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Friday, December 19, 2014

Medications To Avoid If You Have bvFTD Or Other Dementias


It has been almost 3 months since I have written anything. In September I was having many difficult days, and attributed them to allergies and antihistamines. Here in Northwest Ohio we had a cold snap before Thanksgiving accompanied by a few inches of snow. That put an abrupt end to the hayfever season. Now that the weather has turned colder my allergy symptoms have all but disappeared, and I have not been regularly taking any antihistamines. I am also feeling much better.

Surprisingly my recovery was not as rapid as I would have predicted. It has taken a couple months. Once in a while I still have a really bad day where I lock myself away in a dark room and read, but they are becoming less frequent. I am still having great difficulty getting things done, and going out. Christmas shopping has become an almost insurmountable task. Almost! I will manage. Online shopping helps, but seems like too much of a compromise. I need to get out there in the world and do some shopping.
Simple, but SO difficult at the time!

As an example of one of those "bad days", I was putting new tires on a bicycle for Cindy. She had found it at a garage sale. I have changed bicycle tires countless times, but this time I was totally incapable of figuring out how to re-assemble the chain and derailleur. I was SO frustrated. I took a break, and looked up a picture of it on the internet. I finally got it, and it was so simple. bvFTD can strike at the oddest of times.



Back to antihistamines. I have been having some trouble sleeping through the night for a very long time. I tend to wake up after sleeping a few hours, watch TV for a couple hours, and then go back to bed. I very rarely sleep through the entire night.

I saw an advertisement on TV for a sleep aid. I checked up on it, and found that its only ingredient was Benadryl - an antihistamine! Well, since I have been having so much difficulty with antihistamines anyway, I figured I would try some as a sleep aid. bvFTD can really assist in making smart decisions like this. I took a couple tablets before I went to bed, matching the dose in the sleep aid, and slept the whole night through for the first time in months. That was nice.

But, over the following couple of days I was confused, and was right back having what I have come to refer to as a "bad day". Fortunately the bad affects didn't last long. Though I appreciated the good nights sleep overall it wasn't worth it.

This led me to do a little research on just which medications are NOT RECOMMENDED for people with bvFTD and related dementias. The list is surprisingly long, and includes some very commonly prescribed medications. I am going to skip the technical studies for a change, and just include some of the recommendations gleaned from several websites dedicated to dementia. The bulk of this information came from the Alzheimer’s Association, and the University Of Southern California.

Following is the list, some alternatives, and other interesting and related information. Interesting to note that antihistamines figure prominently on this list. As always, remember: Every case of bvFTD is different. Everything here is for informational purposes only. See the medical disclaimer through the link located to the right of this page.


Anticholinergic medications

Anticholinergics decrease acetylcholine activity to balance out the production of dopamine and acetylcholine. They are used to treat incontinence, depression and sleep disorders. Medications with strong anticholinergic effects, such as antihistamines that cause drowsiness, are well known for causing acute cognitive impairment in individuals with dementia and may cause confusion and hallucinations. Furthermore, with the cholinergic deficit in some forms of dementia, they could potentiate this deficit and antagonize any cholinesterase inhibiting medications. Adverse effects may include blurred vision, dry mouth and urinary retention. Single or combination gastrointestinal/urinary antispasmodics products should be avoided.

Several factors that may influence whether a patient develop cognitive impairment when exposed to
anticholinergic drugs:

    the number of AC drugs and the doses of the drugs used,
    baseline cognitive function (determines susceptibility) and
    the patient's response to medications (sensitivity and metabolic processing as determined by their liver and kidney function status).

Carefully evaluate the risk/benefit for these medications and consider alternatives. For example with incontinence, consider the following:

    Functional vs urge incontinence
    Scheduled toileting
    Check post void residuals (especially in males as these medications can cause retention)
    Reducing dose of cholinergic medication

If used, carefully evaluate effectiveness of medication and consider discontinuing if there is no improvement in six weeks.
Examples

    Atropine
    Belladonna alkaloids
    Benzotropine mesylate (Cogentin®)
    Dicyclomine (Bentyl®)
    Flavoxate (Urispas®)
    Hyosyamine (Levsinex®)
    Oxybutynin (Ditropan®)
    Scopolamin
    Tolterodine (Detrol®)
    Trihexyphenidyl HCL (Artane®)

Antihistamines

Antihistamines block the action of histamine, a substance in the body that causes allergic symptoms.
Examples

    Azatadine (Optimine®)
    Brompheniramine (Dimetane®)
    Carbinoxamine, Chlorpheniramine (Chlor-Trimeton®)
    Clemastine (Tavist®)
    Cyproheptadine (Periactin®)
    Dexchlorpheniramine (Polaramine®)
    Diphenhydramine (Benadryl® or Sominex®)
    Hydroxyzine (Atarax®)
    Phenindamine (Nolahist®)
    Promethazine (Phenergan®)
    Tripolidine (Actifed/Myidyl®)

Physicians also recommend that individuals with dementia avoid over-the-counter sleep remedies. The active ingredient in many of these preparations is diphenhydramine (Benadryl®), an antihistamine that tends to make people feel drowsy. Diphenhydramine further suppresses the activity of one of the main brain cell messenger chemicals whose activity is reduced by Alzheimer’s disease.

Examples of over-the-counter sleep aids containing diphenhydramine that should be avoided include:

    Compoz®, Nytol®, Sominex®  and Unisom® diphenhydramine (Benadryl!!! ed.) is also an ingredient in many “nighttime” or “PM” versions of popular pain relievers and cold and sinus remedies 

Barbiturates

Barbiturates cause relaxation and sleepiness. Excessive and prolonged dosages of barbiturate drugs, such as phenobarbital, may produce memory loss, irritability, changes in alertness and decreased interpersonal functioning. Barbiturates may also cause an acute, life-threatening overdose syndrome.
Examples

    Phenobarbital (Luminal® Sodium)

Benzodiazepines

In general, benzodiazepines are frequently associated with increasing confusion, falls and memory impairment in elderly patients. In people with FTD, benzodiazepines have been associated with an increase in behavioral problems and impair both memory and psychomotor skills. Repeated use of large doses or, in some cases, daily use of therapeutic doses of benzodiazepines is associated with amnesia, hostility, irritability and vivid or disturbing dreams, as well as tolerance and physical dependence. Use can result in reduced inhibition and impaired judgment. Benzodiazepines have also been associated with anticholingeric-like effects, such as urinary retention and dry mouth. Anxiolytics recognized as benzodiazepines should be avoided.

Carefully evaluate alternatives for these medications, and if they cannot be avoided, consider using them for only a short time. When used for anxiety, consider nonpharmacological supportive strategies. If co-existing with depression, consider use of paroxitene (Paxil®), citalopram (Celexa®) or buspirone (Buspar®). When used for sleep:

    Consider good sleep hygiene
    Encourage adequate physical activity during the day
    Try melatonin
    Try trazodone (Desyrel®)

Examples

    Short-acting benzodiazepines: triazolam (Halcion®) and Midazolam (Versed®)
    Intermediate-acting benzodiazepines: lorzepam (Ativan®), temazepam (Restoril®), alprazolam (Xanax®), oxazepam (Serax®), estazolam (ProSom®)
    Longer-acting benzodiazepines: diazepam (Valium®), chlordiazepoxide (librium®), clorazepate (Tranxene®), halazepam (Paxipam®), prazepam (Centrax®), quazepam (Doral®) and clonazepam (Klonopin®), flurazepam (Dalmane®)

CNS stimulants

Increased sensitivity to medications affecting the CNS can produce impaired memory and delayed psychomotor performance.
Examples

    Amitriptyline (Limbitrol® or Limbitrol® DS): Amitriptyline is used to treat symptoms of depression
    Fluoxetine (Prozac®, Prozac® Weekly, Sarafem®, Symbyax®): Fluoxetine (Prozac) is used to treat depression, obsessive-compulsive disorder, some eating disorders and panic attacks. Fluoxetine (Sarafem) is used to relieve the symptoms of premenstrual dysphoric disorder, including mood swings, irritability, bloating and breast tenderness.

Muscle relaxants

Muscle relaxants may be used to treat spasticity or muscle spasms associated with spinal cord injuries, stroke, multiple sclerosis, cerebral palsy or other conditions. Several of them can cause severe liver damage.
Examples

    Carisoprodol (Soma®)
    Chlorzoxazone (Parafon Forte®)
    Cyclobenzaprine (Flexeril®)
    Dantrolene Oral (Dantrium®)
    Metaxalone (Skelaxin®)
    Methocarbamol (Robaxin®)
    Orphenadrine (Norflex®)
    Baclofen (Lioresal®)

Tricyclic antidepressants

Some of these medications have anticholinergic properties which may worsen cognition in patients with mild memory problems and antagonize the effects of cholinesterase inhibitors. Carefully evaluate alternatives for these medications. Desipramine (Norpramin® or Pertofrane®) has the least anticholinergic side effects of any of the tricyclics.

When used for neuropathic pain, patients over the age of 65 may do better on gabapentin (Neurontin®) due to a lower risk of side effects. When used for sleep, please consider possible use of trazodone (Desyrel®) due to lower risk for anticholinergic side effects. When used for depression, consider using an alternative antidepressant class.
Examples

    Amitriptyline (Elavil®)
    Clomipramine (Anafranil®)
    Desipramine (Norpramin® or Pertofrane®)
    Doxepin (Sinequan®)
    Imipramine (Tofranil®)
    Protriptyline (Vivactil®)
    Trimipramine (Surmontil®)



There are no medications available to cure or delay the progression of FTD, but there are a number of medications available for symptomatic relief. Medical management includes treatment of concomitant medical conditions including infections, parkinsonian symptoms, seizures, pain and improving nutritional status. It is imperative to review all medications that the patient is taking. This includes prescription drugs, non-prescription drugs, social drugs (caffeine, nicotine, alcohol) and/or alternative products (e.g., herbals, vitamin or minerals). A number of medications can exacerbate behaviors or cognitive problems (e.g., stimulants, depressants, some anti-epileptic medications), so any unnecessary drug should be discontinued. All medications the patient is taking should be fully reassessed for optimal response at the dose prescribed and the patient should only be on necessary medication that are effective in treating underlying conditions.



Early interventions

Nonpharmacological forms of therapy should be initiated first for the management of inappropriate or aggressive behavior. This includes discussing tolerance for disruptive but non-dangerous behavior, a medical alert bracelet for the patient and a note or card to be given to strangers explaining the patient has a disease (click here to download cards that can be printed), providing distraction so that patient diverts attention or alters behavior, and mild forms of bribery with favorite snacks. The family and caregivers should be referred to support groups and local chapters that in addition to providing information and advice, organize respite care. Depression in caregivers is common and leads patients to earlier nursing home placement (Litvan et al, 2001). The need for a power of attorney cannot be overemphasized as the patients quickly, if not at the time of diagnosis, are no longer able to make medical and financial decisions. The behavioral symptoms are often the cause for the institutionalization of patients and so need to be addressed and adequately treated.
Pharmacological review

There are no medications available to cure or delay the progression of FTD, but there are a number of medications available for symptomatic relief. Medical management includes treatment of concomitant medical conditions including infections, parkinsonian symptoms, seizures, pain and improving nutritional status. It is imperative to review all medications that the patient is taking. This includes prescription drugs, non-prescription drugs, social drugs (caffeine, nicotine, alcohol) and/or alternative products (e.g., herbals, vitamin or minerals). A number of medications can exacerbate behaviors or cognitive problems (e.g., stimulants, depressants, some anti-epileptic medications), so any unnecessary drug should be discontinued. All medications the patient is taking should be fully reassessed for optimal response at the dose prescribed and the patient should only be on necessary medication that are effective in treating underlying conditions.
Selective serotonin reuptake inhibitors (SSRIs)

While there is no known treatment that can delay progression, environmental and pharmacological interventions can help with the behavioral management. Certain behaviors, especially aggression and extreme disruptiveness, as well as delusions require medication. Patients with FTD show serotoninergic deficits which appears largely related to postsynaptic defects although presynaptic deficits have been reported (Huey et al, 2006). Selective serotonin reuptake inhibitors (SSRIs) have been used with some success (Huey et al, 2007; Lebert et al, 2004; Swartz et al, 1997). SSRIs have been used to treat compulsions, ritualistic behaviors, carbohydrate cravings, anxiety and behavioral symptoms in patients with FTD (Swartz et al, 1997). Another study reported that paroxetine decreased or eradicated repetitive, ritualistic behavioral in a large proportion of patients (Chow & Mendez, 2002). The side effects were tolerable for most patients. Paroxetine compared to piracetam improved behavioral symptoms (Moretti et al, 2003). However, there is one study, albeit using paroxetine at a higher dose (40mg) that showed no improvement in behavioral symptoms and some learning difficulties in the paroxetine group (Deakin et al, 2004). Trazodone, was shown to be effective compared with placebo in controlling behavior in patients with FTD (Lebert et al, 2004).

Patients with SD share many similarities with FTD and so SSRIs can be tried for the compulsive behaviors. SSRIs can be warranted in PNFA because patients with this condition are often very aware of their deficits, so depression and social withdrawal are common. There are, however, no reported studies of antidepressant efficacy in this group.
Atypical antipsychotics

Low doses of atypical antipsychotics such as quetiapine, olanzepine or risperidone can be used for agitation, aggression or psychotic behavior. The potential benefit of all antipsychotics must be weighed against the potential risks such as cerebrovascular adverse events and even mortality. Typical antipsychotics are associated with extrapyramidal side effects and usually should be avoided, since patients with FTD are likely to show parkinsonism. Medications for behavioral symptoms should be initiated at a low starting dose and then subsequently titrated slowly based on the patient’s response and the presence of adverse effects.
Acetylcholinesterase inhibitors (AChEIs)

Acetylcholinesterase inhibitors, although helpful in AD, do not seem to be effective in managing symptoms of FTD and have been reported to cause agitation in patients with FTD. (Perry & Miller, 2001). They can be dangerous in patients with FTD-MND as they cause increased oral secretions. The most probable explanation for their lack of effectiveness in FTD is that the cholinergic system, in particular the cholinergic neurons in the nucleus basalis of Meynert, are relatively spared in FTD.
NMDA-receptor antagonist

Memantine, an NMDA-receptor antagonist, is approved for the treatment of Alzheimer's disease (AD). Preliminary evidence suggested transient, modest benefit on neuropsychiatric symptoms in FTD, but a prospective trial at UCSF showed no benefit for patients.
Valproic acid

Valproic acid and derivatives (divalproex sodium) have been reported as useful for aggressive behavior and for impulse control, primarily in individuals diagnosed with Alzheimer's disease. In placebo-controlled studies valproic acid displayed little or no benefit. Valproic acid and related drugs may cause liver damage and require blood tests to periodically check liver function. Many practitioners also order blood levels, which adds to the cost of drug therapy.
Gabapentin

Gabapentin has also been reported to be helpful in managing behavioral problems in a few case reports.
Non-pharmacological therapies

Individualized exercise programs can have a positive impact on functional performance in persons with mild to moderate dementia and can be helpful for patients with FTD (and their caregivers). Adequate sleep may reduce behavioral problems. Recognizing and treating concomitant illnesses or infections can also improve dispositions.
Complementary and alternative medicine

Many individuals also use non-prescription and herbal/alternative remedies for symptoms. However, at this time there is no evidence for any herbal/alternative remedies. Gingko biloba (GB) has been widely used in Asian and European medicine, and recent animal studies support a GB antioxidant effect but, to date, there is no evidence of a beneficial effect on cognition or behavior. Vitamin E was reported to be an antioxidant possibly beneficial in Alzheimer's disease (AD), but recent evidence suggests otherwise. There is no evidence to support its use in FTD (Sano et al, 1997, Peterson 2005).
Future treatments

The lack of randomized, placebo-controlled data on most symptomatic treatments for FTD greatly hinders our ability to determine optimal therapies at this time. The development of mouse models of FTD as well as a greater understanding of the pathophysiology offers hope for the development of future therapies. (Lee and Trojanowski 2001)
Language impairment

While there aren't useful medications to help with language impairment. PNFA, but also early SD and bvFTD, warrants a speech pathology assessment and intervention. Maintaining adequate communication can decrease frustration, a common problem in FTD. Refer your patient to our practical tips section for different communication strategies.



(More. . . this didn't copy well, and the table from the article was indecipherable. I am too lazy to fix it, so I deleted the table, but left the rest. If you are interested in the entire piece it is online as a PDF file. Just Google it. I am sure you can figure it out if I did.)

Copyright © 2008 by Therapeutic Research Center
Pharmacist’s Letter / Prescriber’s Letter
~ P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249
www.
pharmacistsletter.com ~
www.prescribersletter.com
Detail-Document #240510
-This Detail-Document accompanies the related article published in-
PHARMACIST’S LETTER / PRESCRIBER’S LETTER
May 2008 ~ Volume 24 ~ Number 240510
Drugs To Avoid in Patients with Dementia
Elderly people with dementia often tolerate drugs
less favorably than healthy older adults. Reasons
include increased sensitivity to certain side effects,
difficulty with adhering to drug regimens, and
decreased ability to recognize and report adverse events
. Elderly adults with dementia are also more
prone than healthy older persons to develop drug-induced cognitive impairment.
1
Medications with strong anticholiner
gic (AC) side effects, such as
sedating antihistamines, are well-
known for causing acute cognitive impairment in people with dementia.
1-3
Anticholinergic-like effects,
such as urinary retention and dry mouth, have also b
een identified in drugs not typically associated with
major AC side effects (e.g., narcotics, benzodiazepines).
3
These drugs are also important causes of acute
confusional states. Factors that may determine
whether a patient will develop cognitive impairment
when exposed to ACs include: 1)
total AC load (determined by number of AC drugs and dose of agents
utilized), 2) baseline cognitive function, and 3) individual patient pharmacodynamic and pharmacokinetic
features (e.g., renal/hepatic function).
1
Evidence suggests that impairment of cholinergic tr
ansmission plays a key role in the development of
Alzheimer’s dementia. Thus, the development of th
e cholinesterase inhibitors (CIs). When used
appropriately, the CIs (donepezil [
Aricept
], rivastigmine [
Exelon
], and galantamine [
Razadyne, Reminyl
in Canada]) may slow the decline of cognitive and f
unctional impairment in people with dementia. In
order to achieve maximum therapeutic effect, they id
eally should not be used in combination with ACs,
agents known to have an opposing mechanism of action.
1,2
Roe et al studied
AC use in 836 elderly
patients.
1
Use of ACs was found to be greater in patie
nts with probable dementia than healthy older
adults (33% vs. 23%, p = 0.001). Patients with dementia may be more apt to take ACs because of
increased prevalence of urinary incontinence (comm
only treated with ACs), us
e of AC antipsychotic
agents for behavioral and psychotic sympto
ms, and side effects caused by CIs.
When selecting drug therapy fo
r patients with dementia, the use of AC medications should be
avoided, or at least limited to medications within a
therapeutic class that have the least AC adverse
effects.