BPAD maudsley

130 Questions

Lithium is the second element of the periodic table, in the same column as hydrogen and sodium.

False

Lithium can increase intracellular concentrations of sodium and calcium in people with bipolar illness.

False

Glycogen synthase kinase 3 (GSK3) is not a potential mechanism of action of lithium.

False

Lithium has been shown to inhibit the creation of new neurons in the hippocampus.

False

Lithium has no neuroprotective effects.

False

Lithium is only present in high levels in the environment.

False

The BAP guidelines suggest that in the event of relapse, a non-urgent plasma lithium level should be obtained to indicate the level of compliance with lithium therapy.

False

Lithium is only effective in treating manic episodes but not depressive episodes in bipolar disorder.

False

The aim of maintenance treatment of bipolar disorder is to achieve partial remission of both manic and depressive episodes.

False

Lithium augmentation of selective serotonin reuptake inhibitors (SSRIs) is most effective at a lithium plasma level of 0.4-0.6 mmol/L.

False

Lithium has been shown to be ineffective in preventing relapses that require hospitalization in unipolar depression.

False

A head-to-head trial of lithium versus quetiapine augmentation in treatment-resistant depression is not underway and will not report in 2021.

False

Lithium has been proposed to treat patients with unipolar depression who have suffered at least three depressive episodes in 5 years.

False

The optimal plasma level range for lithium prophylaxis is 0.4-0.6mmol/L.

False

Lithium can cause an increase in the white blood cell (WBC) count in patients not receiving clozapine.

False

The target plasma level range for prophylaxis in patients who have unipolar depression is 0.6-0.8mmol/L.

True

Blood samples for plasma lithium level estimations should be taken 10-14 hours post dose in patients who are prescribed a twice daily dose of a prolonged release preparation.

False

Lithium citrate liquid is available in three strengths.

False

Lithium levels of >1.2 mmol/L are associated with a higher risk of renal toxicity.

False

Renal effects of lithium treatment can be irreversible after long-term treatment (>10 years).

False

Lithium toxicity reliably occurs at levels >2.5 mmol/L.

False

Thyroid function tests (TFTs) should be checked every 3 months in patients on lithium treatment.

False

Lithium treatment can increase the risk of hypoparathyroidism.

False

Lithium is contraindicated in women of child-bearing age.

False

The use of automated reminder systems has been shown to worsen monitoring rates.

False

Discontinuing lithium treatment abruptly may worsen the natural course of bipolar illness.

True

The risk of relapse can be reduced by increasing the dose rapidly over a period of at least a month.

False

Patients who had been in remission for at least 2 years and had discontinued lithium very slowly had a lower recurrence rate than those who continued lithium.

False

A quarter of patients prescribed lithium took almost all of their prescribed doses.

False

One in five patients prescribed long-term lithium treatment had a plasma level below the therapeutic range.

False

ACE inhibitors can increase renal sodium reabsorption by the kidney, resulting in a decrease in lithium plasma levels.

False

The risk of lithium toxicity is decreased in patients with heart failure, dehydration, and renal impairment.

False

Angiotensin II receptor antagonists do not require frequent monitoring of eGFR and plasma lithium when co-prescribed with lithium.

False

The full effect of ACE inhibitors on lithium plasma levels can be seen immediately after co-prescription.

False

ACE inhibitors can precipitate renal failure when co-prescribed with lithium.

True

Elderly patients have a decreased risk of hospitalization due to lithium toxicity when taking ACE inhibitors.

False

Trandolapril is not an ACE inhibitor.

False

The combination of lithium and loop diuretics is generally well-tolerated without any significant interactions.

False

All NSAIDs can be purchased over-the-counter without a prescription.

False

The risk of an interaction between lithium and loop diuretics is greatest after a year of co-prescription.

False

Valproate's mechanism of action is fully understood and involves only one or two pathways.

False

Thiazide diuretics can reduce the renal clearance of lithium, but the effect is always less than 25%.

False

Carbamazepine does not cause hyponatraemia, which can lead to lithium retention and toxicity.

False

The combination of lithium and COX-2 inhibitors has no potential for interaction and does not require increased plasma lithium monitoring.

False

Valproic acid is responsible for the pharmacological activity of sodium valproate and semi-sodium valproate.

True

A dose of sodium valproate is equivalent to a dose of semi-sodium valproate.

False

Valproate has been shown to be more effective than olanzapine in the treatment of acute mania.

False

A 2020 meta-analysis placed divalproex as the most effective treatment for bipolar depression.

False

RCT data have shown that valproate is effective in the prophylaxis of bipolar affective disorder.

False

Patients with rapid cycling illness had a better response to olanzapine than to valproate in a post hoc analysis.

False

Valproate has been shown to inhibit histone deacetylase, which may confer some effects on neuroplasticity.

True

Valproate is recommended as a first-line option for the treatment of acute episodes of depression in women of child-bearing potential.

False

The BALANCE study found valproate to be numerically superior to lithium in treating bipolar disorder.

False

Aripiprazole alone is superior to valproate alone in treating bipolar disorder.

False

The Cochrane review found strong evidence to support the use of valproate as prophylaxis.

False

Valproate is commonly used to treat anxiety disorders.

True

The use of valproate has decreased in recent years due to the increased use of lithium.

False

Risperidone augmented with valproate is superior to risperidone alone in reducing hostility in patients with schizophrenia.

False

Valproate is sometimes used to treat aggressive behaviors of variable etiology.

True

The NICE recommends valproate as a first-line option for the treatment of acute episodes of mania.

True

Valproate serum levels of $50mg/L are associated with the most robust response in acute mania.

False

Plasma level monitoring is of more limited use with valproate than with lithium or carbamazepine.

True

Starting doses of valproate above $500mg/day can occasionally cause lethargy and confusion.

False

Optimal serum levels during the maintenance phase of valproate treatment are known to be at least $75mg/L.

False

Valproate can cause both gastric irritation and hyperkalemia, leading to nausea.

False

Valproate is associated with an increased risk of suicidal behavior in all patients.

False

The once daily Chrono form of sodium valproate produces higher peak plasma levels than the conventional formulation.

False

Valproate is eliminated mainly through the liver.

False

NICE recommends valproate as a first-line option for the treatment of acute episodes of depression in women of child-bearing potential.

False

The risk of unplanned pregnancy is likely to be below population norms in women with mania who are taking valproate.

False

The therapeutic range of carbamazepine when used as an antiseizure medication is generally considered to be 4-6mg/L

False

Carbamazepine is not considered to be a hepatic enzyme inducer

False

The initial plasma half-life of carbamazepine is around 12 hours

False

Carbamazepine has been shown to be effective in the management of alcohol withdrawal symptoms, and the evidence is strong enough to support its use for this indication

False

Around 10% of patients treated with carbamazepine develop a generalised erythematous rash

False

Carbamazepine has been implicated in an increased risk of suicidal behaviour in patients with bipolar illness.

False

NICE recommends repeating urea and electrolytes, full blood count, and liver function tests after 3 months of carbamazepine treatment.

False

Valproate can decrease the plasma levels of some drugs by inhibition of glucuronidation.

False

The anticonvulsant activity of carbamazepine is increased by drugs that lower the seizure threshold.

False

Carbamazepine is licensed for the treatment of bipolar illness in patients who respond to lithium.

False

Carbamazepine is a potent inhibitor of hepatic cytochrome enzymes and is metabolised by CYP3A4.

False

Valproate is highly protein bound and can be displaced by other protein bound drugs such as warfarin.

False

A dose of at least 100mg aspirin is required to inhibit the metabolism of valproate.

False

The risk of unplanned pregnancy is below population norms in women with mania who are sexually disinhibited.

False

Oxcarbazepine, a structural derivative of carbamazepine, only blocks voltage-dependent sodium channels.

False

Olanzapine/fluoxetine in combination is licensed for maintenance treatment in the European Union.

False

Risperidone has been shown to be superior to lithium in mania treatment according to network meta-analyses.

False

The combination of antipsychotics with mood stabilizers is associated with fewer side effects than monotherapy with either medication.

False

First-generation antipsychotics are less likely to cause depression than haloperidol in bipolar disorder.

False

The use of first-generation antipsychotic depots is well-supported by robust evidence in bipolar disorder.

False

Aripiprazole is not effective in acute treatment of mania as an add-on agent.

False

Quetiapine is not effective in the acute treatment of bipolar depression.

False

Asenapine is not associated with weight gain and metabolic disturbance.

True

Aripiprazole LAI is not effective for prophylaxis in bipolar 1 disorder.

False

Olanzapine is not effective in the acute treatment of bipolar depression when combined with fluoxetine.

False

Paliperidone LAI is effective in the maintenance treatment of bipolar disorder.

True

Lurasidone is not effective in the acute treatment of bipolar depression.

False

Cariprazine is not effective in the acute treatment of bipolar depression.

False

Aripiprazole is effective in the acute treatment of depression in bipolar disorder.

False

Risperidone LAI is not effective in the maintenance treatment of bipolar disorder.

False

Cariprazine has a high propensity for weight gain.

False

Lurasidone is licensed by the FDA as monotherapy for acute treatment of bipolar depression.

True

Olanzapine is not effective in mania.

False

Quetiapine has a high propensity for EPSEs.

False

Risperidone LAI is not effective as prophylaxis against mania in the longer term.

False

Aripiprazole LAI does not protect against manic relapse.

False

Paliperidone LAI has a different effect than risperidone LAI.

False

Clozapine has not been studied in people with treatment-resistant BD.

False

Lurasidone is associated with significant metabolic effects, including weight gain.

False

Iloperidone is not effective in mixed episodes.

False

The largest study conducted with flupentixol LAI showed a significant effect in reducing the risk of depressive episodes.

False

Risperidone LAI has been shown to increase the risk of depressive relapse in bipolar patients.

False

FGA LAIs have been shown to be effective in preventing recurrence of depression in bipolar patients.

False

The use of LAIs offers the advantage of transparency with respect to compliance in bipolar maintenance.

True

A Taiwanese retrospective cohort study found that patients prescribed FGA LAIs had a lower risk of depressive episode recurrence compared to those prescribed risperidone LAI.

False

Haloperidol LAI has been shown to increase the risk of manic relapse in bipolar patients.

False

Flupentixol decanoate (20mg every 2–3 weeks) has been shown to increase the risk of depressive episodes in bipolar patients.

False

The evidence suggests that FGA LAIs are more effective than SGA LAIs in reducing the risk of recurrence of mania/hypomania in bipolar patients.

False

The largest study conducted with flupentixol LAI showed no effect and no superiority over lithium.

True

The use of FGA LAIs is strongly supported by the evidence in bipolar maintenance.

False

The initial dose reduction of lithium or mood stabilizers should be 50% of the current dose

False

Lithium levels of 1.2 mmol/L are considered safe

False

Valproate can increase the plasma levels of some drugs by inhibition of glucuronidation

False

A gradual reduction of lithium or mood stabilizers is not necessary to avoid withdrawal symptoms

False

Ongoing monitoring is not necessary after complete cessation of lithium or mood stabilizers

False

Tablet cutters are not required to achieve small doses of valproate

False

Difficulty reducing medication precludes a further attempt at reduction

False

Other modalities such as family therapy and cognitive behavioural therapy are not effective in treating bipolar disorder

False

Each reduction of lithium or mood stabilizers should be calculated as a fixed amount of the previous dose

False

The final dose of lithium or mood stabilizers before completely stopping may not be very small

False

Study Notes

Clinical Indications

Lithium is effective in treating acute mania, with a plasma level of 0.8-1.0 mmol/L.
In patients with rapid cycling or psychotic symptoms, lithium may be less effective.
In bipolar depression, lithium is widely used but lacks robust evidence for efficacy.

Maintenance Treatment

Aim for a lithium plasma level of 0.6-0.8 mmol/L, with the option to adjust up to 1.0 mmol/L or down to 0.4-0.6 mmol/L.
The goal of treatment is complete remission of both manic and depressive episodes.

Augmentation of Antidepressants

Lithium is a first-choice agent for augmenting antidepressants in treatment-resistant depression.
Effective plasma level for augmentation is 0.6-1.0 mmol/L.
Clinical predictors of a better outcome in lithium augmentation include:
- Severe depressive symptomatology
- Psychomotor retardation
- Significant weight loss
- Family history of major depression
- Personal experience of more than three episodes

Prophylaxis of Unipolar Depression

Lithium can be used for long-term treatment of unipolar depression.
Lithium is significantly superior to antidepressants in preventing relapses that require hospitalization.

Plasma Levels

The minimum effective plasma level for prophylaxis is 0.4 mmol/L.
The optimal plasma level range is 0.6-0.8 mmol/L.
Changes in plasma levels can worsen the risk of relapse.

Adverse Effects

Common side effects are dose- and plasma-level-related, including:
- Mild gastrointestinal upset
- Fine tremor
- Polyuria and polydipsia
- Metallic taste in the mouth
- Ankle oedema
- Weight gain
Lithium can also cause:
- Nephrogenic diabetes insipidus
- Reduction in the glomerular filtration rate (GFR)
- Hypothyroidism
- Hyperthyroidism
- Hyperparathyroidism

Toxicity

Toxic effects occur at levels >1.5 mmol/L.
Symptoms of toxicity include:
- Gastrointestinal effects
- CNS effects (muscle weakness, drowsiness, confusion, ataxia, coarse tremor, and muscle twitching)
Above 2 mmol/L, increased disorientation and seizures can occur.
Above 3 mmol/L, peritoneal or haemodialysis may be used.

Pre-Treatment Tests and Monitoring

Before prescribing lithium, renal, thyroid, and cardiac functions should be checked.
Monitor plasma lithium levels, eGFR, and TFTs every 6 months.
More frequent tests may be required in patients with interacting medications, elderly patients, or those with chronic kidney disease.

Discontinuation

Intermittent treatment with lithium may worsen the natural course of bipolar illness.
Gradually decrease the dose over a period of at least a month to reduce the risk of relapse.
Avoid decremental plasma level reductions of >0.2 mmol/L.### Diuretics and Lithium Interaction
Diuretics can reduce the renal clearance of lithium, with thiazide diuretics having a greater effect than loop diuretics.
Lithium levels can increase by 25-400% within 10 days of taking a thiazide diuretic.
Thiazide diuretics include bendroflumethiazide, chlorthalidone, cyclopenthiazide, indapamide, metolazone, and xipamide.
Loop diuretics can also increase lithium levels, especially in the first month of treatment; extra monitoring is recommended during this time.
Loop diuretics include bumetanide, furosemide, and torasemide.

NSAIDs and Lithium Interaction

NSAIDs can inhibit the synthesis of renal prostaglandins, reducing renal blood flow and increasing lithium reabsorption.
The magnitude of lithium level increase is unpredictable, ranging from 10% to over 400%.
Onset of effect varies from a few days to several months.
Risk of interaction is increased in patients with impaired renal function, renal artery stenosis, heart failure, dehydration, or on a low-salt diet.
NSAIDs do not diminish the therapeutic effects of lithium.

Carbamazepine and Lithium Interaction

There are rare reports of neurotoxicity when carbamazepine is combined with lithium, particularly at high lithium levels.
Carbamazepine can cause hyponatraemia, leading to lithium retention and toxicity.

Valproate

Valproate is a branched-chain fatty acid with a complex mechanism of action, including inhibition of GABA catabolism, reduction of arachidonic acid turnover, and activation of the ERK pathway.
It is available in the UK as sodium valproate, valproic acid, and semi-sodium valproate.
Doses of sodium valproate and semi-sodium valproate are not equivalent, with sodium valproate requiring a slightly higher dose.

Indications and Efficacy

Valproate is effective in the treatment of mania, with a response rate of 50% and a NNT of 2-4.
It may be effective in patients who have failed to respond to lithium.
Valproate may be less effective than olanzapine in acute mania.
It has a small to medium effect size in bipolar depression.
Valproate is sometimes used to treat aggressive behaviors of variable etiology.

Pharmacokinetics and Monitoring

Valproate pharmacokinetics follow a three-compartmental model, with protein-binding saturation.
Plasma level monitoring is of limited use, but may be useful in detecting non-compliance or toxicity.
Serum levels of 94mg/L are associated with the most robust response in acute mania.
Optimal serum levels during the maintenance phase are unknown, but are likely to be at least 50mg/L.

Adverse Effects

Valproate can cause gastric irritation, hyperammonaemia, lethargy, confusion, weight gain, and tremor.
It can also cause hair loss, peripheral oedema, thrombocytopenia, leucopenia, red cell hypoplasia, and pancreatitis.
Valproate is a major human teratogen and may cause fulminant hepatic failure.
It has been associated with an increased risk of suicidal behavior, particularly in patients with depression.

Discontinuation

It is unknown if abrupt discontinuation of valproate worsens the natural course of bipolar illness.
Discontinuation should be done slowly over at least a month.

Use in Women of Child-Bearing Age

Valproate is contraindicated in women of child-bearing age due to its teratogenic potential.
Alternative antiseizure medications are preferred in women with epilepsy.
The valproate toolkit provides resources for patients, GPs, pharmacists, and specialists.
Women who are trying to conceive and require valproate should be prescribed prophylactic folate.### Antiseizure Meds and Bipolar Disorder
Some antiseizure medications have been linked to an increased risk of suicidal behavior, but carbamazepine is not one of them.
Pre-treatment tests for carbamazepine should include baseline urea and electrolytes (U&Es), full blood count (FBC), liver function tests (LFTs), and a weight check.

On-Treatment Monitoring for Carbamazepine

Repeat U&Es, FBC, and LFTs after 6 months, and monitor weight (or BMI) regularly.

Discontinuing Carbamazepine

It's unclear if abruptly stopping carbamazepine worsens bipolar disorder, but it's recommended to taper off the medication over at least a month.

Women of Child-Bearing Age and Carbamazepine

Carbamazepine is a known human teratogen and can increase the risk of unplanned pregnancy in women with mania who are sexually disinhibited.
Ensure adequate contraception and prescribe prophylactic folate if carbamazepine cannot be avoided.

Interactions with Other Drugs

Carbamazepine is a potent inducer of hepatic cytochrome enzymes and can reduce the levels of many medications, including antidepressants, antipsychotics, and oral contraceptives.
Some medications (e.g., fluconazole, cimetidine) can increase carbamazepine levels and precipitate toxicity.

Antipsychotics in Bipolar Disorder

Antipsychotics have been used to treat bipolar disorder since the 1960s and can be effective in both poles of the illness.
Some antipsychotics, like quetiapine and olanzapine, have antidepressant and mood-stabilizing properties.

Valproate Interactions

Valproate can be displaced by other protein-bound drugs like aspirin, leading to toxicity.
Valproate can increase the levels of certain medications, such as warfarin, by inhibiting glucuronidation.

Carbamazepine Mechanism of Action

Carbamazepine blocks voltage-dependent sodium channels, reducing glutamate release and decreasing dopamine and noradrenaline turnover.
Carbamazepine has a similar structure to tricyclic antidepressants.

Indications for Carbamazepine

Carbamazepine is primarily used to treat seizures, trigeminal neuralgia, and bipolar disorder.
It has been shown to be effective in treating mania and depression, but not as effective as lithium in prophylaxis.

Antipsychotics in Mania

Antipsychotics are effective in treating mania, particularly when combined with a mood stabilizer.
Risperidone, olanzapine, and quetiapine are commonly used antipsychotics for mania.

Other Antipsychotics

Cariprazine is effective in treating mania and depression, with a low risk of weight gain.
Lurasidone is licensed for treating bipolar depression and has minimal metabolic effects.
Olanzapine is effective in mania, but has significant metabolic effects.
Quetiapine has a low risk of extrapyramidal symptoms and is effective in preventing depressive relapse.

Antipsychotic Long-Acting Injections in Bipolar Disorder

Long-acting injections are widely used in bipolar disorder, although none are formally licensed in the UK for this indication.
Risperidone LAI is effective in preventing manic relapse, but not depressive relapse.
Aripiprazole LAI is also effective in preventing manic relapse, with a low risk of metabolic effects.

Explore the properties of lithium, the third element of the periodic table, and its potential role in regulating mood and behavior. Learn about its effects on biological processes and its relationship with other elements like sodium and calcium.

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