Pharmacology: Mood Stabilisers

Question 1

True or false:

1. Cyclothymia is cycling of subthreshold symptoms of elevated and depressed mood over a period of at least 2 years
2. A manic episode must always be of more than 7 days in duration
3. Manic patients can demonstrate formal thought disorder
4. The difference between mania and hypomania is the presence of expansive mood
5. A depressive episode is necessary for a diagnosis of BPAD

Answer 1

1. Cyclothymia is cycling of subthreshold symptoms of elevated and depressed mood over a period of at least 2 years - T
2. A manic episode must always be of more than 7 days in duration- F
3. Manic patients can demonstrate formal thought disorder - T
4. The difference between mania and hypomania is the presence of expansive mood - F
5. A depressive episode is necessary for a diagnosis of BPAD - F

Question 2

What is a mood stabiliser?

Answer 2

Medication that helps the stabilise the extremes of mood experienced in psychiatric conditions such as Bipolar affective disorder, Schizoaffective disorder and recurrent depression.

Question 3

What 3 drug classes are used as mood stabilisers?

Answer 3

Three drug classes

• Lithium (carbonate)
• Anti-epileptics: Sodium valproate, Carbamazepine, Lamotrigine
• Atypical antipsychotics

Question 4

What is the gold standard mood stabiliser?

Answer 4

Lithium carbonate

Question 5

What are the effects of lithium? What is the MOA?

Answer 5

Anti-suicide effects

MOA unknown

Question 6

What are the uses of lithium?

Answer 6

Used in the treatment/prophylaxis of:

• bipolar,
• schizoaffective disorder,
• depression (recurrent or treatment resistant)

Question 7

What is the problem with lithium?

Answer 7

Narrow therapeutic range 0.4-1mmol/L hence its one of the reasons why patients need monitoring to ensure they are not at a sub-clinical/toxic dose

Question 8

What are the long term complications of lithium?

Answer 8

Complications of use:

• Teratogen,
• arrthymia

Question 9

What are the common side effects of lithum?

Answer 9

• Fine tremor
• Mild GI upset
• Metallic taste in mouth
• Sedation

Question 10

When are patients at risk of lithium toxicity?

Answer 10

Dehydration - so tell patients to keep hydrated

Renal failure

Drugs -especially diuretics, ACEi/ARBs, NSAIDs, metronidazole

Question 11

What are the persistent adverse effects of lithium?

Answer 11

• Renal disease - polyuria and polydypsia (can cause diabetes insipidus) and CKD
• Hypothyroidism
• Lethargy
• Weight gain
• Persistent tremor
• T wave flattening on ECG
• Mild cognitive impairment
• Mild leucocytosis

Question 12

What are the toxic (>1.5mmol/L) adverse effects of lithium?

Answer 12

• Coarse tremor
• Marked GI upset
• Ataxia
• Dysarthria
• Impaired consciousness
• Epileptic seizures
• Nystagmus
• Renal failure

Question 13

What should be done before starting lithium?

Answer 13

Lithium purple book and register

Pre-lithium: FBC, U&Es, Calcium, TFTs, ECG (if risk factors or known cardiac disease)

Question 14

How often is lithium monitored?

Answer 14

• when checking lithium levels, the sample should be taken 12 hours post-dose (trough level)
• after starting lithium levels should be performed weekly and after each dose change until concentrations are stable
• once established, lithium blood level should ‘normally’ be checked every 3 months (also 3 monthly U&Es, eGFR)
• after a change in dose, lithium levels should be taken a week later and weekly until the levels are stable.
• thyroid and renal function, and a 12-hour serum lithium should be checked every 6 months

Question 15

Name 2 drugs which patients on lithium cannot take concurrently.

Answer 15

Diuretics like ACEi

NSAIDs

Question 16

Can lithium be stopped suddenly?

Answer 16

No - risk of relapse will occur much faster

Question 18

Which antipsychotic can be used as a mood stabiliser?

Answer 18

Olanzapine (others can be used but off-license)

Used in acute mania and prophylaxis

Question 19

Which anticonvulsant mood stabiliser should not be used in women of child bearing age? What can occur?

Answer 19

Sodium valproate (Epilim)

Risk of developmental disorders and congenital malformations including neural tube defects (1.5%)

Question 20

What are the uses of sodium valproate as a mood stabiliser?

Answer 20

Acute mania and prophylaxis

Question 21

What are the side effects of sodium valproate?

Answer 21

• GI upset (nausea, vomiting, dyspepsia, diarrhoea)
• tremor
• sedation
• weight gain
• curly/loss hair
• ankle swelling FBC abnormalities (leucopenia, thrombocytopenia)
• abnormal LFTs

Can cause PCOS if used in women (which it shouldn’t be)

Question 22

What is the use of carbamazepine as a mood stabiliser?

Answer 22

Used for prophylaxis

Question 23

Why must you beware or carbamazepine use?

Answer 23

Strong CYP450 inducer beware interactions

Question 24

What are the side effects of carbamazepine?

Answer 24

• Nausea and vomiting,
• blurred vision,
• ataxia/
• fatigue,
• hepatic failure,
• antidiuretic effect (hyponatraemia),
• FBC abnormalities (leucopenia, thrombocytopenia),
• skin rashes,
• abnormal LFTs

Question 25

What is the use of lamotrigine as a mood stabiliser?

Answer 25

used for prophylaxis

Question 26

What are the side effects of lamotrigine? What is a rare but serious SE?

Answer 26

* Nausea and vomiting, * rash, * headache, * sedation, * insomnia, * aggression **Steven-Johnson syndrome** - therefore slowly titrate over weeks and warn patients to stop should they develop a rahs

Question 27

Mohammed is a 22yr old man who is admitted under S3 MHA due to an acute manic relapse. He is known to mental health services and has a diagnosis of Bipolar affective disorder. He is clearly elated, displays racing thoughts, increased energy, hasn’t slept for several days and is grandiose. He was admitted due to gross neglect of his personal needs and because he displayed limited insight into his mental illness. He declined to work with the home treatment team because he was ‘busy with all my plans’ and he didn’t think he needed support. Upon interaction he is becoming increasingly irritable and its difficult for him to concentrate and engage in conversation. He was prescribed Lithium Carbonate 1g ON by his community psychiatrist and has been stable for the last 3 years. His last serum lithum level taken 4 months ago was 0.7mmol/L. He is not prescribed any other medication and is physically otherwise well. He has no know history of substance misuse and there are no features suggestive of organic illness. 1. What do you want to know? 2. What would you prescribe? What other medications are available in the short term?

Answer 27

1. What do you want to know? * Has not been taking lithium for 5 weeks * Serum lithium is 0.0mmol/L * No other precribed medication * No drugs/illicit substances 2. What would you prescribe? What other medications are available in the short term? * Try lithium again, * Prescribe benzodiazepine for a short period of time

Question 28

Can you tell if there has been long term compliance with lithium?

Answer 28

No - levels do not show long term use.

Question 29

What is the management of acute de novo mania?

Answer 29

1. **FIRST LINE: Antipsychotics**: used in the previously untreated due to their rapid anti-manic effects. Haloperidol, olanzapine, quetiapine, or risperidone. * **Patients on an antidepressant monotherapy**: **Consider stopping** the antidepressant first; then offer an antipsychotic regardless of whether the antidepressant is stopped. (New recommendation.) 2. **+/- Adjunctive benzodiazepine:** such as clonazepam or lorazepam can be used for agitation and insomnia. ## Footnote *RCTs in people with bipolar type I disorder experiencing a manic episode suggest that clonazepam may be as effective as lithium in improving manic symptoms at 1–4 weeks. But guidelines do not recommend it as monotherapy.*

Question 30

What is the management of acute manic relapse in known bipolar patient?

Answer 30

1. **Increasing the dose of mood stabiliser** - must be first option. Lithium: check serum lithium levels and consider establishing a higher serum level if compliance is good. If the person is already on lithium, optimise plasma levels first. 2. **Antipsychotic augmentation** - consider adding haloperidol, olanzapine, quetiapine, or risperidone to lithium. Antipsychotic augmentation can also be done for patients on valproate. 3. **Antipsychotic for psychosis:** For psychosis during a manic or mixed episode that is not congruent with severe affective symptoms, antipsychotics must be used. 4. **ECT**

Question 31

When would you consider use of ECT in acute manic relapse in known BPAD?

Answer 31

ECT may be considered for: 1. Severely ill manic patients with **life-threatening** severity e.g. exhaustion 2. Treatment-**resistant** mania 3. **Preference** for ECT and patients 4. Severe mania during **pregnancy**.

Question 32

What is the management of bipolar depression?

Answer 32

1. **Try olanzapine + fluoxetine (SSRI)** * **_Don't use SSRIs alone_** (needs augmentation with antipsychotic or mood stabiliser) * Could use lamotrigine or quetiapine *Limited evidence*

Question 33

Mrs Pearl is a 32 year old woman who has recently had an episode of pressured speech and delusions that she has the ability to speak multiple foreign languages. She was found by police attempting to gain access to the Foreign Office to speak to various government officials. She was recently treated for depression by her GP. What should be the first management step her treating team consider? * A. Commence aripiprazole * B. Commence sodium valproate * C. Stop her antidepressant medication * D. Carry out a CT head scan

Answer 33

C - stop antidepressant

Question 34

Mr Dunnock is a 57 year old man attending A&E after feeling unwell on the plane home from a holiday in Spain. He has a diagnosis of bipolar affective disorder and his wife reports he has been taking all of his prescribed medication fastidiously. Rank the following investigations in order of property with (1) being the highest priority and (5) being the lowest priority. * TFTs * Lithium Level * Calcium Level * U&Es * LTFs

Answer 34

1. Lithium level 2. U+E 3. TFTs 4. Calcium level - can be affected by lithium but not a good match with symptoms 5. LFTs

Question 35

What is the management of lithium toxicity?

Answer 35

* mild-moderate toxicity may respond to **volume resuscitation with normal saline** * **haemodialysis** may be needed in severe toxicity * **sodium bicarbonate** is sometimes used but there is limited evidence to support this. *(By increasing the alkalinity of the urine it promotes lithium excretion)*