Podcast
Questions and Answers
Lithium is the second element of the periodic table, in the same column as hydrogen and sodium.
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.
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.
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.
Lithium has been shown to inhibit the creation of new neurons in the hippocampus.
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Lithium has no neuroprotective effects.
Lithium has no neuroprotective effects.
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Lithium is only present in high levels in the environment.
Lithium is only present in high levels in the environment.
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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.
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.
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Lithium is only effective in treating manic episodes but not depressive episodes in bipolar disorder.
Lithium is only effective in treating manic episodes but not depressive episodes in bipolar disorder.
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The aim of maintenance treatment of bipolar disorder is to achieve partial remission of both manic and depressive episodes.
The aim of maintenance treatment of bipolar disorder is to achieve partial remission of both manic and depressive episodes.
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Lithium augmentation of selective serotonin reuptake inhibitors (SSRIs) is most effective at a lithium plasma level of 0.4-0.6 mmol/L.
Lithium augmentation of selective serotonin reuptake inhibitors (SSRIs) is most effective at a lithium plasma level of 0.4-0.6 mmol/L.
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Lithium has been shown to be ineffective in preventing relapses that require hospitalization in unipolar depression.
Lithium has been shown to be ineffective in preventing relapses that require hospitalization in unipolar depression.
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A head-to-head trial of lithium versus quetiapine augmentation in treatment-resistant depression is not underway and will not report in 2021.
A head-to-head trial of lithium versus quetiapine augmentation in treatment-resistant depression is not underway and will not report in 2021.
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Lithium has been proposed to treat patients with unipolar depression who have suffered at least three depressive episodes in 5 years.
Lithium has been proposed to treat patients with unipolar depression who have suffered at least three depressive episodes in 5 years.
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The optimal plasma level range for lithium prophylaxis is 0.4-0.6mmol/L.
The optimal plasma level range for lithium prophylaxis is 0.4-0.6mmol/L.
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Lithium can cause an increase in the white blood cell (WBC) count in patients not receiving clozapine.
Lithium can cause an increase in the white blood cell (WBC) count in patients not receiving clozapine.
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The target plasma level range for prophylaxis in patients who have unipolar depression is 0.6-0.8mmol/L.
The target plasma level range for prophylaxis in patients who have unipolar depression is 0.6-0.8mmol/L.
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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.
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.
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Lithium citrate liquid is available in three strengths.
Lithium citrate liquid is available in three strengths.
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Lithium levels of >1.2 mmol/L are associated with a higher risk of renal toxicity.
Lithium levels of >1.2 mmol/L are associated with a higher risk of renal toxicity.
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Renal effects of lithium treatment can be irreversible after long-term treatment (>10 years).
Renal effects of lithium treatment can be irreversible after long-term treatment (>10 years).
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Lithium toxicity reliably occurs at levels >2.5 mmol/L.
Lithium toxicity reliably occurs at levels >2.5 mmol/L.
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Thyroid function tests (TFTs) should be checked every 3 months in patients on lithium treatment.
Thyroid function tests (TFTs) should be checked every 3 months in patients on lithium treatment.
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Lithium treatment can increase the risk of hypoparathyroidism.
Lithium treatment can increase the risk of hypoparathyroidism.
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Lithium is contraindicated in women of child-bearing age.
Lithium is contraindicated in women of child-bearing age.
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The use of automated reminder systems has been shown to worsen monitoring rates.
The use of automated reminder systems has been shown to worsen monitoring rates.
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Discontinuing lithium treatment abruptly may worsen the natural course of bipolar illness.
Discontinuing lithium treatment abruptly may worsen the natural course of bipolar illness.
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The risk of relapse can be reduced by increasing the dose rapidly over a period of at least a month.
The risk of relapse can be reduced by increasing the dose rapidly over a period of at least a month.
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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.
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.
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A quarter of patients prescribed lithium took almost all of their prescribed doses.
A quarter of patients prescribed lithium took almost all of their prescribed doses.
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One in five patients prescribed long-term lithium treatment had a plasma level below the therapeutic range.
One in five patients prescribed long-term lithium treatment had a plasma level below the therapeutic range.
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ACE inhibitors can increase renal sodium reabsorption by the kidney, resulting in a decrease in lithium plasma levels.
ACE inhibitors can increase renal sodium reabsorption by the kidney, resulting in a decrease in lithium plasma levels.
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The risk of lithium toxicity is decreased in patients with heart failure, dehydration, and renal impairment.
The risk of lithium toxicity is decreased in patients with heart failure, dehydration, and renal impairment.
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Angiotensin II receptor antagonists do not require frequent monitoring of eGFR and plasma lithium when co-prescribed with lithium.
Angiotensin II receptor antagonists do not require frequent monitoring of eGFR and plasma lithium when co-prescribed with lithium.
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The full effect of ACE inhibitors on lithium plasma levels can be seen immediately after co-prescription.
The full effect of ACE inhibitors on lithium plasma levels can be seen immediately after co-prescription.
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ACE inhibitors can precipitate renal failure when co-prescribed with lithium.
ACE inhibitors can precipitate renal failure when co-prescribed with lithium.
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Elderly patients have a decreased risk of hospitalization due to lithium toxicity when taking ACE inhibitors.
Elderly patients have a decreased risk of hospitalization due to lithium toxicity when taking ACE inhibitors.
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Trandolapril is not an ACE inhibitor.
Trandolapril is not an ACE inhibitor.
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The combination of lithium and loop diuretics is generally well-tolerated without any significant interactions.
The combination of lithium and loop diuretics is generally well-tolerated without any significant interactions.
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All NSAIDs can be purchased over-the-counter without a prescription.
All NSAIDs can be purchased over-the-counter without a prescription.
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The risk of an interaction between lithium and loop diuretics is greatest after a year of co-prescription.
The risk of an interaction between lithium and loop diuretics is greatest after a year of co-prescription.
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Valproate's mechanism of action is fully understood and involves only one or two pathways.
Valproate's mechanism of action is fully understood and involves only one or two pathways.
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Thiazide diuretics can reduce the renal clearance of lithium, but the effect is always less than 25%.
Thiazide diuretics can reduce the renal clearance of lithium, but the effect is always less than 25%.
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Carbamazepine does not cause hyponatraemia, which can lead to lithium retention and toxicity.
Carbamazepine does not cause hyponatraemia, which can lead to lithium retention and toxicity.
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The combination of lithium and COX-2 inhibitors has no potential for interaction and does not require increased plasma lithium monitoring.
The combination of lithium and COX-2 inhibitors has no potential for interaction and does not require increased plasma lithium monitoring.
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Valproic acid is responsible for the pharmacological activity of sodium valproate and semi-sodium valproate.
Valproic acid is responsible for the pharmacological activity of sodium valproate and semi-sodium valproate.
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A dose of sodium valproate is equivalent to a dose of semi-sodium valproate.
A dose of sodium valproate is equivalent to a dose of semi-sodium valproate.
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Valproate has been shown to be more effective than olanzapine in the treatment of acute mania.
Valproate has been shown to be more effective than olanzapine in the treatment of acute mania.
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A 2020 meta-analysis placed divalproex as the most effective treatment for bipolar depression.
A 2020 meta-analysis placed divalproex as the most effective treatment for bipolar depression.
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RCT data have shown that valproate is effective in the prophylaxis of bipolar affective disorder.
RCT data have shown that valproate is effective in the prophylaxis of bipolar affective disorder.
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Patients with rapid cycling illness had a better response to olanzapine than to valproate in a post hoc analysis.
Patients with rapid cycling illness had a better response to olanzapine than to valproate in a post hoc analysis.
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Valproate has been shown to inhibit histone deacetylase, which may confer some effects on neuroplasticity.
Valproate has been shown to inhibit histone deacetylase, which may confer some effects on neuroplasticity.
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Valproate is recommended as a first-line option for the treatment of acute episodes of depression in women of child-bearing potential.
Valproate is recommended as a first-line option for the treatment of acute episodes of depression in women of child-bearing potential.
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The BALANCE study found valproate to be numerically superior to lithium in treating bipolar disorder.
The BALANCE study found valproate to be numerically superior to lithium in treating bipolar disorder.
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Aripiprazole alone is superior to valproate alone in treating bipolar disorder.
Aripiprazole alone is superior to valproate alone in treating bipolar disorder.
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The Cochrane review found strong evidence to support the use of valproate as prophylaxis.
The Cochrane review found strong evidence to support the use of valproate as prophylaxis.
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Valproate is commonly used to treat anxiety disorders.
Valproate is commonly used to treat anxiety disorders.
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The use of valproate has decreased in recent years due to the increased use of lithium.
The use of valproate has decreased in recent years due to the increased use of lithium.
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Risperidone augmented with valproate is superior to risperidone alone in reducing hostility in patients with schizophrenia.
Risperidone augmented with valproate is superior to risperidone alone in reducing hostility in patients with schizophrenia.
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Valproate is sometimes used to treat aggressive behaviors of variable etiology.
Valproate is sometimes used to treat aggressive behaviors of variable etiology.
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The NICE recommends valproate as a first-line option for the treatment of acute episodes of mania.
The NICE recommends valproate as a first-line option for the treatment of acute episodes of mania.
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Valproate serum levels of $50mg/L are associated with the most robust response in acute mania.
Valproate serum levels of $50mg/L are associated with the most robust response in acute mania.
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Plasma level monitoring is of more limited use with valproate than with lithium or carbamazepine.
Plasma level monitoring is of more limited use with valproate than with lithium or carbamazepine.
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Starting doses of valproate above $500mg/day can occasionally cause lethargy and confusion.
Starting doses of valproate above $500mg/day can occasionally cause lethargy and confusion.
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Optimal serum levels during the maintenance phase of valproate treatment are known to be at least $75mg/L.
Optimal serum levels during the maintenance phase of valproate treatment are known to be at least $75mg/L.
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Valproate can cause both gastric irritation and hyperkalemia, leading to nausea.
Valproate can cause both gastric irritation and hyperkalemia, leading to nausea.
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Valproate is associated with an increased risk of suicidal behavior in all patients.
Valproate is associated with an increased risk of suicidal behavior in all patients.
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The once daily Chrono form of sodium valproate produces higher peak plasma levels than the conventional formulation.
The once daily Chrono form of sodium valproate produces higher peak plasma levels than the conventional formulation.
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Valproate is eliminated mainly through the liver.
Valproate is eliminated mainly through the liver.
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NICE recommends valproate as a first-line option for the treatment of acute episodes of depression in women of child-bearing potential.
NICE recommends valproate as a first-line option for the treatment of acute episodes of depression in women of child-bearing potential.
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The risk of unplanned pregnancy is likely to be below population norms in women with mania who are taking valproate.
The risk of unplanned pregnancy is likely to be below population norms in women with mania who are taking valproate.
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The therapeutic range of carbamazepine when used as an antiseizure medication is generally considered to be 4-6mg/L
The therapeutic range of carbamazepine when used as an antiseizure medication is generally considered to be 4-6mg/L
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Carbamazepine is not considered to be a hepatic enzyme inducer
Carbamazepine is not considered to be a hepatic enzyme inducer
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The initial plasma half-life of carbamazepine is around 12 hours
The initial plasma half-life of carbamazepine is around 12 hours
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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
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
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Around 10% of patients treated with carbamazepine develop a generalised erythematous rash
Around 10% of patients treated with carbamazepine develop a generalised erythematous rash
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Carbamazepine has been implicated in an increased risk of suicidal behaviour in patients with bipolar illness.
Carbamazepine has been implicated in an increased risk of suicidal behaviour in patients with bipolar illness.
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NICE recommends repeating urea and electrolytes, full blood count, and liver function tests after 3 months of carbamazepine treatment.
NICE recommends repeating urea and electrolytes, full blood count, and liver function tests after 3 months of carbamazepine treatment.
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Valproate can decrease the plasma levels of some drugs by inhibition of glucuronidation.
Valproate can decrease the plasma levels of some drugs by inhibition of glucuronidation.
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The anticonvulsant activity of carbamazepine is increased by drugs that lower the seizure threshold.
The anticonvulsant activity of carbamazepine is increased by drugs that lower the seizure threshold.
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Carbamazepine is licensed for the treatment of bipolar illness in patients who respond to lithium.
Carbamazepine is licensed for the treatment of bipolar illness in patients who respond to lithium.
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Carbamazepine is a potent inhibitor of hepatic cytochrome enzymes and is metabolised by CYP3A4.
Carbamazepine is a potent inhibitor of hepatic cytochrome enzymes and is metabolised by CYP3A4.
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Valproate is highly protein bound and can be displaced by other protein bound drugs such as warfarin.
Valproate is highly protein bound and can be displaced by other protein bound drugs such as warfarin.
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A dose of at least 100mg aspirin is required to inhibit the metabolism of valproate.
A dose of at least 100mg aspirin is required to inhibit the metabolism of valproate.
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The risk of unplanned pregnancy is below population norms in women with mania who are sexually disinhibited.
The risk of unplanned pregnancy is below population norms in women with mania who are sexually disinhibited.
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Oxcarbazepine, a structural derivative of carbamazepine, only blocks voltage-dependent sodium channels.
Oxcarbazepine, a structural derivative of carbamazepine, only blocks voltage-dependent sodium channels.
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Olanzapine/fluoxetine in combination is licensed for maintenance treatment in the European Union.
Olanzapine/fluoxetine in combination is licensed for maintenance treatment in the European Union.
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Risperidone has been shown to be superior to lithium in mania treatment according to network meta-analyses.
Risperidone has been shown to be superior to lithium in mania treatment according to network meta-analyses.
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The combination of antipsychotics with mood stabilizers is associated with fewer side effects than monotherapy with either medication.
The combination of antipsychotics with mood stabilizers is associated with fewer side effects than monotherapy with either medication.
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First-generation antipsychotics are less likely to cause depression than haloperidol in bipolar disorder.
First-generation antipsychotics are less likely to cause depression than haloperidol in bipolar disorder.
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The use of first-generation antipsychotic depots is well-supported by robust evidence in bipolar disorder.
The use of first-generation antipsychotic depots is well-supported by robust evidence in bipolar disorder.
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Aripiprazole is not effective in acute treatment of mania as an add-on agent.
Aripiprazole is not effective in acute treatment of mania as an add-on agent.
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Quetiapine is not effective in the acute treatment of bipolar depression.
Quetiapine is not effective in the acute treatment of bipolar depression.
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Asenapine is not associated with weight gain and metabolic disturbance.
Asenapine is not associated with weight gain and metabolic disturbance.
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Aripiprazole LAI is not effective for prophylaxis in bipolar 1 disorder.
Aripiprazole LAI is not effective for prophylaxis in bipolar 1 disorder.
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Olanzapine is not effective in the acute treatment of bipolar depression when combined with fluoxetine.
Olanzapine is not effective in the acute treatment of bipolar depression when combined with fluoxetine.
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Paliperidone LAI is effective in the maintenance treatment of bipolar disorder.
Paliperidone LAI is effective in the maintenance treatment of bipolar disorder.
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Lurasidone is not effective in the acute treatment of bipolar depression.
Lurasidone is not effective in the acute treatment of bipolar depression.
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Cariprazine is not effective in the acute treatment of bipolar depression.
Cariprazine is not effective in the acute treatment of bipolar depression.
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Aripiprazole is effective in the acute treatment of depression in bipolar disorder.
Aripiprazole is effective in the acute treatment of depression in bipolar disorder.
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Risperidone LAI is not effective in the maintenance treatment of bipolar disorder.
Risperidone LAI is not effective in the maintenance treatment of bipolar disorder.
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Cariprazine has a high propensity for weight gain.
Cariprazine has a high propensity for weight gain.
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Lurasidone is licensed by the FDA as monotherapy for acute treatment of bipolar depression.
Lurasidone is licensed by the FDA as monotherapy for acute treatment of bipolar depression.
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Olanzapine is not effective in mania.
Olanzapine is not effective in mania.
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Quetiapine has a high propensity for EPSEs.
Quetiapine has a high propensity for EPSEs.
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Risperidone LAI is not effective as prophylaxis against mania in the longer term.
Risperidone LAI is not effective as prophylaxis against mania in the longer term.
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Aripiprazole LAI does not protect against manic relapse.
Aripiprazole LAI does not protect against manic relapse.
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Paliperidone LAI has a different effect than risperidone LAI.
Paliperidone LAI has a different effect than risperidone LAI.
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Clozapine has not been studied in people with treatment-resistant BD.
Clozapine has not been studied in people with treatment-resistant BD.
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Lurasidone is associated with significant metabolic effects, including weight gain.
Lurasidone is associated with significant metabolic effects, including weight gain.
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Iloperidone is not effective in mixed episodes.
Iloperidone is not effective in mixed episodes.
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The largest study conducted with flupentixol LAI showed a significant effect in reducing the risk of depressive episodes.
The largest study conducted with flupentixol LAI showed a significant effect in reducing the risk of depressive episodes.
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Risperidone LAI has been shown to increase the risk of depressive relapse in bipolar patients.
Risperidone LAI has been shown to increase the risk of depressive relapse in bipolar patients.
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FGA LAIs have been shown to be effective in preventing recurrence of depression in bipolar patients.
FGA LAIs have been shown to be effective in preventing recurrence of depression in bipolar patients.
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The use of LAIs offers the advantage of transparency with respect to compliance in bipolar maintenance.
The use of LAIs offers the advantage of transparency with respect to compliance in bipolar maintenance.
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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.
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.
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Haloperidol LAI has been shown to increase the risk of manic relapse in bipolar patients.
Haloperidol LAI has been shown to increase the risk of manic relapse in bipolar patients.
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Flupentixol decanoate (20mg every 2–3 weeks) has been shown to increase the risk of depressive episodes in bipolar patients.
Flupentixol decanoate (20mg every 2–3 weeks) has been shown to increase the risk of depressive episodes in bipolar patients.
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The evidence suggests that FGA LAIs are more effective than SGA LAIs in reducing the risk of recurrence of mania/hypomania in bipolar patients.
The evidence suggests that FGA LAIs are more effective than SGA LAIs in reducing the risk of recurrence of mania/hypomania in bipolar patients.
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The largest study conducted with flupentixol LAI showed no effect and no superiority over lithium.
The largest study conducted with flupentixol LAI showed no effect and no superiority over lithium.
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The use of FGA LAIs is strongly supported by the evidence in bipolar maintenance.
The use of FGA LAIs is strongly supported by the evidence in bipolar maintenance.
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The initial dose reduction of lithium or mood stabilizers should be 50% of the current dose
The initial dose reduction of lithium or mood stabilizers should be 50% of the current dose
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Lithium levels of 1.2 mmol/L are considered safe
Lithium levels of 1.2 mmol/L are considered safe
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Valproate can increase the plasma levels of some drugs by inhibition of glucuronidation
Valproate can increase the plasma levels of some drugs by inhibition of glucuronidation
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A gradual reduction of lithium or mood stabilizers is not necessary to avoid withdrawal symptoms
A gradual reduction of lithium or mood stabilizers is not necessary to avoid withdrawal symptoms
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Ongoing monitoring is not necessary after complete cessation of lithium or mood stabilizers
Ongoing monitoring is not necessary after complete cessation of lithium or mood stabilizers
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Tablet cutters are not required to achieve small doses of valproate
Tablet cutters are not required to achieve small doses of valproate
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Difficulty reducing medication precludes a further attempt at reduction
Difficulty reducing medication precludes a further attempt at reduction
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Other modalities such as family therapy and cognitive behavioural therapy are not effective in treating bipolar disorder
Other modalities such as family therapy and cognitive behavioural therapy are not effective in treating bipolar disorder
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Each reduction of lithium or mood stabilizers should be calculated as a fixed amount of the previous dose
Each reduction of lithium or mood stabilizers should be calculated as a fixed amount of the previous dose
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The final dose of lithium or mood stabilizers before completely stopping may not be very small
The final dose of lithium or mood stabilizers before completely stopping may not be very small
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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.
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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.
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Lithium levels can increase by 25-400% within 10 days of taking a thiazide diuretic.
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Thiazide diuretics include bendroflumethiazide, chlorthalidone, cyclopenthiazide, indapamide, metolazone, and xipamide.
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Loop diuretics can also increase lithium levels, especially in the first month of treatment; extra monitoring is recommended during this time.
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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.
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Description
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.
