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Psychiatric Times. Vol. 25 No. 14
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CME - Category 1 

Medical Comorbidities in Late-Life Depression

By Abebaw Mengistu Yohannes, PhD and Robert C. Baldwin, MD | December 1, 2008
Dr Yohannes is a reader in the department of physiotherapy at Manchester Metropolitan University, United Kingdom. His PhD dissertation is on geriatric medicine with a focus on mood disorder and physical disability in patients with chronic obstructive pulmonary disease in old age. He is a member of the International Psychogeriatric Association and British Geriatric Society.
Dr Baldwin is a psychiatric consultant on old age at the Manchester Mental Health and Social Care Trust, Manchester Royal Infirmary, and honorary professor of psychiatry at the University of Manchester. He is a Fellow of the Royal College of Psychiatrists, past executive member of the International Psychogeriatric Association, and member of the American Association of Geriatric Psychiatry. The authors report no conflicts of interest concerning the subject matter of this article.


CHRONIC OBSTRUCTIVE PULMONARY DISEASE
COPD is projected to be the third leading cause of death by 2020.49 A recent review of depression comorbid with COPD in the elderly identified a prevalence of 40% (95% CI, 36% - 44%).50 Untreated depression in patients with COPD is associated with increased physical disability, impaired quality of life, increased health care use, and increased mortality.51-53

The mechanisms that link depression to patients with COPD is unclear. Possibilities include factors related to COPD (level of physical disability and fluctuating mood because of dyspnea), smoking (which increases the risk of vascular brain disease), and behavioral factors (lack of exercise, limited activity, and concomitant social isolation). Social factors are important and include the level of perceived and actual support and disruption to life caused by repeated hospital admissions (those with moderate to severe COPD are likely to have 3 or 4 admissions per year) or becoming housebound either through worsening disability or the need for continuous oxygen treatment.51

There are no good trials of antidepressant medication in COPD but given the association of COPD depression with marked anxiety, a more sedating SSRI such as paroxetine(Drug information on paroxetine) or the non-SSRI mirtaza­pine can be tried. Benzodiazepines should be avoided because they depress respiration. Pulmonary rehabilitation based on activation and physical conditioning along with an antidepressant may be an effective approach compared with medication alone.54 Although there are limited data, in 1 study a 2-hour CBT session reduced both depression and anxiety55 Furthermore, in a recent randomized controlled study, 8 weeks of group educational therapy was found to be as effective as CBT in alleviating depression and anxiety symptoms and improving quality of life in patients with COPD.56 It is worth replicating the findings of this study in other settings.

VASCULAR DEPRESSION
Vascular depression is a subgroup of late-onset depression symptoms that present with reduced depressive ideation, greater psychomotor disturbance, apathy, executive dysfunction (slow, inefficient thinking, difficulty in switching mental set), and neuroimaging abnormalities in the basal ganglia and white matter on MRI in older patients.4,5 It may account for 50% of newly diagnosed cases of major depressive disorder in later life.57 The cause of the structural brain changes is thought to be atheromatous damage to small penetrating arterioles deep within the brain.4,5,57 These vessels are end arteries and may be particularly susceptible to pulse-wave changes (pulse-wave encephalopathy) caused by factors such as arterial rigidity and/or hypertension.

Many older adults have evidence of microvascular disease on brain imaging but not all of them have vascular depression or executive dysfunction. Hence, it is important to recognize the interplay of personal predisposition (from genetics or development), cognitive reserve, and cerebral lesion localization as well as overall lesion burden.58,59

Standard antidepressant treatment is less effective in patients with microvascular disease than in nonvascular cases. One recent study demonstrated the benefits of augmenting fluoxetine(Drug information on fluoxetine) treatment with nimodipine(Drug information on nimodipine) in patients with vascular depression.60 Nimodipine is a calcium channel drug used to lower blood pressure, and it may also dampen the systolic pulse wave to the brain. Such studies require replication but raise a question about what would be truly innovative depression-based treatment paradigms for halting vascular damage in those with vascular depression. For example, it is known that drugs such as statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers have vasoprotective properties that extend beyond their primary role. Until this research is carried out, it is as important to address vascular risk factors rigorously in late-onset depression as it is to treat depression.

Another approach is to target symptoms, such as apathy, linked to subcortical brain disease and hence vascular depression. No trials have been undertaken, but it has been suggested that dopamine(Drug information on dopamine)-acting agents may be effective in depressed patients with frontostriatal impairment that leads to low motivation. In addition, antidepressants and other psycho­tropic agents with a-blocking action may inhibit behavioral recovery following ischemic lesions, whereas psychotropic drugs that increase cathecholaminergic activity may promote recovery.61 Such concepts may guide future treatment. Low motivation or apathy has been treated with problem-solving treatment and behavioral activation with some encouraging results.62

CONCLUSION
Several medical conditions that are prevalent in later life are associated with increased rates of depression. The extent to which the link is biological is debatable because, particularly in older people, the causes of depression are multifactorial. There is increasing evidence that depression itself is associated with the development of several diseases, especially those that involve the blood vessels. It is interesting to see if future research is able to identify whether vasoprotective drugs can improve the prognosis for vascular depression.

There is every reason to be optimistic about treating depression in older adults with medical comorbidity. There are effective psychological and antidepressant drug treatments, both for the immediate management and to keep the patient well after recovery from depression.

 

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Drugs Mentioned in This Article
Citalopram (Celexa)
Fluoxetine (Prozac, Sarafem)
Lithium (Eskalith, Lithane, Lithobid)
Methylphenidate (Ritalin LA)
Mirapex (Pramipexole)
Mirtazapine (Remeron)
Moclobemide (Aurox, Manerix)
Modafinil (Provigil)
Nimodipine (Nimotop)
Nortriptyline (Aventyl, Pamelor)
Paroxetine (Paxil)
Selegiline (Emsam, Atapryl, Carbex, others)
Sertraline (Zoloft)
Tianeptine (Stablon)
Valproate/valproic acid (Depakote, others)
Venlafaxine (Effexor)
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Evidence-Based References
Frasure-Smith N, Lespérance F. Depression and anxiety as predictors of 2-year cardiac events in patients with stable coronary artery disease. Arch Gen Psychiatry. 2008;65:62-71.
Salaycik KJ, Kelly-Hayes M, Beiser A, et al. Depressive symptoms and risk of stroke: the Framingham Study. Stroke. 2007;38:16-21.


 
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