Vascular depression confused for Major Depressive Disorder and Dementia*

keywords: vascular, post stroke, depression, major depression, cholesterol, memory loss

Occupation:
Teacher

Question:
Mr X, a 54 year old man, was referred for investigation of recurrent episodes of severe depression that had increased in severity over the past year.

Problem:
Traditional treatments for depression had been unable to help and the patient?s condition was deteriorating further.

Complications:
History of cardiovascular disease and use of cholesterol lowering and blood pressure medications.

Medical practitioners believed Mr X was suffering from an early dementia.

Outcome:
Mr X underwent a brain function assessment. Neuropsychological and neurophysiological (brain function) testing revealed a profile that was not consistent with early dementia, but was more consistent with vascular depression.

Vascular depression is generally a late-onset (over 50 years of age) condition associated with a history of vascular risk factors such as hypertension (Dieguez et al., 2004; Provinciali & Coccia, 2002). Vascular depression is considered to be a consequence of ischemic lesions and structural neurological changes that are associated with cerebrovascular disease (Baldwin & O'Brien, 2002; Baldwin et al., 2005; Fujikawa et al., 1997; Provinciali & Coccia, 2002). It is characterized by profound apathy, tendency for social isolation, loss of interest, cognitive impairment and significant dysfunction in activities of daily living (Provinciali & Coccia, 2002).

Vascular depression has been associated with increased cerebral atrophy (Baldwin et al., 2005) and increased white matter hyperintensities (Firbank et al., 2004; Murata et al., 2001; Provinciali & Coccia, 2002). Major depression in elderly subjects including loss of interest or pleasure, psychomotor retardation, and cognitive impairment is also seen more often in patients with silent cerebral infarct (SCI) than in those without SCI (Fujikawa et al., 1993; 1997; Sekine et al., 2000).

Vascular depression is thought to occur due to vascular damage to frontal-subcortical circuits implicated in mood regulation and cognition (Dieguez et al., 2004; Provinciali & Coccia, 2002). Imaging studies of late-onset depression have fairly consistently shown an abnormal increase in white matter hyperintensities (WMHs), especially in the periventricular areas, deep white matter and subcortical gray matter, and the striato-frontal circuits, including ischemic damage to the dorsolateral prefrontal cortex (Dieguez et al., 2004; Provinciali & Coccia, 2002). These WMHs are of crucial clinical importance, as they are linked to poor response to treatment, residual cognitive impairment, increased relapse rate, and progression to chronic depression (Dieguez et al., 2004).

Conclusion:
Due to the differing aetiology of vascular-related depression, studies suggest that PSD does respond well to typical antidepressants (Provinciali & Coccia, 2002; Sekine et al., 2000; Vataja et al., 2004; 2005).

Recent clinical trials suggest that stimulant medications may be affective in the treatment of vascular depression. Methylphenidate (Ritalin) has been identified as affective in the treatment of apathy in depression (Marin et al., 1995; Padala et al., 2005) and for the treatment of vascular-related depression (Grade et al., 1998; Johnson et al., 1992; Lazarus et al., 1994; Masand et al., 1991; Sekine et al., 2000). Available evidence indicates that psychostimulants are safe and well tolerated in patients and can have a positive therapeutic effect on depressive symptoms (Grade et al., 1998; Johnson et al., 1992; Whyte & Mulsant, 2002).

In addition other stimulant forms such as Modafinil (Provigil, Modavigil) should also be considered. Modafinil, a novel wakefulness-promoting and antidepressant agent that is typically used for narcolepsy and sleep disorders. However, it has been found to be affective in the treatment of atypical or treatment resistant depression and vascular depression (Holder et al., 2002; Sugden & Bourgeois, 2004; Vaishnavi et al., 2006), chronic fatigue and sleepiness (Bobo & Hall, 2004; DeBattista et al., 2003; Turkington et al., 2004), a patient with cardiac comorbidity (Xiong et al., 2005), closed head injury (Teitelman, 2001), and as augmentation to typical antidepressants/SSRIs (Fava et al., 2005a; Konuk et al., 2006; Nasr, 2004; Ninan et al., 2004; Schwartz et al., 2004; Thase et al., 2006).

In addition, Modafinil includes cognitive enhancing properties and has minimal effects on sleep or blood pressure, a low incidence of restlessness and anxiety as side effects (Bobo & Hall, 2004; Sugden & Bourgeois, 2004). For these reasons, Modafinil appears ideally suited as add-on therapy in patients who suffer from chronic fatigue and depression, particularly in those who display a vulnerability for anxiety (Fava et al., 2005b; Konuk et al., 2006; Nasr, 2004; Ninan et al., 2004; Schwartz et al., 2004; Thase et al., 2006).

The choice of Modafinil in the treatment of vascular depression is very appealing because it combines the benefits of both wakefulness-promoting agents and an antidepressants. Compared with methylphenidate, it has a more favourable side effect profile, with less probability of hypertension, tachycardia, insomnia, and anxiety (Bobo & Hall, 2004; Sugden & Bourgeois, 2004).

Therefore, in consultation with appropriate medical practitioners Mr X?s medication was adjusted to a new compound leading to recovery from his depressive symptoms.

References

Baldwin, RC and O'Brien, J (2002). Vascular basis of late-onset depressive disorder. Br J Psychiatry , 180 , 157-160.

Baldwin, R, Jeffries, S, Jackson, A, Sutcliffe, C, Thacker, N, and Burns, A (2005). Neurological findings in late-onset depressive disorder: comparison of individuals with and without depression. Br J Psychiatry , 186 , 308-313.

Dieguez, S, Staub, F, Bruggimann, L, and Bogousslavsky, J (2004). Is poststroke depression a vascular depression? Journal of the Neurological Sciences , 226 , 53-58.

Firbank, MJ, Lloyd, AJ, Ferrier, N, and O'Brien, JT (2004). A Volumetric Study of MRI Signal Hyperintensities in Late-Life Depression. Am J Geriatr Psychiatry , 12 , 606-612.

Fujikawa, T, Yamawaki, S, and Touhouda, Y (1993). Incidence of silent cerebral infarction in patients with major depression. Stroke , 24 , 1631-1634.

Fujikawa, T, Yanai, I, and Yamawaki, S (1997). Psychosocial Stressors in Patients With Major Depression and Silent Cerebral Infarction. Stroke , 28 , 1123-1125.

Murata, T, Kimura, H, Omori, M, Kado, H, Kosaka, H, Iidaka, T, Itoh, H, and Wada, Y (2001). MRI white matter hyperintensities, (1)H-MR spectroscopy and cognitive function in geriatric depression: a comparison of early- and late-onset cases. International Journal of Geriatric Psychiatry , 16 , 1129-1135.

Provinciali, L and Coccia, M (2002). Post-stroke and vascular depression: a critical review. Neurological sciences , 22 , 417-428.

*The case examples are based on clinical experience but are dissimilar from real cases. The examples provided are for illustrative purposes only and any resemblance to a real life case is of coincidence.