Effects on Sleep and Withdrawal Phenomena". Benzodiazepines are often used inappropriately, and clinicians must be careful when designing neurofeedback treatment to consider how its efficacy will be affected by benzodiazepine abuse. With a longer-acting benzodiazepine such as Valium, it may take a few days for symptoms to appear. Since Klonopin acts on the brain quickly but lasts for a long time, medication replacement therapy using a longer-acting benzodiazepine, like Valium, may or may not work. Are We Closer to a Cancer Cure? In those circles, PWS is roughly defined as significant, debilitating, and continuous not minor or occasionally occurring symptoms persisting beyond about one year after total cessation of the drug. Selective serotonin reuptake inhibitors SSRIs are known to increase blood levels of diazepam, and nefazadone may increase alprazolam levels as a result of inhibition of hepatic enzymes that normally serve to metabolize the benzodiazepine. Meditation for Benzodiazepine and Psychiatric Drug Withdrawal
For some patients, this rapid withdrawal process produces an unacceptable level of subjective distress. An alternate approach is to switch to a high-potency, long-acting benzodiazepine such as clonazepam. Most patients seem to tolerate detoxification on clonazepam quite well. Because of the prolonged self-taper during detoxification, patients experience a smoother course of withdrawal with a minimum of rebound anxiety.
Withdrawal from high-potency, short-acting benzodiazepines e. A rapid tapering of these drugs is often poorly tolerated by patients, and a switch to equivalent doses of a long-acting benzodiazepine may mitigate acute withdrawal symptoms. We recommend that clonazepam be substituted for alprazolam, at a dose ratio of 0. Clonazepam should then be continued for 1 to 3 weeks.
A drug taper is not always required, although abrupt discontinuation of even a long-acting agent, such as clonazepam, can be associated with a withdrawal syndrome that includes seizures. Adverse events tend to occur several days after discontinuation, and a 2- to 3-week taper is usually adequate. Although they tend to moderate the severity of physiologic symptoms, they are ineffective in controlling the subjective sense of anxiety, and they do not prevent withdrawal seizures. Buspirone has no cross-tolerance for the benzodiazepines and does not control withdrawal symptoms from this class of drugs.
In the last few years, benzodiazepine misuse has been an important issue, in both clinical and forensic toxicology, for the great variability of available compounds, their metabolic patterns, and low concentrations in biological specimens. Thus, many analytical methods have been developed by means of various techniques and approaches. This chapter aims to present the current state of the art in benzodiazepine detection by reviewing several studies published since The features of the most analyzed biological specimens blood, urine, hair, and oral fluid have been described, even focusing on their pretreatment protein precipitation, hydrolysis, and incubation.
The extraction procedures liquid—liquid, solid-phase, or microextraction have been widely illustrated and their advantages and disadvantages have been also discussed. Moreover, special attention has been applied to the different instrumentations adopted for benzodiazepine detection, from immunoassays to the chromatographic tandem mass systems. Giovanni Martinotti 1 , As previously mentioned, pregabalin is commonly abused in combination with other substances of misuse benzodiazepines, opiates, alcohol, gamma-hydroxybutyrate.
In particular, because pregabalin is a therapeutic option in alcohol use disorder and withdrawal, it is not possible to exclude that addicted patients, who already have an altered brain reward system, may begin to increase prescribed doses of the drug, ending up with a brand new dependence. Alcohol and benzodiazepines are also the most commonly abused substances in combination with pregabalin, as a sedative feeling with slight euphoria is the main desired effect.
The risk of an abuse of pregabalin in this therapeutic setting has to be taken into account and needs to be evaluated before considering it as a potential treatment option. Peculiar populations of addicted patients should therefore be carefully monitored when in treatment with pregabalin, in order to minimize the risk of developing an addiction. Zimmerman, in Clinical Neurotherapy , Benzodiazepines are often used inappropriately, and clinicians must be careful when designing neurofeedback treatment to consider how its efficacy will be affected by benzodiazepine abuse.
Physical dependence can result from prolonged use, and neurofeedback practitioners must be sensitive to cognitive and affective symptoms that emerge as patients are slowly withdrawn from benzodiazepines and progress toward discontinuation. Initial withdrawal symptoms can include rebound anxiety, agitation, insomnia, irritability, muscle tension and restlessness, and in very severe cases hallucinations, psychoses and seizures. A summary of acute and long-term effects of benzodiazepines is given in Table 3.
Mofizul Islam 1 2 , Drug misuse is defined as the use of a substance for a purpose not consistent with legal or medical guidelines, as in the nonmedical use of prescription medications World Health Orgnization, In the context of benzodiazepines, misuse relates principally to two groups of people which can overlap: A spectrum of stages of benzodiazepine use may exist for each of these groups, similar to those proposed by Passik and Kirsh for pharmaceutical opioid use Figure 1.
On the other hand, medical users usually begin using for certain conditions such as anxiety and gradually become dependent. The stages in the continuum do not necessarily progress from one to another. Some users may remain at one stage in the whole life, and some may skip stage s and become dependent and compulsive users early on in the course. Difficulties in controlling substance-taking behavior in terms of its onset, termination, or levels of use;.
Evidence of tolerance, such that increased doses of the psychoactive substance are required in order to achieve effects originally produced by lower doses;. Progressive neglect of alternative pleasures or interests because of psychoactive substance use, increased amount of time necessary to obtain or take the substance or to recover from its effects;.
A recreational user may misuse benzodiazepines periodically without having any dependence. Conversely, a patient with a history of long-term use may be dependent on benzodiazepines, and may not necessarily deliberately misuse them. Misuse can occur in the absence of dependence and vice versa. The abuse liability of a psychoactive substance is determined by the degree to which the substance has reinforcing effects. Benzodiazepines show all three properties, mentioned in the earlier paragraph, of drugs of misuse potential.
The underlying reasons for this variation remain unclear. Prolonged use of benzodiazepine-type drugs can lead to physical dependence. With larger doses, physical dependence develops more rapidly. Abrupt cessation of benzodiazepine use after prolonged treatment at a therapeutic dose can result in a withdrawal syndrome manifested by anxiety, insomnia, headache, dizziness, tinnitus, anorexia, vomiting, nausea, tremor, weakness, perspiration, irritability, palpitations, tachycardia, and postural hypotension.
In severe cases of withdrawal e. The stimulant effect of benzodiazepine derivatives—assessed by drug discrimination procedures—is now well proven Ator, People who commence benzodiazepines as the first-line treatment modality to control anxiety symptoms may not seek other strategies to cope with anxiety. As tolerance grows, gradually benzodiazepines become less effective, so patients either increase the dose to experience the same effect, or potentially may reduce the dose and experience withdrawal symptoms including anxiety to which they have reduced tolerance as a result of a period of medication , making the original condition feel more unmanageable Figure 2.
Despite initial expectations of safety with benzodiazepines, evidence of dependence and misuse emerged soon after their marketing and continued to grow. In addition to detrimental effects on cognition and association with overdose, dependence and misuse now present the main limitations to their use. In general, mood-altering substances are highly reinforcing in patients with chemical dependence if the substance has a rapid onset of action, a high potency, a brief duration of action, high purity and water solubility for intravenous use , or high volatility ability to vaporize if smoked Parran, Thus, certain benzodiazepine derivatives have relatively high misuse potential compared to others.
Clonazepam, a high-potency benzodiazepine with a long half-life, is widely prescribed for a variety of psychiatric and neurologic conditions. Some forms of benzodiazepine preparation such as temazepam capsule gels were found to have more misuse potential due to their soft outer casing and liquid-filled center—easy to inject and give quicker onset and more intoxication. This additional misuse potential and severe complication from injecting of these gelcaps led to restrictions on the sale of that preparation in most countries.
The etiology of benzodiazepine addiction is multifactorial. Findings from a few research studies on the risk factors for benzodiazepine addiction are limited in comparison to the abundant body of evidence on alcohol addiction. It is common knowledge that inappropriate use of benzodiazepine drugs may lead to addiction. The list of basic mistakes includes:. Some authors point out that insufficient self-assertion of the doctor may be an obstacle in coping with patient demands.
The risk groups of inappropriate treatment are not only women but generally elderly patients, especially those, who are residents of social care institutions and also patients abusing alcohol and other psychoactive substances Ashton, The attitude of a physician is crucial in preventing the misuse of benzodiazepines and decreasing the risk of addiction. The proper attitude implies firmness, making decisions based strictly on guidelines and also flexibility in searching for alternative methods of intervention.
These medications are regularly taken recreationally, or abused for nonmedical purposes, in addition to being taken as legitimate prescriptions. Benzodiazepines are not intended to be taken long-term, as prolonged use or abuse can cause the brain to become both physically and psychologically dependent on them. Withdrawal symptoms, ranging from a return of uncomfortable psychological symptoms to physical manifestations such as nausea and diarrhea, may occur when the drugs are removed from the bloodstream.
Some short-acting benzodiazepines, like Xanax, are thought to be more potent than some of the longer-acting ones, such as Valium, as well. While withdrawal will be similar for both, users of short-acting benzos may experience withdrawal symptoms sooner and with more intensity, as benzos with longer half-lives will stay in the body longer, therefore slowing the onset of withdrawal.
Benzodiazepines are all designed as central nervous system depressants; however, they each may work slightly differently at targeting certain symptoms. For example, Restoril, Dalmane flurazepam , and Halcion triazolam are considered primarily hypnotic benzodiazepines prescribed for insomnia, while Xanax, Ativan, Librium chlordiazepoxide , and Valium are classified as anxiolytics used to treat anxiety symptoms. Klonopin is considered primarily an anticonvulsant.
Different metabolites of these medications make them slightly different, which may also affect how quickly they leave the bloodstream. Withdrawal from different benzodiazepines is generally thought to bring the same general symptoms; however, it is possible that an individual withdrawing from a hypnotic may have more disrupted sleep patterns while withdrawal from an anxiolytic may include higher levels of anxiety. The method of ingestion is also related to the onset of withdrawal. For instance, snorting or injecting benzos sends the drugs straight into the bloodstream to take almost instant effect.
Ingesting a pill requires that it be digested through the digestive tract, which can potentially extend the withdrawal period. This is called poly-drug abuse and can influence the withdrawal severity and timeline. The Treatment Episode Data Set TEDS report of published that 95 percent of those admitted to a drug treatment center for benzodiazepine abuse or dependency also abused another drug or alcohol simultaneously.
Abuse of other illicit substances may also increase the type and number of withdrawal symptoms that occur. Instead, medical detox is required for all benzodiazepine addictions. Medical detox generally involves tapering off the drugs with professional care and support. In addition to ensuring that patients remain safe throughout the detox process, medical personnel can also help to alleviate uncomfortable withdrawal symptoms.
In some cases, medical detox will involve substitute a longer-acting benzodiazepine for a shorter-acting one during the tapering process, to make withdrawal smoother and reduce withdrawal symptoms. Other medications may be prescribed during medical detox to treat specific symptoms as well. The British Journal of Clinical Pharmacology published that medications such as flumazenil may be effective during medical detox, for example.
Research is ongoing to find new and improved treatment methods to ease benzodiazepine withdrawal. Benzodiazepine withdrawal may occur in three main phases: The early withdrawal phase usually starts within a few hours to a few days of stopping the medication and may last a few days. During early withdrawal, an individual may experience a return of anxiety and insomnia symptoms as the brain rebounds without the drugs. Symptoms the benzos worked to suppress may come flooding back.
The tapering process frequently used in medical detox may help dampen this rebound effect. After a few days of stopping a benzodiazepine, acute withdrawal may begin. This phase constitutes the bulk of withdrawal.