Diagnosis - The Levodopa Challenge

Reviewed by: HU Medical Review Board | Last reviewed: March 2017

A levodopa challenge is a trial of the medication levodopa, given to patients if a confirmation of a diagnosis of Parkinson’s disease (PD) is needed. Levodopa is used in the treatment of PD and is effective in reducing the motor symptoms of the disease, including rigidity, bradykinesia (slowed movement and the loss of spontaneous movement), impaired balance, and resting tremor.1

PD can be difficult to diagnose, particularly in its early stages. There is no single test, no blood test, or screening that can definitively identify PD. The symptoms of PD are similar to those of other neurological conditions, and approximately 5-10% of patients with PD are misdiagnosed. Up to 20% of patients that are diagnosed with PD are later found to have other conditions. A levodopa challenge is used to confirm a diagnosis of PD if the patient’s symptoms improve while taking the medication. If the patient’s symptoms do not improve while on levodopa, they likely have another neurological condition.1,2

About levodopa

One of the primary characteristics of PD is a loss of neurons in a brain region called the substantia nigra pars compacta. These neurons make and release a chemical messenger, also known as a neurotransmitter, called dopamine. Levodopa is converted to dopamine. Levodopa was developed in the late 1960s to treat PD by increasing dopamine levels and remains the most effective drug for treating PD.

When given by itself, levodopa can cause nausea and vomiting due to its action outside the brain, so it is generally combined with carbidopa to prevent this side effect. Carbidopa prevents levodopa from being converted to dopamine. However, carbidopa cannot cross the blood-brain barrier and get into the brain. Thus, levodopa can get into the brain and increase dopamine levels, but in the body carbidopa prevents increase dopamine levels and side effects. In addition, because carbidopa prevents levodopa from being converted to dopamine in the body, more levodopa is available in the bloodstream, and thus more medication gets to the brain. Brand names for the combined levodopa-carbidopa formulation are Sinemet®, Sinemet CR®, Parcopa®, Rytary™, and Duopa™. Another combination formulation that includes levodopa, carbidopa, and entacapone is Stalevo®.1

Like all medications, levodopa can cause side effects. Side effects increase with prolonged use and increased dosing and may include dyskinesia: spontaneous, involuntary movements. Other side effects experienced by patients while taking levodopa include low blood pressure, confusion, dry mouth, dizziness, sleepiness, risk-taking behavior, impulsive behaviors such as gambling, and hallucinations.1

The accuracy of the levodopa challenge

Several clinical studies have been conducted to evaluate the accuracy of the levodopa challenge as a diagnostic tool for PD. One study that included patients with parkinsonian symptoms without a specific diagnosis who were given a levodopa challenge found that the levodopa challenge was able to predict the clinical diagnosis of PD in 70-81% of cases.3

Other studies that investigated the levodopa challenge have noted that the acute challenge does not differ much from the response to chronic levodopa therapy. Some researchers suggest that the acute challenge tests are redundant and recommend the diagnosis of PD should focus on the symptoms identified through a physical or neurological exam.4

Other tests used in diagnosing Parkinson’s disease

Diagnosis of PD is generally made using a medical history and a physical exam, or a neurological exam. Imaging tests, such as MRI, PET (positron emission tomography) scans, or a newly approved newer imaging technique, the DaTscan, are expensive and are not routinely used.5

An active area of research is discovering “biomarkers” which are molecules in the blood, urine, or cerebrospinal fluid that can reliably diagnose Parkinson’s disease, particularly in the early stages of the disease.

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