Protracted withdrawal syndrome
Protracted withdrawal syndrome refers to symptoms persisting for months or even years. A significant minority of people withdrawing from benzodiazepines, 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 benzodiazepines is alleviated by recommencement of benzodiazepines. 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.
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 benzodiazepines and should generally be avoided; however phenobarbital can be used, as it is relatively safe, see below. Benzodiazepines 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 benzodiazepines has been demonstrated to be still present at four months to two years after withdrawal depending on personal biochemistry. Re-exposures to benzodiazepines typically resulted in a reactivation of the tolerance and benzodiazepine withdrawal syndrome. Bupropion, which is used primarily as an antidepressant and smoking cessation aid, is contraindicated in persons experiencing abrupt withdrawal from benzodiazepines 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 benzodiazepine 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 benzodiazepine withdrawal; however, research is limited and thus the ability of experts to make recommendations on its use for benzodiazepine withdrawal is not possible at present.