Acute Alcohol Poisoning: Clinical Presentation and Treatment

Alcohol is the most used psychoactive and addictive substance in American society, with it being estimated that almost 90% of people consume alcohol at some point in their lives, and up to 30% will develop alcohol use disorders (AD). According to the Global Burden of Disease Study 2019, alcohol abuse represents the ninth risk factor for disability-adjusted life years, accounting for 3.7% risk across all ages, with a 37% increase in period 1990-2019.

Specifically, alcohol consumption was the main risk factor for disability in subjects aged 25 to 49 years, which represents the first preventable cause of disease in this age group. In 2016 in the US, alcohol was the eighth leading cause of preventable death. Alcohol consumption shows a wide dispersion among the population, with a significant impact on health systems.

Alcohol intoxication is largely responsible for traffic accidents, pedestrian injuries, acts of violence, including domestic violence, suicide attempts, head injuries due to falls and crashes. These events are associated with severe post-traumatic disability and mortality.

In particular, studies on the incidence of alcohol poisoning in trauma patients admitted to the emergency department report rates of 24% to 47%. In the US, the rate of emergency department visits for alcohol poisoning increased by 47%, from 1223/100,000 population in 2006 to 1802/100,000 population in 2014, resulting in a 272% increase in total cost of alcohol-related emergency room visits.

Recognition and management of patients presenting with acute alcohol poisoning (AAI) is mandatory , especially for physicians working in emergency departments, where alcohol poisoning as a primary condition currently accounts for around 1.2% of cases. visits. Of these, almost 17% are adolescents <14 years old.

The reasons for the increase in alcohol-related emergency room visits remain unclear but it is possible that, despite small changes in per capita alcohol consumption, patterns of alcohol consumption leading to AAI and emergencies doctors associated with the IAA play an important role. Excessive alcohol consumption is the alcohol consumption pattern that most correlates with AAI.

According to the National Institute on Alcohol Abuse and Alcoholism (NIAAA), it is defined as “the pattern of consumption that brings blood alcohol concentration (BAC) levels to 80 mg/dl. Generally, this occurs after 4 drinks for women and 5 drinks for men, in about 2 hours.” Today in the US, 90% of teens (and up to 67% of teens in Italy) are “binge drinkers . ”

A recent epidemiological survey among Italian high school students found that 79% of adolescents - who should be prohibited from drinking - consume alcoholic beverages, and many of them engage early in drinking practices, such as binge drinking. alcohol (48% reporting at least one binge drinking episode in a year) and daily drinking (1.2%).

This pattern of alcohol consumption is particularly dangerous because liver enzymes are not fully expressed in this age group, preventing proper alcohol metabolism.

On the other hand, early exposure to alcohol, particularly among young people and with a pattern of excessive consumption, has been associated with a higher risk of developing EDs in adulthood. Therefore, the role of the physician addressing IAA should be twofold: to recognize and possibly treat IAA along with its complications, and to facilitate referral to a Drug Addiction Unit to treat the alcohol use disorder, reducing the likelihood of return. to the emergency service.

Acute alcohol poisoning (AAI) is a relevant, potentially transient, clinical event that follows the ingestion of a large amount of alcohol.

In the presence of a patient with suspected AAI, the history data are essential to know the amount of alcoholic beverages consumed, the time of onset of symptoms, and whether any trauma has occurred. It is not uncommon for patients to be unable or unwilling to provide this information, so an accurate physical examination is also essential: vital signs, hydration status, deterioration, and the detection of skin signs potentially related to prolonged alcohol and drug abuse. repeated AAI (e.g., capillary changes, spider nevus , talangiectasias, palmar erythema).

The chest, heart, abdomen and neurological examination should identify possible organic damage. Since a diagnosis of AAI does not exclude the presence of serious coexisting illnesses, the temptation to minimize problems in intoxicated patients should be avoided: physicians should analyze the patient’s clinical status and evaluate both serious illnesses potentially related or not to the poisoning. alcohol.

In particular, attention should be paid to cognitive function, which should be re-evaluated several times during the visit.

In fact, IAA could cause alterations in consciousness, from lethargic depression to violent delirium. It should be noted that, after each episode of excessive alcohol consumption, the patient who has already experienced an AAI will always present similar alterations in mental status. Therefore, if symptoms and mental status alterations are different from those presented above, it is essential to evaluate and exclude other causes of mental status alteration.

Although the physical examination and medical history can guide the diagnosis of IAA, measurement of alcohol in the breath or blood represents the most useful test to determine the severity of IAA and its potential progression. In this sense, the clinical manifestations of IAA are based on blood alcohol concentrations (BAC). Higher levels are more serious and life-threatening characteristics

However, there are individual factors such as age, sex, body weight and alcohol tolerance that can influence alcohol metabolism and disease severity.

In general, men have a higher tolerance for alcohol than women.

This could be explained by the greater bioavailability of ethanol in women, which contributes to their greater vulnerability to acute and chronic complications of alcohol abuse. This difference in bioavailability depends on the lower volume distribution of ethanol in women due to their lower body water content, but there are also gender differences in ethanol metabolism. In fact, gastric alcohol dehydrogenase, responsible for 10% of alcohol metabolism (“first-pass metabolism”), has activity in women, with a consequent decrease in gastric oxidation. The remaining 90% of the ingested ethanol is metabolized to acetaldehyde in the liver through 3 enzymatic pathways: hepatic alcohol dehydrogenase (involved in about 90%), the microsomal ethanol oxidant system (SOEM; almost 8–10%), and catalase (about 0–2%).

Chronic alcohol abuse leads to an expansion of up to 50% of the SOEM. However, this metabolic pathway is responsible for the production of free radicals and their related organ damage.

According to the aforementioned factors, despite having similar CAS, patients may experience different effects of acute alcohol ingestion. According to the Mellanby effect , despite having identical CAS, IAA symptoms are usually more prominent during increasing alcohol levels than during the descending phase.

One unit of alcohol , also called a standard drink , represents the amount of alcohol contained in approximately one 0.33 cm3 beer, a standard glass of red wine (125 ml) or a small glass of liqueur (40 ml). Unfortunately, the authors say, the definition of a standard drink (and consequently the amount of alcohol contained in it) varies from country to country. In particular, a standard drink in the US contains 10-12 grams of ethanol, in the UK 8 grams, in Australia 10 grams and finally in Estonia it contains 14 grams. One drink produces an increase in BAC of about 20 mg/dl and is metabolized in almost 1 hour.

The mild form of IAA usually develops with BAC >50 mg/dl – approximately after 2-3 drinks – and is characterized by feelings of relaxation, euphoria, dysphoria and increased talkativeness, with social disinhibition. However, some tasks requiring skills could be affected. Indeed, IAA could result in inadequate strategies for balance control, with greater postural rigidity and impaired adaptation to perturbations, which contributes to an increased risk of falls.

The signs and symptoms of moderate IAA, which appear with a blood alcohol concentration (BAC) >100 mg/dl, approximately after 4-6 drinks, are mainly represented by a progressive deterioration of control mechanisms (e.g. , sensory, motor and psychological) with neurological manifestations such as altered perception, ataxia, hyperreflexia, incoordination, nystagmus, impaired judgment and prolonged reaction time, difficulty speaking, behavioral changes with alteration of mood and personality and deficits of memory.

Severe alcohol poisoning manifests as a blood alcohol concentration (BAC >200 mg/dL–approximately after 13-26 drinks) with global neurological impairment (e.g., amnesia, diplopia, dysarthria) and autonomic dysfunction (hypothermia). , hypotension, nausea, vomiting.) CAS levels >300-400 mg/dl are associated with respiratory depression, coma, and cardiac arrest.

It is generally accepted that deaths attributable to IAA occur at a blood alcohol concentration (BAC >500 mg/dl).

However, the lethal dose of alcohol varies widely depending on the tolerance of the subject, being lower (300 mg/dl) in “non-tolerant” subjects and much higher (>1200 mg/dl) in patients with ED. Tolerance is an adaptation of the central nervous system (CNS) to chronic alcohol exposure through a negative regulation of GABA transmission and a positive regulation of N-methyl-D-aspartate (NMDA) glutamatergic pathways.

The result is a desensitization of the CNS to the effects of ethanol with long-term reduction of its neurotropic effects. It is noteworthy that the concomitant consumption of another sedative substance (ebenzodiazepines, antihistamines, opioids) increases the risk of potentially fatal AI. Therefore, in subjects who present AAI, it is necessary to investigate the possible coexistence of abuse of other substances. Although IAA is easily recognized by the appearance of behavioral alterations and neurological symptoms, its effects involve several organs and systems.

Acute neurological complications of IAA frequently present as seizures and rhabdomyolysis. Both show an increase in plasma levels of creatine phosphokinase (CPK). However, seizures are usually tonic-clonic while myopathy is characterized by asthenia, myalgia, and flaccidity.

Severe rhabdomyolysis could lead to acute kidney disease, injury, and hyperkalemia . Seizures are frequently associated with trauma and alcohol withdrawal syndrome (AAS). In this sense, repeated episodes of IAA alternate with periods of sobriety and can lead to hypersensitivity of GABA and NMDA receptors, determining the appearance of withdrawal symptoms and an increased risk of developing ED.

The pathophysiology of the neurological manifestations of IAA is related to thiamine deficiency, decreased GABA synthesis, excitotoxic effects of glutamate, acute imbalance of electrolyte levels (dehydration, hypokalemia and hypomagnesemia) and acute barrier damage. hematoencephalic.

Acute alcoholic encephalopathy , also called Gaye-Wernicke encephalopathy, is a rare hemorrhagic encephalopathy with a subacute onset due to impaired thiamine metabolism. Clinical manifestations include oculomotor disorders, cerebellar ataxia, memory deficits, hyperkinesia, and autonomic disorders (e.g., arterial hypertension, orthostatic hypotension, hypothermia or hyperthermia, hyperhidrosis). It can also evolve as chronic Korsakoff syndrome. The development of acute alcoholic encephalopathy could also be related to a reduction in thiamine levels secondary to glucose infusion. Therefore, before administering dextrose solutions parenterally, it is recommended to do so with thiamine solutions.

Other acute manifestations associated with IAA are represented by central pontine myelinolysis (symmetric demyelination in the region of the pons, generally associated with acute fluctuations in sodium levels) manifesting with miosis, tetraplegia, aphonia and alteration of horizontal eye movement. , configuring the so-called locked-in syndrome.

Marchiafava-Bignami syndrome ( demyelination of the corpus callosum), manifesting with memory impairment, tremors, convulsions, rigidity, confusion, progressing to drowsiness and coma; tobacco-alcohol amblyopia, consisting of unilateral or bilateral optic neuritis due to the direct toxic effects of alcohol and tobacco associated with nutritional deficiencies (vitamin B12, lipoic acid).

Finally, repeated episodes of IAA and chronic alcohol abuse have been associated with CNS alterations, including reduced cortical gyrification, reduced gray matter with memory deficits, and the development of long-term dementia due to Microglia-mediated synapse elimination.

The main metabolic alterations associated with IAA are represented by hypoglycemia, hypoalbuminemia, lactic acidosis and electrolyte alterations (hypokalemia, hypomagnesemia, hypocalcemia and hypophosphatemia).

The most common cardiovascular manifestations of IAA are vasodilation and tachycardia, leading to hypotension and heat dispersion. Although these effects have been classically explained by the thermogenetic effect of alcohol that induces arterial dilation, new experimental findings support a direct role of IAA in the induction of heart disease with autonomic dysfunction and ECG modifications (e.g., QRS, QTc ).

It is believed that pathophysiological mechanisms coexist. In fact, an elevation in serum troponin concentration—an expression of myocardial inflammation—has been observed after episodes of excessive alcohol consumption, and a series of “myocardial electrical alterations” (i.e., IAA) have been described after episodes of excessive alcohol consumption. , atrial and/or ventricular tachyarrhythmias, and atrial fibrillation). These presentations may be seen in young patients with no history of heart disease referred to the emergency department on weekends or after vacations due to chest discomfort, and have been defined as " "holiday heart syndrome."

Recently, a survey conducted by the authors of patients with alcohol use disorders without heart disease, has shown an alteration in diastolic function, which they considered an echocardiographic marker of early alcoholic cardiomyopathy, with a direct relationship with the amount of alcohol ingested in the week. prior to the evaluation. The authors also consider that, in the case of IAA, acute diastolic deterioration could favor the appearance of episodes of paroxysmal atrial fibrillation.

In addition to respiratory depression due to altered mental status, patients with IAA are at increased risk for lower respiratory tract infections due to aspiration, ciliary mucosal clearance dysfunction, and alcohol-related immune dysfunction.

On the other hand, IAA can induce gastrointestinal symptoms due to direct inflammation (e.g., gastritis, peptic ulcer, and pancreatitis) manifested by nausea, vomiting, diarrhea, and abdominal pain. Alterations in gastrointestinal motility cause diarrhea while repeated episodes of vomiting could contribute to electrolyte disorders (e.g., hyponatremia). Likewise, hematemesis due to acute laceration of the esophageal mucosa may occur after vomiting (Mallory-Weiss syndrome). 

The liver represents a preferential target for alcohol-induced damage due to its central role in alcohol metabolism.

In particular, IAA could be the trigger of acute alcoholic hepatitis, as well as infections, drug-induced liver injury, and portal vein thrombosis. Alcoholic hepatitis represents a clinical entity characterized by liver inflammation, necrosis and fibrosis that occurs in patients exposed to large amounts of alcohol. Although it can occur after repeated episodes of excessive alcohol consumption in subjects without liver disease, this event is more common among subjects with underlying alcohol-associated liver disease due to chronic alcohol abuse. In these cases, IAA represents only the precipitating factor that breaks a precarious balance between local and systemic inflammation and the altered immune response that can lead to chronic liver failure. When jaundice is associated with hemolytic anemia and hypertriglyceridemia, it forms the features of Zieve syndrome.

It should be emphasized that AAI could represent the tip of an iceberg consisting of psychiatric disorders, affective disorders and suicidal aspects, and that subjects with AAI have a higher risk of injuries, trauma and death. Furthermore, an association has been observed between IAA (excessive alcohol consumption) and crimes (e.g., homicide, assault, robbery, and sexual abuse).

Finally, in patients who present AAI, particularly among young people, there is the possible concomitant abuse of other substances, especially new psychoactive substances, which should always be ruled out. Unfortunately, detection of these new substances in the laboratory could be difficult, as new recreational drugs enter the (cyber) market constantly. Therefore, physicians should be aware of this possibility because the patient’s clinical status could be dramatically complicated by these substances.

> 2.1. Acute alcohol poisoning (AAI) and alcohol withdrawal syndrome (AAS)

Although seemingly opposite, IAA and SAA could represent a disease continuum and, in some cases, share common manifestations.

Apparently, the pathophysiology of these two conditions is opposite because the first is caused by the consumption of high amounts of ethanol while the second develops when patients with ED interrupt or abruptly reduce their consumption.

However, alterations in neural circuits (GABA and NMDA) could be similar in both conditions, particularly in those subjects prone to repeated episodes of IAA (e.g., binge drinkers). Both IAA and SAA could present seizures, the pathophysiology of which is represented by the acute imbalance between inhibitory (GABA) and excitatory (glutamate) neurotransmissions, which occurs in both conditions, particularly in those subjects chronically exposed to high amounts of ethanol, capable of inducing tolerance.

On the other hand, some patients, especially traffic accident victims, may present with IAA upon admission to the hospital and develop AAS during their hospitalization if the underlying ED is not recognized and treated. It should be emphasized that a BAC >200 mg/dl at hospital admission should be considered a risk factor for the subsequent development of severe SAA. On the other hand, IAA treatment could precipitate AAS symptoms in subjects with severe ED experiencing a rapid decrease in ethanol levels.

Finally, although people with ED can develop AAS while still having a positive CAS, people without ED have less tolerance to the effects of ethanol and can develop symptoms and consequences of AAI (e.g., respiratory depression and eat).

In subjects who present AAI, it is essential to begin treatment as soon as possible to prevent the risk of developing respiratory depression and cardiac arrest.

BAC values ​​>300 mg/dl are associated with rapid worsening of respiratory and cardiovascular functions, while BAC >500 mg/dl can cause death.

Therefore, during ED evaluation of patients with AAI, particularly those with severe forms, the primary goal is evaluation of the airway and stabilization of vital functions. For mild to moderate IAA, the two main therapeutic goals are prevention of alcohol’s toxic damage to organ systems and acceleration of the elimination of alcohol from the blood.

> 3.1. Evaluation during first aid

Emergency evaluations in case of acute alcohol poisoning are:

a) Evaluation of the airways and respiratory function.

b) Prevention of aspiration by placing the patient in the lateral safety position.

c) Placement of stable intravenous access for infusions.

> 3.2. Fluid resuscitation

The placement of one, or even two, venous lines is essential to administer intravenous fluids, particularly in those patients who present with hypotension. On the other hand, glucose (hypoglycemia) and electrolyte (hypokalemia) disorders must be corrected. The most adopted protocol is based on dextrose (500 ml of 10% dextrose), electrolytes (500 ml of 0.9% NaCl with 2 g of magnesium sulfate), thiamine (100 mg) and folate (1 mg).

In particular, it is advisable to administer thiamine before any glucose load, due to the risk of accelerating the onset of Wernicke’s encephalopathy. Given that thiamine deficiency is difficult to evaluate by routine laboratory tests and that lack of supplementation in deficient patients could precipitate serious cardiovascular (heart failure, sudden death) and neurological diseases (Wernicke’s encephalopathy, Korsakoff’s psychosis) it should be encourage its parenteral administration to all subjects at risk of deficiency, particularly in the emergency setting. However, in case of severe hypoglycemia, it is not recommended to delay the administration of dextrose while waiting for the preparation and infusion of thiamine.

Multivitamins (vitamin B and C complex) can be added. On the other hand, in case of metabolic (lactic) acidosis, treatment should begin with bicarbonate. In case of hypothermia due to peripheral vasodilation, CNS depression or alteration of the pituitary-adrenal axis, intravenous infusion of warm fluids, hemodialysis or peritoneal dialysis should be performed.

> 3.3. ventilatory support

Patients with IAA may present with respiratory failure . This could be secondary to various causes such as CNS depression, inhalation or infections. Oxygen supplementation with low-flow devices (nasal cannula or Venturi mask) aims at peripheral oxygen saturation. On the other hand, severe cases, especially if respiratory acidosis is present, may require mechanical ventilation.

> 3.4. Antiemetic medications

Repeated episodes of vomiting can expose patients to life-threatening risks such as variceal bleeding, laceration and rupture of the esophagus – called Boerhaave syndrome. In the case of patients with nausea and/or vomiting, it is recommended to place them in a lateral decubitus position and administer antiemetic medications (metoclopramide). Furthermore, prevention of vomiting is useful to limit the development of hyponatremia, which is associated with pontine myelinolysis, particularly if corrected too quickly.

> 3.5. Patient sedation

In patients who present psychomotor agitation or violent attitudes, the use of sedative drugs (haloperidol, droperidol) could be considered in order to prevent harm to themselves and staff. However, in the case of possible combined intoxication with other drugs or in patients treated with multiple therapies for polymorbidities, D2 blockers, such as haloperidol, could cause dystonic reactions and QTc prolongation.

The use of mood stabilizers (eg, pregabalin) could represent an adjuvant treatment. However, the synergistic effect of mixing sedatives with alcohol must be carefully monitored, due to the risk of hypotension and respiratory depression problems. In this sense, cautious use of benzodiazepines is suggested, particularly in patients with comorbidity and in those who report alcohol-associated benzodiazepine abuse, or in those with chronic respiratory comorbidity (COPD). In recent years the use of ketamine has been proposed. The use of containment measures, on the other hand, could show a paradoxical effect.

> 3.6. Therapeutic options for the treatment of acute alcohol poisoning

Metadoxine , a pyrrolidone carboxylate of pyridoxine (pyridoxol L-2-pyrrolidone-5-carboxylate) is currently the only drug indicated for the treatment of IAA, due to its ability to accelerate the elimination of ethanol and, consequently, to reduce CAS by improving the symptoms of poisoning. In detail, pyrrolidone works by maintaining and restoring ATP levels in the brain and liver by improving glutathione synthesis while pyridoxine promotes the degradation of ethanol. Ultimately, the administration of metadoxine increases the activity of acetaldehyde dehydrogenase, promotes the plasma clearance of ethanol and acetaldehyde, and promotes the elimination of ketones.

Metadoxine has an excellent safety profile, making it easy to administer and can be used safely in the most severe poisoning situations. As evidenced in a double-blind trial, patients who received the drug showed a more pronounced decrease in CAS and a more rapid improvement in symptoms than those who received placebo.

The recommended dose is 900 mg intravenously, once. This treatment is optimal for adolescent patients, who are more likely to suffer damage from alcohol poisoning, due to the immaturity of their enzymatic activity to metabolize alcohol. However, metadoxine is currently approved in some European Union countries while it is not in the US. Furthermore, in recent trials, metadoxine has been tested for the treatment of EDs by taking advantage of its action on the receptor of serotonin and its antagonistic action of GABA.

Guerrini et al. showed that patients treated with metadoxine (500 mg, 3/day, orally) increased abstinence from alcoholic beverages at 3 months compared to untreated patients. Preliminary results from a study by Leggio et al. confirmed the effectiveness of metadoxine in EDs, also in patients with alcohol-associated liver disease. Another open-label study conducted in patients with severe alcoholic hepatitis showed that the percentage of patients who remained abstinent at 6 months was higher in those patients who took metadoxine in addition to standard therapy compared to those who did not. On the other hand, due to its antioxidant effect, metadoxine is safe and capable of improving pre-existing liver disease associated with alcohol.

Finally, the combination of metadoxine and prednisone increases the survival of alcoholic patients with acute alcoholic hepatitis, compared with the standard treatment of prednisone alone. Dihydromyricetin, a herbal flavonoid component, has been proposed as a therapeutic option for IAA due to its possible protective effect on the development of steatosis and liver damage.

Preliminary data suggest a favorable effect on alcohol-metabolizing enzymes (reduction of CAS and acetaldehyde in blood), metabolic improvement (less intracellular accumulation of triglycerides) and inflammatory (reduction of proinflammatory cytokine profiles). However, data derived mainly from animal and in vitro models require confirmation by clinical trials. Finally, in vitro and in vivo studies have shown the possibility of using biomimetic nanocomplexes containing alcohol oxidase and catalase to reduce ethanol levels.

> 4.1. Alcoholic hepatitis

A feared complication of AAI is acute alcoholic hepatitis (AH)A, characterized by jaundice (increase in bilirubin >3 mg/dl), increased rates of hepatocytonecrosis (>50 and <400 IU/l), and an elevated AST ratio. /ALT >1.5. This condition is usually associated with hepatomegaly. Unfortunately, this clinical complication frequently occurs at too young an age, as excessive alcohol consumption is becoming increasingly popular in young adolescents.

In the case of severe AAH, the mortality rate is ≥30% at 3 months, so it is very important to treat early. The first-line therapy recommended by the European Association for the Study of the Liver for severe AAH is prednisone and pentoxifylline.

To identify severe forms and establish early treatment that improves survival, the Maddrey discriminative function (DF) is used. A Maddrey FD >32 identifies severe forms and is an indication to start cortisone (or pentoxifylline). In the absence of treatment, the spontaneous survival of patients with severe AAH is 50-65% per month. For now, early liver transplantation is reserved for selected patients.

> 4.2. Alcohol withdrawal syndrome

Another possible complication of IAA is SAA. It is a clinical entity characterized by autonomic hyperactivity (tremor, anxiety, hyperreflexia, hypertension, tachycardia, fever) that usually develops within 6 to 24 h after abrupt discontinuation or reduction of alcohol consumption in patients with ED.

It is noteworthy to underline that IAA treatment could precipitate SAA due to the effect of drugs that promote alcohol metabolism and elimination.

Thus, strict monitoring of the clinical and neurological status of patients is required, particularly those subjects with a known history of ED or repeated attendance at the emergency department for AAI.

The use of clinical assessment scales (CIWA-Ar or AWS) for SAA can help initiate specific treatment to reduce the risk of progression to severe forms of SAA (seizures, depression, coma and death). . The gold standard treatment of AAS is the administration of benzodiazepines, among which long-acting ones such as diazepam and chlordiazepoxide are preferred. In patients with hepatic impairment, oxazepam or lorazepam may be chosen due to their shorter half-life and absence of active metabolites.

> 4.3. Alcohol use disorder

Patients presenting with IAA should be screened for underlying ED. The two most used detection tests for this are:

a) The Alcohol Use Disorders Identification Test (AUDIT) which helps identify risk behaviors for EDs, harmful alcohol use and ED itself.

b) The "Cut Down, Annoyed, Guilty, Eye-opener" (CAGE): a highly sensitive, short and easily applicable instrument for ED in clinical practice. In addition to IAA treatment, ED patients should begin a multidisciplinary drinking cessation program, which combines psychosocial and pharmacological interventions. Currently, different pharmacotherapies are available for ED. Some of them, such as disulfiram, acamprosate, naltrexone and nalmefene, have been approved by the FDA and/or the European Medicines Agency while others, such as sodium oxybate, baclofen, topiramate, lagabapentin and varenicline, are being evaluated. . On the other hand, there are new valid techniques such as transcranial magnetic stimulation for patients with ED who are intolerant or unresponsive to pharmacological therapies.