What is levosulpiride-induced Parkinsonism? And why did a Hyderabad woman on gastric medicine have it?

After reviewing her medical records, Kumar noted several prescriptions for a combination of rabeprazole and levosulpiride (RABEZ L).

Rabeprazole is a proton pump inhibitor used to treat conditions like gastroesophageal reflux disease (GERD), Zollinger-Ellison syndrome, and peptic ulcers,

Levosulpiride is a prokinetic and antipsychotic agent primarily used to treat dyspepsia (indigestion), irritable bowel syndrome (IBS), and symptoms of gastroparesis (delayed gastric emptying).

Levosulpiride is sometimes prescribed for depression and anxiety due to its action on dopamine receptors.

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The diagnosis

After looking at the prescription and the symptoms, Kumar was able to determine what Laxmi was going through.

“The diagnosis was obvious now. It was Levosulpiride-induced Parkinsonism,” he said.

Levosulpiride-induced Parkinsonism is the development of Parkinsonism symptoms as a side-effect of taking levosulpiride, an antipsychotic and prokinetic agent.

Parkinsonism is a syndrome characterised by the presence of symptoms commonly seen in Parkinson’s disease.

It includes tremors, bradykinesia (slowness of movement), rigidity, and postural instability. Here is an overview of the key aspects.

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The Mechanism

Levosulpiride is a selective dopamine D2 receptor antagonist. It works by blocking dopamine receptors in the brain, which can alleviate symptoms of conditions like schizophrenia and gastrointestinal disorders.

However, by inhibiting dopamine pathways, it can inadvertently lead to the symptoms of Parkinsonism.

Dopamine is a crucial neurotransmitter for motor control, and its reduced activity is the underlying cause of Parkinson’s disease and drug-induced Parkinsonism.

In layman’s language, levosulpiride is a medication that helps with certain mental health issues and stomach problems by blocking specific signals in the brain.

These signals are carried by a chemical called dopamine, which is important for controlling movements and various brain functions.

When levosulpiride blocks dopamine too much, it can cause side effects that look like Parkinson’s disease, a condition known for causing tremors, slow movements, stiff muscles, and balance problems.

This happens because dopamine is essential for smooth and coordinated muscle movements, and reducing its activity can lead to these unwanted symptoms.

In even simpler terms, while levosulpiride helps with some issues by blocking dopamine, it can sometimes cause problems with movement and muscle control, similar to Parkinson’s disease.

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Symptoms and diagnosis

Symptoms of levosulpiride-induced Parkinsonism include:

• Tremors, especially at rest
• Muscle rigidity
• Bradykinesia (slowed movements)
• Postural instability (balance problems)
• Difficulty with fine motor tasks

Certain factors may increase the risk of developing Parkinsonism from levosulpiride. They include:

• High doses of the medication
• Prolonged use
• Elderly patients
• Pre-existing neurological conditions

Diagnosis is typically based on:

• Medical history (noting the use of levosulpiride)
• Clinical examination of symptoms
• Exclusion of other causes of Parkinsonism

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Management and prevention

Management of Parkinsonism involves:

1. Discontinuation or reduction of levosulpiride: The primary treatment is to reduce the dose or stop the medication. Symptoms often improve after discontinuation but may take weeks or months to be fully resolved.
2. Switching medications: If levosulpiride is being used for psychiatric or gastrointestinal issues, alternative medications with a lower risk of inducing Parkinsonism may be considered.
3. Symptomatic treatment: In some cases, medications used to treat Parkinson’s disease, such as anticholinergics or dopaminergic agents, may be prescribed to manage symptoms until they subside.

Preventive measures include:

• Using the lowest effective dose of levosulpiride
• Regular monitoring for early signs of Parkinsonism, especially in high-risk patients
• Considering alternative therapies if long-term treatment is required

Levosulpiride-induced Parkinsonism is a potentially reversible condition, provided that it is identified early and managed appropriately by adjusting or discontinuing the causative medication.

“I counselled the patient and attendants about the diagnosis, treatment plan and likely prognosis. I advised her to stop levosulpiride and to avoid it in future too,” said Kumar.

“Levosulpiride is unfortunately commonly used in combination with pantoprazole and rabeprazole for treating non-ulcer dyspepsia, GERD, irritable bowel syndrome, etc. Levosulpiride use can result in Parkinsonism and other movement disorders. Levosulpiride should be avoided, especially in the elderly population,” he added.

A drug prescribed for minor ailment caused a disabling disease

Case details:
65 year Mrs Laxmi (name changed) presented with two months history of tremors of hands (more on right side), slowness of movements and imbalance while walking. She also had features of anxiety and mild… pic.twitter.com/zA3JikB8av

— Dr Sudhir Kumar MD DM (@hyderabaddoctor) May 16, 2024

Levosulpiride-induced Parkinsonism is mostly reversible upon cessation of the drug, but sometimes the symptoms persist, indicating dopaminergic dysfunction unmasked on an earlier occasion.

Parkinsonism has become the most common levosulpiride-induced movement disorder, occurring in 93.4 percent of cases in one study.

In another study, 21 out of 85 patients (24.7 percent) with levosulpiride-induced Parkinsonism were rated as Hoehn and Yahr stage III-V.

Elderly patients above 60 years are more at risk, with 85.7 percent of patients in one study being in this age group.

Levosulpiride-induced Parkinsonism can have an acute onset and be rapidly progressive. Symptoms may persist even after the withdrawal of levosulpiride in some cases.

(Edited by Arkadev Ghoshal)