Clinical Therapeutics/Volume 36, Number 11, 2014
Editor-in-Chief’s Note What Is Depression and Who Is in Depression Studies? For many elderly persons, their so-called golden years are not so golden, particularly for the so-called “old old” (ie, those aged 485 years). Problems can occur in all spheres of life. Some of the most common concerns are: loss of spouses and friends, living on fixed incomes, living alone, diminished visual acuity and depth perception, needing to give up driving, reduced hearing, falls, and increased sensitivity to medications. These are but a small list of changes that can be distressing. I know from my own experiences and those of friends and acquaintances that quality of life can be meaningfully altered. How do such changes affect older people? Some people take them in stride and adjust to each additional limitation. Some are unhappy and do their share of complaining but soldier on. Some become demoralized, but good news and experiences or accomplishments (mastery of problems) can turn things around; still others become clinically depressed. Those in the Richard I. Shader, MD latter group often do not receive the help they need. In the present issue, Professor Kenneth Boockvar, our Topic Editor for Geriatric Therapeutics, has assembled a collection of articles looking at the problems related to depression and mental health in the elderly.1–7 The review by Mattappallil and Mergenhagen1 addresses the need for recognizing the unwanted central nervous system effects of antimicrobial agents in the elderly. Such agents are often overlooked as causes of delirium or psychosis. The study by Reinhardt and coworkers2 looks at problem-solving treatment as an approach to alleviating subsyndromal depression in the elderly. Although I consider this study a valuable contribution to determining how cognitive-behavioral therapy (CBT) can be useful and may even obviate the need for antidepressant medications, I do have questions about what is meant by subsyndromal depression or depression symptoms at a subsyndromal level. Is it possible that people who gained self-esteem through mastery and problem solving had been demoralized rather than depressed? We do not have biomarkers in this or the other related articles in this issue that clearly define which patients are suffering from a clinical depression. Nor do we know if clinical depression is a syndrome with many different etiologies. Are we getting anywhere with finding biomarkers for depression or factors that predict response to treatment? I believe that 3 recently published articles may be helping us along that path. A study by Redei and colleagues8 examined genetic biomarkers in patients with major depressive disorder (MDD) versus control subjects. The authors found that the levels of 9 blood transcripts separated the cohorts. At study entry, the patients with MDD had significantly reduced amounts of ADCY3, DGKA, FAM46A, IGSF4A/CADM1, KIAA1539, MARCKS, PSME1, RAPH1, and TLR7. The DGKA, KIAA1539, and RAPH1 levels continued to be reduced even after a CBT intervention. The authors believe that these latter 3 biomarkers may reveal a predisposition or vulnerability to depression. After 18 weeks, 9 of the 22 patients with MDD were in CBT-related remission. The 9 remitted patients differed from the other 13 in their pretreatment levels of ASAH1, ATP11C, and KIAA1539, and all 3 transcripts were absent in those who did not remit. These are all blood-borne proteins that are encoded by their respective genes. Studies such as this one argue for the existence of 41 type of MDD. A second intriguing study is presented by Wium-Andersen and colleagues.9 This group found a significant correlation between blood levels of C-reactive protein (CRP) and reports of psychological distress and depression. CRP is considered to be a biomarker for inflammation. In relationship to my points about mastery and demoralization, this study found a significant relationship between CRP levels and questions about a wish to give up and a sense of not accomplishing much. The report by Peterson and colleagues7 in this issue measured CRP and several other biomarkers in a subset of patients. However, the relationship between CRP and level of depression was not studied.
November 2014
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Clinical Therapeutics Finally, Leuchter and colleagues10 found that a belief in the effectiveness of their antidepressant agents and a supportive interaction between patients and caregivers were key factors in determining response to treatment. They concluded, not surprisingly, that “belief in the power or effectiveness of the medication may be a contributor to placebo responses in the treatment of depression.” To me, these articles suggest that depression means many things to many people. Before we can perform definitive research, we must have better ways of defining our study populations; we need to have meaningful biomarkers and to rule out those who are placebo responsive. Richard I. Shader, MD Editor-in-Chief
REFERENCES
1. Mattappallil A, Mergenhagen K. Neurotoxicity with antimicrobials in the elderly: a review. Clin Ther. 2014;36:1489–1511. 2. Reinhardt JP, Horowitz A, Cimarolli VR, et al. Addressing depression in a long-term care setting: a phase II pilot of problemsolving treatment. Clin Ther. 2014;36:1531–1537. 3. Linnebur SA, Vande Griende JP, Metz KR, et al. Patient-level medication regimen complexity in older adults with depression. Clin Ther. 2014;36:1538–1546. 4. Garrido MM, Prigerson HG, Penrod JD, et al. Choosing wisely? Benzodiazepine and sedative-hypnotic use among older seriously ill veterans. Clin Ther. 2014;36:1547–1554. 5. Redding SE, Liu S, Hung WW, Boockvar KS. Opioid interruptions, pain, and withdrawal symptoms in nursing home residents. Clin Ther. 2014;36:1555–1563. 6. Zahradnik EK, Grossman H. Palliative care as a primary therapeutic approach in advanced dementia: a narrative review. Clin Ther. 2014;36:1512–1517. 7. Peterson JC, Charlson ME, Wells MT, Altemus M. Depression, coronary artery disease, and physical activity: how much exercise is enough? Clin Ther. 2014;36:1518–1530. 8. Redei EE, Andrus BM, Kwasny MJ, et al. Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy. Transl Psychiatry. 2014;4:e442. 9. Wium-Andersen MK, Ørsted DD, Nielsen SF, et al. Elevated C-reactive protein levels, psychological distress, and depression in 73,131 individuals. JAMA Psychiatry. 2013;70:176–184. 10. Leuchter AF, Hunter AM, Tartter M, et al. Role of pill-taking, expectation and therapeutic alliance in the placebo response in clinical trials for major depression. Br J Psychiatry. 2014 Sep 11. [Epub ahead of print].
http://dx.doi.org/10.1016/j.clinthera.2014.10.016
Geriatric Therapeutics Specialty Updates Geriatric Therapeutics Updates are published annually and available as FREE ACCESS content on the journal’s website. The 2013 Geriatric Therapeutics Update, entitled “Pain Management in Older Adults, was published in Volume 35, Number 11 of Clinical Therapeutics. To view 2013’s Geriatric Therapeutics Update, see the articles below: 1. Boockvar K. Pain Therapeutics in Older Adults. 2. Tracy B, Morrison RS. Pain Management in Older Adults. 3. Atkinson TJ, et al. Medication Pain Management in the Elderly: Unique and Underutilized Analgesic Treatment Options. 4. Yang S, et al. Longitudinal Use of Complementary and Alternative Medicine Among Older Adults With Radiographic Knee Osteoarthritis. 5. Weiner DK, et al. Efficacy of Periosteal Stimulation for Chronic Pain Associated With Advanced Knee Osteoarthritis: A Randomized, Controlled Clinical Trial. 6. Bednar T, et al. Kyphoplasty for Vertebral Augmentation in the Elderly With Osteoporotic Vertebral Compression Fractures: Scenarios and Review of Recent Studies. 7. Morone NE, Weiner DK. Pain as the Fifth Vital Sign: Exposing the Vital Need for Pain Education.
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Volume 36 Number 11
Editor-in-Chief’s Note What Is Depression and Who Is in Depression Studies? For many elderly persons, their so-called golden years are not so golden, particularly for the so-called “old old” (ie, those aged 485 years). Problems can occur in all spheres of life. Some of the most common concerns are: loss of spouses and friends, living on fixed incomes, living alone, diminished visual acuity and depth perception, needing to give up driving, reduced hearing, falls, and increased sensitivity to medications. These are but a small list of changes that can be distressing. I know from my own experiences and those of friends and acquaintances that quality of life can be meaningfully altered. How do such changes affect older people? Some people take them in stride and adjust to each additional limitation. Some are unhappy and do their share of complaining but soldier on. Some become demoralized, but good news and experiences or accomplishments (mastery of problems) can turn things around; still others become clinically depressed. Those in the Richard I. Shader, MD latter group often do not receive the help they need. In the present issue, Professor Kenneth Boockvar, our Topic Editor for Geriatric Therapeutics, has assembled a collection of articles looking at the problems related to depression and mental health in the elderly.1–7 The review by Mattappallil and Mergenhagen1 addresses the need for recognizing the unwanted central nervous system effects of antimicrobial agents in the elderly. Such agents are often overlooked as causes of delirium or psychosis. The study by Reinhardt and coworkers2 looks at problem-solving treatment as an approach to alleviating subsyndromal depression in the elderly. Although I consider this study a valuable contribution to determining how cognitive-behavioral therapy (CBT) can be useful and may even obviate the need for antidepressant medications, I do have questions about what is meant by subsyndromal depression or depression symptoms at a subsyndromal level. Is it possible that people who gained self-esteem through mastery and problem solving had been demoralized rather than depressed? We do not have biomarkers in this or the other related articles in this issue that clearly define which patients are suffering from a clinical depression. Nor do we know if clinical depression is a syndrome with many different etiologies. Are we getting anywhere with finding biomarkers for depression or factors that predict response to treatment? I believe that 3 recently published articles may be helping us along that path. A study by Redei and colleagues8 examined genetic biomarkers in patients with major depressive disorder (MDD) versus control subjects. The authors found that the levels of 9 blood transcripts separated the cohorts. At study entry, the patients with MDD had significantly reduced amounts of ADCY3, DGKA, FAM46A, IGSF4A/CADM1, KIAA1539, MARCKS, PSME1, RAPH1, and TLR7. The DGKA, KIAA1539, and RAPH1 levels continued to be reduced even after a CBT intervention. The authors believe that these latter 3 biomarkers may reveal a predisposition or vulnerability to depression. After 18 weeks, 9 of the 22 patients with MDD were in CBT-related remission. The 9 remitted patients differed from the other 13 in their pretreatment levels of ASAH1, ATP11C, and KIAA1539, and all 3 transcripts were absent in those who did not remit. These are all blood-borne proteins that are encoded by their respective genes. Studies such as this one argue for the existence of 41 type of MDD. A second intriguing study is presented by Wium-Andersen and colleagues.9 This group found a significant correlation between blood levels of C-reactive protein (CRP) and reports of psychological distress and depression. CRP is considered to be a biomarker for inflammation. In relationship to my points about mastery and demoralization, this study found a significant relationship between CRP levels and questions about a wish to give up and a sense of not accomplishing much. The report by Peterson and colleagues7 in this issue measured CRP and several other biomarkers in a subset of patients. However, the relationship between CRP and level of depression was not studied.
November 2014
1483
Clinical Therapeutics Finally, Leuchter and colleagues10 found that a belief in the effectiveness of their antidepressant agents and a supportive interaction between patients and caregivers were key factors in determining response to treatment. They concluded, not surprisingly, that “belief in the power or effectiveness of the medication may be a contributor to placebo responses in the treatment of depression.” To me, these articles suggest that depression means many things to many people. Before we can perform definitive research, we must have better ways of defining our study populations; we need to have meaningful biomarkers and to rule out those who are placebo responsive. Richard I. Shader, MD Editor-in-Chief
REFERENCES
1. Mattappallil A, Mergenhagen K. Neurotoxicity with antimicrobials in the elderly: a review. Clin Ther. 2014;36:1489–1511. 2. Reinhardt JP, Horowitz A, Cimarolli VR, et al. Addressing depression in a long-term care setting: a phase II pilot of problemsolving treatment. Clin Ther. 2014;36:1531–1537. 3. Linnebur SA, Vande Griende JP, Metz KR, et al. Patient-level medication regimen complexity in older adults with depression. Clin Ther. 2014;36:1538–1546. 4. Garrido MM, Prigerson HG, Penrod JD, et al. Choosing wisely? Benzodiazepine and sedative-hypnotic use among older seriously ill veterans. Clin Ther. 2014;36:1547–1554. 5. Redding SE, Liu S, Hung WW, Boockvar KS. Opioid interruptions, pain, and withdrawal symptoms in nursing home residents. Clin Ther. 2014;36:1555–1563. 6. Zahradnik EK, Grossman H. Palliative care as a primary therapeutic approach in advanced dementia: a narrative review. Clin Ther. 2014;36:1512–1517. 7. Peterson JC, Charlson ME, Wells MT, Altemus M. Depression, coronary artery disease, and physical activity: how much exercise is enough? Clin Ther. 2014;36:1518–1530. 8. Redei EE, Andrus BM, Kwasny MJ, et al. Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy. Transl Psychiatry. 2014;4:e442. 9. Wium-Andersen MK, Ørsted DD, Nielsen SF, et al. Elevated C-reactive protein levels, psychological distress, and depression in 73,131 individuals. JAMA Psychiatry. 2013;70:176–184. 10. Leuchter AF, Hunter AM, Tartter M, et al. Role of pill-taking, expectation and therapeutic alliance in the placebo response in clinical trials for major depression. Br J Psychiatry. 2014 Sep 11. [Epub ahead of print].
http://dx.doi.org/10.1016/j.clinthera.2014.10.016
Geriatric Therapeutics Specialty Updates Geriatric Therapeutics Updates are published annually and available as FREE ACCESS content on the journal’s website. The 2013 Geriatric Therapeutics Update, entitled “Pain Management in Older Adults, was published in Volume 35, Number 11 of Clinical Therapeutics. To view 2013’s Geriatric Therapeutics Update, see the articles below: 1. Boockvar K. Pain Therapeutics in Older Adults. 2. Tracy B, Morrison RS. Pain Management in Older Adults. 3. Atkinson TJ, et al. Medication Pain Management in the Elderly: Unique and Underutilized Analgesic Treatment Options. 4. Yang S, et al. Longitudinal Use of Complementary and Alternative Medicine Among Older Adults With Radiographic Knee Osteoarthritis. 5. Weiner DK, et al. Efficacy of Periosteal Stimulation for Chronic Pain Associated With Advanced Knee Osteoarthritis: A Randomized, Controlled Clinical Trial. 6. Bednar T, et al. Kyphoplasty for Vertebral Augmentation in the Elderly With Osteoporotic Vertebral Compression Fractures: Scenarios and Review of Recent Studies. 7. Morone NE, Weiner DK. Pain as the Fifth Vital Sign: Exposing the Vital Need for Pain Education.
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Volume 36 Number 11
