Preventative Care New Medications: Are they Worth the $$?
Amy B. Gonzales, P.A.-C.
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Three new medications that are being advertised on television and in magazines are Strattera, Namenda and Lexapro. One is used for the treatment of Attention Deficit Disorder (with or without hyperactivity) (ADD/ADHD) and concentration, one for memory problems associated with Alzheimer’s disease and the last for treatment of depression. In the field of brain injury, you may also hear about these drugs for the treatment of symptoms in these areas. All are areas where other medications already exist to treat the conditions, so are these newer medications better? Are they worth the money?

Medications used for Attention and Concentration
Neurostimulants were originally used after traumatic brain injury (TBI) to help the individual with a brain injury pay attention to his or her environment, to help decrease distractibility, to assist with concentration in rehabilitation and to aid with memory. The stimulant medication was thought to help the patient emerge from a coma sooner, recover more quickly and speed the cognitive process, as well as combat fatigue. Some evidence shows that stimulants may help the brain recover after an injury by helping the neurons reconnect (Ripley, 2003a).

The original neurostimulant medications contained methylphenidate (Ritalin, Concerta, Methylin, Metadate) or destroamphetamine (Adderall and Dexedrine). They worked well for many people and, of course, are known and FDA approved for their use in treating Attention Deficit Disorder (ADD) or Attention Deficit Hyperactivity Disorder (ADHD). Precautions include patients with seizures, heart conditions, or appetite problems and these medications do have a potential for abuse.

Strattera
Strattera (atomoxetine HCL), produced by Eli Lilly and Company, was FDA approved in November of 2002. It is a non-stimulant medication approved for the treatment of ADHD in both children and adults. It is a selective norepinephrine re-uptake inhibitor. This means that, at the nerve synapse the drug prevents the chemical norepinephrine from returning to its originating nerve end so it is available to continue to stimulate the next nerve. This then strengthens the chemical signal between the nerves that use norepinephrine to send messages. Strattera does not seem to affect dopamine in the brain like the neurostimulant medications except that it may cause some secondary increase in dopamine, but only in the area of the brain located directly behind the eyes, known as the prefrontal cortex.

The structure of Strattera is similar to that of the tricyclic antidepressants, but it is a phenylpropanolamine derivative. It is available as 10 milligram (mg), 18 mg,
25 mg, 40 mg, and 60 mg capsules, and the starting dosage is 0.5 mg/kg/day (this is a mg per body weight calculation) to the maximum of 1.4 mg/kg/day or 100 mg/day, whichever is lower. It is taken as one single morning dosage, but if sedation is a problem, the dose may be changed to the evening. The medication should be taken with food. It does have a gradual onset and may take up to three weeks to have its desired effect.

In studies, Strattera has worked better than placebo for problems with attention, hyperactivity and impulsivity. Side-effects include significant nausea. Appetite suppression, sleep disturbance, jitteriness, irritability, slight increase in pulse and blood pressure, and sedation may also occur. In adults, urinary retention and sexual dysfunction have occurred with this medication. Persons with narrow-angle glaucoma and those taking the antidepressants Prozac, Paxil or MAOIs should not use Strattera. Unlike the neurostimulants, there is minimal abuse potential for Strattera. The long-term effect on growth in young patients has not yet been determined for this medication, and it has not been tested in children under six years of age (Eli Lilly, 2004).

Cost Comparison at Local Pharmacy

STRATTERA

18 mg #30 - $93.58
40 mg #30 - $93.58

RITALIN

10 mg #60 - $53.02
Generic - #33.08

20 mg SR #30 - $57.13
Generic - #38.61

ADDERALL

XR 10 mg #30 - $100.31

XR 20 mg #30 - $100.31

Adderall Regular 5, 10 or 20mg #60 - $120.45
Generic - $70.42

In most states, the stimulant medications require special prescription blanks and refills may not be called into the pharmacy. Strattera is a non-stimulant, non-controlled
substance that may be refillable making continued use much easier. This, however, does not mean that office appointments and follow-ups with the psychiatrist or physician are not as important as with the previous medications available to treat ADHD.

Strattera is more expensive than the stimulant medications. It takes longer to take effect and may cause more nausea and stomach upset. Furthermore, clinicians are used to working with the older medications in the treatment of ADHD, including dosage adjustments and side effects. However, for the treatment of ADHD, or attentional problems, where precautions to the use of stimulant medications are present (such as seizures, drug addiction or heart problems), Strattera may be a viable alternative. For those people who get too jumpy or irritable on the stimulants, Strattera may also be better tolerated. Additionally, Strattera has an anti-depressant effect and has recently been used by many psychiatrists for this property. For those individuals with ADD, ADHD or brain injury who need that extra boost of the neurostimulant medications, Strattera may prove disappointing (The Medical Letter, 2003).

Medications used for Memory
On occasion, medications used to treat Alzheimer’s disease and memory problems may be used for an individual with a brain injury. It is believed that the neurotransmitters that are stimulated by the Alzheimer’s medications may improve brain functioning from coma stage to early recovery stage. Alzheimer’s medications work by affecting neurotransmitters involved with cognition: primarily dopamine, norepinephrine, and acetylcholine. Dopamine and norepinephrine are involved with arousal and attention, while dopamine also helps with language function. Acetycholine is involved in memory function.

If it sounds odd to use a medication for Alzheimer’s Disease for brain injury, consider the cognitive deficits described in the following partial list of diagnostic criteria for Dementia
of the Alzheimer’s Type (American Psychiatric Association, 1994):

Development of multiple cognitive deficits manifested by both:

1. Progressive Memory Loss and

2. One or more of the following cognitive disturbances:

• Aphasia-disturbance of language

• Apraxia-impairment in carrying out motor activities despite intact motor function

• Agnosia–inability to recognize or identify objects despite intact sensory function

• Disturbance in executive functions, such as planning, organizing, sequencing, and abstracting

In addition, following are the Seven Warning Signs of Alzheimer’s Disease provided by the University of Southern Florida Suncoast Gerontology Center (2001):

1. Asking the same question repeatedly

2. Repeatedly telling the same story, word-for-word

3. Forgetting how to cook, do repairs, play cards, carry out usual activities

4. Losing the ability to pay bills or balance a checkbook

5. Getting lost in familiar surroundings or misplacing objects

6. Neglecting to bathe or wearing the same clothes over and over again, while insisting that they had a bath and the clothes are clean

7. Relying on somebody else (e.g. family member) to make decisions or answer questions that they previously would have handled themselves

Do any of these descriptions “fit” some of the situations present for an individual with a brain injury whom you know or care for? Obviously, behavioral changes found in aging, senile dementia, and Alzheimer’s disease may be similar to the cognitive and behavioral changes seen in individuals with brain injury. So, will the same medications work for persons with brain injury and persons with Alzheimer’s disease? Unfortunately, studies are few
regarding the use of Alzheimer’s medications in brain injury. In some cases, however, these Alzheimer’s medications may be helpful for individuals with behavioral problems associated with loss of inhibition (frontal-lobe damage) (Ripley, 2003b). In the past, the dementia
or Alzheimer’s medications have included Aricept (donepezil), Exelon (rivastigmine), and Reminyl (galantamine). In October of 2003, Forest Laboratories released a new Alzheimer’s treatment, Namenda.

Namenda
Namenda, or memantine HCL, is indicated for moderate to severe Alzheimer’s disease. All the previously FDA approved medications were only approved for mild to moderate disease. Moderate Alzheimer’s involves deterioration of intellect, logic, behavior and functioning. Severe Alzheimer’s involves loss of long-term memory and language skills, and the individual may require 24-hour care, as they can no longer complete basic self-care tasks like washing, eating and toileting.

Namenda is different than the other Alzheimer medications. It works by targeting glutamate, a chemical in the brain. The other medications target acetylcholine. Glutamate is thought to have an affinity to the NMDA or N-methyl-D-aspartate receptor antagonist. It is thought that the over-excitation of NMDA receptors by the neurotransmitter glutamate may play a role in Alzheimer’s disease, since glutamate plays a role in the neural pathways associated with learning and memory. The excitotoxicity of abnormal levels of glutamate may be responsible for the nerve cell dysfunction in Alzheimer’s. Namenda is thought to block the effects of abnormal glutamate transmission (Forest Pharmaceuticals, 2004b).

Cost Comparison at Local Pharmacy

NAMENDA

5 mg #60 - $138.69
10 mg #60 - $138.69

ARICEPT

5 mg #60 - $308.66
10 mg #60 - $308.66

Namenda’s starting dose is 5 mg once a day to a maximum of 10 mg twice a day. Tablets are available as 5 mg and 10 mg and can be taken with or without food. Adverse reactions include dizziness, confusion, headache and constipation. So far, there are no studies to evaluate this medication in patients with seizure disorders.

Unfortunately, there is no cure for Alzheimer’s disease. While studies on this medication target the elderly population, there is evidence of some slowing in the progressive loss of
cognitive, intellectual, and functional abilities seen in the disease. A Journal of the American Medical Association (JAMA) article showed a significant benefit of combination therapy using Namenda and Aricept (donepezil) (Tariot, Farlow, Grossberg, Graham, et al., 2004).

Namenda has several advantages over the older medications, including the indication for moderate to severe Alzheimer’s problems, being less expensive, and having minimal
side effects. Combination therapy with the older Alzheimer’s disease medications is also an option for severe cognitive difficulties. Since studies are just beginning involving brain injury and Alzheimer’s medications that have been available on the market for almost 40 years, this author doubts that studies with the Alzheimer’s medication, Namenda, will be completed quickly. Hopefully, future studies in the treatment of memory and cognitive problems using Alzheimer’s medications will help guide us in the care of persons with brain injury.

Medications used for Depression
Many relatively new anti-depressants, known as Selective Seratonin Re-uptake Inhibitors (SSRIs), are currently on the market. In August of 2002, Forest Labs received approval from the FDA to market Lexapro, also know as escitalopram oxalate, for the treatment of major depressive disorder and generalized anxiety disorder. A major depressive episode involves a relatively persistent two-week episode of depressed or dysphoric mood that usually interferes with daily functioning and includes five of the following nine symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt or suicidal ideation.

Generalized anxiety disorder is characterized by excessive anxiety and worry that is persistent for at least six months and which the person finds difficult to control. It must be associated with at least three of the following symptoms: restlessness or feeling keyed up or on edge, being easily fatigued, difficulty concentrating or mind going blank, irritability, muscle tension, and sleep disturbance. (American Psychiatric Association, 1994).

Lexapro
Lexapro is available in 5 mg, 10 mg, and 20 mg tablets and a 5 mg/5 ml peppermint flavored oral solution. The recommended starting dosage is 10 mg, once daily, with or without food, taken either in the morning or the evening.

Lexapro is in the class of SSRIs with Prozac, Paxil, Zoloft, Effexor and its predecessor Celexa. Celexa or citalopram hydrobomide was FDA approved in July of 1998 and is
produced also by Forest Labs. The newer drug, Lexapro, basically is a revamped version of Celexa or the pure S-en antiomer of Celexa (Warner, 2002b). This author thinks of it as Celexa with all the inactive ingredients taken out and the more important, potent part of the medication left in. The results are a reduction in side effects including nausea, insomnia, ejaculation disorder, sleepwalking and fatigue. Lexapro, like Celexa, should not be used with the MAOI antidepressants, and caution should be used when combining it with the tricyclic antidepressants. There have been cases of abnormal bleeding problems when this drug is used with aspirin and non-steroidal anti-inflammatory drugs like ibuprofen (Forest Pharmaceuticals, 2004a).

Cost Comparison at Local Pharmacy

LEXAPRO

10 mg #30 - $70.66
20 mg #30 - $82.07

CELEXA

20 mg #30 - $78.82
40 mg #30 - $81.40

ZOLOFT

50 mg #30 - $82.07

PROZAC

20 mg #30 - $118.57
40 mg #30 - $236.55
90 mg #4 - $94.30

Generic:
20 mg #30 - $23.77
40 mg #30 - $67.62

Studies on Lexapro show that it is effective in the treatment of depression and anxiety associated with depression. Its side effects and drug interactions are lower than many of the other antidepressants because of its metabolism sites. A comparison study between
Lexapro and Effexor XR by Stuart Montgomery of the Imperial College School of Medicine at the University of London found that, although Effexor XR and Lexapro both eased the symptoms of depression in most patients, Lexapro worked faster and had fewer side effects (Warner, 2002a).

Forest Labs have priced Lexapro just below the cost of Celexa, and the cost is fairly equivalent, or lower than the other similar SSRI antidepressants on the market. Fewer side effects may make Lexapro the drug of choice for many people with depression, or anxiety with symptoms of depression. Also, with Lexapro being the more pure form
of Celexa, it makes sense to choose Lexapro over Celexa when initiating new treatment in a patient requiring this type of medication.

As a practitioner in a rehabilitation setting, I am seeing more initial start usage of Lexapro due to its low number of drug interactions and side effects. It is especially useful
in persons with brain injury who may have cognitive or physical impairments or for whom drug interactions are a concern.

Conclusion
Medications can be confusing and it is important to have a basic knowledge of some of the newer medications in case the health care practitioner recommends them for an individual with a brain injury whom you care for. Whether you are a caregiver, survivor, family member, case manager, rehabilitation counselor, staff member or professional, you must deal with medication issues daily. Hopefully, Strattera, Namenda and Lexapro will be easier for you to remember now, and you will know some of the fundamentals regarding their use to help assist you in your medical decisions.

References

American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: Author.

Eli Lilly & Company (2004). Safety information. Straterra (atomoxetine HCI). Retrieved September, 2004, from
http://www.strattera.com/1_2_taking_strattera/1_2_4_safety.jsp

Forest Pharmaceuticals, Inc. (2004a). About Lexapro (escitalopram oxalate). Retrieved September, 2004, from
http://www.lexapro.com/english/about_lexapro/default.aspx

Forest Pharmaceuticals, Inc. (2004b). Namenda (memantine HCI). How Namenda Works. Retrieved September, 2004, from
http://www.namenda.com/treating/how.asp

Ripley, D. (2003a). Classic stimulants: Cognitive enhancing agents. Memory & Cognitive Syndromes. Retrieved January 26, 2004, from the
Brain Injury Resource Foundation Web site: http://www.birf.info/artman/publish/article_97.shtml

Ripley, D. (2003b). Memory enhancing agents. Memory & Cognitive Syndromes. Retrieved January 26, 2004, from the
Brain Injury Resource Foundation Web site: http://www.birf.info/artman/publish/article_98.shtml

Tariot, P., Farlow, M., Grossberg, T., Graham, S. et al. (2004, January 21). Memantine treatment in patients with moderate to severe Alzheimer Disease
already receiving donepezil. Journal of the American Medical Association, 291(3), 317-324.

The Medical Letter On Drugs and Therapeutics. (2003, February 3). Atomoxetine (Strattera) for ADHD (Volume 45, Issue No. 1149).
Retrieved September, 2004, from http://www.medicalletter.org/scripts/search.cgi

University of South Florida Suncoast Gerontology Center. (2001, July). Frequently asked questions about Alzheimer’s. Agelines. Retrieved, January, 2004, from http://www.med.usf.edu/suncoast/alzheimer/faqad.htm

Warner, J. (2002a, October 9). Lexapro bests Effexor in depression study: First head-to-head comparison of the popular antidepressants. Retrieved January 26, 2004,
from WebMD Web site: http://my.webmd.com/content/article/51/40714.htm?lastselectedguid={5FE84E90-BC77-4056-A91C-9531713CA348}

Warner, J. (2002b, August 15). New antidepressant approved: Revamped version of Celexa has few side effects. Retrieved January 26, 2004, from
WebMD Web site: http://my.webmd.com/content/article/49/40120.htm?lastselectedguid={5FE84E90-BC77-4056-A91C-9531713CA348}

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