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42 Interventions in Alzheimer’s Disease <strong>KCE</strong> Reports 111<br />
4.4.1 Antidepressants<br />
Depression, often including symptoms of anxiety, is common in dementia and may<br />
worsen cognitive impairment. The best approach to diagnosing depression in <strong>the</strong> contex<br />
of dementia is not yet clear. 68<br />
There is only limited evidence supporting <strong>the</strong> efficacy of antidepressants in dementia<br />
patients. 8 In a meta-analysis based on only 82 subjects treated in 5 studies<br />
(antidepressants were imipramine, clomipramine, sertraline, or fluoxetine), a NNT of 5<br />
(95%CI, 3 to 59) was calculated. 79<br />
If antidepressive drugs are used, agents with an anticholinergic profile should be<br />
avoided, and <strong>the</strong> starting dose should be low. 8 SBU concludes <strong>the</strong> research on <strong>the</strong><br />
treatment of depression in patients with severe dementia is inconclusive. 14 There is<br />
limited evidence that SSRIs are tolerated well and are effective for <strong>the</strong> treatment of<br />
depression in mild to moderate dementia.(Evidence Grade 3). 14, 78 Tricyclic<br />
antidepressants have shown conflicting results, and <strong>the</strong>re is only limited evidence for an<br />
effect on depressive symptoms in dementia (Evidence Grade 3). 14<br />
Tricyclic antidepressants produce prominent side-effects, including reduced cognitive<br />
14, 78<br />
functions, in dementia (Evidence Grade 3).<br />
There is limited evidence that serotonin-active antidepressants reduce behavioral<br />
symptoms in dementia (Evidence Grade 3). 14 According to Hermann and Lanctôt, more<br />
data are required to determine <strong>the</strong> efficacy of trazodone (a serotinine modulator) and<br />
<strong>the</strong> SSRIs for <strong>the</strong> treatment of agitation and o<strong>the</strong>r BPSD. 78 Negative results were<br />
obtained in studies evaluating <strong>the</strong> effect of antidepressive drugs on agitation in dementia<br />
patients. 10 With <strong>the</strong> possible exception of citalopram, antidepressant agents did not<br />
reduce agitation. 82<br />
4.4.2 Treatment of Behavioral and Psychological Signs and Symptoms of<br />
dementia<br />
Psychotic symptoms are seen in 34% of dementia patients, but <strong>the</strong> use of antipsychotic<br />
drugs has been mainly to treat behavioral symptoms included in <strong>the</strong> concept of BPSD<br />
(Behavioral and Psychological Signs and Symptoms of dementia). 14 The majority of <strong>the</strong><br />
studies did not differentiate dementia diagnoses. BPSD may account for up to 30% of<br />
<strong>the</strong> total cost of care of dementia patients. 78 A frequently used ra<strong>the</strong>r broad scale to<br />
evaluate BPSD is <strong>the</strong> 144 point NPI scale, rating <strong>the</strong> frequency and severity of 12<br />
behaviors.<br />
Before one considers a pharmacological intervention, one should rule out underlying<br />
disorders, conditions which could explain <strong>the</strong> psychosis (eg delirium) or reduce <strong>the</strong><br />
triggers, and try non-pharmacological interventions, unless <strong>the</strong> patient or o<strong>the</strong>rs are at<br />
8, 78<br />
risk of harm.<br />
As a reminder, approval of a pharmaceutical intervention typically requires evidence<br />
based on a minimum of two high-quality RCTs. As discussed in <strong>the</strong> section on nonpharmaceutical<br />
interventions it is important to note that for none of <strong>the</strong> non-drug<br />
interventions this level of evidence has been demonstrated. 78<br />
The results obtained with ChEIs for <strong>the</strong> treatment of behavioral problems in AD<br />
patients are contradictory. Moreover, in <strong>the</strong> studies demonstrating a positive effect, <strong>the</strong><br />
clinical relevance has been questioned. For memantine, <strong>the</strong> positive effect on<br />
neuropsychiatric symptoms remained limited to <strong>the</strong> subgroup of moderate and severe<br />
AD, and was not detected in AD patients with mild to moderate disease. 10 In a recent<br />
meta-analysis an improvement in NPI of nearly 2 points was found for memantine. 84<br />
Hermann and Lanctôt conclude <strong>the</strong>re is emerging evidence that ChEIs and memantine<br />
have beneficial effects on behaviour. They suggest that for untreated patients with mild<br />
to moderate BPSD, initial treatment with a ChEI and (or) memantine might be<br />
preferable to treatment with o<strong>the</strong>r psychotropic agents, given <strong>the</strong> efficacy of <strong>the</strong> former<br />
for cognition and function as well. 78<br />
In combination with donepezil, but not in mono<strong>the</strong>rapy, memantine slightly improves<br />
BPSD in moderately severe (MMSE 10-14) AD patients (effect size < 0.5 SD). 19