Dear Maryam,

My answer is of course YES. First I will give you some basic things:

1. PSYCHIATRIC COMORBIDITY IN PATIENTS WITH AD

I work as clinical pharmacist specialist in psychiatry and usually deal with these patiens almost every day. Because, depression, SCH, delusions, restlessness and very common in patients with AD (more than 50 % of patients have at least one psychiatric comorbidity).

2. POLYPHARMACY (INCLUDING PSYCHIATRIC)

Polypharmacy is very common in the elderly patients and we know that many patient take usually more than 10 drugs. Polypharmacy is often consequence of inappropriate prescribing and therefore many DDIs are possible. To reduce inappropriate polypharmacy we use different tools, such as STOP/START, Priscus list, Lexi etc ...

3. NON-PSYCHIATRIC COMORBIDITY

More than 50 % of elderly psychiatric patients have problem with hypertension/hypotension and therefore after new treatment for AD drug adjustment is needed. Arrhythmias are also included and many drugs for AD (e.g. donepezil most) have impact on arrhythmias. Usually i do not suggest donepezil in these patients.

IMPORTANT INTERACTIONS:

a) PHARMACOKINETIC

Be careful If some of your patients have antidepressants which have serious CYP2D6 metabolism (e.g. paroxetine, fluoxetine). Then do not use donepezil, which has serious 2D6 metabolism and impact on it. Rivastigmin is the best option among parasympathomimetic agents if you cannot change the antidepressant. On the another side You can change antidepressant, for example use escitalopram instead of paroxetine or even trazodone, however be careful especially within first 2 weeks for possible arrhythmias. Please avoid the use of alpha-blockers in these patients (serious hypotension can occur). They are however not advisable for use in the elderly patients (Priscus list, START/STOP). If You have patient with benign prostatic hyperplasia use finasteride for example.

When You use donepezil be careful about the use of metoprolol and carvedilol and SWITCH TO bisoprolol (beta-blocker that affects the heart and circulation).

In the view of DDIs (pharmacokinetic) rivastigmin is the best option, if we know that there are almost no differences in efficacy of different parasympathomimetic agents. Especially avoid of the use of donepezil, because of DDIs and high Vd, which means that when the adverse event occur, you need long time to eliminate donepezil.

b) PHARMACODYNAMIC

Do not use the anticholinergic agents in these patients or try to avoid it (e.g. carbamazepine, olanzapine, clozapine, darifenacin, solifenacin etc ...). Try to use agents with little or small impact on anticholinergic activity. For example, small doses of quetiapine and trazodone have little impact, however high doses of these drugs have high impact (negative) and therefore you use small doses of quetiapine and trazodone if it necessary. If You use antipsychotics use them very careful and use the drug discontinuation when restlessness is removed (e.g. 2-4 months usually). Be very careful about the use of antiholinergic agent biperiden (an antiparkinsonian agent of the anticholinergic type), which is often use too often in the patients with AD and this drug should be discontinued. Also if you use clozapine (no another option, or Parkinson with AD) you use for hypersalivation drugs very careful, especially do not use Trospium chloride for a long time. In these cases use the Butylscopolamine.

c) MEMANTINE

Memantine is the first in a novel class of Alzheimer's disease medications acting on the glutamatergic system by blocking NMDA receptors and has relative few DDIs with another drugs. Especially be careful about lower kidney function (dose adjustment) and interactions with methotrexate and antibiotics (Trimethoprim/sulfamethoxazole (TMP/SMX) or co-trimoxazole). Do not use this antibiotic in these patients, please use penicilines or even norfloxacin. Nitrofurantoin is advisable to avoid in these patients, however it is first line treatment. Infection in these patients are important, because more of 20 % elderly are also infected and antibiotics are needed. if you use methotrexate (MTX) be very careful about toxicity of MTX and measure kidney, liver and blood parameters more often.

If I sum up if it is very important issue and interesting question. Because DDIs are very important in selecting the most appropriate drug for AD patients, it is important to collaborate with clinical pharmacist and/or pharmacologist to choose the most appropriate strategy for these patients. However we need appopriate treatment strategy for AD, we should keep in mind that those drugs are not very effective (NNT=app. 12-16) and in the patients with polypharmacy is should be calculated  and consequently the pharmacotherapeutic priorities should be chosen before prescribing the drug for AD. Next to the knowledge of DDIs you should use the knowledge of basic pharmacology, because of multiple combinations for which we do not have appropriate clinical trials and outcomes.

I hope that it was helpful,

Regards,

Matej, Clinical Pharmacist

Thank you very much really it is very useful. I am really grateful

I am looking for drugs passage through the BBB

Best regards 

Alzheimer-patients are more prone to side effects, so unfavorable drug interaction will cause even more problems !

Dear Herwig,

I agree with that and consequently these drugs have relative high percentage of adverse effects. Because these drugs are quite small in term of efficacy, treatment discontinuation should be calculated after serious adverse events and/or treatment inefficacy. This step is often missing in the elderly patients, where smth no benefits are clearly seen.

If the knowledge about efficacy of these drug is very easy; on the other hand there are many choices among them if we look pharmacokinetics, which is very interesting and therefore a cooperation between clinician and clinical pharmacist is benefitial in these patients. About adverse events ... It is necessary to control them especially in first 2 weeks and in donepezil even more. Please measure heart rate and pressure, do not use donepezil in patients with serious CV problems (e.g. CHF, AF). About memantine please be careful about serious psychiatric adverse events, especially delusions, restlessness, insomnia and trial with discontinuation should be calculated (especially small activity on D2 receptors is problematic).

Regards,

Mathew

Mathew, You are right! Less is more (helpful)! Far to many elderly persons take more that 5 drugs with high risk of unfavorable interactions and sideeffects. 

Tx Herwig! Very good! Less in more (i like it).

We should ask ourself what is the benefit of polypharmacy in 85-year old patient with several diseases? So called 'time to death' trials are very important and observed adverse events. Drugs which are not effective in the elderly patients and are even worse problematic should be discontinued in several cases (e.g. digoxin, TCA, antipsychotic polypharmacy, irrational antidepressant combinations, calcium carbonate). The same story is for very low efficacy drugs, where NNT is 20 or more.

My suggestion:

1. indications for drugs (several off label drugs treatment discontinuation ASIP)

2. observed adverse events and drug interactions (contraindicated DDIs should be discontinued); adverse event's drug should be terminated for some days and withdrawal if it is possible (bigger evidence is established; see Naranjo scale).

3. Check every disease if you have drugs with great benefit (e.g. betablockers for CHF with EF less than 35-40 %, antidepressant for depression, ACE-inhibitors for hypertensio ...)

4. Write your treatment goals for elderly and calculate time to death for your patients and check if you have drugs where no benefits is shown in this period (e.g. calcium, vitamin D, bisphosphonates, Aspirin in some cases, omeprazol ... ).

5. Suggest treatment discontinuation of some drugs and maybe new starting, where there are no drugs for clear indication (e.g. antidepressant for depression, ACE-inhibitor for CHF and AF). Plan discontinuation of the inappropriate drugs for elderly (Priscus list, START STOP, no clear benefits; high NNT and low NNH).

6. Write down your new treatment goals and monitor the patient.

Regards,

Mathew

Thanks for your comments

Is there any increasing in drugs effectivity in AD? due to BBB

This is my point

Regards

 Interesting question!

At the moment we do not have evidence about significant differences in term of efficacy! However, we have these results, there are big differences in penetration in to the CNS, especially drugs with high Vd have more possibility to penetrate (e.g. donepezil). On the other way drugs like Rivastigmine have smaller Vd.

It is interesting to measure real concentration in these patients, because smth lower efficacy can be a consequence of low CNS penetration, for example it is seen in drug atomoxetine, which has very low concentration in compare with methylphenidate.

This question opens opinion why clinical pahrmacist with his knowledge of pharmacology is important in these patients!

Regards,

Mathew

Interactions with what? Do you mean side effect with other drugs. The question is not stated precisely  and thus it is interesting that you seem to be getting advice. 

Thanks Matej Stuhec for your useful answers 

Merrill F Elias

I but the question open to hear from you and I get the suggestion and if you read the chat, you can understand what is the idea

I mean the interaction between drugs and their penetration though the BBB in AD patients 

please if any one have papers about the drug interactions in AD please send it

Best regards