Benzodiazepine withdrawal symptoms

Tyrer P, Rutherford D, Huggett T Benzodiazepine withdrawal symptoms and propranolol. Lancet 1 520—522, 1981... 

Tolerance to benzodiazepines Flumazenil may cause benzodiazepine withdrawal symptoms in individuals who have been taking benzodiazepines long enough to have some degree of tolerance. Slower titration rates of 0.1 mg/min and lower total doses may help reduce the frequency of emergent confusion and agitation. 

Unlike benzodiazepines, buspirone is not associated with sedative or abuse problems, but some clinicians have observed that bus-pirone s anxiolytic properties do not appear to be as potent as those of benzodiazepines, particularly in patients who have previously received a benzodiazepine. Because buspirone is not sedating and has no psychomotor effects, it has a distinct advantage over benzodiazepines when optimal alertness and motor performance are necessary. Response to buspirone occurs in approximately 2-4 weeks. Buspirone does not show cross-tolerance with benzodiazepines and other sedative or hypnotic drugs such as alcohol, barbiturates, and chloral hydrate. Therefore, buspirone does not suppress benzodiazepine withdrawal symptoms. In anxious patients who are taking a benzodiazepine and who require a switch to buspirone, the benzodiazepine must be tapered gradually to avoid withdrawal symptoms, despite the fact that the patient is receiving buspirone. 

Buspirone is generally less effective and slower in action than benzodiazepines emd does not improve sleep it does not benefit benzodiazepine withdrawal symptoms. The advantages are that it does not seem to cause dependence or withdrawal reactions and does not interact with alcohol. It appears to be less effective in patients who have previously received benzodiazepines and is therefore probably best used in benzodiazepine naive patients. A disadvantage is that useful anxiolytic effect is delayed for 2 or more weeks. 

After delivery, the maternal response to drug treatment and, if appropriate, serum drug concentrations should be monitored, because the disposition of anticonvulsants can change. The neonate should be monitored for potential residual effects of transplacentally acquired anticonvulsants and, in the case of barbiturates and benzodiazepines, withdrawal symptoms such as irritability and feeding difficulties. 

In another study, Malsch and Kieser (2001) investigated the anxiolytic effects of WS 1490 compared to placebo in patients previously treated with a benzodiazepine. They evaluated the potential of the kava preparation as a replacement for the benzodiazepine, as well as the ability of the kava preparation to reduce benzodiazepine withdrawal symptoms. This was a five-week randomized, double blind placebo-controlled study in outpatients with non-psychotic anxiety (e.g., generalized anxiety disorder, social phobia, and simple phobia). Forty patients were included, and all had been on benzodiazepines (i.e., lorazepam, bromazepam, oxazepam, or alprazolam) for a mean duration of 20 months prior to entering the study. Of the 40 patients, 25 were males, and the mean age of the total sample was 40 years (range 21—75 years). 

A placebo-controlled study in 12 healthy subjects found that nefazodone 200 mg twice daily caused an almost twofold increase in the plasma levels of alprazolam 1 mg twice daily taken for 7 days. Another study found that impairment of psychomotor performance and increased sedation occurred when nefazodone was given with alprazolam. A case report describes benzodiazepine withdrawal symptoms in a woman taking alprazolam after nefazodone was withdrawn following several years of concurrent use. She needed an alprazolam dosage increase from 500 micrograms to 4 mg daily to control her symptoms. ... 

A case of heart failure with delirium was reported in a man with a significant history of cardiovascular disease who had taken valerian (500-2000 mg daily) for 5 years and was also taking numerous other medications and supplements (isosorbide dinitrate, digoxin, furosemide, benazepril, aspirin, lovastatin, ibuprofen, potassium, zinc, and vitamins). The reporting physicians stated that valerian is considered to exert a benzodiazepine-like action through the enhancement of y-aminobutyric acid neurotransmission they suggested that symptoms reported in this case were similar to benzodiazepine withdrawal symptoms and hypothesized that the cardiac failure was due to valerian withdrawal (Garges et al. 1998). 

Benzodiazepine withdrawal may occur when use of the antianxiety drugs is abruptly discontinued after 3 to 4 months of therapy. Occasionally, withdrawal symptoms may occur after as little as 4 to 6 weeks of therapy. Symptoms of benzodiazepine withdrawal include increased anxiety, concentration difficultiesi, tremor, and sensory disturbances, such as paresthesias photophobia, hypersomnia, and metallic taste. To help prevent withdrawal symptoms, the nurse must make sure the dosage of the benzodiazepine is gradually decreased over a period of time, usually 4 to 6 weeks... 

Although rare, benzodiazepine toxicity may occur from an overdose of the drug. Benzodiazepine toxicity causes sedation, respiratory depression, and coma. Flumazenil (Romazicon) is an antidote (antagonist) for benzodiazepine toxicity and acts to reverse die sedation, respiratory depression, and coma within 6 to 10 minutes after intravenous administration. The dosage is individualized based on the patient s response, widi most patients responding to doses of 0.6 to 1 mg. However, die drug s action is short, and additional doses may be needed. Adverse reactions of flumazenil include agitation, confusion, seizures, and in some cases, symptoms of benzodiazepine withdrawal. Adverse reactions of flumazenil related to the symptoms of benzodiazepine withdrawal are relieved by die administration of die benzodiazepine. 

Control of early withdrawal symptoms, which prevents their progression to more serious symptoms, is the indication for which medications are most widely prescribed in the treatment of alcohol dependence. The most commonly used agents to treat alcohol withdrawal are the benzodiazepines, a class of drugs that, by virtue of their agonist activity at the GABA receptor complex, suppress the hyperexcitability associated with alcohol withdrawal. With widespread use of anticonvulsant medications for bipolar disorder and other disorders associated with behavioral disinhibition and CNS hyperexcitability, anticonvulsants have also been examined for use in the treatment of alcohol withdrawal. 

A dramatically different pattern is found in surveys of drug abuse treatment facilities. Substance abuse treatment centers have reported that more than 20% of patients use benzodiazepines weekly or more frequently, with 30%— 90% of opioid abusers reporting illicit use (Iguchi et al. 1993 Stitzer et al 1981). Methadone clinics reported that high proportions ofurine samples are positive for benzodiazepines (Darke et al. 2003 Dinwiddle et al. 1996 Ross and Darke 2000 Seivewright 2001 Strain et al. 1991 Williams et al. 1996). The reasons for the high rates of benzodiazepine use in opioid addicts include self-medication of insomnia, anxiety, and withdrawal symptoms, as well as attempts to boost the euphoric effects of opioids. 

Secobarbital exhibits the same pharmacologic properties as other members of the barbiturate class. Most nonmedical use is with short-acting barbiturates, such as secobarbital. Although there may be considerable tolerance to the sedative and intoxicating effects of the drug, the lethal dose is not much greater in addicted than in normal persons. Tolerance does not develop to the respiratory effect. The combination of alcohol and barbiturates may lead to fatalities because of their combined respiratory depressive effects. Similar outcomes may occur with the benzodiazepines. Severe withdrawal symptoms in epileptic patients may include grand mal seizures and delirium. 

The answer is d. (Hardman, p 564.) A long-acting benzodiazepine, such as diazepam, is effective in blocking the secobarbital withdrawal symptoms. The anxiolytic effects of bus pi rone take several days to develop, obviating its use for acute severe anxiety... 

Detoxification, as mentioned in Chapter 2, may involve the use of certain medications to prevent severe discomfort or even possible medical side effects related to withdrawal symptoms. These medicines can range from tranquilizers (often benzodiazepines) and antidepressants to anticonvulsives and antihypertensives, and the medical protocol for detox will depend on the drug or drugs being abused, the client s vital signs and other symptoms, and the known risk for certain withdrawal symptoms associated with the drugs being used. The duration... 

The use of benzodiazepines should be avoided. There are other safer pharmacological alternatives. Benzodiazepine withdrawal may play a role in the occurrence of delirium in the elderly. Other withdrawal symptoms include tremor, agitation, insomnia and seizures (Turnheim 2003). Thus, when there is long-term use of benzodiazepines abrupt discontinuation might be difficult. Discontinuation should however not be withheld but done slowly and step-wise. If benzodiazepines are used in the elderly, short-acting benzodiazepines such as oxazepam are preferred, because they do not accumulate in the elderly to the same extent (Kompoliti and Goetz 1998). If short-acting benzodiazepines are used they should be prescribed with caution, at low doses, and for short periods. As with all pharmacotherapy the effects should be evaluated. Benzodiazepines are sometimes used as a behavioural control. One should always ask if this use is for the benefit of staff or the benefit of the patient. The presence of staff may be sufficient for behavioural control. 

Substance-Induced Anxiety Disorder. Numerous medicines and drugs of abuse can produce panic attacks. Panic attacks can be triggered by central nervous system stimulants such as cocaine, methamphetamine, caffeine, over-the-counter herbal stimulants such as ephedra, or any of the medications commonly used to treat narcolepsy and ADHD, including psychostimulants and modafinil. Thyroid supplementation with thyroxine (Synthroid) or triiodothyronine (Cytomel) can rarely produce panic attacks. Abrupt withdrawal from central nervous system depressants such as alcohol, barbiturates, and benzodiazepines can cause panic attacks as well. This can be especially problematic with short-acting benzodiazepines such as alprazolam (Xanax), which is an effective treatment for panic disorder but which has been associated with between dose withdrawal symptoms. 

Naloxone (Narcan). Naloxone, like naltrexone, is a potent opioid receptor blocker. Its primary use has been to reverse opiate toxicity after an overdose. However, some physicians have found it is also useful for a process known as rapid opiate detoxification. Although opiate withdrawal is not life threatening, it can be extremely unpleasant. Most opiate addicts are fearful of the withdrawal symptoms therefore, it usually requires a slow, deliberate detoxification to keep the withdrawal symptoms in check. Rapid opiate detoxification is an alternative approach that keeps the taper and detoxification as brief as possible. In this approach, naloxone is used in conjunction with general anesthesia or a nonopiate sedative such as the benzodiazepine mid-... 

Q68 Benzodiazepines with a short elimination half-life present a less severe withdrawal after drug discontinuation than drugs with a long elimination half-life. Symptoms of benzodiazepine withdrawal syndrome include anxiety, depression, insomnia and headache. 

Benzodiazepines with a short half-life are excreted more rapidly than benzodiazepines with a long half-life and hence the risk of severe withdrawal side-effects is higher. Withdrawal symptoms include anxiety, depression, insomnia, headache and hallucinations. 

---