A 2006 meta-analysis found evidence for the efficacy of stepped care: minimal intervention (e.g. send an advisory letter, or meet a large number of patients to advise discontinuation), followed by systematic tapered discontinuation alone without augmentation if the first try was unsuccessful. Cognitive behavioral therapy improved discontinuation success rates for panic disorder, melatonin for insomnia, and flumazenil or sodium valproate for general long-term<unk>  use. A ten-year follow-up found that more than half of those who had successfully withdrawn from long-term use were still abstinent two years later and that if they were able to maintain this state at two years, they were likely to maintain this state at the ten-year follow-up. One study found that after one year of abstinence from long-term use of<unk> s, cognitive, neurological and intellectual impairments had returned to normal. Those who had a prior psychiatric diagnosis had a similar success rate from a gradual taper at a two-year follow-up. Withdrawal from<unk> s did not lead to an increased use of antidepressants. Withdrawal process It can be too difficult to withdraw from short- or intermediate-acting<unk> s because of the intensity of the rebound symptoms felt between doses. Moreover, short-acting<unk> s appear to produce a more intense withdrawal syndrome. For this reason, discontinuation is sometimes carried out by first substituting an equivalent dose of a short-acting<unk>  with a longer-acting one like diazepam or chlordiazepoxide. Failure to use the correct equivalent amount can precipitate a severe withdrawal reaction.<unk> s with a half-life of more than 24 hours include chlordiazepoxide, diazepam, clobazam, clonazepam, chlorazepinic acid, ketazolam, medazepam, nordazepam, and prazepam.<unk> s with a half-life of less than 24 hours include alprazolam, bromazepam, brotizolam, flunitrazepam, loprazolam, lorazepam, lormetazepam, midazolam, nitrazepam, oxazepam, and temazepam. The resultant equivalent dose is then gradually reduced. The consensus is to reduce dosage gradually over several weeks, e.g. 4 or more weeks for diazepam doses over 30 mg/day, with the rate determined by the person's ability to tolerate symptoms. The recommended reduction rates range from 50% of the initial dose every week or so, to 10-25% of the daily dose every 2 weeks. For example, the reduction rate used in the Heather Ashton protocol calls for eliminating 10% of the remaining dose every two to four weeks, depending on the severity and response to reductions with the final dose at 0.5 mg dose of diazepam or 2.5 mg dose of chlordiazepoxide. For most people, discontinuation over 4–6 weeks or 4–8 weeks is suitable. A prolonged period of reduction for longer than six months should be avoided to prevent the withdrawal process from becoming a "morbid focus" for the person. Duration After the last dose has been taken, the acute phase of the withdrawal generally lasts for about two months although withdrawal symptoms, even from low-dose use, can persist for six to twelve months gradually improving over that period, however, clinically significant withdrawal symptoms may persist for years, although gradually declining. A clinical trial of patients taking the<unk>  alprazolam for as short as eight weeks triggered protracted symptoms of memory deficits which were still present up to eight weeks after cessation of alprazolam. Protracted withdrawal syndrome Protracted withdrawal syndrome refers to symptoms persisting for months or even years. A significant minority of people withdrawing from<unk> s, perhaps 10% to 15%, experience a protracted withdrawal syndrome which can sometimes be severe. Symptoms may include tinnitus, psychosis, cognitive deficits, gastrointestinal complaints, insomnia, paraesthesia (tingling and numbness), pain (usually in limbs and extremities), muscle pain, weakness, tension, painful tremor, shaking attacks, jerks, dizziness and blepharospasm and may occur even without a pre-existing history of these symptoms. Tinnitus occurring during dose reduction or discontinuation of<unk> s is alleviated by recommencement of<unk> s. Dizziness is often reported as being the withdrawal symptom that lasts the longest. A study testing neuropsychological factors found psychophysiological markers differing from normals, and concluded that protracted withdrawal syndrome was a genuine iatrogenic condition caused by the long-term use. The causes of persisting symptoms are a combination of pharmacological factors such as persisting drug induced receptor changes, psychological factors both caused by the drug and separate from the drug and possibly in some cases, particularly high dose users, structural brain damage or structural neuronal damage. Symptoms continue to improve over time, often to the point where people eventually resume their normal lives, even after years of incapacity. A slow withdrawal rate significantly reduces the risk of a protracted or severe withdrawal state. Protracted withdrawal symptoms can be punctuated by periods of good days and bad days. When symptoms increase periodically during protracted withdrawal, physiological changes may be present, including dilated pupils as well as an increase in blood pressure and heart rate. The change in symptoms has been proposed to be due to changes in receptor sensitivity for GABA during the process of tolerance reversal. A meta-analysis found cognitive impairments in many areas due to<unk>  use show improvements after six months of withdrawal, but significant impairments in most areas may be permanent or may require more than six months to reverse. Protracted symptoms continue to fade over a period of many months or several years. There is no known cure for protracted<unk>  except time, however, the medication flumazenil was found to be more effective than placebo in reducing feelings of hostility and aggression in patients who had been free of<unk> s for 4–266 weeks. This may suggest a role for flumazenil in treating protracted<unk>  withdrawal symptoms.
Benzodiazepine withdrawal syndrome
Delirium tremens
Post-acute-withdrawal syndrome
Nicotine withdrawal
Opioid withdrawal
Antidepressant discontinuation syndrome
Alcohol withdrawal syndrome
Drug withdrawal