Tricyclic antidepressants are highly protein bound and have a large volume of distribution; therefore removal of these compounds from the blood with hemodialysis, hemoperfusion or other techniques are unlikely to be of any significant benefit.

Administration of intravenous sodium bicarbonate as an antidote has been shown to be an effective treatment for resolving the metabolic acidosis and cardiovascular complications of TCA poisoning. If sodium bicarbonate therapy fails to improve cardiac symptoms, conventional antidysrhythmic drugs or magnesium can be used to reverse any cardiac abnormalities. However, no benefit has been shown from Class 1 antiarrhythmic drugs; it appears they worsen the sodium channel blockade, slow conduction velocity, and depress contractility and should be avoided in TCA poisoning. Low blood pressure is initially treated with fluids along with bicarbonate to reverse metabolic acidosis (if present), if the blood pressure remains low despite fluids then further measures such as the administration of epinephrine, norepinephrine, or dopamine can be used to increase blood pressure.

Another potentially severe symptom is seizures: Seizures often resolve without treatment but administration of a benzodiazepine or other anticonvulsive may be required for persistent muscular overactivity. There is no role for physostigmine in the treatment of tricyclic toxicity as it may increase cardiac toxicity and cause seizures. In cases of severe TCA overdose that are refractory to conventional therapy, intravenous lipid emulsion therapy has been reported to improve signs and symptoms in moribund patients suffering from toxicities involving several types of lipophilic substances, therefore lipids may have a role in treating severe cases of refractory TCA overdose.

The distribution of naloxone to injection drug users and other opioid drug users decreases the risk of death from overdose. The Centers for Disease Control and Prevention (CDC) estimates that U.S. programs for drug users and their caregivers prescribing take-home doses of naloxone and training on its utilization are estimated to have prevented 10,000 opioid overdose deaths. Healthcare institution-based naloxone prescription programs have also helped reduce rates of opioid overdose in the U.S. state of North Carolina, and have been replicated in the U.S. military. Nevertheless, scale-up of healthcare-based opioid overdose interventions is limited by providers' insufficient knowledge and negative attitudes towards prescribing take-home naloxone to prevent opioid overdose. Programs training police and fire personnel in opioid overdose response using naloxone have also shown promise in the US.

Stabilization of the victim's airway, breathing, and circulation (ABCs) is the initial treatment of an overdose. Ventilation is considered when there is a low respiratory rate or when blood gases show the person to be hypoxic. Monitoring of the patient should continue before and throughout the treatment process, with particular attention to temperature, pulse, respiratory rate, blood pressure, urine output, electrocardiography (ECG) and O saturation. Poison control centers and medical toxicologists are available in many areas to provide guidance in overdoses to both physicians and the general public.

Medical observation and supportive care are the mainstay of treatment of benzodiazepine overdose. Although benzodiazepines are absorbed by activated charcoal, gastric decontamination with activated charcoal is not beneficial in pure benzodiazepine overdose as the risk of adverse effects would outweigh any potential benefit from the procedure. It is recommended only if benzodiazepines have been taken in combination with other drugs that may benefit from decontamination. Gastric lavage (stomach pumping) or whole bowel irrigation are also not recommended. Enhancing elimination of the drug with hemodialysis, hemoperfusion, or forced diuresis is unlikely to be beneficial as these procedures have little effect on the clearance of benzodiazepines due to their large volume of distribution and lipid solubility.

Flumazenil (Romazicon) is a competitive benzodiazepine receptor antagonist that can be used as an antidote for benzodiazepine overdose. Its use, however, is controversial as it has numerous contraindications. It is contraindicated in patients who are on long-term benzodiazepines, those who have ingested a substance that lowers the seizure threshold, or in patients who have tachycardia, widened QRS complex on ECG, anticholinergic signs, or a history of seizures. Due to these contraindications and the possibility of it causing severe adverse effects including seizures, adverse cardiac effects, and death, in the majority of cases there is no indication for the use of flumazenil in the management of benzodiazepine overdose as the risks in general outweigh any potential benefit of administration. It also has no role in the management of unknown overdoses. In addition, if full airway protection has been achieved, a good outcome is expected, and therefore flumazenil administration is unlikely to be required.

Flumazenil is very effective at reversing the CNS depression associated with benzodiazepines but is less effective at reversing respiratory depression. One study found that only 10% of the patient population presenting with a benzodiazepine overdose are suitable candidates for flumazenil. In this select population who are naive to and overdose solely on a benzodiazepine, it can be considered. Due to its short half life, the duration of action of flumazenil is usually less than 1 hour, and multiple doses may be needed. When flumazenil is indicated the risks can be reduced or avoided by slow dose titration of flumazenil. Due to risks and its many contraindications, flumazenil should be administered only after discussion with a medical toxicologist.

The primary treatment of digoxin toxicity is digoxin immune fab, which is an antibody made up of anti-digoxin immunoglobulin fragments. This antidote has been shown to be highly effective in treating life-threatening signs of digoxin toxicity such as hyperkalemia, hemodynamic instability, and arrhythmias. Fab dose can be determined by two different methods. First method is based on the amount of digoxin ingested whereas the second method is based on the serum digoxin concentration and the weight of the person.

Other treatment that may be used to treat life-threatening arrhythmias until Fab is acquired are magnesium, phenytoin, and lidocaine. Magnesium suppresses digoxin-induced ventricular arrhythmias while phenytoin and lidocaine suppresses digoxin-induced ventricular automaticity and delay afterdepolarizations without depressing AV conduction. In the case of an abnormally slow heart rate (bradyarrhythmias), Atropine, catecholamines (isoprenaline or salbutamol), and/or temporary cardiac pacing can be used.

Limiting the availability of paracetamol tablets has been attempted in some countries. In the UK, sales of over-the-counter paracetamol are restricted to packs of 32 x 500 mg tablets in pharmacies, and 16 x 500 mg tablets in non-pharmacy outlets. Pharmacists may provide up to 100 tablets for those with chronic conditions at the pharmacist's discretion. In Ireland, the limits are 24 and 12 tablets, respectively. Subsequent study suggests that the reduced availability in large numbers had a significant effect in reducing poisoning deaths from paracetamol overdose.

One suggested method of prevention is to make paracetamol a prescription-only medicine, or to remove it entirely from the market. However, overdose is a relatively minor problem; for example, 0.08% of the UK population (over 50 thousand people) present with paracetamol overdose each year. In contrast, paracetamol is a safe and effective medication that is taken without complications by millions of people. In addition, alternative pain relief medications such as aspirin are more toxic in overdose, whereas non-steroidal anti-inflammatory drugs are associated with more adverse effects following normal use.

One strategy for reducing harm done by acetaminophen overdoses is selling paracetamol pre-combined in tablets either with an emetic or an antidote. Paradote was a tablet sold in the UK which combined 500 mg paracetamol with 100 mg methionine, an amino acid formerly used in the treatment of paracetamol overdose.

There have been no studies so far on the effectiveness of paracetamol when given in combination with its most commonly used antidote, acetylcysteine.

Calcitriol, the active metabolite of vitamin D, appears to be a catalyst for glutathione production. Calcitriol was found to increase glutathione levels in rat astrocyte primary cultures on average by 42%, increasing glutathione protein concentrations from 29 nmol/mg to 41 nmol/mg, 24 and 48 hours after administration; it continued to have an influence on glutathione levels 96 hours after administration. It has been proposed that co-administration of calcitriol, via injection, may improve treatment outcomes.

During the latter part of the 20th century, the number of poisonings from salicylates declined, mainly because of the increased popularity of other over-the-counter analgesics such as paracetamol (acetaminophen). Fifty-two deaths involving single-ingredient aspirin were reported in the United States in 2000; however, in all but three of these cases, the reason for the ingestion of lethal doses was intentional—predominantly suicidal.

Following a declination or total extinction in response to a previously therapeutic dose of an antidepressant, the issue is clinically addressed as stemming from tolerance development. Several strategies are available, such as exploring drug options from a different drug class used to treat depression. The patient can also choose to switch to another SSRI (or MAOI, if applicable) while maintaining proportionate dose. If tolerance develops in a drug from the same class, the clinician may recommend a regular cycle consisting of all effective treatments within the SSRI or MAOI classes, in order to minimize transitional side effects while maximizing therapeutic efficacy.

Other options include increasing dose of the same medication, or supplementation with another antidepressant. Dual reuptake inhibitors, also known as tricyclic antidepressants have been shown to have lower rates of tachyphylaxis.

The level of digoxin for treatment is typically 0.5-2 ng/mL. Since this is a narrow therapeutic index, digoxin overdose can happen. A serum digoxin concentration of 0.5-0.9 ng/mL among those with heart failure is associated with reduced heart failure deaths and hospitalizations. It is therefore recommended that digoxin concentration be maintained in approximately this range if it is used in heart failure patients.

High amounts of the electrolyte potassium (K+) in the blood (hyperkalemia) is characteristic of digoxin toxicity. Digoxin toxicity increases in individuals who have kidney impairment. This is most often seen in elderly or those with chronic renal insufficiency or end-stage kidney disease.

Hemodialysis can be used to enhance the removal of salicylate from the blood. Hemodialysis is usually used in those who are severely poisoned. Example of severe poisoning include people with high salicylate blood levels: 7.25 mmol/L (100 mg/dL) in acute ingestions or 40 mg/dL in chronic ingestions, significant neurotoxicity (agitation, coma, convulsions), kidney failure, pulmonary edema, or cardiovascular instability. Hemodialysis also has the advantage of restoring electrolyte and acid-base abnormalities while removing salicylate.

ADT tachyphylaxis specifically occurs in depressed patients using SSRIs and MAOIs. Currently, SSRIs are the preferred treatment for depression among clinicians, as MAOIs require the patient to avoid certain foods and other medications due to the potential for interactions capable of inducing dangerous side effects. Provided is a list of medications known to be subject to Poop-out.

These headaches are treated by determining the cause of the headache and treating or removing this cause

Antifreeze products for automotive use containing propylene glycol in place of ethylene glycol are available, and are generally considered safer to use, as it possesses an unpleasant taste in contrast to the perceived "sweet" taste of toxic ethylene glycol-based coolants, and only produces lactic acid in an animal's body, as their muscles do when exercised.

When using antifreeze products containing ethylene glycol, recommended safety measures include:

- Cleaning up any spill immediately and thoroughly. Spills may be cleaned by sprinkling cat litter, sand or other absorbent material directly on the spill. Once fully absorbed, while wearing protective gloves, the material may be scooped into a plastic bag, sealed and disposed. The spill area may be scrubbed with a stiff brush and warm, soapy water. The soapy water is not recommended to be drained in a storm drain.

- Checking vehicles regularly for leaks.

- Storing antifreeze in clearly marked original sealed containers, in areas that are inaccessible to pets or small children.

- Keeping pets and small children away from the area when draining the car radiator.

- Disposing of used antifreeze only by taking to a service station.

- If antifreeze is placed in toilets, ensuring the lid is down and the door closed.

In addition to antidotes, an important treatment for poisoning is the use of hemodialysis. Hemodialysis is used to enhance the removal of unmetabolized ethylene glycol, as well as its metabolites from the body. It has been shown to be highly effective in the removal of ethylene glycol and its metabolites from the blood. Hemodialysis also has the added benefit of correcting other metabolic derangements or supporting deteriorating kidney function. Hemodialysis is usually indicated in patients with severe metabolic acidosis (blood pH less than 7.3), kidney failure, severe electrolyte imbalance, or if the patient's condition is deteriorating despite treatment. Often both antidotal treatment and hemodialysis are used together in the treatment of poisoning. Because hemodialysis will also remove the antidotes from the blood, doses of antidotes need to be increased to compensate. If hemodialysis is not available, then peritoneal dialysis also removes ethylene glycol, although less efficiently.

Treatment for hyperthermia includes reducing muscle overactivity via sedation with a benzodiazepine. More severe cases may require muscular paralysis with vecuronium, intubation, and artificial ventilation. Suxamethonium is not recommended for muscular paralysis as it may increase the risk of cardiac dysrhythmia from hyperkalemia associated with rhabdomyolysis. Antipyretic agents are not recommended as the increase in body temperature is due to muscular activity, not a hypothalamic temperature set point abnormality.

Headaches due to environmental causes are usually diagnosed by taking an exposure history.

Upon the discontinuation of serotonergic drugs, most cases of serotonin syndrome resolve within 24 hours, although in some cases delirium may persist for a number of days. Symptoms typically persist for a longer time frame in patients taking drugs which have a long elimination half-life, active metabolites, or a protracted duration of action.

Cases have reported muscle pain and weakness persisting for months, and antidepressant discontinuation may contribute to ongoing features. Following appropriate medical management, serotonin syndrome is generally associated with a favorable prognosis.

The mechanisms of antidepressant withdrawal syndrome have not yet been conclusively identified. The leading hypothesis is that after the antidepressant is discontinued, there is a temporary deficiency in the brain of one or more essential neurotransmitters that regulate mood, such as serotonin, dopamine, norepinephrine, and gamma-aminobutyric acid, and since neurotransmitters are an interrelated system, dysregulation of one affects the others.

Cardiac resuscitation guidelines (ACLS/BCLS) advise that Cardiopulmonary resuscitation should be initiated promptly to maintain cardiac output until the PEA can be corrected. The approach in treatment of PEA is to treat the underlying cause, if known (e.g. relieving a tension pneumothorax). Where an underlying cause for PEA cannot be determined and/or reversed, the treatment of pulseless electrical activity is similar to that for asystole. There is no evidence that external cardiac compression can increase cardiac output in any of the many scenarios of PEA, such as hemorrhage, in which impairment of cardiac filling is the underlying mechanism producing loss of a detectable pulse.

An intravenous or intraosseous line should be started to provide medications through. The mainstay of drug therapy for PEA is epinephrine (adrenaline) 1 mg every 3–5 minutes. Although previously the use of atropine was recommended in the treatment of PEA/asystole, this recommendation was withdrawn in 2010 by the American Heart Association due to lack of evidence for therapeutic benefit. Epinephrine too has a limited evidence base, and it is recommended on the basis of its mechanism of action.

Sodium bicarbonate 1meq per kilogram may be considered in this rhythm as well, although there is little evidence to support this practice. Its routine use is not recommended for patients in this context, except in special situations (e.g. preexisting metabolic acidosis, hyperkalemia, tricyclic antidepressant overdose).

All of these drugs should be administered along with appropriate CPR techniques. Defibrillators cannot be used to correct this rhythm, as the problem lies in the response of the myocardial tissue to electrical impulses.

Discontinuation syndrome is often prevented by taking medication as directed, and when discontinuing, doing so gradually. When discontinuing an antidepressant with a short half-life, switching to a drug with a longer half-life (e.g. fluoxetine or citalopram) and then discontinuing from that drug can decrease the likelihood and severity of symptoms.

Treatment is dependent on the severity of the discontinuation reaction and whether or not further antidepressant treatment is warranted. In cases where further antidepressant treatment is required then the only step required is restarting the antidepressant; this is usually the case following patient noncompliance with the drug. If antidepressants are no longer required, treatment depends on symptom severity. Mild reactions may only require reassurance. Moderate cases may require symptom management. If symptoms of discontinuation are severe, or do not respond to symptom management, the antidepressant can be reinstated and then withdrawn more cautiously. In rare but severe cases, hospitalization may be required.

The management of AAlPP remains purely supportive because no specific antidote exists. Mortality rates approach 60%. Correction of metabolic acidosis is a cornerstone of treatment. The role of magnesium sulfate as a potential therapy in AlP poisoning may decrease the likelihood of a fatal outcome, and has been described in many studies. After ingestion, removal of unabsorbed poison from the gut ("gut decontamination"), especially if administered within 1–2 hours, can be effective. Potassium permanganate (1:10,000) gastric lavage can decompose the toxin. All patients of severe AlP poisoning require continuous invasive hemodynamic monitoring and early resuscitation with fluid and vasoactive agents.

Current antidotes for OP poisoning consist of a pretreatment with carbamates to protect AChE from inhibition by OP compounds and post-exposure treatments with anti-cholinergic drugs. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of "-oximes" has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally. These antidotes are effective at preventing lethality from OP poisoning, but current treatment lack the ability to prevent post-exposure incapacitation, performance deficits, or permanent brain damage. While the efficacy of atropine has been well-established, clinical experience with pralidoxime has led to widespread doubt about its efficacy in treatment of OP poisoning.

Enzyme bioscavengers are being developed as a pretreatment to sequester highly toxic OPs before they can reach their physiological targets and prevent the toxic effects from occurring. Significant advances with cholinesterases (ChEs), specifically human serum BChE (HuBChE) have been made. HuBChe can offer a broad range of protection for nerve agents including soman, sarin, tabun, and VX. HuBChE also possess a very long retention time in the human circulation system and because it is from a human source it will not produce any antagonistic immunological responses. HuBChE is currently being assessed for inclusion into the protective regimen against OP nerve agent poisoning. Currently there is potential for PON1 to be used to treat sarin exposure, but recombinant PON1 variants would need to first be generated to increase its catalytic efficiency.

One other agent that is being researched is the Class III anti-arrhythmic agents. Hyperkalemia of the tissue is one of the symptoms associated with OP poisoning. While the cellular processes leading to cardiac toxicity are not well understood, the potassium current channels are believed to be involved. Class III anti-arrhythmic agents block the potassium membrane currents in cardiac cells, which makes them a candidate for become a therapeutic of OP poisoning.