6 monthly: Body weight or Body mass index Estimated glomerular filtration rate Serum calcium Thyroid function tests Urea and electrolytes

Question 59

Which patient groups are considered high risk that require ongoing 3 monthly monitoring?

Answer 59

Age 65 years and older Taking drugs that interact with lithium Risk of impaired renal function: e.g. eGFR declines over two or more tests; or urea and creatinine elevated At risk of impaired thyroid function Raised calcium levels or other complications Significant change in a patient’s sodium or fluid intake Have poor symptom control or poor adherence The last serum-lithium concentration was 0.8 mmol/litre or higher (Norfolk Lithium database this is 1 Lithium level above 1mmol/L)

Question 60

What is the ideal Lithium range?

Answer 60

Between 0.4 to 1 mmol/L with the aim of 0.8 mmol/L for mania

Question 61

What is the dosing for Lithium?

Answer 61

It is individualised based upon the clinical response and titrated according to serum levels however usual starting dose is: 200mg in the elderly and 40mmg in adults Maintenance is usually 400-1.2 grams daily with dose reduction with those with hepatic impairment and patients under 50kg.

Question 62

What are some of the side effects associated with Lithium therapy?

Answer 62

Upset stomach usually at the start of treatment Fine tremor of the hands Metallic taste within the mouth Swelling of the ankles which requires dose reduction Increased thirst and urine output, can cause renal impairment Weight gain of up to 27kg

Question 63

At what levels does Lithium toxicity occur?

Answer 63

Blood concentration over 1.5 mmol/L might be fatal Over 2.0 mmol/L requires urgent medical attention

Question 64

What are some of the symptoms associated with Lithium toxicity?

Answer 64

Severe hand tremor Muscle weakness Stomach ache with nausea and diarrhoea Unsteady on feet Slurring of words Blurred vision Confusion Unusually sleepy Muscle twitches

Question 65

What are some of the signs of severe Lithium toxicity?

Answer 65

Convulsions Coma Renal/circulatory failure Hyperreflexia Toxic psychosis

Question 66

What are some of the key drug interactions that increase Lithium levels?

Answer 66

ACE inhibitors and ARBs NSAIDs COX-2 inhibitors Metronidazole SSRIs Diuretics and aldosterone antagonists

Question 67

If diuretics need to be used which are the best to use?

Answer 67

Bumetanide/Furosemide are the least risky whereas thiazide diuretics have the highest risk

Question 68

Which drugs decrease Lithium levels?

Answer 68

Sodium bicarbonate Caffeine

Question 69

What are some of the other key interactions regarding Lithium therapy?

Answer 69

When used with Amiodarone ventricular arrhythmias can occur Increased risk of neurotoxicity when used alongside Methyldopa and some antipsychotics

Question 70

How does sodium depletion influence Lithium levels?

Answer 70

Causes increased Lithium levels due to competitive reabsorption renally. Monitor patients for: Dehydration Changes in salt level in the diet Infection Vomiting and diarrhoea

Question 71

How long does Lithium therapy take to work?

Answer 71

Usually takes six months for patients to be fully established on Lithium and the minimum duration is between 2-3 years

Question 72

What happens if the patient stops taking Lithium suddenly?

Answer 72

Increased risk of suicide, if it is agreed between a healthcare professional and the patient that Lithium will be stopped it is normally done over 4 weeks but can be up to six months.

Question 73

What are the key counselling points regarding Lithium for patients?

Answer 73

Lithium should be taken once daily at night in order to minimalise the renal damage Do not stop taking the medication suddenly Seek medical attention if you have vomiting/diarrhoea Do not take OTC NSAIDs Must attend regular monitoring of Lithium level Warn of signs of Lithium toxicity Ensure fluid intake is maintained

Question 74

What must patients taking Lithium present with in the community pharmacy before the medication can be dispensed?

Answer 74

Their Lithium therapy record book which details information regarding the brand, dose and most recent Lithium level in addition to their thyroid, renal function and weight chart.