MODAFINIL / PROVIGIL

DESCRIPTION / DEFINITIONS: Modafinil® – also sold under the name of Provigil®, Alertec®, Modavigil®, and others – is a central nervous system (CNS) stimulant used to promote wakefulness in adults who suffer from  narcolepsy, shift work sleep disorder (SWSD), idiopathic hypersomnia (excessive daytime sleepiness), and excessive daytime sleepiness associated with obstructive sleep apnea (OSA). It is also used as a study drug – although not approved by the FDA for that purpose – and the set of symptoms known as Attention Deficity Hyperactivity Disorder (ADHD). It is not approved for children under 17.

ABUSE: Modafinil is a Schedule IV drug, which means it has a medical use and is not highly prone to abuse. Despite this designation, the label on the drug cautions that it has the same effect as methylphenidate (Concerta®, Ritalin®, Methylin®) and doctors should keep a close eye on patients for signs of abuse. See more information below.

ADDICTION / DEPENDENCE: Several studies indicate a potential for addiction and dependence. See more below, as well as half life and metabolism.

SIDE EFFECTS: Among the many side effects are anxiety, altered thinking, abnormal liver function, and life-threatening rashes. See more below.

WITHDRAWAL SYMPTOMS: Patients have reported excessive sleepfulness, lack of focus and depression. See more below.

TREATMENT: Treatment is dependent on how long the person has been taking Modafinil and at what dosage, as well as how they react to the drug and to quitting it.

 

Modafinil – also sold under the name of Provigil, Alertec, Modavigil, and others – is a central nervous system stimulant used to promote wakefulness in adults who suffer from  narcolepsy, shift work sleep disorder (SWSD), idiopathic hypersomnia (excessive daytime sleepiness), and excessive daytime sleepiness associated with obstructive sleep apnea (OSA).

It is also used as a study drug – Provigil is very common on college campuses – although not approved by the FDA for that purpose.

It is not approved for children under 17.

Modafinil is also being prescribed for ADHD. It has not been approved for this purpose by the FDA. 

Although it’s not understood how Modafinil works to promote wakefulness, it has wake-promoting activity similar to amphetamine and methylphenidate.

It also inhibits the reuptake of dopamine, a neurotransmitter associated with the reward and pleasure center of the brain, thereby causing a dopamine excess. Because dopamine makes us feel more pleasure, taking Modafinil makes us want to take it again – which can be the beginning of addiction. 

Modafinil creates psychoactive and euphoric effects, alterations in mood, perception, thinking, and feelings typical of other CNS stimulants.

 

Modafinil is apparently not as prone to abuse as Ritalin, Concerta and other drugs. But doctors still recommend keeping a very close eye on patients for signs of abuse, especially in those who have had dependence or addiction problems in the past. 

 

Modafinil creates psychoactive and euphoric effects, alterations in mood, perception, thinking, and feelings typical of other CNS stimulants. It also makes a person feel better when they take it – which can make them want to continue to take it – and, in addition to helping someone stay awake, it improves focus (which is why it’s used as a study drug).  

Anyone prone to addiction could become addicted to Modafinil.

HALF LIFE AND METABOLISM

The biological half life of a substance is the time it takes for a drug to lose half of its pharmacologic activity. This is significant because it affects how soon withdrawal symptoms may appear.

The half life of Modafinil is approximately 15 hours, considerably longer than similar drugs. 

Modafinil is metabolized primarily through the P- 450 in the liver using the (CYP) 3A4 enzyme. 

The CYP enzymes are the major enzymes involved in drug metabolism, and since many drugs may increase or decrease the activity of various CYP isozymes, this is a major source of adverse drug interactions, since changes in CYP enzyme activity may affect the metabolism and clearance of various drugs. For example, if one drug inhibits the CYP-mediated metabolism of another drug, the second drug may accumulate within the body to toxic levels, possibly causing an overdose.

 

The following side effect information is taken from the Modafinil label:

  • abnormal liver function
  • abnormal vision
  • aggression
  • agitation
  • agranulocytosis-  a deficiency of a type of white blood cell (called granulocytes), causing increased vulnerability to infection
  • altered judgment
  • altered thinking
  • anaphylaxis – a serious, life-threatening allergic reaction that manifests as difficulty in swallowing or breathing, swelling of face, eyes, lips, tongue or larynx, and hoarseness.
  • angioedema
  • anorexia
  • anxiety
  • asthenia – abnormal physical weakness or lack of energy
  • asthma
  • auditory hallucinations
  • back pain
  • chest Pain
  • chills
  • confusion
  • constipation
  • delusions
  • depression
  • diarrhea
  • dizziness
  • dry mouth
  • dyskinesia  – impairment of voluntary movements resulting in fragmented or jerky motions (as in Parkinson’s disease)
  • dyspepsia – indigestion
  • edema
  • emotional lability – exaggerated changes in mood or emotions in quick succession
  • eosinophilia – an increase in the number of eosinophils (white blood cells that fight disease) in the blood, occurring in response to some allergens, drugs, and parasites, and in some types of leukemia.
  • epistaxis – nosebleed
  • fever
  • flatulence
  • hallucinations
  • headache
  • hepatitis
  • hypertension
  • hypertonia – Increased tightness of muscle tone and reduced capacity of the muscle to stretch caused by damage to the motor nerve pathways in the central nervous system. Untreated hypertonia can lead to loss of function and deformity. Treatment can include physical and/or occupational therapy or medications.
  • insomnia
  • myocarditis – inflammation of the heart muscle
  • nausea
  • nervousness
  • new or increased use of antihypertensive medications
  • palpitation
  • paranoid delusions
  • paresthesia – “pins and needles”, caused primarily by pressure on or damage to peripheral nerves
  • persistent sleepiness – degree of wakefulness may not return to normal in those who experience abnormal levels of sleepiness on Modafinil 
  • pharyngitis – sore throat (caused by inflammation of the pharynx, a cavity at the back of the throat)
  • problem with motor skills
  • pruritus – severe skin itching
  • psychomotor hyperactivity – extreme restlessness accompanied by an increase in motor activity including muscle spasms, tremors and twitching. In addition, patients may engage in other restless activity such as pacing, crossing and uncrossing the legs and other nervous activity. It is the physical manifestation of various internal conditions ranging from diseases to adverse reactions by the nervous system to toxins within the body or drug side effects.
  • rhinitis – irritation and swelling of the mucous membrane in the nose, usually caused by viral infection of the nose and throat or an allergy. Symptoms are itchy or runny nose, sneezing, nasal congestion, itchy, watery eyes and sneezing.
  • serious rash, including Stevens-Johnson Syndrome
  • sleep deprivation
  • suicidal ideation
  • sweating
  • tachycardia
  • taste perversion
  • thirst
  • thrombocytopenia – a deficiency of platelets in the blood, causing bleeding into the tissues, bruising, and slow blood clotting after injury.
  • tremor
  • urine abnormality
  • vasodilatation
  • vertigo
  • vomiting

Life-Threatening Skin Rashes

According to the drug label, one of the most dangerous side effects associated with Modafinil is a skin rash. Getting a rash may not always be a big problem, but the type of rash you can get with Modafinil can be life-threatening or can cause permanent disabling or disfiguring. Unfortunately, you can’t necessarily tell how dangerous a rash is going to become until it’s too late to prevent the worst.

Therefore, with any sign of a rash, it’s important to stop the drug and get to the doctor or hospital immediately.

The rashes that are dangerous are Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Drug Rash with Eosinophilia and Systemic Symptoms (DRESS). They’ve all been reported in adults and children around the world as a reaction to Modafinil.

SJS – a severe reaction to a drug. It often begins with a fever and flu-like symptoms. Then, within a few days, that’s followed by a painful red or purplish rash that spreads and blisters. It can also involve the mucous membranes, including the mouth, nose, eyes and genitals. The top layer of skin dies and sheds, then begins to heal. However, there can be serious complications – local infections, sepsis, scarring of the mucous membranes in the eyes (causing restricted sight and even blindness), scarring that results in hair falling out, fingernails and toenails not growing in normally, and respiratory failure.

TEN and DRESS are equally, if not more, dangerous. DRESS has a longer incubation period.

Correct diagnosis and treatment is vital as soon as possible. Treat any rash as an emergency – stop the drug, and get to the doctor or hospital.

In addition to skin rashes, the Modafinil label warns against other serious reactions, the symptoms of which are covered above:

  • Angioedema and Anaphylaxis Reactions
  • Multi-organ Hypersensitivity Reactions
  • Persistent Sleepiness
  • Psychiatric Symptoms
  • Effects on Ability to Drive and Use Machinery
  • Cardiovascular Events

 

The Modafinil label cites one study which concludes that there are no withdrawal symptoms. However, other studies are cited online which contradict that. There is also anecdotal evidence of withdrawal symptoms.

The reported withdrawal symptoms include:

  • excessive sleepfulness
  • lack of focus
  • extreme depression
  • being completely devoid of energy to the point where it’s difficult to do everyday easy tasks
  • borderline personality disorder
  • lack of motivation
  • reduced appetite

 

Treatment when quitting Modafinil depends on how much of the drug you’ve been taking and for how long. How you react to the drug and to withdrawal are also factors. Always check with a medical professional on the best method. In some cases, a medically-supervised drug detox program may be recommended. Call us for more information.