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Ms. S, age 53, has bipolar disorder, dyslipidemia, and drug-induced tremor and presents to the clinic complaining of increasing depressive symptoms despite a history of response to her current medication regimen (Table 1). When informed that her lithium and divalproex levels are subtherapeutic, Ms. S admits that she doesn’t always take her medication. She understands her psychiatric and medical conditions and rationale for her current medications; however, she recently changed jobs, which has affected her ability to adhere to her regimen. Ms. S says the only thing preventing her from adhering to her medication is the frequency of administration.
Only approximately one-half of patients with chronic illness adhere to their medication regimen.1 Nonadherence has been reported in 20% to 72% of patients with schizophrenia, 20% to 50% of those with bipolar disorder, and 28% to 52% with major depressive disorder.2 Medication nonadherence can impact a patient’s health outcomes1 and could lead to increased hospitalizations, homelessness, substance use, decreased quality of life, and suicide; however, it is difficult to fully determine the extent of medication nonadherence due to lack of standard measurement methodology.2
Factors that affect medication adherence in patients with psychiatric diagnoses include:
- patient-related (ie, demographic factors)
- psychological (eg, lack of insight into illness, negative emotions toward medications)
- social and environmental (eg, therapeutic alliance with the physician, housing stability and support, and discharge planning)
- medication-related (eg, complex dosing schedule).2
Medication regimen tolerability, complexity, and cost; patient understanding of medication indications and onset of therapeutic effect; and patient’s view of benefits can impact adherence.1,3 Assessing medication adherence and identifying barriers specific to the patient is essential when developing a treatment plan. If complexity is a barrier, simplify the medication regimen.
Claxton et al4 found an inverse relationship between medication dosing and adherence. Reviewing data from 76 studies that used electronic monitoring (records the time and date of actual dosing events) the overall rate of medication adherence was 71% ± 17%. Adherence rates were significantly higher with once daily (79% ± 14%) vs 3 times daily (65% ± 16%) or 4 times daily (51% ± 20%), and twice daily (69% ± 15%) was significantly better than 4 times daily dosing. Adherence between once daily and twice daily or twice daily and 3 times daily did not result in a significant difference. The authors noted that electronic monitoring has limitations; patients could have opened the medication bottle but not ingested the drug.4
Consider these factors and strategies when developing a treatment plan (Table 2).3,5,6
Ease of administration
Medication packaging. Patients with limited dexterity might not be able to remove the medication from blister packaging or child-proof cap, measure non-unit dose liquid preparations, or split tablets in half.3 Patients with limited patience could get frustrated and skip medications that take longer to remove from packaging or have to be measured. Consult a pharmacist about medication packaging options or formulations that might be appropriate for some patients (ie, individuals with dysphagia), such as oral-disintegrating or sublingual tablets.
Assess pill burden. Although it might not be appropriate when titrating medications, consider adjusting the maintenance dosage to reduce the number of tablets (eg, a patient prescribed divalproex delayed-release, 2,750 mg/d, will take eleven 250-mg tablets vs taking divalproex delayed-release, 2,500 mg/d, which is five 500-mg tablets).
Keep in mind availability of combination medications (eg, olanzapine/fluoxetine) to reduce pill burden. Also, if possible, consider comorbid disease states that allow for prescribing 1 medication that can treat 2 conditions to reduce pill burden (eg, duloxetine for depression and diabetic neuropathy).3
Food recommendations. Review food requirements (ie, administration on an empty stomach vs the need for a specific caloric amount) and whether these are recommendations to improve tolerability or required to ensure adequate absorption. Nonadherence with dietary recommendations that can affect absorption may result in reduced effectiveness despite taking the medication.
Administration instructions
Keep administration instructions simple and be consistent with instructions and terminology.3 For example, if all medications are to be administered once daily in the morning, provide specific instructions (ie, “every morning”) because it may be confusing for patients if some medications are written for “once daily” and others for “every morning.” Some patients might prefer to have the medication indication noted in the administration instructions. Additionally, be aware of the patient’s literacy, and ensure the patient is able to read and understand instructions before leaving the office.
Administration frequency
Consider the required administration frequency and the patient’s self-reported ability to adhere to that frequency before initiating a new medication. Ask the patient what frequencies he (she) can best manage and evaluate his (her) regimen to determine if a less frequent schedule is possible. Consider formulations that may allow for less frequent dosing (eg, controlled-release, sustained-release, long-acting, or extended-release formulations) or consolidating divided doses to once daily if possible.3 Some of these formulations may be preferred for tolerability advantages vs extending the dosing interval (eg, regular-release and extended-release lithium tablets have the same half-life of approximately 18 to 36 hours; however, the extended-release formulation has a longer time to peak serum concentration, approximately 2 to 6 hours vs 0.5 to 3 hours, respectively. As a result, the extended-release formulation may offer improved tolerability in terms of peak-related side effects,5,7 which may be advantageous, especially when dosing lithium once daily). Keep in mind, for some patients every other day administration is more difficult to adhere to than once daily.
Review drug or prescribing information to determine an appropriate conversion before switching from an immediate-release to a longer-acting formulation. The switch may result in different drug serum concentrations (eg, propranolol sustained-release has different pharmacokinetics and produces lower blood levels than the immediate-release formulation). When switching between formulations, monitor patients to ensure the desired therapeutic effect is maintained.8
Consider collaborating with pharmacists, primary care providers, and other prescribers to simplify medical and psychiatric medications.
Other considerations
Lab monitoring requirements for drugs, such as clozapine, lithium, or divalproex, could affect a patient’s willingness to adhere. Use of weekly or monthly medication organizers, mobile apps, alarms (on cell phones or clocks), medication check-off sheets or calendars, and family or friend support could help improve medication adherence.
Case continued
After reviewing the medication regimen and consulting with a pharmacist, Ms. S’s regimen is simplified to once-daily administration, and pill burden is reduced by using extended-release formulations and consolidating doses at bedtime (Table 1). Additionally, trazodone is discontinued because divalproex, now taken once daily at bedtime, is sedating and aids in sleep.
For medications that require therapeutic blood monitoring such as lithium and divalproex, check drug levels when switching formulations. In the case of Ms. S, lithium, propranolol, and divalproex dosages were switched to extended-release preparations and consolidated to once daily at bedtime; the divalproex dosage was increased because an increase in total daily dose between 8% to 20% may be required to maintain similar serum concentrations.5 Lithium immediate-release was switched to the extended-release, which reduced the pill burden and could help tolerability if Ms. S experiences peak concentration-related side effects. Consolidating the lithium dosage from divided to once daily at bedtime can increase the lithium serum level by up to 25%.6
With a change in formulation, monitor tolerability and effectiveness of the medication regimen in regard to mood stabilization and tremor control, as well as check serum lithium and divalproex levels, creatinine, and sodium after 5 days, unless signs and symptoms of toxicity occur.
1. World Health Organization. Adherence to long-term therapies: evidence for action. http://apps.who.int/iris/bitstream/10665/42682/1/9241545992.pdf. Published 2003. Accessed November 29, 2015.
2. Julius RJ, Novitsky MA, Dubin WR. Medication adherence: a review of the literature and implications for clinical practice. J Psychiatr Pract. 2009;15(1):34-44.
3. Atreja A, Bellam N, Levy SR. Strategies to enhance patient adherence: making it simple. MedGenMed. 2005;7(1):4.
4. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23(8):1296-1310.
5. Lexicomp Online, Lexi-Drugs, Hudson, Ohio: Lexi-Comp, Inc.; February 28, 2016.
6. Malhi GS, Tanious M. Optimal frequency of lithium administration in the treatment of bipolar disorder: clinical and dosing considerations. CNS Drugs. 2011;25(4):289-298.
7. Jefferson JW, Greist JH, Ackerman DL, et al. Lithium: an overview. In: Lithium encyclopedia for clinical practice. 2nd ed. Washington, DC: American Psychiatric Press; 1987.
8. Inderal LA (propranolol extended release) [package insert]. Cranford, NJ: Akrimax Pharmaceuticals; November 2015.
Ms. S, age 53, has bipolar disorder, dyslipidemia, and drug-induced tremor and presents to the clinic complaining of increasing depressive symptoms despite a history of response to her current medication regimen (Table 1). When informed that her lithium and divalproex levels are subtherapeutic, Ms. S admits that she doesn’t always take her medication. She understands her psychiatric and medical conditions and rationale for her current medications; however, she recently changed jobs, which has affected her ability to adhere to her regimen. Ms. S says the only thing preventing her from adhering to her medication is the frequency of administration.
Only approximately one-half of patients with chronic illness adhere to their medication regimen.1 Nonadherence has been reported in 20% to 72% of patients with schizophrenia, 20% to 50% of those with bipolar disorder, and 28% to 52% with major depressive disorder.2 Medication nonadherence can impact a patient’s health outcomes1 and could lead to increased hospitalizations, homelessness, substance use, decreased quality of life, and suicide; however, it is difficult to fully determine the extent of medication nonadherence due to lack of standard measurement methodology.2
Factors that affect medication adherence in patients with psychiatric diagnoses include:
- patient-related (ie, demographic factors)
- psychological (eg, lack of insight into illness, negative emotions toward medications)
- social and environmental (eg, therapeutic alliance with the physician, housing stability and support, and discharge planning)
- medication-related (eg, complex dosing schedule).2
Medication regimen tolerability, complexity, and cost; patient understanding of medication indications and onset of therapeutic effect; and patient’s view of benefits can impact adherence.1,3 Assessing medication adherence and identifying barriers specific to the patient is essential when developing a treatment plan. If complexity is a barrier, simplify the medication regimen.
Claxton et al4 found an inverse relationship between medication dosing and adherence. Reviewing data from 76 studies that used electronic monitoring (records the time and date of actual dosing events) the overall rate of medication adherence was 71% ± 17%. Adherence rates were significantly higher with once daily (79% ± 14%) vs 3 times daily (65% ± 16%) or 4 times daily (51% ± 20%), and twice daily (69% ± 15%) was significantly better than 4 times daily dosing. Adherence between once daily and twice daily or twice daily and 3 times daily did not result in a significant difference. The authors noted that electronic monitoring has limitations; patients could have opened the medication bottle but not ingested the drug.4
Consider these factors and strategies when developing a treatment plan (Table 2).3,5,6
Ease of administration
Medication packaging. Patients with limited dexterity might not be able to remove the medication from blister packaging or child-proof cap, measure non-unit dose liquid preparations, or split tablets in half.3 Patients with limited patience could get frustrated and skip medications that take longer to remove from packaging or have to be measured. Consult a pharmacist about medication packaging options or formulations that might be appropriate for some patients (ie, individuals with dysphagia), such as oral-disintegrating or sublingual tablets.
Assess pill burden. Although it might not be appropriate when titrating medications, consider adjusting the maintenance dosage to reduce the number of tablets (eg, a patient prescribed divalproex delayed-release, 2,750 mg/d, will take eleven 250-mg tablets vs taking divalproex delayed-release, 2,500 mg/d, which is five 500-mg tablets).
Keep in mind availability of combination medications (eg, olanzapine/fluoxetine) to reduce pill burden. Also, if possible, consider comorbid disease states that allow for prescribing 1 medication that can treat 2 conditions to reduce pill burden (eg, duloxetine for depression and diabetic neuropathy).3
Food recommendations. Review food requirements (ie, administration on an empty stomach vs the need for a specific caloric amount) and whether these are recommendations to improve tolerability or required to ensure adequate absorption. Nonadherence with dietary recommendations that can affect absorption may result in reduced effectiveness despite taking the medication.
Administration instructions
Keep administration instructions simple and be consistent with instructions and terminology.3 For example, if all medications are to be administered once daily in the morning, provide specific instructions (ie, “every morning”) because it may be confusing for patients if some medications are written for “once daily” and others for “every morning.” Some patients might prefer to have the medication indication noted in the administration instructions. Additionally, be aware of the patient’s literacy, and ensure the patient is able to read and understand instructions before leaving the office.
Administration frequency
Consider the required administration frequency and the patient’s self-reported ability to adhere to that frequency before initiating a new medication. Ask the patient what frequencies he (she) can best manage and evaluate his (her) regimen to determine if a less frequent schedule is possible. Consider formulations that may allow for less frequent dosing (eg, controlled-release, sustained-release, long-acting, or extended-release formulations) or consolidating divided doses to once daily if possible.3 Some of these formulations may be preferred for tolerability advantages vs extending the dosing interval (eg, regular-release and extended-release lithium tablets have the same half-life of approximately 18 to 36 hours; however, the extended-release formulation has a longer time to peak serum concentration, approximately 2 to 6 hours vs 0.5 to 3 hours, respectively. As a result, the extended-release formulation may offer improved tolerability in terms of peak-related side effects,5,7 which may be advantageous, especially when dosing lithium once daily). Keep in mind, for some patients every other day administration is more difficult to adhere to than once daily.
Review drug or prescribing information to determine an appropriate conversion before switching from an immediate-release to a longer-acting formulation. The switch may result in different drug serum concentrations (eg, propranolol sustained-release has different pharmacokinetics and produces lower blood levels than the immediate-release formulation). When switching between formulations, monitor patients to ensure the desired therapeutic effect is maintained.8
Consider collaborating with pharmacists, primary care providers, and other prescribers to simplify medical and psychiatric medications.
Other considerations
Lab monitoring requirements for drugs, such as clozapine, lithium, or divalproex, could affect a patient’s willingness to adhere. Use of weekly or monthly medication organizers, mobile apps, alarms (on cell phones or clocks), medication check-off sheets or calendars, and family or friend support could help improve medication adherence.
Case continued
After reviewing the medication regimen and consulting with a pharmacist, Ms. S’s regimen is simplified to once-daily administration, and pill burden is reduced by using extended-release formulations and consolidating doses at bedtime (Table 1). Additionally, trazodone is discontinued because divalproex, now taken once daily at bedtime, is sedating and aids in sleep.
For medications that require therapeutic blood monitoring such as lithium and divalproex, check drug levels when switching formulations. In the case of Ms. S, lithium, propranolol, and divalproex dosages were switched to extended-release preparations and consolidated to once daily at bedtime; the divalproex dosage was increased because an increase in total daily dose between 8% to 20% may be required to maintain similar serum concentrations.5 Lithium immediate-release was switched to the extended-release, which reduced the pill burden and could help tolerability if Ms. S experiences peak concentration-related side effects. Consolidating the lithium dosage from divided to once daily at bedtime can increase the lithium serum level by up to 25%.6
With a change in formulation, monitor tolerability and effectiveness of the medication regimen in regard to mood stabilization and tremor control, as well as check serum lithium and divalproex levels, creatinine, and sodium after 5 days, unless signs and symptoms of toxicity occur.
Ms. S, age 53, has bipolar disorder, dyslipidemia, and drug-induced tremor and presents to the clinic complaining of increasing depressive symptoms despite a history of response to her current medication regimen (Table 1). When informed that her lithium and divalproex levels are subtherapeutic, Ms. S admits that she doesn’t always take her medication. She understands her psychiatric and medical conditions and rationale for her current medications; however, she recently changed jobs, which has affected her ability to adhere to her regimen. Ms. S says the only thing preventing her from adhering to her medication is the frequency of administration.
Only approximately one-half of patients with chronic illness adhere to their medication regimen.1 Nonadherence has been reported in 20% to 72% of patients with schizophrenia, 20% to 50% of those with bipolar disorder, and 28% to 52% with major depressive disorder.2 Medication nonadherence can impact a patient’s health outcomes1 and could lead to increased hospitalizations, homelessness, substance use, decreased quality of life, and suicide; however, it is difficult to fully determine the extent of medication nonadherence due to lack of standard measurement methodology.2
Factors that affect medication adherence in patients with psychiatric diagnoses include:
- patient-related (ie, demographic factors)
- psychological (eg, lack of insight into illness, negative emotions toward medications)
- social and environmental (eg, therapeutic alliance with the physician, housing stability and support, and discharge planning)
- medication-related (eg, complex dosing schedule).2
Medication regimen tolerability, complexity, and cost; patient understanding of medication indications and onset of therapeutic effect; and patient’s view of benefits can impact adherence.1,3 Assessing medication adherence and identifying barriers specific to the patient is essential when developing a treatment plan. If complexity is a barrier, simplify the medication regimen.
Claxton et al4 found an inverse relationship between medication dosing and adherence. Reviewing data from 76 studies that used electronic monitoring (records the time and date of actual dosing events) the overall rate of medication adherence was 71% ± 17%. Adherence rates were significantly higher with once daily (79% ± 14%) vs 3 times daily (65% ± 16%) or 4 times daily (51% ± 20%), and twice daily (69% ± 15%) was significantly better than 4 times daily dosing. Adherence between once daily and twice daily or twice daily and 3 times daily did not result in a significant difference. The authors noted that electronic monitoring has limitations; patients could have opened the medication bottle but not ingested the drug.4
Consider these factors and strategies when developing a treatment plan (Table 2).3,5,6
Ease of administration
Medication packaging. Patients with limited dexterity might not be able to remove the medication from blister packaging or child-proof cap, measure non-unit dose liquid preparations, or split tablets in half.3 Patients with limited patience could get frustrated and skip medications that take longer to remove from packaging or have to be measured. Consult a pharmacist about medication packaging options or formulations that might be appropriate for some patients (ie, individuals with dysphagia), such as oral-disintegrating or sublingual tablets.
Assess pill burden. Although it might not be appropriate when titrating medications, consider adjusting the maintenance dosage to reduce the number of tablets (eg, a patient prescribed divalproex delayed-release, 2,750 mg/d, will take eleven 250-mg tablets vs taking divalproex delayed-release, 2,500 mg/d, which is five 500-mg tablets).
Keep in mind availability of combination medications (eg, olanzapine/fluoxetine) to reduce pill burden. Also, if possible, consider comorbid disease states that allow for prescribing 1 medication that can treat 2 conditions to reduce pill burden (eg, duloxetine for depression and diabetic neuropathy).3
Food recommendations. Review food requirements (ie, administration on an empty stomach vs the need for a specific caloric amount) and whether these are recommendations to improve tolerability or required to ensure adequate absorption. Nonadherence with dietary recommendations that can affect absorption may result in reduced effectiveness despite taking the medication.
Administration instructions
Keep administration instructions simple and be consistent with instructions and terminology.3 For example, if all medications are to be administered once daily in the morning, provide specific instructions (ie, “every morning”) because it may be confusing for patients if some medications are written for “once daily” and others for “every morning.” Some patients might prefer to have the medication indication noted in the administration instructions. Additionally, be aware of the patient’s literacy, and ensure the patient is able to read and understand instructions before leaving the office.
Administration frequency
Consider the required administration frequency and the patient’s self-reported ability to adhere to that frequency before initiating a new medication. Ask the patient what frequencies he (she) can best manage and evaluate his (her) regimen to determine if a less frequent schedule is possible. Consider formulations that may allow for less frequent dosing (eg, controlled-release, sustained-release, long-acting, or extended-release formulations) or consolidating divided doses to once daily if possible.3 Some of these formulations may be preferred for tolerability advantages vs extending the dosing interval (eg, regular-release and extended-release lithium tablets have the same half-life of approximately 18 to 36 hours; however, the extended-release formulation has a longer time to peak serum concentration, approximately 2 to 6 hours vs 0.5 to 3 hours, respectively. As a result, the extended-release formulation may offer improved tolerability in terms of peak-related side effects,5,7 which may be advantageous, especially when dosing lithium once daily). Keep in mind, for some patients every other day administration is more difficult to adhere to than once daily.
Review drug or prescribing information to determine an appropriate conversion before switching from an immediate-release to a longer-acting formulation. The switch may result in different drug serum concentrations (eg, propranolol sustained-release has different pharmacokinetics and produces lower blood levels than the immediate-release formulation). When switching between formulations, monitor patients to ensure the desired therapeutic effect is maintained.8
Consider collaborating with pharmacists, primary care providers, and other prescribers to simplify medical and psychiatric medications.
Other considerations
Lab monitoring requirements for drugs, such as clozapine, lithium, or divalproex, could affect a patient’s willingness to adhere. Use of weekly or monthly medication organizers, mobile apps, alarms (on cell phones or clocks), medication check-off sheets or calendars, and family or friend support could help improve medication adherence.
Case continued
After reviewing the medication regimen and consulting with a pharmacist, Ms. S’s regimen is simplified to once-daily administration, and pill burden is reduced by using extended-release formulations and consolidating doses at bedtime (Table 1). Additionally, trazodone is discontinued because divalproex, now taken once daily at bedtime, is sedating and aids in sleep.
For medications that require therapeutic blood monitoring such as lithium and divalproex, check drug levels when switching formulations. In the case of Ms. S, lithium, propranolol, and divalproex dosages were switched to extended-release preparations and consolidated to once daily at bedtime; the divalproex dosage was increased because an increase in total daily dose between 8% to 20% may be required to maintain similar serum concentrations.5 Lithium immediate-release was switched to the extended-release, which reduced the pill burden and could help tolerability if Ms. S experiences peak concentration-related side effects. Consolidating the lithium dosage from divided to once daily at bedtime can increase the lithium serum level by up to 25%.6
With a change in formulation, monitor tolerability and effectiveness of the medication regimen in regard to mood stabilization and tremor control, as well as check serum lithium and divalproex levels, creatinine, and sodium after 5 days, unless signs and symptoms of toxicity occur.
1. World Health Organization. Adherence to long-term therapies: evidence for action. http://apps.who.int/iris/bitstream/10665/42682/1/9241545992.pdf. Published 2003. Accessed November 29, 2015.
2. Julius RJ, Novitsky MA, Dubin WR. Medication adherence: a review of the literature and implications for clinical practice. J Psychiatr Pract. 2009;15(1):34-44.
3. Atreja A, Bellam N, Levy SR. Strategies to enhance patient adherence: making it simple. MedGenMed. 2005;7(1):4.
4. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23(8):1296-1310.
5. Lexicomp Online, Lexi-Drugs, Hudson, Ohio: Lexi-Comp, Inc.; February 28, 2016.
6. Malhi GS, Tanious M. Optimal frequency of lithium administration in the treatment of bipolar disorder: clinical and dosing considerations. CNS Drugs. 2011;25(4):289-298.
7. Jefferson JW, Greist JH, Ackerman DL, et al. Lithium: an overview. In: Lithium encyclopedia for clinical practice. 2nd ed. Washington, DC: American Psychiatric Press; 1987.
8. Inderal LA (propranolol extended release) [package insert]. Cranford, NJ: Akrimax Pharmaceuticals; November 2015.
1. World Health Organization. Adherence to long-term therapies: evidence for action. http://apps.who.int/iris/bitstream/10665/42682/1/9241545992.pdf. Published 2003. Accessed November 29, 2015.
2. Julius RJ, Novitsky MA, Dubin WR. Medication adherence: a review of the literature and implications for clinical practice. J Psychiatr Pract. 2009;15(1):34-44.
3. Atreja A, Bellam N, Levy SR. Strategies to enhance patient adherence: making it simple. MedGenMed. 2005;7(1):4.
4. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23(8):1296-1310.
5. Lexicomp Online, Lexi-Drugs, Hudson, Ohio: Lexi-Comp, Inc.; February 28, 2016.
6. Malhi GS, Tanious M. Optimal frequency of lithium administration in the treatment of bipolar disorder: clinical and dosing considerations. CNS Drugs. 2011;25(4):289-298.
7. Jefferson JW, Greist JH, Ackerman DL, et al. Lithium: an overview. In: Lithium encyclopedia for clinical practice. 2nd ed. Washington, DC: American Psychiatric Press; 1987.
8. Inderal LA (propranolol extended release) [package insert]. Cranford, NJ: Akrimax Pharmaceuticals; November 2015.
