Withdrawal

Withdrawal can refer to any sort of separation, but is most commonly used to describe the group of symptoms that occurs upon the abrupt discontinuation/separation or a decrease in dosage of the intake of medications, recreational drugs, and/or alcohol. In order to experience the symptoms of withdrawal, one must have first developed a physical dependence (often referred to as chemical dependency). This happens after consuming one or more of these substances for a certain period of time, which is both dose dependent and varies based upon the drug consumed. For example, prolonged use of an anti-depressant is most likely to cause a much different reaction when discontinued than the repeated use of an opioid, such as heroin. In fact, the route of administration, whether intravenous, intramuscular, oral or otherwise, can also play a role in determining the severity of withdrawal symptoms. There are different stages of withdrawal as well. Generally, a person will start to feel worse and worse, hit a plateau, and then the symptoms begin to dissipate. However, withdrawal from certain drugs (benzodiazapines, alcohol) can be fatal and therefore the abrupt discontinuation of any type of drug is not recommended. The term "cold turkey" is used to describe the sudden cessation use of a substance and the ensuing physiologic manifestations.

Substances
Examples (and ICD-10 code) of withdrawal syndrome include:


 * F10.1 alcohol withdrawal syndrome (which can lead to delirium tremens)
 * F11.1 opioids, including methadone withdrawal
 * F12.1 cannabis withdrawal
 * F13.1 benzodiazepine withdrawal syndrome
 * F14.1 cocaine withdrawal
 * F15.1 caffeine withdrawal
 * F17.1 nicotine withdrawal

F16.1 is the ICD-10 code for withdrawal from hallucinogens (such as LSD), but this is not currently a recognized disorder.

The term "withdrawal" can sometimes be used to describe the results of discontinuing prescription medicine, as in SSRI discontinuation syndrome, though the term rebound effect is also used to characterize these conditions.

Classified separately is the "neonatal abstinence syndrome".

Overview
The sustained use of many kinds of drugs causes adaptations within the body that tend to lessen the drug's original effects over time, a phenomenon known as drug tolerance. At this point, one is said to also have a physical dependency on the given chemical. This is the stage that withdrawal may be experienced upon discontinuation. Some of these symptoms are generally the opposite of the drug's direct effect on the body. Depending on the length of time a drug takes to leave the bloodstream elimination half-life, withdrawal symptoms can appear within a few hours to several days after discontinuation and may also occur in the form of cravings. A craving is the strong desire to obtain, and use a drug or other substance similar to other cravings one might experience for food and hunger.

Although withdrawal symptoms are often associated with the use of recreational drugs, many drugs have a profound effect on the user when stopped. When withdrawal from any medication occurs it can be harmful or even fatal; hence prescription warning labels explicitly saying not to discontinue the drug without doctor approval.

The symptoms from withdrawal may be even more dramatic when the drug has masked prolonged malnutrition, disease, chronic pain, or sleep deprivation, conditions that drug abusers often suffer as a secondary consequence of the drug. Many drugs (including alcohol) suppress appetite while simultaneously consuming any money that might have been spent on food. When the drug is removed, the discomforts return in force and are sometimes confused with addiction withdrawal symptoms, which they quite properly are not.

Withdrawal from drugs of abuse
Central to the role of nearly all drugs that are commonly abused is the reward circuitry or the "pleasure center" of the brain. The science behind the production of a sense of euphoria is very complex and still questioned within the scientific community. While neurologists have discovered that addiction encompasses several areas of the brain, the amygdala, Prefrontal Cortex, and the nucleus accumbens are specifically responsible for the pleasurable feelings one may experience when using a mind or mood-altering substance. Within the nucleus accumbens is the neurotransmitter dopamine, so while specific mechanisms vary, nearly every drug either stimulates dopamine release or enhances its activity, directly or indirectly. Sustained use of the drug results in less and less stimulation of the nucleus accumbens until eventually it produces no euphoria at all. Discontinuation of the drug then produces a withdrawal syndrome characterized by dysphoria &mdash; the opposite of euphoria &mdash; as nucleus accumbens activity declines below normal levels.

Withdrawal symptoms can vary significantly among individuals, but there are some commonalities. Subnormal activity in the nucleus accumbens is often characterized by depression, anxiety and craving, and if extreme can drive the individual to continue the drug despite significant harm &mdash; the definition of addiction &mdash; or even to suicide. In general, the longer the half-life of the drug, the longer the acute abstinence syndrome is likely to last. However, with drugs with a longer half life, the acute abstinence syndrome will be much milder than that of those with shorter half lives.

However, addiction is to be carefully distinguished from physical dependence. Addiction is a psychological compulsion to use a drug despite harm that often persists long after all physical withdrawal symptoms have abated. On the other hand, the mere presence of even profound physical dependence does not necessarily denote addiction, e.g., in a patient using large doses of opioids to control chronic pain under medical supervision.

As the symptoms vary, some people are, for example, able to quit smoking "cold turkey" (i.e., immediately, without any tapering off) while others may never find success despite repeated efforts. However, the length and the degree of an addiction can be indicative of the severity of withdrawal.

Withdrawal is a more serious medical issue for some substances than for others. While nicotine withdrawal, for instance, is usually managed without medical intervention, attempting to give up a benzodiazepine or alcohol dependency can result in seizures and worse if not carried out properly. An instantaneous full stop to a long, constant alcohol use can lead to delirium tremens, which may be fatal. Additionally, benzodiazepines have clearly been shown to induce a withdrawal syndrome in some people that is often severe and protracted in course. Doctors Ashton and Lader are two separate internationally recognized contributors who researched and described this condition that is now referred to as protracted benzodiazepine withdrawal syndrome (PBWS). Noteworthy, some patients become physically dependent on a small duration and dose (therapeutically prescribed dosages) of benzodiazepines. Patients may develop physical and psychological adaptations that may manifest while taking the medications and/or up on cessation that may lead to a severe withdrawal and discontinuation syndrome (PBWS). There is no known cure for PBWS, except time (in some cases 4, 5, or perhaps 6 years or more is needed for the withdrawal symptoms to slowly fade from 'misery' to 'comfort'). Paxil (an antidepressant) and benzodiazepines share this unique phenomenon known as 'discontinuation syndrome'. Although a distinguishing characteristic of a benzodiazepine is that the withdrawal effects clearly may protract in course for an inordinate amount of time. Iatrogenic dependence (doctor induced) can be an overlooked phenomenon with benzodiazepines. When patients begin to complain and/or shown signs of tolerance, dependence, interdose withdrawal, withdrawal, or protracted withdrawal to tranquilizers such as benzodiazepines, the patient may be misdiagnosed with yet another physical or psychological classification or diagnoses. This is because a great majority of health care providers have minimal training in addictionology/chemical dependency, especially with recognizing the signs and symptoms related to benzodiazepine dependency en route to tranquilizer withdrawal. Doctors may become perplexed or frustrated with such patients and assign the patient with a diagnoses such as anxiety, psychosis, somatization disorder, or other diagnoses pertaining to the wide range of symptoms that tranquilizer dependent patients may complain about while on the medications or up on cessation of these medications. It would be prudent to redirect such patients and/or doctors to refer to what has become known as the "Ashton Manual" available on-line to help patients or victims of tranquilizer dependency regain their physical and/or psychological well-being. Unfortunately, a sizeable minority of tranquilizer victims endure the withdrawal syndrome with minimal help from the medical community, while finding support from various organizations or internet support groups with individuals who have made their lives and stories available to help support others who are trying to recover. For those susceptible individuals who manifest with PBWS, recovering from benzodiazepine dependency is serious business requiring an understanding of the 'slow and waxing-waning nature of the withdrawal' as well as extreme patience.

An interesting side-note is that while physical dependence (and withdrawal on discontinuation) is virtually inevitable with the sustained use of certain classes of drugs, notably the opioids, psychological addiction is much less common. Most chronic pain patients, as mentioned earlier, are one example. There are also documented cases of soldiers who used heroin recreationally in Vietnam during the war, but who gave it up when they returned home (see Rat Park for experiments on rats showing the same results). It is thought that the severity or otherwise of withdrawal is related to the person's preconceptions about withdrawal. In other words, people can prepare to withdraw by developing a rational set of beliefs about what they are likely to experience. Self-help materials are available for this purpose.

Withdrawal from prescription medicine
As mentioned earlier, many drugs should not be stopped abruptly without the advice and supervision of a physician, especially if the medication induces dependence or if the condition they are being used to treat is potentially dangerous and likely to return once medication is stopped, such as diabetes, asthma, heart conditions and many psychological or neurological conditions, like epilepsy, hypertension, schizophrenia and psychosis. To be safe, consult a doctor before discontinuing any prescription medication.

Sudden cessation of the use of an antidepressant can deepen the feel of depression significantly (see "Rebound" below), and some specific antidepressants can cause a unique set of other symptoms as well when stopped abruptly.

Discontinuation of selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed class of antidepressants, (and the related class serotonin-norepinephrine reuptake inhibitors or SNRIs) is associated with a particular syndrome of physical and psychological symptoms known as SSRI discontinuation syndrome. Effexor (venlafaxine) and Paxil (paroxetine), both of which have relatively short half-lives in the body, are the most likely of the antidepressants to cause withdrawals. Prozac (fluoxetine), on the other hand, is the least likely of SSRI and SNRI antidepressants to cause any withdrawal symptoms, due to its exceptionally long half-life.

Rebound
Many substances can cause rebound effects (significant return of the original symptom in absence of the original cause) when discontinued, regardless of their tendency to cause other withdrawal symptoms. Rebound depression is common among users of any antidepressant who stop the drug abruptly, whose states are sometimes worse than the original before taking medication. This is somewhat similar (though generally less intense and more drawn out) to the 'crash' that users of ecstasy, amphetamines, and other stimulants experience. Occasionally light users of opiates that would otherwise not experience much in the way of withdrawals will notice some rebound depression as well. Extended use of drugs that increase the amount of serotonin or other neurotransmitters in the brain can cause some receptors to 'turn off' temporarily or become desensitized, so, when the amount of the neurotransmitter available in the synapse returns to an otherwise normal state, there are fewer receptors to attach to, causing feelings of depression until the brain re-adjusts.

Other drugs that commonly cause rebound are:
 * Nasal decongestants, such as Afrin (oxymetazoline) and Otrivin (xylometazoline), which can cause rebound congestion if used for more than a few days
 * Many analgesics including Advil, Motrin (ibuprofen), Aspirin (acetylsalicylic acid), Tylenol (acetaminophen or paracetamol), and some prescription but non-narcotic painkillers, which can cause rebound headaches when taken for extended periods of time.
 * Sedatives and benzodiazepines, which can cause rebound insomnia when used regularly as sleep aids.

With these drugs, the only way to relieve the rebound symptoms is to stop the medication causing them and weather the symptoms for a few days; if the original cause for the symptoms is no longer present, the rebound effects will go away on their own.

Pseudoabstinence
Pseudoabstinence is a term used by some authors to describe signs of withdrawal although the dose remains constant. Such signs may arise in use of benzodiazepines and amphetamines.