Late-life depression: Managing mood in patients with vascular disease
Initiate preventive strategies to protect your patient’s brain and reduce the risk of stroke
® Dowden Healthewly diagnosed Media major depressive disorder (MDD) in patients age ≥65 often has a vascu- Nlar component. Concomitant cerebrovascular CopyrightFor personaldisease use (CVD) only does not substantially alter the manage- ment of late-life depression, but it may affect present- ing symptoms, complicate the diagnosis, and influence treatment outcomes. The relationship between depression and CVD progression remains to be fully explained, and no disease-specific interventions exist to address vascular depression’s pathophysiology. When planning treat- ment, however, one can draw inferences from existing studies. This article reviews the evidence on late-life depression accompanied by CVD and vascular risk factors, the “vascular depression” concept, and ap- © 2009 Getty / Henri Silberman proaches to primary and secondary prevention and Helen Lavretsky, MD, MS treatment. Associate professor of psychiatry Semel Institute for Neuroscience and Human Behavior David Geffen School of Medicine at UCLA CVD etiology of depression Los Angeles, CA Vascular depression constitutes a subgroup of late- Thomas Meeks, MD life depression, usually associated with neuroimaging Assistant professor of psychiatry abnormalities in the basal ganglia and white matter Division of geriatric psychiatry 1 VA San Diego Healthcare System on MRI. The cause of the structural brain changes is Sam and Rose Stein Institute thought to be sclerosis in the small arterioles.2 These for Research on Aging end-artery vessels may be particularly susceptible to University of California, San Diego pulse-wave changes caused by arterial rigidity or hyper tension. Alexopoulos et al1 and Krishnan et al3 proposed the concept of vascular depression on the premise that Current Psychiatry 20 December 2009 CVD may be etiologically related to geriatric depressive
For mass reproduction, content licensing and permissions contact Dowden Health Media. Figure Subcortical cerebrovascular disease in late-life depression
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1 Clinical Point
Structural MRIs of elderly adults with major depressive disorder consistently show high rates With psychomotor of brain abnormalities. Subcortical white matter abnormalities manifest as (1) periventricular retardation, apathy, hyperintensities [halos or rims adjacent to ventricles] and (2) deep white matter hyperintensities [single, patchy, or confluent foci]. Strategic subcortical gray matter infarctions (3) are observed, and pronounced particularly in the basal ganglia, thalamus, and pons. disability, vascular depression looks like a medial frontal lobe syndromes. Krishnan et al3 examined clini- its underlying abnormalities.5 Executive cal and demographic characteristics of dysfunction also predicts limited response syndrome depressed elderly patients with vascular to antidepressants.8 Thus, the presenta- lesions on brain MRI. Those with clinically tion and course of depression-executive defined vascular depression experienced dysfunction syndrome are consistent with greater cognitive dysfunction, disability, those of subcortical ischemic depression. and psychomotor retardation but less agi- tation and guilt feelings than patients with nonvascular depression. Neuroimaging support Clinically, vascular depression resem- The vascular depression hypothesis is bles a medial frontal lobe syndrome, with supported by observations related to MRI prominent psychomotor retardation, apa- hyperintensities (HI): thy, and pronounced disability.4 Depression • CT and MRI studies identify HI in per- with vascular stigmata or cerebrovascular sons with late-life depression. lesions on neuroimaging is characterized • HI are associated with age and cere- by poor outcomes, including persistent brovascular risk factors. depressive symptoms, unstable remission, • Pathophysiologic evidence indicates and increased risk for dementia.5,6 Patients that HI are associated with widespread with depression and subcortical vascular diminution in cerebral perfusion.9 lesions have been shown to respond poorly Neuropathologic correlates of HI are to antidepressants.6 diverse and represent ischemic changes, Impaired brain function also may pre- together with demyelination, edema, and dispose to geriatric depression, described gliosis.9-11 The putative link between HI by Alexopoulos as “depression-executive and vascular disease is central to the vascu- dysfunction syndrome of late life.”7 This lar theory of depression. common syndrome’s presentation—psy- In a study of 56 patients age ≥50 meet- chomotor retardation, lack of interest, lim- ing DSM-III-R criteria for MDD, Fujikawa ited depressive ideation and insight, and et al12 reported “silent cerebral infarctions” Current Psychiatry prominent disability—is consistent with on MRI in 60% of patients. High rates of Vol. 8, No. 12 21 Table 1 tributed by a silent cardiovascular disease, increases the risk of vascular damage, Shared risk factors for which in turn further promotes depression. depression and heart disease • Vascular pathogenesis affecting heart Decreased heart rate variability and brain is likely to increase the risk for de- pression through a variety of mechanisms. Vascular inflammation (increased interleukin-6 and C-reactive protein) Vascular Endothelial dysfunction Post-stroke depression (PSD) occurs with- depression in 12 to 24 months after a cerebrovascular Platelet dysfunction accident.13 DSM-IV-TR categorizes PSD as Atherosclerosis a “mood disorder due to a general medical Dyslipidemia condition with the specifiers of (a) depres- Smoking sive features, (b) major depressive-like epi- sodes, or (c) mixed features.” Source: References 26-29 Although important in depression’s pathophysiology, the location of stroke le- Clinical Point abnormalities consistently have been sions is not the exclusive etiologic factor. Patients with observed on MRIs of older adults with Personal diathesis for depression, psycho- 10,11 depression and MDD, and these can be classified into 3 social factors, and physical and social im- types (Figure, page 21): pairment related to post-stroke neurologic subcortical vascular • Periventricular HI are halos or rims deficits also may contribute to PSD.16 lesions have adjacent to ventricles that in severe PSD patients with right-sided lesions been shown to forms may invade surrounding deep often have family histories of depressive 17 respond poorly to white matter. illness. Different serotonergic mecha- • Deep white matter HI are single, nisms might be responsible for depressive antidepressants patchy, or confluent foci observed in illness associated with right-sided vs left- subcortical white matter. sided lesions. This notion is supported by • Deep gray matter HI may be found, observed lateralized changes in serotonin particularly in the basal ganglia, thala- type-2 (5-HT2) receptors18 and the influ- mus, and pons.9 ence of lateralized lesions on prolactin re- Exploring the New Frontier of These leukoaraiosis (or encephalomala- sponsivity to d-fenfluramine challenge in cia) occur more frequently in patients with PSD.19 Damage closer to the frontal lobes Psychiatric and Neurologic Pharmacy geriatric depression than in normal con- is likely to affect catecholamine-mediated 4HE #OLLEGE OF 0SYCHIATRIC AND .EUROLOGIC 0HARMACISTS #0.0 IS A PROFESSIONAL ASSOCIATION OF PSYCHIATRIC AND NEUROLOGIC trols13 or patients with Alzheimer’s disease14 brain activity. PHARMACISTS 4HE #0.0 !NNUAL -EETING OFFERS CUTTING EDGE INFORMATION IDEAL FOR THE PHARMACIST PHYSICIAN NURSE PRACTITIONER OR OTHER HEALTHCARE PROFESSIONAL INVOLVED IN THE MEDICATION THERAPY MANAGEMENT OF PSYCHIATRIC ANDOR NEUROLOGIC PATIENTS and may be comparable to the rate associat- The 8-year Framingham study20 exam- ed with vascular dementia.15 Observations ined the risk of developing cerebrovascular -EETING (IGHLIGHTS-EETING (IGHLIGHTS in older adults11 suggest that diminished events in persons age ≤65 vs those age >65. s 0RE -EETING 7ORKSHOP ! HOUR WORKSHOP ON -ANAGING $IABETES IN 0ATIENTS WITH 0SYCHIATRIC )LLNESS WILL BE brain volume (especially in frontal regions) Subjects age ≤65 with significant depres- OFFERED ON !PRIL 4HIS WORKSHOP WILL REVIEW AND IMPLEMENT THE !MERICAN $IABETES !SSOCIATION STANDARDS OFFERED ON !PRIL 4HIS WORKSHOP WILL REVIEW AND IMPLEMENT THE !MERICAN $IABETES !SSOCIATION STANDARDS and HI may provide additive, albeit autono- sive symptoms—Center for Epidemiologic OF CARE IN MANAGING DIABETES USING CASE BASED DISCUSSIONS ON l RST LINE AGENTS ADVERSE EFFECTS AND MONITORING RST LINE AGENTS ADVERSE EFFECTS AND MONITORING mous, pathways to late-life MDD. Vascular Studies Depression scale score >1621—were TECHNIQUES TO MAINTAIN SAFE AND ADEQUATE CARE TECHNIQUES TO MAINTAIN SAFE AND ADEQUATE CARE and nonvascular medical comorbidity con- 4 times more likely to develop stroke or s $AILY +EYNOTE !DDRESSES )NCLUDE 4ERRY 7ISE *$ OFFERING UNIQUE APPROACHES TO TREATING SUICIDAL PATIENTS FROM THE PERSPECTIVE OF SOMEONE WHO SURVIVED HER OWN NEAR FATAL SUICIDE ATTEMPT THE PERSPECTIVE OF SOMEONE WHO SURVIVED HER OWN NEAR FATAL SUICIDE ATTEMPT $RS 0ETER "UCKLEY AND (ENRY tribute to HI, which in turn facilitate MDD. transient ischemic attack compared with .ASRALLAH .ASRALLAH TWO WELL KNOWN RESEARCHERS ENGAGING IN A DEBATE ON !NTIPSYCHOTIC %Fl CACY VS !DVERSE %FFECTS the same age group without depression. 7HICH 4RUMPS 7HICH 4RUMPS 0HILIP (ARVEY 0H$ FOCUSING ON ADJUNCTIVE TREATMENTS IN 4REATMENT OF #OGNITIVE )MPAIRMENT IN Another study found a link between de- 3CHIZOPHRENIA 3CHIZOPHRENIA ,ASTLY ,ARRY %RESHEFSKY 0HARM$ "#00 &##0 DELVES INTO LEADING BIOSURROGATE MARKERS IN THE Bidirectional relationship pression and stroke risk across the adult AREA OF !LZHEIMERS $ISEASE !$ WITH AREA OF !LZHEIMERS $ISEASE !$ WITH 3TRATEGIES TO $EVELOP $ISEASE -ODIFYING $RUGS 22 Online The relationship between depression and age range. Mechanisms by which depres- s 0ROGRAMMING 2EGISTRANTS HAVE HOURS OF !#0% AND #-% APPROVED PROGRAMMING TO CHOOSE FROM ALONG Only cardiovascular disease appears to be bi sive symptoms may predispose to stroke WITH AN ANTICIPATED l VE INDUSTRY SUPPORTED SYMPOSIA OPPORTUNITIES WITH AN ANTICIPATED l VE INDUSTRY SUPPORTED SYMPOSIA OPPORTUNITIES directional: are not fully known, but depression has s 2ESEARCH !LONG WITH TWO DAYS OF POSTER DISPLAYS ON !PRIL THREE HOURS OF DEDICATED TIME WILL BE Discuss this article at PROVIDED TO NETWORK WITH AN ANTICIPATED POSTER AUTHORS !BSTRACT AND !WARD SUBMISSIONS ARE DUE PROVIDED TO NETWORK WITH AN ANTICIPATED POSTER AUTHORS !BSTRACT AND !WARD SUBMISSIONS ARE DUE • Depression may be the first clinical been shown to affect autonomic function http://CurrentPsychiatry. *ANUARY blogspot.com expression of an underlying cardiovascular and platelet activation.23 s 2EGISTRATION 2EGISTRATIONS ARE NOW BEING ACCEPTED AT disease, which is expressed as an increased HTTPCPNPORGEDMEETINGREGISTRATION risk for ischemic events. CHD and depression. In the United States, Current Psychiatry 6ISIT 6ISIT HTTPCPNPORGEDMEETING FOR MORE INFORMATION 22 December 2009 • Depression itself, whether or not con- approximately 20% of coronary heart dis- #0.0 !NNUAL -EETING !PRIL s 'RAND (YATT s 3AN !NTONIO 4EXAS Table 2 Clinical management of late-life vascular depression
Decision point Assessment/intervention Diagnosis Apply DSM-IV-TR diagnostic criteria based on results of comprehensive assessment (neuropsychiatric, neuropsychological, structural neuroimaging, vascular and genetic risk factors) Prevention Identify and treat modifiable risk factors for the development or worsening of cerebrovascular disease, especially in high-risk populations (Table 4, page 29) Treatment goals Target 1: Achieve remission of depressive symptoms, improved cognition and function Target 2: Maintain remission and prevent relapse Managing Step 1: Consider psychotherapy addressing existing stressors and psychological and environmental management in patients with mild-to-moderate depression behavioral symptoms Step 2: If depression is severe or Step 1 is ineffective, an antidepressant trial* is highly recommended (Table 3, page 24); consider ECT or TMS in severe cases Clinical Point *Avoid medications that could worsen cognition or motor functioning, such as tricyclic antidepressants or neuroleptics A history of depression ECT: electroconvulsive therapy; TMS: transcranial magnetic stimulation has been shown to ease (CHD) patients have clinically signifi- The association between depression and increase the relative cant depressive symptoms.24 A history of CHD is unclear but likely includes: risk of developing depression also has been shown to increase • direct biological mechanisms such as coronary heart disease the relative risk of developing CHD by autonomic dysfunction and dysregu- by more than 80% >80%.25 lated inflammation continued
Exploring the New Frontier of Psychiatric and Neurologic Pharmacy 4HE #OLLEGE OF 0SYCHIATRIC AND .EUROLOGIC 0HARMACISTS #0.0 IS A PROFESSIONAL ASSOCIATION OF PSYCHIATRIC AND NEUROLOGIC PHARMACISTS 4HE #0.0 !NNUAL -EETING OFFERS CUTTING EDGE INFORMATION IDEAL FOR THE PHARMACIST PHYSICIAN NURSE PRACTITIONER OR OTHER HEALTHCARE PROFESSIONAL INVOLVED IN THE MEDICATION THERAPY MANAGEMENT OF PSYCHIATRIC ANDOR NEUROLOGIC PATIENTS
-EETING (IGHLIGHTS-EETING (IGHLIGHTS s 0RE -EETING 7ORKSHOP ! HOUR WORKSHOP ON -ANAGING $IABETES IN 0ATIENTS WITH 0SYCHIATRIC )LLNESS WILL BE OFFERED ON !PRIL 4HIS WORKSHOP WILL REVIEW AND IMPLEMENT THE !MERICAN $IABETES !SSOCIATION STANDARDS OFFERED ON !PRIL 4HIS WORKSHOP WILL REVIEW AND IMPLEMENT THE !MERICAN $IABETES !SSOCIATION STANDARDS OF CARE IN MANAGING DIABETES USING CASE BASED DISCUSSIONS ON l RST LINE AGENTS ADVERSE EFFECTS AND MONITORING RST LINE AGENTS ADVERSE EFFECTS AND MONITORING TECHNIQUES TO MAINTAIN SAFE AND ADEQUATE CARE TECHNIQUES TO MAINTAIN SAFE AND ADEQUATE CARE s $AILY +EYNOTE !DDRESSES )NCLUDE 4ERRY 7ISE *$ OFFERING UNIQUE APPROACHES TO TREATING SUICIDAL PATIENTS FROM THE PERSPECTIVE OF SOMEONE WHO SURVIVED HER OWN NEAR FATAL SUICIDE ATTEMPT THE PERSPECTIVE OF SOMEONE WHO SURVIVED HER OWN NEAR FATAL SUICIDE ATTEMPT $RS 0ETER "UCKLEY AND (ENRY .ASRALLAH .ASRALLAH TWO WELL KNOWN RESEARCHERS ENGAGING IN A DEBATE ON !NTIPSYCHOTIC %Fl CACY VS !DVERSE %FFECTS 7HICH 4RUMPS 7HICH 4RUMPS 0HILIP (ARVEY 0H$ FOCUSING ON ADJUNCTIVE TREATMENTS IN 4REATMENT OF #OGNITIVE )MPAIRMENT IN 3CHIZOPHRENIA 3CHIZOPHRENIA ,ASTLY ,ARRY %RESHEFSKY 0HARM$ "#00 &##0 DELVES INTO LEADING BIOSURROGATE MARKERS IN THE AREA OF !LZHEIMERS $ISEASE !$ WITH AREA OF !LZHEIMERS $ISEASE !$ WITH 3TRATEGIES TO $EVELOP $ISEASE -ODIFYING $RUGS s 0ROGRAMMING 2EGISTRANTS HAVE HOURS OF !#0% AND #-% APPROVED PROGRAMMING TO CHOOSE FROM ALONG WITH AN ANTICIPATED l VE INDUSTRY SUPPORTED SYMPOSIA OPPORTUNITIES WITH AN ANTICIPATED l VE INDUSTRY SUPPORTED SYMPOSIA OPPORTUNITIES s 2ESEARCH !LONG WITH TWO DAYS OF POSTER DISPLAYS ON !PRIL THREE HOURS OF DEDICATED TIME WILL BE PROVIDED TO NETWORK WITH AN ANTICIPATED POSTER AUTHORS !BSTRACT AND !WARD SUBMISSIONS ARE DUE PROVIDED TO NETWORK WITH AN ANTICIPATED POSTER AUTHORS !BSTRACT AND !WARD SUBMISSIONS ARE DUE *ANUARY s 2EGISTRATION 2EGISTRATIONS ARE NOW BEING ACCEPTED AT HTTPCPNPORGEDMEETINGREGISTRATION 6ISIT 6ISIT HTTPCPNPORGEDMEETING FOR MORE INFORMATION #0.0 !NNUAL -EETING !PRIL s 'RAND (YATT s 3AN !NTONIO 4EXAS Table 3 Recommended antidepressant dosing for elderly patients with vascular depression*
Starting daily dosage Side effect profile Drug (usual therapeutic range) (patient characteristics) SSRIs Vascular Escitalopram 5 mg (10 to 20 mg) Nausea, headaches, GI upset, insomnia, depression anxiety Fluoxetine 10 mg (10 to 60 mg) Paroxetine 10 mg (10 to 30 mg)
Sertraline 25 mg (50 to 150 mg) Others Bupropion 75 mg (75 to 300 mg) GI upset, anxiety (may be useful for patients with high apathy) Clinical Point Mirtazapine 7.5 mg (15 to 45 mg) Sedation, weight gain (may be useful for patients with severe insomnia or anorexia) CT or MRI may not Venlafaxine 37.5 mg (75 to 300 mg) Nausea, headaches, anxiety, blood pressure elevation, insomnia (may be be necessary for Duloxetine 20 mg (30 to 120 mg) useful for patients with chronic pain) diagnosis when *Avoid medications that could worsen cognition or motor functioning, such as tricyclic antidepressants or neuroleptics depression onset GI: gastrointestinal; SSRIs: selective serotonin reuptake inhibitors is associated with strong physical • behavioral factors such as smoking or proposed deficits in parasympathetic mod- poor self-care (Table 1, page 22). ulation of immunity and coagulation as the evidence of a stroke A recent analysis of 13 cross-sectional cause. In contrast, Whooley et al29 found studies26 suggests that reduced heart rate no association between major depression variability (HRV) related to autonomic and inflammatory markers—including dysfunction may be the link between de- CRP, fibrinogen, and interleukin-6—in pression and CHD risk. The studies’ effect 984 outpatients with CHD. Differences in sizes were small, however, and their meth- assessment scales and sample heterogene- odologies varied considerably. ity may have contributed to these dispa- C-reactive protein (CRP), interleukin- rate findings. 6, tumor necrosis factor-α (TNF-α), and fibrinogen are inflammatory markers. In Diabetes and depression. As with CHD, a 2-year follow-up study, Frasure-Smith et a bidirectional relationship exists between al27 investigated the relationship between depression and diabetes mellitus, although depression and inflammatory markers in depression is only a modest risk factor for 741 patients (602 male) with acute coro- diabetes.30 Possible explanations include nary syndrome. Two months after an acute hypercortisolemia and increased inflam- coronary event, depressive symptoms and mation resulting in increased insulin resis- elevated CRP levels were overlapping risk tance and metabolic syndrome. factors for future cardiac events in men. Carney et al28 showed that fibrinogen was most associated with altered heart rate Diagnosis of vascular depression variability in depressed CHD patients and Vascular depression is characterized by a clinical diagnosis of DSM-IV-TR-defined MDD, dysthymia, or depression not- For more information, go to otherwise-specified, accompanied by: CurrentPsychiatry.com • evidence of CVD or • known vascular risk factors vascular, depression (hypertension, diabetes, hyperlipid- Current Psychiatry Current Psychiatry 24 December 2009 emia, stroke, heart failure, etc.). continued on page 29 continued from page 24 Table 4 Preventing vascular causes of late-life depression
Decision point Assessment/intervention Comment Primary, secondary Identify and treat modifiable risk Consider as high-risk patients prevention of stroke, factors (hypertension, alcohol use, having ≥1 of these features: age vascular depression, smoking, hyperlipidemia, diabetes >50; male gender; Asian, Hispanic, and cognitive mellitus), especially in high-risk or African-American heritage; low impairment patients educational achievement; concurrent vascular risk factors Tertiary prevention Intensively treat vascular risk Collaborate with primary care of worsened illness factors physician to manage arterial in patients with hypertension, myocardial established vascular infarction, atrial fibrillation, disease coronary heart disease, diabetes, atherosclerosis, hyperlipidemia, obesity, and smoking Rapidly identify and treat acute stroke to limit ischemic brain Clinical Point changes and promote recovery Methylphenidate, Prevent stroke recurrence by Let CVD etiology guide treatment aggressively treating vascular 5 to 20 mg/d, may risk factors improve apathy and CVD: cerebrovascular disease Source: Adapted from Lavretsky H. Diagnosis and treatment of vascular dementia. Directions in Psychiatry. 2006;26(1):49-68 social withdrawal, but evidence for its use in vascular In performing thorough neurologic, treatment. Investigate environmental fac- neuropsychiatric, and neuropsychologi- tors such as financial and marital prob- depression is lacking cal examinations, look for soft neurologic lems or loneliness in patients’ depressive signs with regional weakness, apathy, symptoms, and develop corresponding in- and executive dysfunction. Useful bed- terventions—such as education, nutrition, side scales include the clock-drawing exercise, socialization, or pain and stress test, word list generation, brief demen- management. Cognitive rehabilitation tia screens, and the Apathy Evaluation training and cognitive-behavioral therapy Scale.31 can reduce cognitive impairment and as- CT or MRI can provide supportive sociated depression. evidence by demonstrating signs of sub- cortical or cortical stroke. Neuroimaging Antidepressants. A trial of antidepres- studies may not be necessary, however, sant therapy is advisable for moderate-to- when depression onset is temporally as- severe, chronic vascular depression, even sociated with strong physical evidence of though comorbid CVD may diminish the a stroke (such as falling, peripheral muscle antidepressant response. In elderly pa- weakness, or incontinence). tients, start with one-third to one-half the usual adult antidepressant dosage and in- crease while balancing efficacy and toler- Treating depression symptoms ability. When treating vascular depression, clinical Match the medication’s side-effect pro- goals are to ameliorate affective symptoms, file with the patient’s target symptoms improve quality of life, and help patients (such as anxiety vs apathy).32 Selective perform activities of daily living (Table 2, serotonin reuptake inhibitors are proba- page 23). bly first-line, but bupropion, venlafaxine, duloxetine, or mirtazapine may be more Psychosocial interventions. When de- appropriate for some patients (Table 3, pression is less than severe, consider page 24). Current Psychiatry psychosocial interventions as first-line In PSD, nortriptyline has shown a Vol. 8, No. 12 29 significantly greater response rate than Treating vascular factors fluoxetine or placebo in improving anxi- In addition to treating your patients’ de- ety symptoms and recovery of activities pressive symptoms, collaborate with their of daily living.33 Tricyclic antidepressants’ primary care physicians to modify physi- anticholinergic properties are a safety ologic and behavioral factors that increase concern in patients with heart disease, the risk for vascular injury—such as hy- however. In general, avoid agents with pertension, diabetes mellitus, cigarette Vascular substantial anticholinergic effects in el- smoking, and hyperlipidemia. All can be depression derly patients to minimize the risk of cog- controlled in presymptomatic or mildly nitive impairment and other side effects, symptomatic stages (Table 4, page 29). such as urinary retention or worsening of glaucoma. Anticoagulation. In appropriate patients, Because of the substantial risk of postur- anticoagulation can prevent thromboem- al hypotension, nonselective monoamine bolic strokes, although risks such as in- oxidase inhibitors are probably appropri- creased hemorrhagic complications must ate only for geriatric patients with highly be considered.37 In elderly adults, base Clinical Point treatment-refractory depression. Dopami- treatment decisions on individual risk fac- ECT appears to nergic agents such as methylphenidate in tors, goals of treatment, and quality-of-life be quite safe in a relatively moderate dose (such as 5 to expectancy. In a study of low-dose aspirin 20 mg/d) may improve apathy and social (81 mg/d) and low-intensity oral antico- depressed older withdrawal, but research into their use in agulation in men at risk of cardiovascular patients, especially vascular depression is lacking. disease, verbal fluency and mental flexibil- if not used in the ity were significantly better in men taking first 6 months after Other options. Clinical experience sug- antithrombotic medications (especially as- gests that electroconvulsive therapy (ECT) pirin) than in those taking placebo.38 a stroke is effective for patients who do not respond to antidepressants. ECT appears quite safe Antihypertensives and statins. Patients in older patients, especially if not used in with vascular depression may benefit from the first 6 months post-stroke. Strategies calcium channel blockers or angiotensin- to reduce the risk of cognitive side effects converting enzyme (ACE) inhibitors for include: hypertension and HMG-CoA reductase • 2 rather than 3 weekly treatments inhibitors (statins) for hyperlipidemia. • unilateral or bifrontal rather than bi- Statins seem to decrease the generation of lateral treatments amyloid precursor protein, the neuronal • frontal lead placement.34 secretion of β-amyloid, and cholesterol In the only study of transcranial mag- synthesis.39 Some epidemiologic stud- netic stimulation (TMS) for geriatric pa- ies suggest an association between statin tients with depression (N=92), those with use for cholesterol reduction and reduced treatment-resistant vascular depression prevalence of Alzheimer’s disease and showed higher remission rates with TMS vascular dementia.40 (27.3%) compared with sham TMS (3.5%). Potential preventive strategies are not Response rates to TMS were negatively cor- without controversy, however: related with advancing age and positively • Beta blockers and ACE inhibitors have correlated with higher frontal gray matter been linked to depression, although the evi- volumes.35 dence has been conflicting. Fish oil or vitamin B complex may be • Lipid-lowering therapies and cal- used to manage hyperlipidemia or nu- cium-channel blockers have been linked tritional deficiencies.36 Herbal prepara- to an increased risk of suicide.41 tions such as St. John’s wort (Hypericum • A more recent population-based study perforatum) or S-adenosyl-L-methionine did not support an association between an (SAMe) have shown some efficacy in increased risk of suicide and cardiovascular adults with MDD, but further study is drugs (except perhaps for angiotensin- Current Psychiatry 30 December 2009 needed. receptor antagonists).42 References 1. Alexopoulos GS, Meyers BS, Young RC, et al. Clinically Related Resources defined vascular depression. Am J Psychiatry. 1997;154: 562-565. • Lavretsky H, Chui H. Vascular dementia. In: Agronin ME, Maletta GJ, eds. Principles and practice of geriatric psychiatry. 2. Newberg AR, Davydow DS, Lee HB. Cerebrovascular disease basis of depression: post-stroke depression and New York, NY: Lippincott, Williams, and Wilkins; 2005: vascular depression. Int Rev Psychiatry. 2006;18:433-441. 301-310. 3. Krishnan KR, Hays JC, Blazer DG. MRI-defined vascular • Baldwin RC, O’Brien J. Vascular basis of late-onset depressive depression. Am J Psychiatry. 1997;154:497-501. disorder. Br J Psychiatry. 2002;180:157-160. 4. Krishnan KR, Taylor WD, McQuoid DR, et al. Clinical • Kendler KS, Gardner CO, Fiske A, et al. Major depression and characteristics of magnetic resonance imaging-defined coronary heart disease in the Swedish twin registry. Arch Gen subcortical ischemic depression. Biol Psychiatry. 2004;5(4): 390-397. Psychiatry. 2008;66(8):857-863. 5. Alexopoulos GS, Kiosses DN, Klimstra S, et al. Clinical Drug Brand Names presentation of the “depression-executive dysfunction syndrome” of late life. Am J Geriatr Psychiatry. 2002;10: Bupropion • Wellbutrin Mirtazapine • Remeron 98-102. Duloxetine • Cymbalta Nortriptyline • Aventyl, Pamelor Escitalopram • Lexapro Paroxetine • Paxil 6. Taylor WD, Steffens DC, Krishnan KR. Psychiatric disease in the twenty-first century: the case for subcortical ischemic Fluoxetine • Prozac Sertraline • Zoloft depression. Biol Psychiatry. 2006;60(12):1299-1303. Methylphenidate • Ritalin, Venlafaxine • Effexor 7. Alexopoulos GS. The depression-executive dysfunction Concerta, others syndrome of late life: a specific target for D3 receptor Disclosures agonists? Am J Geriatr Psychiatry. 2001;9:1-8. 8. Alexopoulos GS. Depression in the elderly. Lancet. Dr. Lavretsky receives grant/research support from Forest Clinical Point 2005;365:1961-1970. Research Institute and is a consultant to Forest Laboratories, 9. Sackeim H. Brain structure and function in late-life Myriad Pharmaceuticals, and Accera, Inc. Collaborate with depression. In: Morihisa JM, ed. Advances in brain imaging. Dr. Meeks reports no financial relationship with any Arlington, VA: American Psychiatric Publishing, Inc.; patients’ physicians 2001:83-122. company whose products are mentioned in this article or with manufacturers of competing products. 10. Kumar A, Bilker W, Jin Z, et al. Atrophy and high intensity to modify risks for lesions: complementary neurobiological mechanisms in Acknowledgments late-life major depression. Neuropsychopharmacology. vascular injury, such 2000;22:264-274. This work was supported by National Institute of Health 11. Kumar A, Mintz J, Bilker W, et al. Autonomous grants R01 MH077650 and R-21 AT003480 (Dr. Lavretsky), as hypertension, neurobiological pathways to late-life major depressive the U.S. Department of Health and Human Services, Health disorder: clinical and pathophysiological implications. Resources and Services Administration (Geriatric Academic diabetes, smoking, Neuropsychopharmacology. 2002;26:229-236. Career Award), and the Sam and Rose Stein Institute for 12. Fujikawa T, Yamawaki S, Fujita Y, et al. [Clinical study of Research on Aging (Dr. Meeks). and hyperlipidemia correlation pre-senile, senile depressive state with silent cerebral infarction—MRI findings and its distribution]. Seishin Shinkeigaku Zasshi. 1992;94(9):851-863. 13. Kumar A, Cummings J. Depression in neurodegenerative 19. Ramasubbu R, Flint A, Brown G, et al. A neuroendocrine disorders and related conditions in Alzheimer’s disease study of serotonin function in depressed stroke patients and related conditions. In: Gothier S, Cummings J, eds. compared to nondepressed stroke patients and healthy Alzheimer’s disease and related disorders. London, UK: controls. J Affect Disord. 1999;52:121-133. Martin Dunitz; 2001:123-141. 20. Salaycik KJ, Kelly-Hayes M, Beiser A, et al. Depressive 14. Erkinjuntti T, Gao F, Lee DH, et al. Lack of difference in brain symptoms and risk of stroke. The Framingham study. hyperintensities between patients with early Alzheimer’s Stroke. 2007;38:16-21. disease and control subjects. Arch Neurol. 1994;51:260-268. 21. Radloff LS. The CES-D scale: a self-report depression 15. Zubenko G, Sullivan P, Nelson J, et al. Brain imaging scale for research in the general population. Appl Psychol abnormalities in mental disorders of late life. Arch Neurol. Measurement. 1977;1:385-401. 1990;47:1107-1111. 22. Jonas BS, Mussolino ME. Symptoms of depression as 16. Birkett DP. The psychiatry of stroke. Arlington, VA: a prospective risk factor for stroke. Psychosom Med. 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Bottom Line Prominent psychomotor retardation, apathy, and pronounced disability are hallmarks of late-life vascular depression. First-line treatments for many patients are psychosocial interventions or selective serotonin reuptake inhibitors. Other antidepressants, methylphenidate, ECT, or TMS may be appropriate for others. Collaborate with medical providers to modify cerebrovascular risk factors such as Current Psychiatry hypertension, diabetes mellitus, smoking, and hyperlipidemia. Vol. 8, No. 12 31 continued on page 38 continued from page 31
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Current Psychiatry 38 December 2009