Chlordiazepoxide, 5 mg capsules, are sometimes used as an alternative to diazepam for<unk>  withdrawal. Like diazepam, it has a long elimination half-life and long-acting active metabolites. Management of<unk>  dependence involves considering the person's age, comorbidity and the pharmacological pathways of<unk> s. Psychological interventions may provide a small but significant additional benefit over gradual dose reduction alone at post-cessation and at follow-up. The psychological interventions studied were relaxation training, cognitive-behavioral treatment of insomnia, and self-monitoring of consumption and symptoms, goal-setting, management of withdrawal and coping with anxiety. There is no standard approach to managing<unk>  withdrawal. With sufficient motivation and the proper approach, almost anyone can successfully withdraw from<unk> s. However, a prolonged and severe withdrawal<unk>  can cause profound disability, which may lead to breakdown of relationships, loss of employment, financial difficulties, as well as more serious adverse effects such as hospitalization and suicide. As such, long-term users should not be forced to discontinue against their will. Over-rapid withdrawal, lack of explanation, and failure to reassure individuals that they are experiencing temporary withdrawal symptoms led some people to experience increased panic and fears they are going mad, with some people developing a condition similar to post-traumatic stress disorder as a result. A slow withdrawal regimen, coupled with reassurance from family, friends, and peers improves the outcome. According to a 2015 Cochrane review, cognitive behavior therapy plus taper was effective in achieving discontinuation in the short-term but the effect was not certain after six months. Medications While some substitutive pharmacotherapies may have promise, current evidence is insufficient to support their use. Some studies found that the abrupt substitution of substitutive pharmacotherapy was actually less effective than gradual dose reduction alone, and only three studies found benefits of adding melatonin, paroxetine, trazodone, or valproate in conjunction with a gradual dose reduction. *Antipsychotics are generally ineffective for<unk>  withdrawal-related psychosis. Antipsychotics should be avoided during<unk>  withdrawal as they tend to aggravate withdrawal symptoms, including convulsions. Some antipsychotic agents may be riskier than others during withdrawal, especially clozapine, olanzapine or low potency phenothiazines (e.g., chlorpromazine), as they lower the seizure threshold and can worsen withdrawal effects; if used, extreme caution is required. *Barbiturates are cross tolerant to<unk> s and should generally be avoided; however phenobarbital can be used, as it is relatively safe, see below.<unk> s or cross tolerant drugs should be avoided after discontinuation, even occasionally. These include the nonbenzodiazepines Z-drugs, which have a similar mechanism of action. This is because tolerance to<unk> s has been demonstrated to be still present at four months to two years after withdrawal depending on personal biochemistry. Re-exposures to<unk> s typically resulted in a reactivation of the tolerance and<unk> . *Bupropion, which is used primarily as an antidepressant and smoking cessation aid, is contraindicated in persons experiencing abrupt withdrawal from<unk> s or other sedative-hypnotics (e.g. alcohol), due to an increased risk of seizures. *Buspirone augmentation was not found to increase the discontinuation success rate. *Caffeine may worsen withdrawal symptoms because of its stimulatory properties. At least one animal study has shown some modulation of the<unk>  site by caffeine, which produces a lowering of seizure threshold. *Carbamazepine, an anticonvulsant, appears to have some beneficial effects in the treatment and management of<unk>  withdrawal; however, research is limited and thus the ability of experts to make recommendations on its use for<unk>  withdrawal is not possible at present. *Ethanol, the primary alcohol in alcoholic beverages, even mild to moderate use, has been found to be a significant predictor of withdrawal failure, probably because of its cross tolerance with<unk> s. *Flumazenil has been found to stimulate the reversal of tolerance and the normalization of receptor function. However, further research is needed in the form of randomised trials to demonstrate its role in the treatment of<unk>  withdrawal. Flumazenil stimulates the up-regulation and reverses the uncoupling of<unk>  receptors to the GABAA receptor, thereby reversing tolerance and reducing withdrawal symptoms and relapse rates. Because of limited research and experience compared to the possible risks involved, the flumazenil detoxification method is controversial and can only be done as an inpatient procedure under medical supervision. :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. :A study into the effects of the<unk>  receptor antagonist, flumazenil, on<unk>  withdrawal symptoms persisting after withdrawal was carried out by Lader and Morton. Study subjects had been<unk> -free for between one month and five years, but all reported persisting withdrawal effects to varying degrees. Persistent symptoms included clouded thinking, tiredness, muscular symptoms such as neck tension, depersonalisation, cramps and shaking and the characteristic perceptual symptoms of<unk>  withdrawal, namely, pins and needles feeling, burning skin, pain and subjective sensations of bodily distortion. Therapy with 0.2–2 mg of flumazenil intravenously was found to decrease these symptoms in a placebo-controlled study. This is of interest as<unk>  receptor antagonists are neutral and have no clinical effects. The author of the study suggested the most likely explanation is past<unk>  use and subsequent tolerance had locked the conformation of the GABA-BZD receptor complex into an inverse agonist conformation, and the antagonist flumazenil resets<unk>  receptors to their original sensitivity. Flumazenil was found in this study to be a successful treatment for protracted<unk> , but further research is required. A study by Professor Borg in Sweden produced similar results in patients suffering from protracted withdrawal. In 2007, Hoffmann–La Roche the makers of flumazenil, acknowledged the existence of protracted<unk> s, but did not recommended flumazenil to treat the condition. *Fluoroquinolone antibiotics have been noted to increase the incidence of a CNS toxicity from 1% in the general population, to 4% in<unk> -dependent population or in those undergoing withdrawal from them. This is probably the result of their GABA antagonistic effects as they have been found to competitively displace<unk> s from<unk>  receptor sites. This antagonism can precipitate acute withdrawal symptoms, that can persist for weeks or months before subsiding. The symptoms include depression, anxiety, psychosis, paranoia, severe insomnia, paresthesia, tinnitus, hypersensitivity to light and sound, tremors, status epilepticus, suicidal thoughts and suicide attempt. Fluoroquinolone antibiotics should be contraindicated in patients who are dependent on or in<unk>  withdrawal. NSAIDs have some mild GABA antagonistic properties and animal research indicate that some may even displace<unk> s from their binding site. However, NSAIDs taken in combination with fluoroquinolones cause a very significant increase in GABA antagonism, GABA toxicity, seizures, and other severe adverse effects. *Imidazenil has received some research for management of<unk>  withdrawal, but is not currently used in withdrawal. *Imipramine was found to statistically increase the discontinuation success rate. *Melatonin augmentation was found to statistically increase the discontinuation success rate for people with insomnia. *Phenobarbital, (a barbiturate), is used at "detox" or other inpatient facilities to prevent seizures during rapid withdrawal or cold turkey. The phenobarbital is followed by a one- to two-week taper, although a slow taper from phenobarbital is preferred. In a comparison study, a rapid taper using<unk> s was found to be superior to a phenobarbital rapid taper. *Pregabalin may help reduce the severity of<unk>  withdrawal symptoms, and reduce the risk of relapse. *Propranolol was not found to increase the discontinuation success rate. *SSRI antidepressants have been found to have little value in the treatment of<unk>  withdrawal. *Trazodone was not found to increase the discontinuation success rate. Inpatient treatment Inpatient drug detox or rehabilitation facilities may be inappropriate for those who have become tolerant or dependent while taking the drug as prescribed, as opposed to recreational use. Such inpatient referrals may be traumatic for these individuals.
Benzodiazepine withdrawal syndrome
Delirium tremens
Post-acute-withdrawal syndrome
Nicotine withdrawal
Opioid withdrawal
Antidepressant discontinuation syndrome
Alcohol withdrawal syndrome
Drug withdrawal