Drug-induced Parkinsonism: Causes & Symptoms APDA

Parkinsonism-hyperpyrexia disorder, also known as akinetic crisis, is a rare but potentially fatal complication of Parkinson’s disease. It involves a syndrome of significantly worsening parkinsonism (with or without encephalopathy), hyperpyrexia, autonomic instability and elevated creatine kinase.4-6 The disorder is most commonly seen in patients with Parkinson’s disease who have reduced or stopped their antiparkinsonian drugs. It can also be precipitated by an infection or other metabolic disturbance. It is also important to exclude alternative causes, including an underlying infection, metabolic abnormalities, or stroke. Tetrabenazine is an earlier VMAT-2 inhibitor; however, it is used as an agent of last resort due to its risk of significant side effects (eg, depression and suicidal ideation).

Insights into Pathophysiology from Medication-induced Tremor

A physical and neurologic examination revealed no additional abnormalities. If you believe you drug induced tremors or your loved one’s movement disorder results from drug use, it is best to seek professional help. A professional drug rehabilitation program will help by offering advice, providing a correct diagnosis, or discussing treatment options. Several treatment options are available for those struggling with heroin addiction, including pharmacological treatment and behavioral therapy. You may have to undergo both pharmacological treatment and behavioral therapy to make a full recovery.

It is a sense of internal restlessness, irritability and tension without necessarily manifesting with physical signs, unlike restless legs syndrome which is typically more severe and worse at night. Akathisia has been reported with dopamine receptor blockers, selective serotonin reuptake inhibitors (SSRIs), antiepileptic drugs, and cocaine. It can occur either after starting a dopamine receptor blocker, dose escalation, or when switching to an alternative drug. It is symmetrical and occurs acutely following drug ingestion or dose escalation. Exceptions include tremor secondary to valproate, which can appear at therapeutic or during stable treatment, or, rarely, tardive tremor.

• According to National Center for Drug Abuse Statistics, 12.9 million Americans aged 12 years and above have abused illicit drugs at some point in their lives.
• A number of medications can cause parkinsonism because they block the dopamine receptor and thereby mimic the symptoms of PD that are caused by loss of dopamine neurons in the brain.
• Obtaining a complete psychiatric history from someone who has developed abnormal muscle movements is crucial to refining the differential diagnosis and mapping out a treatment plan.
• In addition to the elevated creatine kinase, laboratory investigations usually find leucocytosis, abnormal electrolytes, renal impairment, abnormal liver function tests, and altered coagulation studies.
• Drug-induced movement disorders (DIMDs), also commonly referred to as extrapyramidal symptoms (EPS), represent a variety of iatrogenic and clinically distinct movement disorders, including akathisia, tardive dyskinesia, dystonia, and parkinsonism (TABLE 1).
• Symptoms of drug-induced tremors interfere with the performance of day-to-day motor tasks, interpersonal communication, and social functioning.

Etiology, Prevention, and Management of TD

Unfortunately, the tremors may also indicate a more serious underlying issue. Alcohol tremors are a symptom of  Wernicke-Korsakoff Syndrome, a medical condition that can easily result in death. Alcohol abuse may also cause bilateral flapping tremors, characterized by arrhythmic interruptions of sustained voluntary muscle contraction. When you abstain from alcohol, you may experience a tremor similar to an essential tremor. However, alcohol tremors have a higher frequency, mainly involving the hands.

Table 1. Common Medication-induced Tremors and Typical Tremor Phenomenology.

Like most commonly abused drugs, opioids raise dopamine levels by blocking the inhibitory gamma-aminobutyric acid (GABA). Symptoms of drug-induced tremors interfere with the performance of day-to-day motor tasks, interpersonal communication, and social functioning. Additionally, Drug-Induced Movement Disorders will interfere with your quality of life. Drug-induced parkinsonism is a movement disorder that is caused by taking medication that interferes with dopamine transmission in the brain.

Treatment

EPT is by far the most common mechanism of tremor generation by medications17,18 (Table 2). Physiological tremor has many components that can be influenced by medications with some influencing the central component (amitriptyline) and others altering the peripheral component (β-adrenergic agonists, cyclosporine, etc.). Other mechanisms include blockade of dopaminergic neurotransmission in the nigrostriatal pathway by DBA or dopamine-depleting agents.

The altered mental status, autonomic instability, and spasticity or rigidity with raised creatine kinase, overlap with neuroleptic malignant syndrome. In serotonin syndrome the onset is hyperacute, within hours rather than days, and the signs of central nervous system hyperexcitability are more prominent. Management consists of altering the dose of, or if possible stopping, the offending drug, or switching to an alternative drug. Should the offending drug need to be continued, discuss the risks of the adverse effects versus the benefits of continuing to ensure the patient is informed. If the drug is continued, drugs typically used for essential tremor (for example, propranolol) can occasionally be beneficial.

• Tardive movement disorders include dyskinesias (typically orobuccolingual), stereotypies, akathisia, dystonia (focal, segmental or generalised), myoclonus, tremor and tics.
• Some medications (epinephrine) that cause EPT likely lead to tremor by peripheral mechanisms in the muscle (β-adrenergic agonists), but others may influence the central component (amitriptyline).
• If neuroleptic malignant syndrome is suspected, acute hospital admission is warranted.
• Both therapeutic and illicit drugs can cause neurological adverse effects, including movement disorders.
• It is a sense of internal restlessness, irritability and tension without necessarily manifesting with physical signs, unlike restless legs syndrome which is typically more severe and worse at night.
• The prescription medication that blocked the dopamine receptor, was the proverbial “straw that broke the camel’s back”, inducing the full-fledged symptoms of dopamine depletion and revealing that the person did in fact have PD.
• Medication-induced tremor (MIT) is common in clinical practice and there are many medications/drugs that can cause or exacerbate tremors.

Tremors can occur in the setting of withdrawal states, especially with benzodiazepines, ethanol, and opiates. One well-performed study found that patients undergoing ethanol withdrawal had tremors in the range of 8–12 Hz.74 When patients abruptly stop β-adrenergic antagonists such as propranolol, an increase in action and postural tremor can be observed as well. Even 1 month after discontinuing propranolol, increased tremor power was observed in subjects without underlying tremor disorders who were being treated for cardiac conditions.75 Most withdrawal-related tremors appear typical of EPT as with most MIT.

Antioxidants, including vitamin E, vitamin B6 and Ginkgo biloba, have also been studied. Vitamin E had conflicting results, while vitamin B6 and Ginkgo biloba are probably useful in treating tardive movement disorders.17,18 Caution is needed with Ginkgo biloba because of its antiplatelet effects, especially in patients taking antiplatelet drugs or anticoagulants. Anticholinergic drugs to prevent, or reduce the severity of, drug-induced movement disorders have been suggested, however there is no evidence to support this. Subacute drug-induced movement disorders occur within days to weeks of drug ingestion.

Tremor can occur secondary to many drugs, including SSRIs, lithium, tricyclic antidepressants, antiepileptics (particularly valproate), bronchodilators, amiodarone and immunosuppressives. Another underlying aetiology, such as Parkinson’s disease, essential tremor or hyperthyroidism, needs to be excluded. Drug-induced tremors are common in clinical practice, but often underrecognized or misdiagnosed. There are a myriad of drugs that can cause or exacerbate tremors, making the diagnosis difficult. Many tremorigenic drugs are frequently and widely prescribed, such as amiodarone, valproic acid, lithium, bronchodilators, antipsychotics, and antidepressants. Little is known regarding the mechanism by which these drugs cause tremor; however, it is important for clinicians to recognize potential tremorigenic drugs and develop management strategies for symptomatic patients.

Another important part of the history is the family history of inherited and genetic disorders (like Huntington’s disease and Wilson’s disease) that affect the basal ganglia and typically present with abnormal movements (including chorea, athetosis, and dystonia). Similarly, a substance use history that includes prior manifestations of intoxication or withdrawal should be obtained. Both therapeutic and illicit drugs can cause neurological adverse effects, including movement disorders. The most common causes of drug-induced movement disorders are dopamine receptor blocking drugs, including antipsychotics and antiemetics (Table 1).