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When is lamotrigine a good choice?
FDA-approved for maintenance treatment of bipolar I disorder, lamotrigine is more effective than lithium for preventing depressive relapses. Lamotrigine combined with lithium, carbamazepine, or valproate provides good protection against recurrences of mania and depression.
Unlike selective serotonin reuptake inhibitors and other antidepressants, lamotrigine does not appear to increase risk of hypomania or mania in bipolar patients.1 Unlike valproate and lithium, it is weight-neutral and requires no serum level monitoring.2 Although lamotrigine’s slow titration and prolonged period until reaching therapeutic effect limits its efficacy as monotherapy in an inpatient setting, the drug can be initiated along with quicker acting agents in the hospital and then titrated after discharge. This strategy allows close monitoring during initial exposure.
Consider lamotrigine as an adjunct for treatment-resistant major depression.3 It is useful for treating aggression and agitation in patients with traumatic brain injury4 or dementia.5 Borderline personality disorder patients treated with lamotrigine may show less affective lability, impulsivity, or aggression.6,7 Lamotrigine can act synergistically with clozapine in some patients with refractory schizophrenia.8
Metabolism and drug interactions
Lamotrigine is metabolized via glucuronidation and eliminated renally. Other drugs metabolized by glucuronidation could interact with lamotrigine (Table).9
Table
Drug interactions associated with lamotrigine
| Interacting drug | Effect on lamotrigine | Management |
|---|---|---|
| Carbamazepine Phenytoin Phenobarbital Primidone Rifampin | Increased clearance | Double dose of lamotrigine when used concomitantly |
| Oral contraceptives containing estrogen | Increased clearance | Lamotrigine dose may need to be increased. Efficacy of oral contraceptives may be decreased; dose modification of oral contraceptive also may be required |
| Valproic acid | Decreased clearance | Reduce dose by at least half, even if your patient is on a medication with the potential to increase clearance |
| Source: Reference 9 | ||
Adverse reactions
Lamotrigine is well tolerated chronically, with fewer adverse effects than other mood stabilizers. Serious rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in 0.08% to 0.13% of patients treated with lamotrigine for bipolar disorder or other mood disorders.9 The risk of developing a skin rash within 2 to 8 weeks of therapy necessitates starting with a low dose, usually 25 mg/d, and gradually titrating.2,9
The FDA added a warning about increased risk of suicidality to the labeling of all anticonvulsants, regardless of indication.10 In a meta-analysis of 199 trials, for every 530 patients treated with anticonvulsants there was 1 additional case of suicidality—not completed suicide.10 Inform patients and their families about the potential risk for increased suicidality and document this discussion of risk vs benefit. All patients should be monitored for worsening depression or suicidal thoughts or behavior throughout treatment.
Other potential side effects occurring in at least 5% of patients receiving lamotrigine include somnolence, headache, rash, and the dose-related side effects of nausea, vomiting, dizziness, ataxia, blurred vision, and diplopia.9
1. Bowden CL. Lamotrigine in the treatment of bipolar disorder. Expert Opin Pharmacother. 2002;3(10):1513-1519.
2. Goldsmith DR, Wagstaff AJ, Ibbotson T, et al. Lamotrigine: a review of its use in bipolar disorder. Drugs. 2003;63(19):2029-2050.
3. Gabriel A. Lamotrigine adjunctive treatment in resistant unipolar depression: an open descriptive study. Depress Anxiety. 2006;23:485-488.
4. Pachet A, Friesen S, Winkelaar D, et al. Beneficial behavioural effects of lamotrigine in traumatic brain injury. Brain Inj. 2003;17(8):715-722.
5. Sajatovic M, Ramsay E, Nanry K, et al. Lamotrigine therapy in elderly patients with epilepsy, bipolar disorder or dementia. Int J Geriatr Psychiatry. 2007;22:945-950.
6. Pinto OC, Akiskal HS. Lamotrigine as a promising approach to borderline personality: an open case series without concurrent DSM-IV major mood disorder. J Affect Disord. 1998;51:333-343.
7. Bellino S, Paradiso E, Bogetto F. Efficacy and tolerability of pharmacotherapies for borderline personality disorder. CNS Drugs. 2008;22(8):671-692.
8. Dursun SM, Deakin JF. Augmenting antipsychotic treatment with lamotrigine or topiramate in patients with treatment-resistant schizophrenia: a naturalistic case-series outcome study. J Psychopharmacol. 2001;15:297-301.
9. Lamictal [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2007.
10. Food and Drug Administration Statistical review and evaluation: antiepileptic drugs and suicidality. Available at: http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugsSafetyInformationforpatientsand%20providers/ucm192556.pdf. Accessed August 23, 2010.
FDA-approved for maintenance treatment of bipolar I disorder, lamotrigine is more effective than lithium for preventing depressive relapses. Lamotrigine combined with lithium, carbamazepine, or valproate provides good protection against recurrences of mania and depression.
Unlike selective serotonin reuptake inhibitors and other antidepressants, lamotrigine does not appear to increase risk of hypomania or mania in bipolar patients.1 Unlike valproate and lithium, it is weight-neutral and requires no serum level monitoring.2 Although lamotrigine’s slow titration and prolonged period until reaching therapeutic effect limits its efficacy as monotherapy in an inpatient setting, the drug can be initiated along with quicker acting agents in the hospital and then titrated after discharge. This strategy allows close monitoring during initial exposure.
Consider lamotrigine as an adjunct for treatment-resistant major depression.3 It is useful for treating aggression and agitation in patients with traumatic brain injury4 or dementia.5 Borderline personality disorder patients treated with lamotrigine may show less affective lability, impulsivity, or aggression.6,7 Lamotrigine can act synergistically with clozapine in some patients with refractory schizophrenia.8
Metabolism and drug interactions
Lamotrigine is metabolized via glucuronidation and eliminated renally. Other drugs metabolized by glucuronidation could interact with lamotrigine (Table).9
Table
Drug interactions associated with lamotrigine
| Interacting drug | Effect on lamotrigine | Management |
|---|---|---|
| Carbamazepine Phenytoin Phenobarbital Primidone Rifampin | Increased clearance | Double dose of lamotrigine when used concomitantly |
| Oral contraceptives containing estrogen | Increased clearance | Lamotrigine dose may need to be increased. Efficacy of oral contraceptives may be decreased; dose modification of oral contraceptive also may be required |
| Valproic acid | Decreased clearance | Reduce dose by at least half, even if your patient is on a medication with the potential to increase clearance |
| Source: Reference 9 | ||
Adverse reactions
Lamotrigine is well tolerated chronically, with fewer adverse effects than other mood stabilizers. Serious rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in 0.08% to 0.13% of patients treated with lamotrigine for bipolar disorder or other mood disorders.9 The risk of developing a skin rash within 2 to 8 weeks of therapy necessitates starting with a low dose, usually 25 mg/d, and gradually titrating.2,9
The FDA added a warning about increased risk of suicidality to the labeling of all anticonvulsants, regardless of indication.10 In a meta-analysis of 199 trials, for every 530 patients treated with anticonvulsants there was 1 additional case of suicidality—not completed suicide.10 Inform patients and their families about the potential risk for increased suicidality and document this discussion of risk vs benefit. All patients should be monitored for worsening depression or suicidal thoughts or behavior throughout treatment.
Other potential side effects occurring in at least 5% of patients receiving lamotrigine include somnolence, headache, rash, and the dose-related side effects of nausea, vomiting, dizziness, ataxia, blurred vision, and diplopia.9
FDA-approved for maintenance treatment of bipolar I disorder, lamotrigine is more effective than lithium for preventing depressive relapses. Lamotrigine combined with lithium, carbamazepine, or valproate provides good protection against recurrences of mania and depression.
Unlike selective serotonin reuptake inhibitors and other antidepressants, lamotrigine does not appear to increase risk of hypomania or mania in bipolar patients.1 Unlike valproate and lithium, it is weight-neutral and requires no serum level monitoring.2 Although lamotrigine’s slow titration and prolonged period until reaching therapeutic effect limits its efficacy as monotherapy in an inpatient setting, the drug can be initiated along with quicker acting agents in the hospital and then titrated after discharge. This strategy allows close monitoring during initial exposure.
Consider lamotrigine as an adjunct for treatment-resistant major depression.3 It is useful for treating aggression and agitation in patients with traumatic brain injury4 or dementia.5 Borderline personality disorder patients treated with lamotrigine may show less affective lability, impulsivity, or aggression.6,7 Lamotrigine can act synergistically with clozapine in some patients with refractory schizophrenia.8
Metabolism and drug interactions
Lamotrigine is metabolized via glucuronidation and eliminated renally. Other drugs metabolized by glucuronidation could interact with lamotrigine (Table).9
Table
Drug interactions associated with lamotrigine
| Interacting drug | Effect on lamotrigine | Management |
|---|---|---|
| Carbamazepine Phenytoin Phenobarbital Primidone Rifampin | Increased clearance | Double dose of lamotrigine when used concomitantly |
| Oral contraceptives containing estrogen | Increased clearance | Lamotrigine dose may need to be increased. Efficacy of oral contraceptives may be decreased; dose modification of oral contraceptive also may be required |
| Valproic acid | Decreased clearance | Reduce dose by at least half, even if your patient is on a medication with the potential to increase clearance |
| Source: Reference 9 | ||
Adverse reactions
Lamotrigine is well tolerated chronically, with fewer adverse effects than other mood stabilizers. Serious rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in 0.08% to 0.13% of patients treated with lamotrigine for bipolar disorder or other mood disorders.9 The risk of developing a skin rash within 2 to 8 weeks of therapy necessitates starting with a low dose, usually 25 mg/d, and gradually titrating.2,9
The FDA added a warning about increased risk of suicidality to the labeling of all anticonvulsants, regardless of indication.10 In a meta-analysis of 199 trials, for every 530 patients treated with anticonvulsants there was 1 additional case of suicidality—not completed suicide.10 Inform patients and their families about the potential risk for increased suicidality and document this discussion of risk vs benefit. All patients should be monitored for worsening depression or suicidal thoughts or behavior throughout treatment.
Other potential side effects occurring in at least 5% of patients receiving lamotrigine include somnolence, headache, rash, and the dose-related side effects of nausea, vomiting, dizziness, ataxia, blurred vision, and diplopia.9
1. Bowden CL. Lamotrigine in the treatment of bipolar disorder. Expert Opin Pharmacother. 2002;3(10):1513-1519.
2. Goldsmith DR, Wagstaff AJ, Ibbotson T, et al. Lamotrigine: a review of its use in bipolar disorder. Drugs. 2003;63(19):2029-2050.
3. Gabriel A. Lamotrigine adjunctive treatment in resistant unipolar depression: an open descriptive study. Depress Anxiety. 2006;23:485-488.
4. Pachet A, Friesen S, Winkelaar D, et al. Beneficial behavioural effects of lamotrigine in traumatic brain injury. Brain Inj. 2003;17(8):715-722.
5. Sajatovic M, Ramsay E, Nanry K, et al. Lamotrigine therapy in elderly patients with epilepsy, bipolar disorder or dementia. Int J Geriatr Psychiatry. 2007;22:945-950.
6. Pinto OC, Akiskal HS. Lamotrigine as a promising approach to borderline personality: an open case series without concurrent DSM-IV major mood disorder. J Affect Disord. 1998;51:333-343.
7. Bellino S, Paradiso E, Bogetto F. Efficacy and tolerability of pharmacotherapies for borderline personality disorder. CNS Drugs. 2008;22(8):671-692.
8. Dursun SM, Deakin JF. Augmenting antipsychotic treatment with lamotrigine or topiramate in patients with treatment-resistant schizophrenia: a naturalistic case-series outcome study. J Psychopharmacol. 2001;15:297-301.
9. Lamictal [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2007.
10. Food and Drug Administration Statistical review and evaluation: antiepileptic drugs and suicidality. Available at: http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugsSafetyInformationforpatientsand%20providers/ucm192556.pdf. Accessed August 23, 2010.
1. Bowden CL. Lamotrigine in the treatment of bipolar disorder. Expert Opin Pharmacother. 2002;3(10):1513-1519.
2. Goldsmith DR, Wagstaff AJ, Ibbotson T, et al. Lamotrigine: a review of its use in bipolar disorder. Drugs. 2003;63(19):2029-2050.
3. Gabriel A. Lamotrigine adjunctive treatment in resistant unipolar depression: an open descriptive study. Depress Anxiety. 2006;23:485-488.
4. Pachet A, Friesen S, Winkelaar D, et al. Beneficial behavioural effects of lamotrigine in traumatic brain injury. Brain Inj. 2003;17(8):715-722.
5. Sajatovic M, Ramsay E, Nanry K, et al. Lamotrigine therapy in elderly patients with epilepsy, bipolar disorder or dementia. Int J Geriatr Psychiatry. 2007;22:945-950.
6. Pinto OC, Akiskal HS. Lamotrigine as a promising approach to borderline personality: an open case series without concurrent DSM-IV major mood disorder. J Affect Disord. 1998;51:333-343.
7. Bellino S, Paradiso E, Bogetto F. Efficacy and tolerability of pharmacotherapies for borderline personality disorder. CNS Drugs. 2008;22(8):671-692.
8. Dursun SM, Deakin JF. Augmenting antipsychotic treatment with lamotrigine or topiramate in patients with treatment-resistant schizophrenia: a naturalistic case-series outcome study. J Psychopharmacol. 2001;15:297-301.
9. Lamictal [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2007.
10. Food and Drug Administration Statistical review and evaluation: antiepileptic drugs and suicidality. Available at: http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugsSafetyInformationforpatientsand%20providers/ucm192556.pdf. Accessed August 23, 2010.
LITHIUM: Using the comeback drug
Lithium is making a comeback for good reason. Aside from its tried and true efficacy for bipolar disorder, lithium has neuroprotective effects and antisuicide properties.1,2
Psychiatry residents who were taught to use divalproex and atypical antipsychotics to treat bipolar disorder are discovering lithium’s benefits. However, all psychiatrists might need a refresher—outlined by the mnemonic LITHIUM—on the fundamentals of this “old school” medication.
Levels between 0.6 and 1.0 mEq/L are sufficient to maintain most bipolar patients, although acute manic patients might require higher levels.2,3 Some patients who cannot tolerate lithium’s side effects might benefit from lower levels near 0.4 to 0.5 mEq/L. Remember, lithium levels are standardized in 12-hour trough plasma concentrations.
Interactions. Nonsteroidal anti-inflammatory drugs (except aspirin and sulindac), angiotensin-converting enzyme inhibitors, thiazide and loop diuretics, verapamil, and diltiazem can increase lithium concentration.4 Caffeine, theophylline, sodium bicarbonate, and dialysis could decrease lithium levels. Be careful when adding lithium to anticonvulsants or antipsychotics because of increased neurotoxicity risk.
Toxicity can lead to coma, seizures, cardiovascular collapse, and death, especially when serum concentrations exceed 3.5 mEq/L.2,4,5 Be alert to early toxicity symptoms such as drowsiness, confusion, coarse hand tremor, worsening gastrointestinal complaints, dysarthria, impaired consciousness, cogwheel rigidity, and ataxia. Lithium’s narrow therapeutic index requires prudent monitoring. Some patients could experience toxicity at low plasma concentrations, such as 1.0 to 1.5 mEq/L.
Half-life varies depending on the patient’s renal function. Steady state is usually reached within 5 days2 but can take up to 10 days because of prolonged half-life in elderly and renally impaired patients (Table). Drawing lithium levels too early could lead to lithium toxicity in these patients, who require modified dosing regimens and monitoring.
Table
Renal metabolism of lithium
| Renal function | Half-life (hours)4 | Steady state (days)* |
|---|---|---|
| Normal | 20 to 27 | 2.5 to 5.6 |
| Renally impaired or elderly patients | 36 to 50 | 4.5 to 10.4 |
| * Steady state is reached after 3 to 5 half-lives | ||
Indications. Lithium is FDA-approved for acute mania and bipolar maintenance, but it also has been used for bipolar depression, antidepressant augmentation, schizoaffective disorder, and mixed manic states.3 Consider combining lithium with an atypical antipsychotic for inpatients with severe bipolar mania with psychotic features. Also consider lithium therapy for patients with recurrent unipolar depression who have been successfully treated with antidepressants but then relapse.
Urinary excretion. Order creatinine measurements every 2 to 3 months for the first 6 months of therapy, then every 6 to 12 months. Although lithium is not a first-line mood-stabilizing drug for patients with renal impairment, it can be used safely in patients with hepatic dysfunction.2,4 Dehydration and a low-sodium diet can cause lithium accumulation, so evaluate patients’ sodium and water balance at the beginning of and throughout lithium therapy. Encourage patients to keep their sodium and water intake as consistent as possible to avoid fluctuations in lithium levels.
Managing side effects is essential to maximize lithium’s effectiveness. Consider switching to a slow-release preparation if your patient cannot tolerate various side effects of regular lithium. If the patient continues to have side effects, consider lowering the dose in 300-mg increments or as clinically indicated. Closely monitor the patient for improved side effects while aiming to maintain an appropriate therapeutic level. Also, moving the entire lithium dose to bedtime could minimize side effects. If these strategies are not adequate, consider adding:
- thyroid replacement to manage elevated thyroid stimulating hormone or frank hypothyroidism
- propranolol, 40 to 100 mg/d in divided doses, for tremor
- amiloride, 5 to 10 mg/d, for polyuria
- loperamide as needed for diarrhea.2,5
Educate your patients on potential side effects, and encourage them to report any unwanted effects. Developing a good patient-provider relationship is essential to maximizing treatment adherence.
1. Chuang DM. Neuroprotective and neurotrophic actions of the mood stabilizer lithium: can it be used to treat neurodegenerative diseases? Crit Rev Neurobiol 2004;16(1-2):83-90.
2. American Psychiatric Association Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 2002;159 (suppl 4):1-50.
3. Schou M, Grof P. Lithium treatment: focus on long-term prophylaxis. In: Akiskal HS, Tohen M, eds. Bipolar psychopharmacotherapy: caring for the patient. West Sussex, England: John Wiley & Sons Ltd; 2006:9–26.
4. Antimanic agents In: McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, Inc.; 2007:2566–75.
5. Dunner DL. Optimizing lithium treatment. J Clin Psychiatry 2000;61(suppl 9):76-81.
Lithium is making a comeback for good reason. Aside from its tried and true efficacy for bipolar disorder, lithium has neuroprotective effects and antisuicide properties.1,2
Psychiatry residents who were taught to use divalproex and atypical antipsychotics to treat bipolar disorder are discovering lithium’s benefits. However, all psychiatrists might need a refresher—outlined by the mnemonic LITHIUM—on the fundamentals of this “old school” medication.
Levels between 0.6 and 1.0 mEq/L are sufficient to maintain most bipolar patients, although acute manic patients might require higher levels.2,3 Some patients who cannot tolerate lithium’s side effects might benefit from lower levels near 0.4 to 0.5 mEq/L. Remember, lithium levels are standardized in 12-hour trough plasma concentrations.
Interactions. Nonsteroidal anti-inflammatory drugs (except aspirin and sulindac), angiotensin-converting enzyme inhibitors, thiazide and loop diuretics, verapamil, and diltiazem can increase lithium concentration.4 Caffeine, theophylline, sodium bicarbonate, and dialysis could decrease lithium levels. Be careful when adding lithium to anticonvulsants or antipsychotics because of increased neurotoxicity risk.
Toxicity can lead to coma, seizures, cardiovascular collapse, and death, especially when serum concentrations exceed 3.5 mEq/L.2,4,5 Be alert to early toxicity symptoms such as drowsiness, confusion, coarse hand tremor, worsening gastrointestinal complaints, dysarthria, impaired consciousness, cogwheel rigidity, and ataxia. Lithium’s narrow therapeutic index requires prudent monitoring. Some patients could experience toxicity at low plasma concentrations, such as 1.0 to 1.5 mEq/L.
Half-life varies depending on the patient’s renal function. Steady state is usually reached within 5 days2 but can take up to 10 days because of prolonged half-life in elderly and renally impaired patients (Table). Drawing lithium levels too early could lead to lithium toxicity in these patients, who require modified dosing regimens and monitoring.
Table
Renal metabolism of lithium
| Renal function | Half-life (hours)4 | Steady state (days)* |
|---|---|---|
| Normal | 20 to 27 | 2.5 to 5.6 |
| Renally impaired or elderly patients | 36 to 50 | 4.5 to 10.4 |
| * Steady state is reached after 3 to 5 half-lives | ||
Indications. Lithium is FDA-approved for acute mania and bipolar maintenance, but it also has been used for bipolar depression, antidepressant augmentation, schizoaffective disorder, and mixed manic states.3 Consider combining lithium with an atypical antipsychotic for inpatients with severe bipolar mania with psychotic features. Also consider lithium therapy for patients with recurrent unipolar depression who have been successfully treated with antidepressants but then relapse.
Urinary excretion. Order creatinine measurements every 2 to 3 months for the first 6 months of therapy, then every 6 to 12 months. Although lithium is not a first-line mood-stabilizing drug for patients with renal impairment, it can be used safely in patients with hepatic dysfunction.2,4 Dehydration and a low-sodium diet can cause lithium accumulation, so evaluate patients’ sodium and water balance at the beginning of and throughout lithium therapy. Encourage patients to keep their sodium and water intake as consistent as possible to avoid fluctuations in lithium levels.
Managing side effects is essential to maximize lithium’s effectiveness. Consider switching to a slow-release preparation if your patient cannot tolerate various side effects of regular lithium. If the patient continues to have side effects, consider lowering the dose in 300-mg increments or as clinically indicated. Closely monitor the patient for improved side effects while aiming to maintain an appropriate therapeutic level. Also, moving the entire lithium dose to bedtime could minimize side effects. If these strategies are not adequate, consider adding:
- thyroid replacement to manage elevated thyroid stimulating hormone or frank hypothyroidism
- propranolol, 40 to 100 mg/d in divided doses, for tremor
- amiloride, 5 to 10 mg/d, for polyuria
- loperamide as needed for diarrhea.2,5
Educate your patients on potential side effects, and encourage them to report any unwanted effects. Developing a good patient-provider relationship is essential to maximizing treatment adherence.
Lithium is making a comeback for good reason. Aside from its tried and true efficacy for bipolar disorder, lithium has neuroprotective effects and antisuicide properties.1,2
Psychiatry residents who were taught to use divalproex and atypical antipsychotics to treat bipolar disorder are discovering lithium’s benefits. However, all psychiatrists might need a refresher—outlined by the mnemonic LITHIUM—on the fundamentals of this “old school” medication.
Levels between 0.6 and 1.0 mEq/L are sufficient to maintain most bipolar patients, although acute manic patients might require higher levels.2,3 Some patients who cannot tolerate lithium’s side effects might benefit from lower levels near 0.4 to 0.5 mEq/L. Remember, lithium levels are standardized in 12-hour trough plasma concentrations.
Interactions. Nonsteroidal anti-inflammatory drugs (except aspirin and sulindac), angiotensin-converting enzyme inhibitors, thiazide and loop diuretics, verapamil, and diltiazem can increase lithium concentration.4 Caffeine, theophylline, sodium bicarbonate, and dialysis could decrease lithium levels. Be careful when adding lithium to anticonvulsants or antipsychotics because of increased neurotoxicity risk.
Toxicity can lead to coma, seizures, cardiovascular collapse, and death, especially when serum concentrations exceed 3.5 mEq/L.2,4,5 Be alert to early toxicity symptoms such as drowsiness, confusion, coarse hand tremor, worsening gastrointestinal complaints, dysarthria, impaired consciousness, cogwheel rigidity, and ataxia. Lithium’s narrow therapeutic index requires prudent monitoring. Some patients could experience toxicity at low plasma concentrations, such as 1.0 to 1.5 mEq/L.
Half-life varies depending on the patient’s renal function. Steady state is usually reached within 5 days2 but can take up to 10 days because of prolonged half-life in elderly and renally impaired patients (Table). Drawing lithium levels too early could lead to lithium toxicity in these patients, who require modified dosing regimens and monitoring.
Table
Renal metabolism of lithium
| Renal function | Half-life (hours)4 | Steady state (days)* |
|---|---|---|
| Normal | 20 to 27 | 2.5 to 5.6 |
| Renally impaired or elderly patients | 36 to 50 | 4.5 to 10.4 |
| * Steady state is reached after 3 to 5 half-lives | ||
Indications. Lithium is FDA-approved for acute mania and bipolar maintenance, but it also has been used for bipolar depression, antidepressant augmentation, schizoaffective disorder, and mixed manic states.3 Consider combining lithium with an atypical antipsychotic for inpatients with severe bipolar mania with psychotic features. Also consider lithium therapy for patients with recurrent unipolar depression who have been successfully treated with antidepressants but then relapse.
Urinary excretion. Order creatinine measurements every 2 to 3 months for the first 6 months of therapy, then every 6 to 12 months. Although lithium is not a first-line mood-stabilizing drug for patients with renal impairment, it can be used safely in patients with hepatic dysfunction.2,4 Dehydration and a low-sodium diet can cause lithium accumulation, so evaluate patients’ sodium and water balance at the beginning of and throughout lithium therapy. Encourage patients to keep their sodium and water intake as consistent as possible to avoid fluctuations in lithium levels.
Managing side effects is essential to maximize lithium’s effectiveness. Consider switching to a slow-release preparation if your patient cannot tolerate various side effects of regular lithium. If the patient continues to have side effects, consider lowering the dose in 300-mg increments or as clinically indicated. Closely monitor the patient for improved side effects while aiming to maintain an appropriate therapeutic level. Also, moving the entire lithium dose to bedtime could minimize side effects. If these strategies are not adequate, consider adding:
- thyroid replacement to manage elevated thyroid stimulating hormone or frank hypothyroidism
- propranolol, 40 to 100 mg/d in divided doses, for tremor
- amiloride, 5 to 10 mg/d, for polyuria
- loperamide as needed for diarrhea.2,5
Educate your patients on potential side effects, and encourage them to report any unwanted effects. Developing a good patient-provider relationship is essential to maximizing treatment adherence.
1. Chuang DM. Neuroprotective and neurotrophic actions of the mood stabilizer lithium: can it be used to treat neurodegenerative diseases? Crit Rev Neurobiol 2004;16(1-2):83-90.
2. American Psychiatric Association Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 2002;159 (suppl 4):1-50.
3. Schou M, Grof P. Lithium treatment: focus on long-term prophylaxis. In: Akiskal HS, Tohen M, eds. Bipolar psychopharmacotherapy: caring for the patient. West Sussex, England: John Wiley & Sons Ltd; 2006:9–26.
4. Antimanic agents In: McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, Inc.; 2007:2566–75.
5. Dunner DL. Optimizing lithium treatment. J Clin Psychiatry 2000;61(suppl 9):76-81.
1. Chuang DM. Neuroprotective and neurotrophic actions of the mood stabilizer lithium: can it be used to treat neurodegenerative diseases? Crit Rev Neurobiol 2004;16(1-2):83-90.
2. American Psychiatric Association Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 2002;159 (suppl 4):1-50.
3. Schou M, Grof P. Lithium treatment: focus on long-term prophylaxis. In: Akiskal HS, Tohen M, eds. Bipolar psychopharmacotherapy: caring for the patient. West Sussex, England: John Wiley & Sons Ltd; 2006:9–26.
4. Antimanic agents In: McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, Inc.; 2007:2566–75.
5. Dunner DL. Optimizing lithium treatment. J Clin Psychiatry 2000;61(suppl 9):76-81.