RLS is a common disease that affects about 10% of the general population [1].

1. What Is the Main Cause of Restless Leg Syndrome?

Although the cause is unknown, it is thought that the main cause of restless leg syndrome (RLS) is associated with an imbalance in the function of the neurotransmitter dopamine due to low levels of iron in the brain and body [1].

Dopamine is an organic chemical involved in the transmission of instructions between neurons to control muscle movements and reward-motivated behavior [2].

Other potential causes involve heredity, pregnancy, attention deficit hyperactivity disorder (ADHD), and medications.

1.1. What Is the Relation Between Restless Leg Syndrome and Heredity?

A role of heredity in RLS is associated with the high frequency of family history of RLS in patients diagnosed with this disease [3].

Monozygotic and dizygotic twin studies confirmed heredity involvement in RLS by showing the existence of a high concordance of RLS in monozygotic twins compared with that in dizygotic twins.

1.2. What Is the Relation Between Restless Leg Syndrome and Pregnancy?

Due to hormonal changes during the third semester of pregnancy, some women may experience RLS which disappears after delivery [4].

These changes involve an increase in the production of hormones, including estrogens, prolactin, progesterone, and thyroid hormone.

A reduction of iron and folate levels during pregnancy also appears to contribute to RLS due to their involvement in the synthesis of dopamine which further highlights the role of dopamine as the main cause of restless leg syndrome.

The prevalence of RLS during pregnancy was estimated to be in the range of 2.9-32% which is about 2-3 times higher than that in non-pregnant women.

1.3. What Is the Relation Between Restless Leg Syndrome and ADHD?

A relation Between Restless Leg Syndrome and ADHD was proposed by a study that showed that 44% of individuals with ADHD also had RLS.

Another important piece of information to add is that both ADHD and RLS have alterations related to dopamine levels in the brain [5].

1.4. What Is the Relation Between Restless Leg Syndrome and Medications?

Certain medications have been associated with restless leg syndrome, such as antidepressants (e.g., SSRIs, Tricyclics), withdrawal from sedative-hypnotic drugs (e.g., benzodiazepines), antiemetics (e.g., anticholinergics), antipsychotics, anticonvulsants, and antihistamines (e.g., diphenhydramine) [6].

Furthermore, alcohol and opioid withdrawal have also been associated with RLS.

2. Who Is Prone to Restless Leg Syndrome?

Restless leg syndrome (RLS) can develop at any age but is more common in women than men. There are also some factors that can increase the risk of RLS:

• Low Iron Levels
• Kidney Failure
• Neuropathy
• Rheumatoid Arthritis
• Diabetes Mellitus
• Celiac Disease
• Alcohol
• Iron Deficiency Anemia
• Parkinson’s Disease

2.1. Low Iron Levels

Iron is an essential cofactor in the production of dopamine and its deficiency can trigger RLS. Low iron levels can be due to blood loss through internal hemorrhage (e.g., gastrointestinal bleeding), excessive menstrual bleeding, frequent blood donations, or malabsorption.

2.2. Kidney Failure

Patients with chronic kidney disease on dialysis have decreased levels of iron due to the depletion of its storage in the blood.

2.3. Neuropathy

Increased levels of glucose in the blood such as during diabetes can lead to damage of nerves resulting in RLS.

2.4. Rheumatoid Arthritis

There is an elevated prevalence of RLS in patients with rheumatoid arthritis reaching between 27.7-31% [7].

2.5. Alcohol

Excessive consumption of alcohol (alcoholism) can lead to damage of nerves leading to RLS.

2.6. Celiac Disease

Celiac disease is an intestinal chronic disease characterized by a loss of appetite, malabsorption, and diarrhea due to gluten intolerance.

Celiac disease can also lead to iron deficiency which may lead to RLS. In fact, a study showed that 40% of studied patients with celiac disease had an iron deficiency [8].

2.7. Parkinson’s Disease

The characteristic dysfunction of dopamine in Parkinson’s Disease may explain why RLS is observed in some PD patients [9].

2.8. Iron Deficiency Anemia

Iron deficiency anemia is caused by a lack of iron in the body resulting in a reduction of the number of red blood cells leading to anemia. This lack of iron can also affect dopamine production.

3. What Symptoms Come with Restless Leg Syndrome?

Restless leg syndrome manifests with the following symptoms:

• An urge to move the legs due unpleasant sensations in the legs.
• An urge to move the legs during periods of rest or inactivity.
• The urge to move the legs may partially or totally be relieved by movement, such as walking or stretching.
• The urge to move the legs is increased in the evening or night than during the day.

4. Is Restless Leg Syndrome Psychological?

Although restless leg syndrome (RLS) is considered a neurological disease, a study that included 38 patients with RLS and 42 non-RLS controls, showed that patients with RLS have a lower internal locus of control (ability to impact its own health) and negative sleep-related personality traits compared to the non-RLS controls [10].

A negative sleep-related personality trait is associated with lower self-confidence, depression, higher mental arousal, and poorer quality of life.

5. How do you get rid of restless legs syndrome?

The treatment of RLS is aimed at relieving the associated symptoms that are caused by underlying physical conditions such as diabetes, celiac disease, or iron deficiency.

Medications to relieve the symptoms of RLS involve the use of dopaminergic drugs to improve dopamine effects, opioids to relieve the symptoms of severe RLS, and benzodiazepines for restful sleep.

Changes in lifestyle such as stopping alcohol, exercising (e.g., aerobics, stretching), taking iron supplements, respecting a regular sleep pattern, can help relieve some of the moderate symptoms.

Conclusion

Restless leg syndrome (RLS) can cause uncomfortable sensations that can affect sleep and the quality of life of the affected individual. The cause is unknown, but many studies highlighted the potential involvement of dopamine as the main cause.

RLS is also associated with several diseases which share with RLS the deficiency in iron which is an essential cofactor in the production of dopamine. However, other diseases and conditions such as diabetes or alcoholism can lead to nerve damage due to high blood levels of glucose or alcohol, respectively.

Although there is no specific treatment for RLS, dealing with this disease involves symptomatic treatments that aim at alleviating or reducing the undesirable and overwhelming manifestations of RLS.

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1. What Is Excitability and Irritability?

Excitation is a physiologic transition from a state of rest to a state of brain activity caused by stimuli, while irritability is the ability to respond to stimuli with an excessive sensitivity after excitability.

Irritability is also one of the symptoms of anxiety but also a symptom associated with several psychological and neurological disorders.

2. What Are Anxiety Disorders?

Anxiety disorders are the most prevalent psychiatric disorders characterized by uncontrollable worries and fear associated with emotions, thoughts, ideas, and places.

Anxiety disorders can significantly affect the daily life of an individual and commonly manifest with symptoms, including irritability, focusing difficulties, chest pain, increased heart rate, and abdominal discomfort [1].

2.1. What Are the Types of Anxiety Disorders?

There are several types of anxiety disorders, including:

• Panic Disorder
• Agoraphobia
• Generalized Anxiety Disorder
• Social Anxiety Disorder (Social Phobia)
• Specific Phobia
• Separation Anxiety Disorder
• Selective Mutism
• Mixed Anxiety and Depressive Disorder

2.1.1. Panic Disorder

A panic disorder is characterized by sudden and repeated episodes of intense fear attacks that physically manifest with the following symptoms:

Palpitations

• Tremor
• Chest pain
• Sweating
• Palpitations
• Feeling of choking
• Abdominal discomfort
• Paraesthesia (Abnormal sensations of the skin)
• Feeling of unreality

2.1.2. What Is Agoraphobia?

Agoraphobia is the fear of being unsafe in places such as closed spaces, public transports, crowds, elevators, or being outside of the home, and which results in panic attacks.

2.1.3. What Is Generalized Anxiety Disorder?

Generalized anxiety disorder is characterized by excessive and unrealistic worries about events and activities. It manifests with the following symptoms:

• Palpitations
• Tremors
• Nausea
• Dizziness
• Muscle tension
• Insomnia
• Nervousness
• Constant worries

2.1.4. What Is Social Anxiety Disorder?

Social anxiety disorder or social phobia is characterized by a fear of being the center of attention in situations where we might be negatively evaluated, such as public speaking, job evaluation by line managers, or discussion with persons from the opposite sex.

2.1.5. What Is Specific Phobia?

Specific phobia is characterized by an overwhelming fear of a specific situation (e.g., Airplanes), animal (e.g., Spider), or natural phenomena (e.g., Heights).

2.1.6. What is Separation Anxiety Disorder?

Separation anxiety disorder is an overwhelming fear of being separated from places or individuals to whom we are attached. This anxiety disorder is only diagnosed in children.

2.1.7. What Is Selective Mutism?

Selective mutism is characterized by the fear to speak in situations in which the individual is expected to speak while being able to speak in other situations.

2.1.8. What Is Mixed Anxiety and Depressive Disorder?

Mixed anxiety and depressive disorder is characterized by the presence of a balanced mix of anxiety and depression symptoms which makes a diagnosis of either anxiety disorder or depression difficult.

2.2. How Are Anxiety Disorders Treated?

Treatment of anxiety disorders involves lifestyle changes, psychotherapy, and pharmacotherapy (medications).

Lifestyle changes involve:

• Tacking a time out to clear your head
• Limiting alcohol and caffeine consumption
• Getting enough sleep
• Consumption of well-balanced meals
• Exercising to maintain health and reduce stress
• Maintaining a positive attitude
• Learn about your anxiety disorder and what triggers it.

Psychotherapy involves cognitive behavioral therapy which involves changing and challenging distorted behaviors, thoughts, beliefs, and attitudes, to reduce the symptoms of anxiety disorders.

However, if the symptoms of the anxiety disorder are severe such as suicidal thoughts, alcohol abuse, or secondary depression, anxiolytics are used to alleviate the symptoms.

3. What Are Sedatives and Anxiolytics?

Sedatives and anxiolytics are used to alleviate symptoms of anxiety, treat insomnia, and reduce excitation and irritability to restore calmness.

They grouped into the following categories:

• Barbiturates
• Benzodiazepines
• Selective Serotonin Reuptake Inhibitors
• Miscellaneous Sedatives and anxiolytics

3.1. What Are Barbiturates?

Barbiturates are used for the treatment of anxiety, insomnia, and epileptic seizures. They exert their effects by enhancing the activity of GABA.

GABA (Gamma-Aminobutyric acid) is a chemical messenger and the major inhibitor of neurotransmission by reducing nerve impulses (action potential).

They also bind to AMPA receptors which prevent the binding of glutamate and block the excitation of neurons.

Barbiturates include drugs such as primidone (Mysoline), phenobarbital (Luminal, Mebaral), butabarbital (Butisol), and pentobarbital (Nembutal).

3.2. What Are Benzodiazepines?

Benzodiazepines prevent the excitation of neurons by enhancing the effect of GABA on GABA_A receptors.

GABA (Gamma-Aminobutyric acid) is a chemical messenger and the major inhibitor of neurotransmission by reducing nerve impulses (action potential).

Therefore, it has an opposite action to that of glutamate and ensures balanced neurotransmission [2].

Benzodiazepines are used for the treatment of anxiety, panic disorder, sleep disorders (e.g., insomnia), epileptic seizures, as a muscle relaxant, and for the treatment of alcohol withdrawal.

Benzodiazepines include drugs such as diazepam (Valium), midazolam (Versed), clonazepam (Klonopin), clobazam (Onfi), lorazepam (Ativan), temazepam (Restoril), flurazepam (Dalmane), oxazepam (Serax), and clorazepate (Tranxene T-Tab).

3.3. What Are Selective Serotonin Reuptake Inhibitors (SSRIs)?

Selective serotonin reuptake inhibitors (SSRIs) increase extracellular neuronal concentrations of serotonin by inhibiting its reuptake by monoamine transporters; however, this high concentration results later in the downregulation of serotonin receptors, and therefore, serotonin activity.

Serotonin is a chemical messenger involved in the neurotransmission of information related to mood, reward, learning, memory, and cognition.

Selective serotonin reuptake inhibitors (SSRIs) are primarily used as antidepressants for the treatment of major depression but also for anxiety disorders.

SSRIs include drugs such as citalopram (Celexa), fluoxetine (Prozac), paroxetine (Paxil), escitalopram (Lexapro), and sertraline (Zoloft).

3.3. What Are Miscellaneous Sedatives and Anxiolytics?

Miscellaneous sedatives and anxiolytics are drugs that cannot be classified into the above categories due to their different mechanisms of action.

They are used in the treatment of anxiety, insomnia, alcohol withdrawal, opiates, or barbiturates withdrawal, and for post-operative pain.

Miscellaneous sedatives and anxiolytics include drugs such as buspirone (Buspar), diphenhydramine (Tranquil), doxylamine (Unisom), sodium oxybate (Xyrem), zolpidem (Ambien), melatonin, and ramelteon (Rozerem).

Conclusion

Excitation and irritability are symptoms of anxiety disorders and medications that treat them are also used for the treatment of anxiety disorders.

However, sedatives and anxiolytics are mainly used for severe anxiety disorders, while mild and moderate symptoms are treated through lifestyle changes and cognitive behavioral therapy.

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