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BRAIN AND NERVOUS SYSTEM DISORDERS

Alzheimer's Disease

Alzheimer's disease, a neurological condition that affects an estimated four million people nationwide, results in the death of nerve cells in the brain. Symptom onset begins gradually, often as mild forgetfulness, and may be falsely attributed to normal aging. As the disease progresses cognitive abilities decrease, people are unable to make decisions or perform everyday tasks, and some patients may undergo personality changes. In its later stages, Alzheimer's disease causes dementia and ultimately death.

Commonly Prescribed (On-Label) Drugs:Donepezil, Galantamine, Memantine, Rivastigmine, Tacrine

OFF-LABEL PRESCRIPTION DRUGS

BREAKTHROUGH OPTIONS

Generic:Aripiprazole(ay-ri-PIP-ray-zole)

Brand:Abilify

Aripiprazole belongs to the class of drugs known as antipsychotics and is used mainly for schizophrenia and schizoaffective disorder. It works to control psychotic symptoms by regulating two key brain chemicals associated with emotional health, serotonin and dopamine. By interacting with these brain chemicals, aripiprazole adjusts and restores balance to the levels of serotonin and dopamine in the brain.

There is evidence that aripiprazole may be useful in treating Alzheimer's patients who exhibit psychotic symptoms. A 10-week study of 208 patients with Alzheimer's disease-associated psychosis inJournal of Clinical Psychopharmacologycompared the safety, effectiveness, and tolerability of aripiprazole versus placebo. The aripiprazole group showed significant reduction in psychosis symptoms, suggesting that this drug is safe and well tolerated.

For more information see page 1025.

Generic:Atorvastatin(a-TORE-va-stat-in)

Brand:Lipitor

Atorvastatin belongs to the class of drugs called HMG-CoA reductase inhibitors, more commonly known as statins. It is used to lower cholesterol, primarily LDL cholesterol or "bad" cholesterol, which is responsible for the development of arterial plaque leading to a heart attack or stroke. Unlike other statins, atorvastatin can also reduce fat levels, another risk factor for heart disease. Statins prevent the liver from producing cholesterol by blocking the cholesterol production enzyme.

Laboratory evidence shows that the cholesterol-induced production of a neurotoxin may precipitate Alzheimer's disease. Therefore, by reducing the production of cholesterol by using a cholesterol-lowering statin, the production of this neurotoxin may also decrease, potentially slowing the progression of Alzheimer's disease.

In a clinical trial, patients with mild to moderate Alzheimer's disease received atorvastatin calcium or placebo. The study found that reducing the circulation cholesterol levels improved measurements of Alzheimer's disease compared with placebo. However, these data, while encouraging, were not deemed statistically significant. Researchers believe the results of the study are promising, but additional clinical trials are needed to establish further the role of atorvastatin in treating Alzheimer's.

For more information see page 1030.

Generic:Buspirone(byoo-SPYE-rone)

Brand:BuSpar

Buspirone is an antianxiety medication used to treat anxiety disorders or short-term symptoms of anxiety. It works by stimulating nerve cells and altering neurochemically transmitted messaging. Unlike the more commonly prescribed antianxiety medications in the benzodiazepine class, you will not feel the effects of this therapy until after two or more weeks of treatment.

In Alzheimer's disease, buspirone is thought to alleviate depression and psychosis that complicate dementia. Studies of its use in Alzheimer's disease are very limited, but in an evaluation of studies, approximately 40% of patients had a positive response to buspirone.

For more information see page 1061.

Generic:Carbamazepine(kar-ba-MAZ-e-peen)

Brands:Carbatrol, Epitol, Tegretol, Tegretol XR

Carbamazepine is used to control seizures in epilepsy, to relieve pain due to trigeminal neuralgia, and in the treatment of mania and bipolar disorders. In Alzheimer's disease, this drug may modify brain chemical (neurotransmitter) activity.

Several small studies suggest that carbamazepine may reduce agitation in people with dementia including Alzheimer's patients. In a six-week study, 21 patients with Alzheimer's disease who had been previously and unsuccessfully treated with antipsychotics received either carbamazepine or placebo. Researchers followed up with patients at six weeks, evaluated them using a variety of psychiatric scales, and found significant improvements in symptoms of Alzheimer's disease, although the hallucination evaluation favored the placebo group. The study provided support for initial reports of the efficacy of carbamazepine in improving and stabilizing hostility in patients with Alzheimer's disease; however, additional long-term studies are needed to extend these findings.

For more information see page 1068.

Generic:Citalopram(sye-TAL-oh-pram)

Brand:Celexa

Citalopram, from the class of drugs known as selective serotonin reuptake inhibitors or SSRIs, is used to treat depression and acts to restore the brain's chemical balance by increasing the supply of the neurotransmitter serotonin. It acts as an emotional stabilizer and, theoretically, may be effective in treating many of the symptoms associated with Alzheimer's disease.

A study of 98 people inBritish Journal of Psychiatryevaluated the clinical efficacy of citalopram versus placebo in Alzheimer's patients. After four weeks, patients treated with citalopram showed a significant reduction in emotional bluntness, confusion, irritability, anxiety, fear/panic, depressed mood, and restlessness. Only very few, mild side effects were reported. Another study of citalopram in patients with Alzheimer's disease and dementia found similar results with the drug reducing emotional disturbance symptoms, but showing no improvement in psychomotor and cognitive behavior. Both studies were small, but indicate promise in the treatment of emotional symptoms associated with Alzheimer's disease dementia.

For more information see page 1096.

Generic:Divalproex(DI-val-PROE-ix)

Brands:Depakote Delayed Release, Depakote ER, Depakote Sprinkle

Divalproex is an anticonvulsant drug used in the treatment of manic episodes associated with bipolar disorder, complex partial seizures associated with epilepsy, and for the prevention of migraine headaches. Although how it works has not yet been established, its activity may be related to increased brain levels of gamma-aminobutyric acid (GABA).

In patients with Alzheimer's disease, divalproex seems to reduce behavioral agitation, a common manifestation of dementia. In a 10-patient study, patients were started on divalproex sodium and evaluated between two to five weeks. Of the ten patients enrolled, five patients showed improvement, which suggests that divalproex may be effective for behavioral agitation in elderly patients with dementia; however, larger studies are needed.

For more information see page 1147.

Generic:Fluoxetine(floo-OKS-e-teen)

Brands:Prozac, Prozac Weekly, Sarafem

Fluoxetine is an antidepressant from the selective serotonin reuptake inhibitor (SSRI) class, used to treat depression, obsessive-compulsive disorder (OCD), bulimia nervosa, premenstrual dysphoric disorder, and panic disorder. Compared to other SSRIs fluoxetine has a strong energizing effect, making it highly effective for treating depressed mood and lack of energy.

There have been several studies and case reports of fluoxetine treating Alzheimer's disease symptoms. One study reported success with fluoxetine for six months in the treatment of severe obsessive-compulsive symptoms in an Alzheimer's disease patient. Another researcher reported that fluoxetine also exhibited positive mental reasoning effects in treating depression in people with Alzheimer's.

For more information see page 1192.

Generic:Gabapentin(GA-ba-pen-tin)

Brand:Neurontin

Gabapentin is used to manage post-herpetic neuralgia in adults and partial seizures associated with epilepsy. It has also been used to control agitation and aggression in people with dementia based on the rationale that certain anticonvulsant medications have positive effects in reducing mania and aggressive behavior.

While no specific studies of gabapentin in the treatment of Alzheimer's disease patients have been conducted, several case reports and studies have reviewed gabapentin in treating elderly patients with dementia. In a 24-patient, two-year review published inAmerican Journal of Geriatric Psychiatry,researchers analyzed gabapentin's effects on aggressive and agitated behaviors in nursing home patients diagnosed with dementia. Seventeen of 22 patients were deemed much or greatly improved, four were minimally improved, and only one was noted as unchanged. Two of the patients had to discontinue use of gabapentin due to excessive sedation, but no other significant side effects were reported. Further data are needed to support the findings of the study.

For more information see page 1206.

Generic:Haloperidol(ha-loe-PER-i-dole)

Brands:Haldol, Haldol Decanoate

Haloperidol is used to treat psychotic disorders and control tics and vocal utterances associated with Tourette's syndrome. It works by interfering with the effects of brain chemicals on the nerves. Haloperidol has had some success in treating Alzheimer's disease-related psychosis and delusions. One study showed that neuroleptic drugs such as haloperidol resolve delusions and psychotic behavior in about 20% more patients than placebo; however, there is limited evidence of one neuroleptic being superior than another. Another study compared high-dose haloperidol, low-dose haloperidol, and placebo in 71 people with Alzheimer's disease and psychosis or disruptive behavior. High-dose haloperidol produced a 30% greater improvement in symptoms than low-dose or placebo; however, 20% of patients receiving the high dose experienced tremors, restlessness, and muscle contractions.

For more information see page 1217.

Generic:Olanzapine(oh-LAN-za-peen)

Brands:Zyprexa, Zyprexa Zydis

Olanzapine belongs to the class of drugs known as atypical antipsychotics. In tablet form, it is used in the treatment of schizophrenia, acute bipolar mania, and bipolar disorder. In injection form, olanzapine is used to treat agitation associated with schizophrenia and bipolar mania. The most common side effects associated with olanzapine are a feeling of being unable to sit still, constipation, dizziness, drowsiness, objectionable behavior, orthostatic hypotension, and weight gain.

In people with Alzheimer's disease, olanzapine has been shown to be an effective treatment for psychotic behavior. Low doses are more effective than higher doses. An eight-week trial published inJournal of Neuropsychiatry & Clinical Neurosciencesstudy found that olanzapine may be beneficial for Alzheimer's disease patients experiencing neuropsychiatric symptoms.

For more information see page 1381.

Generic:Paroxetine(pa-ROKS-e-teen)

Brands:Paxil, Paxil CR

Paroxetine, an antidepressant in the class of drugs called selective serotonin reuptake inhibitors (SSRIs), is used to manage depression, obsessive-compulsive disorder, panic disorder, and premenstrual dysphoric disorder. It blocks the reuptake of serotonin by the nerves that release it, an action that allows more serotonin to be available to be taken up by other nerves.

Data is limited about paroxetine in the treatment of people with Alzheimer's disease. Some reports say it is successful in reducing agitation in Alzheimer's disease patients. In a study of patients with coexisting depression and dementia, paroxetine reduced the severity of illness and showed global improvement at weeks two, four, eight and at the study's conclusion. The study found paroxetine to be effective and well tolerated.

For more information see page 1395.

Generic:Quetiapine(kwe-TYE-a-peen)

Brand:Seroquel

Quetiapine is in the class of drugs known as atypical antipsychotic and is used in treating schizophrenia and mania associated with bipolar disorder.

In a study, 333 patients with Alzheimer's disease, vascular dementia, or mixed dementia and severe clinical symptoms of agitation received quetiapine or placebo. A total of 219 patients completed the 10-week study, which found that quetiapine reduced agitation in elderly patients with Alzheimer's disease without leading to a decline in mental function. Fifty-seven percent of patients were noted as much improved or very much improved, compared to 32% in the placebo group. Quetiapine was generally well tolerated.

For more information see page 1440.

Generic:Risperidone(ris-PEER-i-dohn)

Brands:Risperdal, Risperdal M-TAB

Risperidone is an antipsychotic medication that works by interfering with several brain chemicals. Side effects with risperidone are usually mild and may include insomnia, hypotension, weight gain, and extrapyramidal symptoms.

Several studies have been conducted to evaluate the effects of risperidone in the treatment of aggression, agitation, and psychosis associated with dementia and Alzheimer's disease. In one clinical trial, 345 elderly patients received placebo or risperidone for a 12-week period. The study found that low-dose risperidone resulted in significant improvement in aggression, agitation, and psychosis associated with dementia. These results have been repeated in other smaller studies with good drug tolerability.

For more information see page 1456.

Generic:Sertraline(SER-tra-leen)

Brand:Zoloft

Sertraline belongs to the drug class known as selective serotonin reuptake inhibitors (SSRIs), which change the level of serotonin in the brain. It is used to treat depression, obsessive-compulsive disorder, panic disorder, and post-traumatic stress.

Several studies have evaluated sertraline in the treatment of Alzheimer's disease-related symptoms. One study of 44 people with Alzheimer's disease-related depression showed that, in the sertraline-treated group, 38% of patients responded positively, 46% partially responded, compared with 20% and 15% respectively in the placebo group. A similar study of 22 patients published inInternational Journal of Geriatric Psychiatryproduced equivalent results. Like many other drugs in this class, however, additional studies are needed to fully assess their effect on Alzheimer's disease.

For more information see page 1468.

Generic:Trazodone(TRAZ-oh-done)

Brand:Desyrel

Trazodone, primarily used to treat depression, is in a class of medications called serotonin modulators. It works by increasing the amount of serotonin to help maintain mental balance. Studies conducted in patients with Alzheimer's disease and dementia have shown that trazodone improves diverse symptoms including sadness, emotional disorders, irritability, fear, psychomotor instability, and delirant ideas.

For more information see page 1521.

Excerpted from Prescription Drugs: Alternative Uses, Alternative Cures: Over 1,500 New Uses for FDA-Approved Drugs by Kevin Loughlin, Joyce Generali
All rights reserved by the original copyright owners. Excerpts are provided for display purposes only and may not be reproduced, reprinted or distributed without the written permission of the publisher.

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Prescription Drugs: Alternative Uses, Alternative Cures : Over 1,500 New Uses for FDA-Approved Drugs

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