Withdrawal Syndromes

Article Author:
Mohit Gupta

Article Editor:
Fibi Attia

Editors In Chief:
David Wood
Andrew Wilt
Hajira Basit

Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon

9/26/2019 11:20:31 PM


Withdrawal from drugs and alcohol is a common medical problem seen in most countries. The withdrawal response after discontinuation of a particular drug or alcohol can depend on how long it was used for. There is a tremendous variability in the withdrawal response. When people consume alcohol for at least 1 to 3 months or even consume large quantities for at least seven to ten days, the withdrawal response can occur within 6 to 24 hours after cessation of alcohol. The withdrawal response is relieved immediately by consuming additional alcohol.[1][2][3][4]


The body attempts to maintain homeostasis. When a substance is removed, the residual counter-regulatory mechanisms produce unopposed effects, and withdrawal symptoms occur.[5][6][7][8]

AlcoholEthanol intoxication and withdrawal is complex. Most effects can be explained by the interaction of ethanol with neurotransmitters and neuroreceptors including gamma-aminobutyric acid (GABA), glutamate (NMDA), and opiates which result in changes in the inhibitory and excitation neurotransmitters disrupting the neurochemical balance in the brain, causing symptoms of withdrawal. Ethanol inhibits opioid binding to P-opioid receptors, and long-term use results in upregulation of opioid receptors. Opioid receptors in the nucleus accumbens and the ventral tegmental area of the brain modulate ethanol-induced dopamine release, this, in turn, produces alcohol craving and use of opioid antagonists to prevent this craving.Opioids

In opioid or benzodiazepine addiction, chronic stimulation of specific receptors for these drugs suppresses endogenous production of neurotransmitters, endorphins or GABA. Removal of the exogenous drug allows unopposed counter-regulatory effects. When the exogenous drug is removed, inadequate production of endogenous transmitters and unopposed stimulation by counter-regulatory transmitters results in withdrawal symptoms. The time it takes to restore homeostasis by synthesis of endogenous transmitters determines the time course of withdrawal.


Withdrawal from drugs and alcohol is a common medical problem. Five to ten percent of the population has alcoholism. As many as 5% of these patients may develop delirium tremens (DT) when they withdraw from chronic alcohol use. The number of people addicted to opioids, sedatives, and stimulants is not known. The mortality rate from alcohol withdrawal and DT is high if untreated. Opiate withdrawal is uncomfortable, but fatalities are rare. Withdrawal from cocaine and amphetamine results in sedation and a state resembling adrenergic blockade, death is rare. Chronic alcoholism and withdrawal are more common in men than women.

History and Physical


The signs and symptoms of alcohol withdrawal may range from a simple tremor to a fully blown delirium tremens characterized by autonomic hyperactivity, tachypnea, hyperthermia, and diaphoresis. About 25% of patients may develop alcohol hallucinations which are commonly auditory. Some alcoholics may develop seizures which are brief.

On exam, the alcoholic withdrawal response signs may include hyperventilation, tachycardia, tremor, hypertension, diaphoresis or hypothermia. Signs of chronic alcoholism may include spider angiomata, flushed facies, paralysis of extraocular muscles (Wernicke encephalopathy), poor dentition, skull or facial trauma (as a result of falls) and tongue lacerations (biting tongue during seizures). Other features of chronic alcoholism include ascites, hepatosplenomegaly, and melena. Thinning of hair, spider angioma, and gynecomastia are all also seen in chronic alcoholics.

Many patients with alcohol withdrawal have additional medical or traumatic conditions that may increase their associated risk of morbidity and mortality. Risk factors associated with increased mortality include cirrhosis, the presence of DTs at the time of diagnosis, the existence of underlying chronic pathology other than liver disease, and a need for endotracheal intubation. 

Barbiturates and Benzodiazepines

Use of sedatives like barbiturates and benzodiazepines can also produce withdrawal responses that resemble alcohol withdrawal syndrome. Autonomic and psychomotor dysfunction often characterize the withdrawal symptoms. The symptoms tend to develop 2 to 10 days after discontinuation of the agent. Gamma Hydroxybutyrate (GHB) is now a common club drug abused at nightclubs and all-night parties. The withdrawal response is mild, resembles a sedative withdrawal syndrome with psychotic symptoms. Severe withdrawal symptoms tend to occur in chronic users and can also present with seizures and rhabdomyolysis.


Opiate withdrawal response is usually mild and not life-threatening. It usually resembles a flu-like illness characterized by yawning, sneezing, rhinorrhea, nausea, diarrhea, vomiting, and dilated pupils. Depending on the half-life of the drug, the symptoms may last for three to ten days. Also, individuals who abuse IV drugs are prone to infections like endocarditis, osteomyelitis, cellulitis, hepatitis, and septic emboli.

Opiate addicts may have signs of a cough, hemoptysis, and tachypnea due to opportunistic infections as a result of acquiring HIV and PCP. IV drug users may have scars and needle marks.

Cocaine and Amphetamines

Central nervous system (CNS) stimulants like cocaine and amphetamine can also produce a withdrawal response. Like opiates, the withdrawal response is mild and not life-threatening. Often the individual will develop marked depression, excessive sleep, hunger, dysphoria, and severe psychomotor retardation but all vital functions are well preserved. These individuals are not motivated to do anything but sleep. Recovery is usually slow, and depression can last for several weeks.


The workup required depends on the severity of the patient's condition. [9][10][11] Tests to be considered include:

  • Glucose - liver disease due to alcoholism may reduce glycogen stores, and ethanol impairs gluconeogenesis. As a consequence, patients in alcohol withdrawal develop anxiety, agitation, tremor, seizures, and diaphoresis, all of which can occur with hypoglycemia.
  • Arterial blood gas (ABG) - mixed acid-base disorders are common and often result from alcoholic ketoacidosis (AKA), volume-contraction alkalosis, and respiratory alkalosis.
  • Complete blood count (CBC) - long-term alcohol ingestion causes myelosuppression, thrombocytopenia, and anemia. Megaloblastic anemia occurs with dietary deficiency of vitamin B-12 and folate; increased mean corpuscular volume suggests this condition
  • Metabolic panel - look for acidosis, dehydration, concurrent renal disease, and other abnormalities that can occur in chronic alcoholism. Calculate anion and delta gaps, which are helpful in differentiating mixed acid-base disorders. A low BUN value is expected in alcoholic liver disease. Expect an elevated lipase level if pancreatitis is suspected. Obtain the blood ammonia level if hepatic encephalopathy is suspected.
  • Magnesium, calcium, and liver function tests (LFTs) - may be indicated because patients with chronic alcoholism usually have a dietary magnesium deficiency and concurrent alcoholic hepatitis. Alcoholic pancreatitis may cause hypocalcemia.
  • Urinalysis - check for ketones, as patients may have associated alcoholic ketoacidosis (AKA). Ketonuria without glycosuria to exclude alcoholic ketoacidosis and the ingestion of isopropyl alcohol. Myoglobinuria from rhabdomyolysis may be suspected when hematuria is noted on urinalysis.
  • Cardiac markers - elevated creatine kinase (CK) and cardiac troponin levels may indicate myocardial infarction. Elevated CK level may be from rhabdomyolysis, which may be associated with adrenergic hyperactivity from alcohol withdrawal or myonecrosis if immobile.
  • Prothrombin time - useful index of liver function; patients with cirrhosis are at risk for coagulopathy.
  • Toxicology screening - consider measuring serum osmolality and screening for toxic alcohols if severely acidaemic. Other recreational drugs may be present as well.
  • Imaging - chest radiography to evaluate for aspiration pneumonia, cardiomyopathy, and chronic heart failure.
  • Head computed tomography (CT) - risk for intracranial bleeding because of cortical atrophy and coagulopathy.
  • ECG - a prolonged QTc interval has been described in patients with alcohol withdrawal syndrome.
  • Lumbar puncture - to rule out meningitis or subarachnoid hemorrhage.
  • Blood cultures may also be indicated if sepsis or endocarditis is suspected.

Treatment / Management


Patients in alcohol withdrawal may have numerous potentially life-threatening medical problems. Administration of intravenous glucose to patients with seizures is controversial because this is thought to precipitate acute Wernicke encephalopathy in chronic alcoholism unless thiamine is also administered. Lorazepam can be administered to control seizures. If glucose testing reveals hypoglycemia, dextrose 50% in water (D50W) 25 mL to 50 mL and Thiamine 100 mg intravenously (IV) is also indicated. Low doses of clonidine can help reverse central adrenergic discharge, relieving tachypnea, tachycardia, hypertension, tremor, and craving for alcohol. In an agitated patient, neuroleptics such as haloperidol 5 mg IV or intramuscularly (IM) may be added to sedative-hypnotic agents as an adjunctive therapy. Caution must be taken because haloperidol may decrease the seizure threshold as well as prolong the QT interval.


Patients exposed to opioids for longer than 14 days usually need to be weaned over time. Withdrawal symptoms should be assessed with the Sophia Observation Withdrawal Symptoms Scale. Weaning protocols should consider the length of opioid exposure and total daily opioid dose. Opioid withdrawal is treated with a long-acting opioid agonist, such as methadone or buprenorphine. Clonidine may also decrease the severity of symptoms. Long-acting benzodiazepines may be used to control insomnia and muscle cramps.Sedative-Hypnotic

Sedative-hypnotic withdrawal is treated with substituting drugs that have a long duration of action, benzodiazepine or phenobarbital for a few days followed by a decreasing dose over 2 to 3 weeks.


GHB withdrawal can initially be treated with high doses of benzodiazepines, refractory cases have responded to pentobarbital, chloral hydrate, and baclofen.


Stimulant-withdrawal syndrome is treated with observation.

Pearls and Other Issues

Patients with DTs or other severe withdrawal symptoms may require admission to the intensive care unit due to the risk of mortality.

Patients with chronic alcoholism or intravenous drug use should be evaluated for inpatient and outpatient treatment programs. Treatment programs are only successful if the patient is motivated. Often individuals addicted to opiates will be placed on methadone or buprenorphine.

  • Methadone, a long-acting opiate that prevents somatic withdrawal symptoms but does not cause euphoria equivalent to heroin, may be prescribed.
  • Buprenorphine is a Mu-opioid agonist/antagonist prescribed similarly to methadone.

Psychiatric evaluation is strongly recommended to rule out mental health concerns such as suicidal ideation, major depression, and poly-substance abuse.

Enhancing Healthcare Team Outcomes

The management of patients undergoing withdrawal symptoms is interdisciplinary. The severity of the withdrawal symptoms depends on the type of agent and duration of use. Some patients with mild withdrawal symptoms can be managed as outpatients but those with alcohol withdrawal may require admission. Besides the psychiatrist, other healthcare professionals that should be involved in the management of these patients include the internist, neurologist, pain specialist, intensivist, mental health nurse, pharmacist, and sometimes a cardiologist. The nurse should assist in patient monitoring and education. The pharmacist should evaluate for drug-drug interactions and assist in selection and dosing of drugs used to control withdrawal symptoms. The outcomes depend on the agent ingested. For most patients relapses and remissions are very common following addiction to drugs and alcohol. (Level V)



Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Withdrawal Syndromes - Questions

Take a quiz of the questions on this article.

Take Quiz
Select the correct term for symptoms resulting from cessation of a substance taken over certain duration.

Click Your Answer Below

Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.

Sign Up
A disheveled patient with track marks on their forearm presents to triage with lacrimation, piloerection, sneezing, rhinorrhea, yawning, abdominal and leg cramping, nausea, vomiting, diarrhea, mydriasis, arthralgia, and myalgia. Which of the following also may occur in this patient? Select all that apply.

Click Your Answer Below

Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.

Sign Up
A 16-year-old female presents to the emergency department with altered mental status. She is difficult to arouse and has slurred speech. On examination, she has track marks on her arms and legs. Her vital signs reveal a heart rate of 98 beats/min, blood pressure 100/60 mmHg, respiratory rate 16/minute, and oxygen saturation 98% on room air. Her urine toxicology screen is positive for benzodiazepines, cannabinoids, opiates, and alcohol. She is admitted for monitoring and intravenous fluid administration. On day 2 of hospitalization, she complains of nausea, vomiting, diarrhea, and abdominal pain. Her pupils are noted to be equal and dilated. What is the likely cause of her symptoms on day 2?

Click Your Answer Below

Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.

Sign Up
A 32-year-old young male presents to the emergency department with complaints of rhinorrhea, diarrhea, and malaise. History reveals that he had recent surgery for an ankle fracture after a fall and required intensive physical therapy along with high doses of opiate medications for pain control. On examination, he is afebrile with normal blood pressure and heart rate. The physical exam is essentially normal except for mild pupil dilation. What is the next step in the management of this patient?

Click Your Answer Below

Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.

Sign Up

Withdrawal Syndromes - References


Gulati P,Chavan BS,Sidana A, Comparative efficacy of baclofen and lorazepam in the treatment of alcohol withdrawal syndrome. Indian journal of psychiatry. 2019 Jan-Feb;     [PubMed]
Mangat AK,Schmölzer GM,Kraft WK, Pharmacological and non-pharmacological treatments for the Neonatal Abstinence Syndrome (NAS). Seminars in fetal     [PubMed]
Cooney G,Heydtmann M,Smith ID, Baclofen and the Alcohol Withdrawal Syndrome-A Short Review. Frontiers in psychiatry. 2018;     [PubMed]
Tang B,Wang XT,Chen WJ,Zhu SH,Chao YG,Zhu B,He W,Wang B,Cao FF,Liu YJ,Fan XJ,Yang H,Xu QH,Zhang H,Gong RC,Chai WZ,Zhang HM,Shi GZ,Li LH,Huang QB,Zhang LN,Yin MG,Shang XL,Wang XM,Tian F,Liu LX,Zhu R,Wu J,Wu YQ,Li CL,Zong Y,Hu JT,Liu J,Zhai Q,Deng LJ,Deng YY,Liu DW, [Experts consensus on the management of delirium in critically ill patients]. Zhonghua nei ke za zhi. 2019 Feb 1;     [PubMed]
Ibarra F Jr, Single dose phenobarbital in addition to symptom-triggered lorazepam in alcohol withdrawal. The American journal of emergency medicine. 2019 Jan 30;     [PubMed]
Glann JK,Carman M,Thompson J,Olson D,Nuttall C,Fleming H,Reese C, Alcohol Withdrawal Syndrome: Improving Recognition and Treatment in the Emergency Department. Advanced emergency nursing journal. 2019 Jan/Mar;     [PubMed]
Duceppe MA,Perreault MM,Frenette AJ,Burry LD,Rico P,Lavoie A,Gélinas C,Mehta S,Dagenais M,Williamson DR, Frequency, risk factors and symptomatology of iatrogenic withdrawal from opioids and benzodiazepines in critically Ill neonates, children and adults: A systematic review of clinical studies. Journal of clinical pharmacy and therapeutics. 2018 Dec 19;     [PubMed]
Bichaff P,Setani KT,Motta EHG,Delgado AF,Carvalho WB,Luglio M, Opioid tapering and weaning protocols in pediatric critical care units: a systematic review. Revista da Associacao Medica Brasileira (1992). 2018 Oct;     [PubMed]
Mo Y,Thomas MC,Laskey CS,Shcherbakova N,Bankert ML,Halloran RH, Current Practice Patterns in the Management Of Alcohol Withdrawal Syndrome. P     [PubMed]
Campbell EJ,Lawrence AJ,Perry CJ, New steps for treating alcohol use disorder. Psychopharmacology. 2018 Jun;     [PubMed]
Lumish R,Goga JK,Brandt NJ, Optimizing Pain Management Through Opioid Deprescribing. Journal of gerontological nursing. 2018 Jan 1;     [PubMed]


The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Pediatrics-Medical Student. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Pediatrics-Medical Student, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Pediatrics-Medical Student, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Pediatrics-Medical Student. When it is time for the Pediatrics-Medical Student board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Pediatrics-Medical Student.