Insights into Pathophysiology from Medication-induced Tremor

Intention tremor is a subheading of kinetic tremor that is a terminal kinetic tremor (as can be seen when nearing the target on finger-to-nose testing). Finally, isometric tremor is a kinetic tremor that occurs with active muscle contraction against a fixed object. Exposure to toxic levels of certain drugs (e.g., ethanol, lithium, etc.) for longer periods of time can lead to permanent tremors, especially if they affect the cerebellum. Levodopa-induced dyskinesia is a common cause of dyskinesia in individuals with Parkinson’s disease. It occurs due to the relationship between dopaminergic loss and the resultant response to levodopa, rather than being due to excess levodopa ingestion only. Risk factors for developing dyskinesia include young age at onset of Parkinson’s disease, higher levodopa dose, low body weight, and more severe disease.10 A careful history is vital in establishing a pattern to the timing and duration of dyskinesias, which can then assist in altering the levodopa dose.

• Drug-induced tremors typically are symmetric or equal on both sides of the body.
• Drug-induced movement disorders occur either during exposure or within weeks of stopping a drug and are present for at least one month.1,11-14 The minimum duration of exposure to the drug is three months, or one month in adults aged over 60 years.
• Exposure to toxic levels of certain drugs (e.g., ethanol, lithium, etc.) for longer periods of time can lead to permanent tremors, especially if they affect the cerebellum.
• Details of the location and nature of the abnormal movements, their onset and progression, and their aggravating and relieving factors are essential.
• These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.
• No good evidence exists regarding the management of tardive drug-induced movement disorders.15 Treatment usually consists of withdrawing the offending drug, and a trial of a combination of drugs.
• A report by the National Institute on Drug Abuse revealed that in 2020, approximately 92,000 U.S citizens died from a drug-related overdose of both illegal drugs and prescription opioids.

Drug-Induced Movement Disorders: A Primer

Withdrawal-emergent dyskinesia can occur on abrupt cessation of long-term antipsychotic treatment, particularly in children. Acute dystonic reactions most commonly occur in younger patients soon after taking to dopamine receptor blocking drugs, including antiemetics (e.g. metoclopramide or prochlorperazine) and antipsychotics. Acute sustained dystonic spasm of craniocervical muscles is typical, but oculogyric crises, truncal spasm causing opisthotonos, or limb dystonia can also occur. Acute laryngeal dystonia can be life-threatening due to airway obstruction and requires emergency medical care.

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.

Tremors or Drug-Induced Movement Disorders (DIMD) may harm your quality of life and general well-being. You may find it challenging to perform easy tasks, which may, in turn, affect your social functioning and interpersonal communication. You may also lose your independence as you’d need help performing easy tasks. Tremors may also result in other symptoms like depression and anxiety, which may have severe consequences. Alcohol tremors primarily affect the hands, but they affect the legs and arms in some circumstances. The tremors manifest approximately 8 hours after you stop drinking and peak about 30 hours after your last drink.

Selective serotonin reuptake inhibitors

Cocaine abuse may also cause subtle parkinsonian symptoms like tremors at rest. Crack dancing is characterized by involuntary limb movements that last for several days at a time. If you are an addict, the spontaneous movements may not seem apparent to you. Cocaine abuse has numerous adverse side effects on the body, such as involuntary tremors. One common symptom reported or seen in drug addicts is tremors, also called Drug-Induced Movement Disorders (DIMD).

Rethinking the stages of Parkinson’s disease

• One common symptom reported or seen in drug addicts is tremors, also called Drug-Induced Movement Disorders (DIMD).
• 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.
• You may find it challenging to perform easy tasks, which may, in turn, affect your social functioning and interpersonal communication.
• 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).
• 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.
• Other mechanisms include blockade of dopaminergic neurotransmission in the nigrostriatal pathway by DBA or dopamine-depleting agents.
• In addition to the elevated creatine kinase, laboratory investigations usually find leucocytosis, abnormal electrolytes, renal impairment, abnormal liver function tests, and altered coagulation studies.

Common illegal drugs that cause Drug-Induced Movement Disorders (DIMD) are cocaine, opioids, amphetamine, and heroin. There are key differences to note between parkinsonism from PD and parkinsonism as a side effect of medication. If the benefit of the medicine is greater than the problems caused by the tremor, your provider may have you try different dosages drug induced tremors of the medicine. In rare cases, a medicine such as propranolol may be added to help control the tremor. You may not need treatment or changes in the medicine if the tremor is mild and does not interfere with your daily activity.

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

The most visually dramatic movement disorder caused by cocaine is transient chorea, also called crack dancing and buccolingual dyskinesias. 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 report by the National Institute on Drug Abuse revealed that in 2020, approximately 92,000 U.S citizens died from a drug-related overdose of both illegal drugs and prescription opioids. The American Parkinson Disease Association (APDA) is a nationwide grassroots network dedicated to fighting Parkinson’s disease (PD) and works tirelessly to help the approximately one million with PD in the United States live life to the fullest in the face of this chronic, neurological disorder. Founded in 1961, APDA has raised and invested more than $282 million to provide outstanding patient services and educational programs, elevate public awareness about the disease, and support research designed to unlock the mysteries of PD and ultimately put an end to this disease. The bottom line is, whether you are or are not diagnosed with PD, be aware of changes that may occur upon starting a new medication.

MIT has provided some insight into the mechanisms of tremors we see in clinical practice. The exact mechanism of MIT is unknown for most medications that cause tremor, but it is assumed that in most cases physiological tremor is influenced by these medications. 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).

In cases in which withdrawal of an antipsychotic does not reduce TD and when a VMAT-2 inhibitor or other agents are not used, some evidence indicates that switching to clozapine monotherapy can treat or reduce antipsychotic-induced TD. Amantadine may also be used to treat TD; however, evidence supporting its use is still weak. In addition to drug-induced parkinsonism, which includes rest tremor and is caused by medications that block the dopamine receptor, there are also a wide variety of medications that do not block the dopamine receptor, but can cause other types of tremors, such as postural and action tremors. So if you have these types of tremors, but without the slowness, stiffness and other PD-like symptoms, you could have drug-induced tremor (not drug-induced parkinsonism).

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).

APDA has created a list of Medications to be Avoided or Used With Caution in Parkinson’s Disease. It is important to note that there are anti-psychotics and anti-nausea medications which do not cause parkinsonism and can be used safely by people with PD. We performed a PubMed literature search for published articles dealing with MIT and attempted to identify articles that especially dealt with the medication’s mechanism of inducing tremor. Contact your provider if you are taking a medicine and a tremor develops that interferes with your activity or is accompanied by other symptoms. Your health care provider can make the diagnosis by performing a physical exam and asking about your medical and personal history. We have both inpatient and outpatient treatment programs, so you are free to select a program that suits you best.