With the rise in awareness of neurodegenerative diseases at the end of the 20th century, novel drugs were in development in hopes of countering the deleterious effects of these diseases. One of the main drugs that came into creation in 1985 was rivastigmine. With its approval by the FDA, rivastigmine is indicated to treat mild to moderate dementia of the Alzheimer’s type. Its indications also include the treatment of mild to moderate dementia that is associated with Parkinson disease. 

Recent studies have also shown that rivastigmine can improve gait stability to help reduce the risk of falls in patients with Parkinson disease.[1] Additionally, a study done in 2016 has shown that perioperative rivastigmine use can decrease the incidence of postoperative delirium in older patients that have cognitive dysfunction.[2] Researchers have also conducted small studies to see the effectiveness of acetylcholinesterase inhibitors like rivastigmine in hopes of helping cognitive dysfunction in multiple sclerosis patients. Overall, these studies showed that there were no significant benefits over placebo to improve cognitive function.[3]

Multiple studies have also shown that drugs like rivastigmine and other cholinesterase inhibitors can improve cognition in patients with dementia with Lewy bodies based on a computerized cognitive exam. Compared to the placebo group, patients receiving rivastigmine had an improvement of 30% or more as well as being overall less anxious and fewer episodes of hallucinations.[4]

In the brain, two different cholinesterase enzymes hydrolyze acetylcholine. These two enzymes are acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). AChE is mainly present at the synaptic nerve junctions, as well as areas that have high activity in the cerebral cortex. BuChE is found in the glial cells of the brain and helps mediate cholinergic activity. As humans age, the activity of both of these cholinesterase enzymes increases. In pathologic states like Alzheimer disease and Parkinson disease, the upregulation of cholinesterase enzymes is much higher than normal. Rivastigmine, unlike other cholinesterase inhibitors, has been shown to inhibit both of these enzymes, causing an overall increase in acetylcholine.[5] 

Rivastigmine indications include mild to moderate Alzheimer's dementia and dementia associated with Parkinson's disease. A mini-mental state examination (MMSE) is performed on patients to see if they qualify for cholinesterase inhibitor therapy. If the MMSE score is between 24 to 26 and 10 to 11 for mild to moderate dementia, respectively, the patient is a candidate for therapy. Studies show that long term treatment at a maximum dosage of rivastigmine has the greatest improvement in cognitive performance.[6] In addition, discontinuation of acetylcholinesterase inhibitors should be done carefully due to the possible worsening of cognitive impairment.[7]

Rivastigmine comes in two major formulations, an oral capsule, and a transdermal patch. 

• Capsule
  • 1.5 mg - 6 mg
• Transdermal Patch
  • 4.6 mg/24 hours - 13.3 mg/24 hours

The transdermal patch recommended starting dose is 4.6 mg/24 hours, and the prescriber can titrate the dose up every four weeks. The capsule formulation has a recommended starting dose of 1.5 mg twice daily and can be titrated up every four weeks as well by 1.5 mg per dose (total 3 mg increase per day). 

Adverse effects for this drug have received thorough study as it has been on the market for some time. The main adverse effects associated with the use of rivastigmine are gastrointestinal. The primary symptoms are nausea and vomiting. These acute effects primarily occur during the initial dose-escalation phase of therapy upward dose titration of the drug to achieve a therapeutic dose. These events can be minimized by using a slow titration schedule and taking the medication with food if prescribing an oral formulation. In a study done to analyze the safety and tolerability of cholinesterase inhibitors used to treat Alzheimer dementia, researchers found rivastigmine to be the drug to have the highest rate of gastrointestinal side effects.[8] 

Common adverse effects include extrapyramidal symptoms, sleep disturbances, as well as muscle cramps and weakness. These issues are less frequent during the maintenance phase of therapy when the dose is not adjusted, but when the drug is being taken for a long period, central nervous system effects can occur. However, these central nervous system effects are rather rare in rivastigmine and are more common with its counterpart drug, donepezil.[9]  

Studies have shown that using the transdermal patch to deliver rivastigmine is associated with fewer reports of nausea and vomiting.[10] Rivastigmine also has a rare case of angioedema related to its use, although overall very uncommon.[11] While the transdermal route offers decreased rates of gastrointestinal effects, reactions like contact dermatitis, are prevalent. Also, allergic reactions to the transdermal patch can manifest as vesicles and edema beyond the boundaries of the patch. 

Long term use of rivastigmine has also been associated with an increased risk of death when compared to patients treated with donepezil.[12]

Relatively few contraindications exist for the usage of rivastigmine in clinical practice. A patient with a history of hypersensitivity to rivastigmine or other drugs with carbamate derivatives should not be prescribed rivastigmine, and other treatment options should merit consideration. Also, severe reactions to other anticholinergic agents should lead clinicians to be on the lookout for similar effects. Patients who have taken anticholinergic medications before who have experienced a cholinergic crisis should also be wary of a potential repeat with the use of rivastigmine.