Long term effects of benzodiazepines
Encyclopedia
The long-term effects of benzodiazepines include drug dependence
as well as the possibility of adverse effects on cognitive function, physical health, and mental health. There are significant risks associated with the long-term use of benzodiazepines. However, not all people experience problems associated with the long-term use of benzodiazepines. There is evidence that reduction or withdrawal from benzodiazepines can lead to a reduction in anxiety symptoms. There are a number of side-effects associated with addiction to benzodiazepines such as depression and flu-like symptoms. Due to these increasing physical and mental symptoms from long-term use of benzodiazepines, slowly withdrawing from benzodiazepines is recommended for many long-term users.
Some of the symptoms that may occur as a result of long-term use of benzodiazepines include emotional clouding, nausea
, headaches, dizziness
, irritability
, lethargy, sleep problems, memory impairment, personality changes, aggression
, depression
, agoraphobia
, anxiety
, and panic attacks, social deterioration as well as employment difficulties. While benzodiazepines are highly effective in the short term, adverse effects associated with long-term use including impaired cognitive abilities, memory problems, mood swings, overdoses when combined with other drugs may make the risk-benefit ratio unfavourable. In addition, benzodiazepines have reinforcing properties in some individuals and thus are considered to be addictive drugs; in addition, a physical dependence can develop after a few weeks or months of use. Many of these adverse effects of long-term use of benzodiazepines begin to show improvements three to six months after withdrawal.
Other concerns about the long-term effects of benzodiazepines include dose escalation, benzodiazepine abuse, tolerance and benzodiazepine dependence
and benzodiazepine withdrawal problems. Both physiological tolerance and dependence can lead to a worsening of the adverse effects of benzodiazepines. Increased risk of death has been associated with long-term use of benzodiazepines in several studies, however, other studies have not found increased mortality. Due to conflicting findings in studies regarding benzodiazepines and increased risks of death including from cancer, further research in long-term use of benzodiazepines and mortality risk has been recommended. Most of the research has been conducted in prescribed users of benzodiazepines; even less is known about the mortality risk of illicit benzodiazepine users. The long-term use of benzodiazepines is controversial and has generated significant controversy within the medical profession. Views on the nature and severity of problems with long-term use of benzodiazepines differ from expert to expert and even from country to country; some experts even question whether there is any problem with the long-term use of benzodiazepines. Political controversy, in particular in the UK, also surrounds the long-term use of benzodiazepines, and was subject to the largest class-action lawsuit in the 1980s and 1990s. There have also been allegations of a cover-up by medical bureaucracies and the government.
recommends that individuals on long-term benzodiazepines are monitored at least every 3 months and also recommends against long-term substitution therapy in benzodiazepine drug misusers due to a lack of evidence base for effectiveness and due to the risks of long-term use. The long-term effects of benzodiazepines are very similar to the long-term effects of alcohol
(apart from organ toxicity) and other sedative-hypnotics. Withdrawal effects and dependence are almost identical. A report in 1987 by the Royal College of Psychiatrists in Great Britain reported that any benefits of long-term use of benzodiazepines are likely to be far outweighed by the risks of long-term use. Despite this benzodiazepines are still widely prescribed. The socioeconomic costs of the continued widespread prescribing of benzodiazepines is high.
Long-term effects of benzodiazepines may include disinhibition
, impaired concentration and memory, depression
, as well as sexual dysfunction
. The long-term effects of benzodiazepines may differ from the adverse effects seen after acute administration of benzodiazepines. Concerns regarding the long-term effects of benzodiazepines have been raised since 1980. These concerns are still not fully answered. A review of the literature on use of benzodiazepine and nonbenzodiazepine hypnotics concluded that more research is needed to evaluate the long-term effects of hypnotic drugs. An analysis of cancer patients found that those who took tranquillisers or sleeping tablets had a substantially poorer quality of life on all measurements conducted, as well as a worse clinical picture of symptomatology. Worsening of symptoms such as fatigue, insomnia
, pain
, dyspnea
and constipation
was found when compared against those who did not take tranquillisers or sleeping tablets. Most individuals who successfully discontinue hypnotic
therapy after a gradual taper and do not take benzodiazepines for 6 months have less severe sleep and anxiety problems, are less distressed and have a general feeling of improved health at 6 month follow up.
, including sustained attention, verbal learning and memory
and psychomotor
, visuo-motor and visuo-conceptual abilities. These effects on cognition exist, although their impact on patient's daily functioning is in most but not all cases insignificant. Transient changes in the brain have been found using neuroimaging
studies, but no brain abnormalities have been found in patients treated long term with benzodiazepines. When benzodiazepine users cease long-term benzodiazepine therapy, their cognitive function improves in the first six months, although deficits may be permanent or take longer than six months to return to baseline. In the elderly, long-term benzodiazepine therapy is a risk factor for amplifying cognitive decline, although gradual withdrawal
is associated with improved cognitive status. A study of alprazolam
found that 8 weeks administration of alprazolam resulted in persisting deficits still detectable several weeks later.
can be adversely affected by benzodiazepine dependence. Possible adverse effects on sleep include induction or worsening of sleep disordered breathing. Long-term use is associated with increased alpha and beta activity, a decrease in K complexes and delta activity. There is also a decrease in stage 1 NREM, NREM stage 3 and 4 sleep and REM sleep as well as a decrease in REM sleep eye movements.
affecting over 10 percent of patients attending memory clinics. Long-term use of benzodiazepines in the elderly can lead to a pharmacological syndrome with symptoms including drowsiness, ataxia
, fatigue, confusion
, weakness
, dizziness
, vertigo
, syncope
, reversible dementia
, depression
, impairment of intellect, psychomotor
and sexual dysfunction
, agitation
, auditory
and visual hallucinations, paranoid ideation, panic
, delirium
, depersonalisation, sleepwalking
, aggressivity, orthostatic hypotension
and insomnia
. Depletion of certain neurotransmitters and cortisol
levels and alterations in immune function and biological markers can also occur. Elderly individuals who have been long-term users of benzodiazepines have been found to have a higher incidence of post-operative confusion. Benzodiazepines have been associated with increased body sway in the elderly, which can potentially lead to fatal accidents including falls. Discontinuation of benzodiazepines leads to improvement in the balance of the body and also leads to improvements in cognitive functions in the elderly benzodiazepine hypnotic
users without worsening of insomnia.
A review of the evidence has found that whilst long-term use of benzodiazepines impairs memory, its association with causing dementia is not clear and requires further research. A more recent study found that benzodiazepines are associated with an increased risk of dementia and it is recommended that benzodiazepines are avoided in the elderly.
medication had no improvements in their insomnia, anxiety, or general health ratings. A study found that individuals having withdrawn from benzodiazepines showed a marked reduction in use of medical and mental health services.
Approximately half of patients attending mental health services for conditions including anxiety disorders such as panic disorder
or social phobia
may be the result of alcohol or benzodiazepine dependence. Sometimes anxiety disorders pre-existed alcohol
or benzodiazepine dependence but the alcohol or benzodiazepine dependence
often act to keep the anxiety disorders going and often progressively making them worse. Many people who are addicted to alcohol or prescribed benzodiazepines when it is explained to them they have a choice between ongoing ill mental health or quitting and recovering from their symptoms decide on quitting alcohol and or their benzodiazepines. It was noted that every individual has an individual sensitivity level to alcohol or sedative hypnotic drugs and what one person can tolerate without ill health another will suffer very ill health and that even moderate drinking can cause rebound anxiety syndromes and sleep disorders. A person who is suffering the toxic effects of alcohol or benzodiazepines will not benefit from other therapies or medications as they do not address the root cause of the symptoms. Recovery from benzodiazepine dependence tends to take a lot longer than recovery from alcohol but people can regain their previous good health. A review of the literature regarding benzodiazepine hypnotic
drugs concluded that these drugs cause an unjustifiable risk to the individual and to public health. The risks include dependence
, accidents and other adverse effects. Gradual discontinuation of hypnotics leads to improved health without worsening of sleep.
Chronic long-term use of benzodiazepines is associated with an increased risk of impulsive
, aggressive
, and violent behaviour. A study showed that 53% of long-term benzodiazepine users showed violent characteristics, whereas only 5.3% of patients receiving psychotherapy developed violent or aggressive behavioural patterns, though controlled studies are needed to confirm this data. Daily users of benzodiazepines are also at a higher risk of experiencing psychotic symptomatology such as delusions and hallucinations. A medical paper published findings that of 42 patients treated with alprazolam, up to a third of long-term users of the benzodiazepine drug alprazolam (Xanax) develop depression
. Studies have shown that long-term use of benzodiazepines and the benzodiazepine receptor agonist nonbenzodiazepine
Z drugs are associated with causing depression as well as a markedly raised suicide risk and an overall increased mortality
risk.
A study of 50 patients who attended a benzodiazepine withdrawal clinic found that long-term use of benzodiazepines causes a wide range of psychological and physiological disorders. It was found that, after several years of chronic benzodiazepine use, a large portion of patients developed various mental and physical health problems including agoraphobia
, irritable bowel syndrome
, paraesthesiae, increasing anxiety, and panic attacks, which were not preexisting. The mental health and physical health symptoms induced by long-term benzodiazepine use gradually improved significantly over a period of a year following completion of a slow withdrawal. Three of the 50 patients had wrongly been given a preliminary diagnosis of multiple sclerosis
when the symptoms were actually due to chronic benzodiazepine use. Ten of the patients had taken drug overdoses whilst on benzodiazepines, despite the fact that only two of the patients had any prior history of depressive symptomatology. After withdrawal, no patients took any further overdoses after 1 year post-withdrawal. The cause of the deteriorating mental and physical health in a significant proportion of patients was hypothesised to be caused by increasing tolerance where withdrawal type symptoms emerged, despite the administration of stable prescribed doses. Another theory is that chronic benzodiazepine use causes subtle increasing toxicity, which in turn leads to increasing psychopathology in long-term users of benzodiazepines.
Long-term use of benzodiazepines can induce perceptual disturbances and depersonalisation in some people, even in those taking a stable daily dosage, and it can also become a protracted withdrawal feature of the benzodiazepine withdrawal syndrome
.
In addition, chronic use of benzodiazepines is a risk factor for blepharospasm
. Drug-induced symptoms that resemble withdrawal-like effects can occur on a set dosage as a result of prolonged use, also documented with barbiturate
-like substances, as well as alcohol and benzodiazepines. This demonstrates that the effects from chronic use of benzodiazepine drugs is not unique but occurs with other GABAergic sedative hypnotic drugs, i.e., alcohol and barbiturates.
. Care should be taken when prescribing especially to at risk patients. Depressed adolescents who were taking benzodiazepines were found to have a greatly increased risk of self harm or suicide
, although the sample size was small. The effects of benzodiazepines in individuals under the age of 18 requires further research. Additional caution is required in using benzodiazepines in depressed adolescents. Benzodiazepine dependence
often results in an increasingly deteriorating clinical picture, which includes social deterioration leading to comorbid alcoholism
and drug abuse
. Suicide is a common outcome of chronic benzodiazepine dependence. Benzodiazepine misuse or misuse of other CNS depressants increases the risk of suicide in drug misusers. 11% of males and 23% of females with a sedative
hypnotic
misuse habit commit suicide.
conducted a survey of over 1.1 million participants. A marked increased risk of cancer was found in the users of sleeping pills, mainly benzodiazepines. There have been 15 epidemiologic studies that have suggested that benzodiazepine
or nonbenzodiazepine
hypnotic
drug use is associated with increased mortality
, mainly due to increased cancer
deaths in humans. The cancers included cancer of the brain
, lung
, bowel, breast
, and bladder
, and other neoplasms. It has been hypothesised that either depressed immune function or the viral infections themselves were the cause of the increased rates of cancer. While initially U.S. Food and Drug Administration reviewers expressed concerns about approving the nonbenzodiazepine
Z drugs due to concerns of cancer, ultimately they changed their minds and approved the drugs. A recent case-control study, however, found no link between use of benzodiazepines and cancers of the breast, lung, large bowel, lung, uterine lining, ovaries, testes, thyroid, liver, or Hodgkin's Disease, melanoma, or non-Hodgkin's lymphoma. More specific case-control studies since 2000 have shown no link between benzodiazepine use and breast cancer
. One study found an association between self-reported benzodiazepine use and development of ovarian cancer
, whereas another study found no relationship.
In a study in 1980 in a group of 55 consecutively admitted patients having abused exclusively sedatives or hypnotics, neuropsychological performance was significantly lower and signs of intellectual impairment significantly more often diagnosed than in a matched control group taken from the general population. These results suggested a relationship between abuse of sedatives or hypnotics and cerebral disorder.
A publication has asked in 1981 if lorazepam
is more toxic than diazepam
.
In a study in 1984, 20 patients having taken long-term benzodiazepines were submitted to brain CT scan examinations. Some scans appeared abnormal. The mean ventricular/brain area measured by planimetry was increased over mean values in an age- and sex-matched group of control subjects but was less than that in a group of alcoholics. There was no significant relationship between CT scan appearances and the duration of benzodiazepine therapy. The clinical significance of the findings was unclear.
In 1986, it was presumed that permanent brain damage may result from chronic use of benzodiazepines similar to alcohol related brain damage.
In 1987, 17 high-dose inpatient abusers of benzodiazepines have anecdotally shown enlarged cerebrospinal fluid
spaces with associated brain shrinkage.
Brain shrinkage reportedly appeared to be dose dependent with low-dose users having less brain shrinkage than higher-dose users.
However, a CT study in 1987 found no evidence of brain shrinkage in prescribed benzodiazepine users.
In 1989, in a 4- to 6-year follow-up study of 30 inpatient benzodiazepine abusers, Neuropsychological function was found to be permanently affected in some chronic high-dose abusers of benzodiazepines . Brain damage
similar to alcoholic brain damage was observed. The CT scan abnormalities showed dilatation of the ventricular system. However, unlike alcoholics, sedative hypnotic abusers showed no evidence of widened cortical sulci
. The study concluded that, when cerebral disorder is diagnosed in sedative hypnotic benzodiazepine abusers, it is often permanent.
A CT study in 1993 investigated brain damage in benzodiazepine users and found no overall differences to a healthy control group.
A study in 2000 found that long-term benzodiazepine therapy does not result in brain abnormalities.
Withdrawal from high-dose abuse of nitrazepam
anecdotally was alleged in 2001 to have caused severe hypoperfusion of the whole brain with diffuse slow activity on EEG
in one patient after 25 years of abuse. After withdrawal, abnormalities in hypofrontal brain wave patterns persisted beyond the withdrawal syndrome, which suggested to the authors that organic brain damage occurred from chronic high-dose abuse of nitrazepam.
Professor Ashton, a leading expert on benzodiazepines from Newcastle University Institute of Neuroscience, has been cautious in jumping to any firm conclusions and was an advocate for further research into long-lasting or possibly permanent symptoms of long-term use of benzodiazepines as of 1996. She has stated that she believes that the most likely explanation for lasting symptoms is persisting but slowly resolving functional changes at the GABAA benzodiazepine receptor level. Newer and more detailed brain scanning technologies such as PET scans and MRI scans had as of 2002 to her knowledge never been used to investigate the question of whether benzodiazepines cause functional or structural brain damage. As of 2002, the question of whether benzodiazepines cause structural or functional brain damage remained unanswered to her knowledge.
was seen. An increase in orofacial clefts was not demonstrated however and it was concluded that benzodiazepines are not major teratogens.
Neurodevelopmental disorders
and clinical symptoms are commonly found in babies exposed to benzodiazepines in utero
. Benzodiazepine-exposed babies have a low birth weight
but catch up to normal babies at an early age, but smaller head circumferences found in benzo babies persists. Other adverse effects of benzodiazepines taken during pregnancy are deviating neurodevelopmental and clinical symptoms including craniofacial
anomalies, delayed development of pincer grasp, deviations in muscle tone
and pattern of movements. Motor impairments in the babies are impeded for up to 1 year after birth. Gross motor development impairments take 18 months to return to normal but fine motor function impairments persist. In addition to the smaller head circumference found in benzodiazepine-exposed babies mental retardation
, functional deficits, long-lasting behavioural anomalies, and lower intelligence occurs.
Benzodiazepines, like many other sedative hypnotic drugs causes apoptotic neuronal cell death. However, benzodiazepines do not cause as severe apoptosis
to the developing brain as alcohol does. The prenatal toxicity of benzodiazepines is most likely due to their effects on neurotransmitter systems, cell membranes and protein synthesis. This however, is complicated in that neuropsychological or neuropsychiatric effects of benzodiazepines, if they occur, may not become apparent until later childhood
or even adolescence
. A review of the literature found data on long-term follow-up regarding neurobehavioural outcomes is very limited. However, a study was conducted that followed up 550 benzodiazepine-exposed children, which found that, overall, most children developed normally. There was a smaller subset of benzodiazepine-exposed children who were slower to develop, but by four years of age most of this subgroup of children had normalised. There were a small number benzodiazepine-exposed children who had continuing developmental abnormalities at 4-year follow-up, but it was not possible to conclude whether these deficits were the result of benzodiazepines or whether social and environmental factors explained the continuing deficits.
Concerns regarding whether benzodiazepines during pregnancy cause major malformations, in particular cleft palet have been hotly debated in the literature. A meta analysis of the data from cohort studies found no link but meta analysis of case control studies did find a significant increase in major malformations (however, the cohort studies were homogenous and the case control studies were heterogeneous, thus reducing the strength of the case control results). There have also been several reports that suggest that benzodiazepines have the potential to cause a syndrome similar to fetal alcohol syndrome
, but this has been disputed by a number of studies. As a result of conflicting findings use of benzodiazepines during pregnancy is controversial. The best available evidence suggests that benzodiazepines are not a major cause of birth defects, i.e. major malformations or cleft lip or cleft palet.
recommended that research into the long-term effects of benzodiazepines must be carried out. The view of the Department of Health is that they have made every effort to make doctors aware of the problems associated with the long-term use of benzodiazepines, as well as the dangers of benzodiazepine drug addiction.
In 1980, the Medicines and Healthcare products Regulatory Agency
's Committee on the Safety of Medicines
issued guidance restricting the use of benzodiazepines to short-term use and updated and strengthened these warnings in 1988. When asked by Phil Woolas
in 1999 whether the Department of Health had any plans to conduct research into the long-term effects of benzodiazepines, the Department replied, saying they have no plans to do so, as benzodiazepines are already restricted to short-term use and monitored by regulatory bodies. In a House of Commons debate, Phil Woolas has claimed that there has been a cover-up with regard to the problems associated with benzodiazepines because they are of too large of a scale for governments, regulatory bodies, and the pharmaceutical industry to deal with. John Hutton
stated in response that the Department of Health take the problems of benzodiazepines extremely seriously and are not sweeping the issue under the carpet. In 2010, the All-Party Parliamentary Group on Involuntary Tranquilliser Addiction filed a complaint with the Equality and Human Rights Commission under the Disability Discrimination Act 1995
against the Department of Health and the Department for Work and Pensions
alleging discrimation against people with a benzodiazepine prescription drug dependence as a result of denial of specialised treatment services, exclusion from medical treatment, non-recognition of the protracted benzodiazepine withdrawal syndrome
, as well as denial of rehabilitation and back to work schemes. Additionally the APPGITA complaint alleged that there is a "virtual prohibition" on the collection of statistical information on benzodiazepines across government departments, whereas with other controlled drugs there are enormous volumes of statistical data. The complaint alleged that the discrimination is deliberate, large scale and that government departments are aware of what they are doing.
held a closed meeting among top UK medical doctors and representatives from the pharmaceutical industry between the dates of 30 October 1980 and 3 April 1981. The meeting was classified under the Public Records Act 1958
until 2014 but became available in 2005 as a result of the Freedom of Information Act. The meeting was called due to concerns that 10–100,000 people could be dependent; this estimate was later revised by the Chairman Professor Malcolm Lader, of the meeting to approximately half a million members of the British public were suspected of being dependent on therapeutic dose levels of benzodiazepines, about half of those on long-term benzodiazepines. It was reported that benzodiazepines may be the third- or fourth-largest drug problem in the UK (the largest being alcohol and tobacco). The Chairman of the meeting followed up after the meeting with additional information, which was forwarded to the Medical Research Council neuroscience board, raising concerns regarding tests that showed definite cortical atrophy in 2 of 14 individuals tested and borderline abnormality in five others. He felt that, due to the methodology used in assessing the scans, the abnormalities were likely an underestimate, and more refined techniques would be more accurate. Also discussed were findings that tolerance to benzodiazepines can be demonstrated by injecting diazepam into long-term users; in normal subjects, increases in growth hormone
occurs, whereas in benzodiazepine-tolerant individuals this effect is blunted. Also raised were findings in animal studies that showed the development of tolerance in the form of a 15 percent reduction in binding capacity of benzodiazepines after seven days administration of high doses of the partial agonist benzodiazepine drug flurazepam
and a 50 percent reduction in binding capacity after 30 days of a low dose of diazepam. The Chairman was concerned that papers soon to be published would "stir the whole matter up" and wanted to be able to say that the Medical Research Council "had matters under consideration if questions were asked in parliament". The Chairman felt that it "was very important, politically that the MRC should be 'one step ahead" and recommended epidemiological studies be funded and carried out by Roche Pharmaceuticals and MRC sponsored research conducted into the biochemical effects of long-term use of benzodiazepines. The meeting aimed to identify issues that were likely to arise, alert the Department of Health to the scale of the problem and identify the pharmacology and nature of benzodiazepine dependence and the volume of benzodiazepines being prescribed. The World Health Organisation was also interested in the problem and it was felt the meeting would demonstrate to the WHO that the MRC was taking the issue seriously. Among the psychological effects of long-term use of benzodiazepines discussed was a reduced ability to cope with stress. The Chairman stated that the "withdrawal symptoms from valium were much worse than many other drugs including, e.g., heroin". It was stated that the likelihood of withdrawing from benzodiazepines was "reduced enormously" if benzodiazepines were prescribed for longer than four months. It was concluded that benzodiazepines are often prescribed inappropriately, for a wide range of conditions and situations. Dr Mason (DHSS) and Dr Moir (SHHD), felt it important to determine the effectiveness and toxicity of benzodiazepines due to the large numbers of people using benzodiazepines for long periods of time before deciding what regulatory action to take.
Controversy resulted in 2010 when the previously secret files came to light over the fact that the Medical Research Council was warned that benzodiazepines prescribed to millions of patients appeared to cause brain shrinkage similar to alcohol abuse in some patients and failed to carry out larger and more rigorous studies. The Independent on Sunday reported allegations that "scores" of the 1.5 million the UK public who use benzodiazepines long-term have symptoms that are consistent with brain damage. It has been described as a 'huge scandal' by Jim Dobbin, and legal experts and MPs have predicted a class action lawsuit. A solicitor said she was aware of the past failed litigation against the drug companies and the relevance the documents had to that court case and said it was strange that the documents were kept 'hidden' by the MRC.
Professor Lader, who chaired the MRC meeting, declined to speculate as to why the MRC declined to support his request to set up a unit to further research benzodiazepines and why they did not set up a special safety committee to look into these concerns. Professor Lader stated that he regrets not being more proactive on pursuing the issue, stating that he did not want to be labeled as the guy who pushed only issues with benzos. Professor Ashton also submitted proposals for grant-funded research using MRI, EEG, and cognitive testing in a ramdomised controlled trial to assess whether benzodiazepines have permanent damage to the brain, but similar to Professor Lader got turned down by the MRC.
The MRC spokesperson said they accept the conclusions of Professor Lader's research and said that they fund only research that meets required quality standards of scientific research, and stated that they were and continue to remain receptive to applications for research in this area. No explanation was reported for why the documents were sealed by the Public Records Act.
Jim Dobbin, who chairs the All-Party Parliamentary Group for Involuntary Tranquilliser Addiction, stated that:
The legal director of Action Against Medical Accidents said urgent research must be carried out and said that, if the results of larger studies confirm professor Lader's research, the government and MRC could be faced with one of the biggest group actions for damages the courts have ever seen given the large number of people potentially affected. People who report enduring symptoms post-withdrawal such as neurological pain, headaches, cognitive impairment, and memory loss have been left in the dark as to whether these symptoms are drug-induced damage or not due to the MRC's inaction, it was reported. Professor Lader reported that the results of his research did not surprise his research group given that it was already known that alcohol could cause permanent brain changes.
and withdrawal
. This led some doctors to require a signed consent form from their patients and to recommend that all patients be adequately warned of the risks of dependence and withdrawal before starting treatment with benzodiazepines. The court case against the drug manufacturers never reached a verdict; legal aid
had been withdrawn, leading to the collapse of the trial, and there were allegations that the consultant psychiatrists, the expert witnesses, had a conflict of interest. This litigation led to changes in the British law, making class action law suits more difficult.
Benzodiazepine dependence
Benzodiazepine dependence or benzodiazepine addiction is a condition during which a person is dependent on benzodiazepine drugs. Dependence can be either a psychological dependence, physical dependence, or a combination of the two...
as well as the possibility of adverse effects on cognitive function, physical health, and mental health. There are significant risks associated with the long-term use of benzodiazepines. However, not all people experience problems associated with the long-term use of benzodiazepines. There is evidence that reduction or withdrawal from benzodiazepines can lead to a reduction in anxiety symptoms. There are a number of side-effects associated with addiction to benzodiazepines such as depression and flu-like symptoms. Due to these increasing physical and mental symptoms from long-term use of benzodiazepines, slowly withdrawing from benzodiazepines is recommended for many long-term users.
Some of the symptoms that may occur as a result of long-term use of benzodiazepines include emotional clouding, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, headaches, dizziness
Dizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
, irritability
Irritability
Irritability is an excessive response to stimuli. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimuli; It is usually used to refer to anger or frustration....
, lethargy, sleep problems, memory impairment, personality changes, aggression
Aggression
In psychology, as well as other social and behavioral sciences, aggression refers to behavior between members of the same species that is intended to cause humiliation, pain, or harm. Ferguson and Beaver defined aggressive behavior as "Behavior which is intended to increase the social dominance of...
, depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, agoraphobia
Agoraphobia
Agoraphobia is an anxiety disorder defined as a morbid fear of having a panic attack or panic-like symptoms in a situation from which it is perceived to be difficult to escape. These situations can include, but are not limited to, wide-open spaces, crowds, or uncontrolled social conditions...
, anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
, and panic attacks, social deterioration as well as employment difficulties. While benzodiazepines are highly effective in the short term, adverse effects associated with long-term use including impaired cognitive abilities, memory problems, mood swings, overdoses when combined with other drugs may make the risk-benefit ratio unfavourable. In addition, benzodiazepines have reinforcing properties in some individuals and thus are considered to be addictive drugs; in addition, a physical dependence can develop after a few weeks or months of use. Many of these adverse effects of long-term use of benzodiazepines begin to show improvements three to six months after withdrawal.
Other concerns about the long-term effects of benzodiazepines include dose escalation, benzodiazepine abuse, tolerance and benzodiazepine dependence
Benzodiazepine dependence
Benzodiazepine dependence or benzodiazepine addiction is a condition during which a person is dependent on benzodiazepine drugs. Dependence can be either a psychological dependence, physical dependence, or a combination of the two...
and benzodiazepine withdrawal problems. Both physiological tolerance and dependence can lead to a worsening of the adverse effects of benzodiazepines. Increased risk of death has been associated with long-term use of benzodiazepines in several studies, however, other studies have not found increased mortality. Due to conflicting findings in studies regarding benzodiazepines and increased risks of death including from cancer, further research in long-term use of benzodiazepines and mortality risk has been recommended. Most of the research has been conducted in prescribed users of benzodiazepines; even less is known about the mortality risk of illicit benzodiazepine users. The long-term use of benzodiazepines is controversial and has generated significant controversy within the medical profession. Views on the nature and severity of problems with long-term use of benzodiazepines differ from expert to expert and even from country to country; some experts even question whether there is any problem with the long-term use of benzodiazepines. Political controversy, in particular in the UK, also surrounds the long-term use of benzodiazepines, and was subject to the largest class-action lawsuit in the 1980s and 1990s. There have also been allegations of a cover-up by medical bureaucracies and the government.
Background
Benzodiazepines when introduced in 1961 were widely believed to be safe drugs but as the decades went by increased awareness of adverse effects connected to their long-term use became known. There was initially widespread public approval but this was followed by widespread public disapproval and recommendations for more restrictive medical guidelines followed. The majority of the problems of benzodiazepines are related to their long-term use rather than their short-term use. There is growing evidence of the harm of long-term use of benzodiazepines, especially at higher doses. The Department of HealthDepartment of Health (United Kingdom)
The Department of Health is a department of the United Kingdom government with responsibility for government policy for health and social care matters and for the National Health Service in England along with a few elements of the same matters which are not otherwise devolved to the Scottish,...
recommends that individuals on long-term benzodiazepines are monitored at least every 3 months and also recommends against long-term substitution therapy in benzodiazepine drug misusers due to a lack of evidence base for effectiveness and due to the risks of long-term use. The long-term effects of benzodiazepines are very similar to the long-term effects of alcohol
Long-term effects of alcohol
The long term effects of alcohol range from possible health benefits for low levels of alcohol consumption to severe detrimental effects in cases of chronic alcohol abuse...
(apart from organ toxicity) and other sedative-hypnotics. Withdrawal effects and dependence are almost identical. A report in 1987 by the Royal College of Psychiatrists in Great Britain reported that any benefits of long-term use of benzodiazepines are likely to be far outweighed by the risks of long-term use. Despite this benzodiazepines are still widely prescribed. The socioeconomic costs of the continued widespread prescribing of benzodiazepines is high.
Long-term effects of benzodiazepines may include disinhibition
Disinhibition
Disinhibition is a term in psychology used to describe a lack of restraint manifested in several ways, including disregard for social conventions, impulsivity, and poor risk assessment. Disinhibition affects motor, instinctual, emotional, cognitive and perceptual aspects with signs and symptoms...
, impaired concentration and memory, depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, as well as sexual dysfunction
Sexual dysfunction
Sexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm....
. The long-term effects of benzodiazepines may differ from the adverse effects seen after acute administration of benzodiazepines. Concerns regarding the long-term effects of benzodiazepines have been raised since 1980. These concerns are still not fully answered. A review of the literature on use of benzodiazepine and nonbenzodiazepine hypnotics concluded that more research is needed to evaluate the long-term effects of hypnotic drugs. An analysis of cancer patients found that those who took tranquillisers or sleeping tablets had a substantially poorer quality of life on all measurements conducted, as well as a worse clinical picture of symptomatology. Worsening of symptoms such as fatigue, insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
, pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
, dyspnea
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
and constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
was found when compared against those who did not take tranquillisers or sleeping tablets. Most individuals who successfully discontinue hypnotic
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
therapy after a gradual taper and do not take benzodiazepines for 6 months have less severe sleep and anxiety problems, are less distressed and have a general feeling of improved health at 6 month follow up.
Cognitive status
Long-term benzodiazepine use can lead to a generalised impairment of cognitionCognition
In science, cognition refers to mental processes. These processes include attention, remembering, producing and understanding language, solving problems, and making decisions. Cognition is studied in various disciplines such as psychology, philosophy, linguistics, and computer science...
, including sustained attention, verbal learning and memory
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
and psychomotor
Psychomotor
Psychomotor can refer to:* Psychomotor learning* Psychomotor retardation* Psychomotor agitation...
, visuo-motor and visuo-conceptual abilities. These effects on cognition exist, although their impact on patient's daily functioning is in most but not all cases insignificant. Transient changes in the brain have been found using neuroimaging
Neuroimaging
Neuroimaging includes the use of various techniques to either directly or indirectly image the structure, function/pharmacology of the brain...
studies, but no brain abnormalities have been found in patients treated long term with benzodiazepines. When benzodiazepine users cease long-term benzodiazepine therapy, their cognitive function improves in the first six months, although deficits may be permanent or take longer than six months to return to baseline. In the elderly, long-term benzodiazepine therapy is a risk factor for amplifying cognitive decline, although gradual withdrawal
Withdrawal
Withdrawal can refer to any sort of separation, but is most commonly used to describe the group of symptoms that occurs upon the abrupt discontinuation/separation or a decrease in dosage of the intake of medications, recreational drugs, and alcohol...
is associated with improved cognitive status. A study of alprazolam
Alprazolam
Alprazolam is a short-acting anxiolytic of the benzodiazepine class of psychoactive drugs. Alprazolam, like other benzodiazepines, binds to specific sites on the GABAA gamma-amino-butyric acid receptor...
found that 8 weeks administration of alprazolam resulted in persisting deficits still detectable several weeks later.
Effect on sleep
Sleep architectureSleep architecture
Sleep architecture describes the structure and pattern of sleep and encompasses several variables. Sleep quotas refer to the amount of time spent in REM and NREM sleep. Sleep duration is the total time spent asleep in a 24 hour period. The duration of a NREM-REM cycle is also an important aspect...
can be adversely affected by benzodiazepine dependence. Possible adverse effects on sleep include induction or worsening of sleep disordered breathing. Long-term use is associated with increased alpha and beta activity, a decrease in K complexes and delta activity. There is also a decrease in stage 1 NREM, NREM stage 3 and 4 sleep and REM sleep as well as a decrease in REM sleep eye movements.
Elderly
Significant toxicity from benzodiazepines can occur in the elderly as a result of long-term use. Benzodiazepines, along with antihypertensives and drugs affecting the cholinergic system are the most common cause of drug-induced dementiaDementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
affecting over 10 percent of patients attending memory clinics. Long-term use of benzodiazepines in the elderly can lead to a pharmacological syndrome with symptoms including drowsiness, ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
, fatigue, confusion
ConFusion
ConFusion is an annual science fiction convention organized by the Stilyagi Air Corps and its parent organization, the Ann Arbor Science Fiction Association. Commonly, it is held the third weekend of January. It is the oldest science fiction convention in Michigan, a regional, general SF con...
, weakness
Weakness
Weakness is a symptom represented, medically, by a number of different conditions, including: lack of muscle strength, malaise, dizziness, or fatigue. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a...
, dizziness
Dizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
, vertigo
Vertigo (medical)
Vertigo is a type of dizziness, where there is a feeling of motion when one is stationary. The symptoms are due to a dysfunction of the vestibular system in the inner ear...
, syncope
Syncope (medicine)
Syncope , the medical term for fainting, is precisely defined as a transient loss of consciousness and postural tone characterized by rapid onset, short duration, and spontaneous recovery due to global cerebral hypoperfusion that most often results from hypotension.Many forms of syncope are...
, reversible dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
, depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, impairment of intellect, psychomotor
Psychomotor
Psychomotor can refer to:* Psychomotor learning* Psychomotor retardation* Psychomotor agitation...
and sexual dysfunction
Sexual dysfunction
Sexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm....
, agitation
Psychomotor agitation
Psychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...
, auditory
Auditory hallucination
An auditory hallucination, or paracusia, is a form of hallucination that involves perceiving sounds without auditory stimulus. A common form involves hearing one or more talking voices...
and visual hallucinations, paranoid ideation, panic
Panic
Panic is a sudden sensation of fear which is so strong as to dominate or prevent reason and logical thinking, replacing it with overwhelming feelings of anxiety and frantic agitation consistent with an animalistic fight-or-flight reaction...
, delirium
Delirium
Delirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...
, depersonalisation, sleepwalking
Sleepwalking
Sleepwalking, also known as somnambulism, is a sleep disorder belonging to the parasomnia family. Sleepwalkers arise from the slow wave sleep stage in a state of low consciousness and perform activities that are usually performed during a state of full consciousness...
, aggressivity, orthostatic hypotension
Orthostatic hypotension
Orthostatic hypotension, also known as postural hypotension, orthostasis, and colloquially as head rush or dizzy spell, is a form of hypotension in which a person's blood pressure suddenly falls when the person stands up or stretches. The decrease is typically greater than 20/10 mm Hg, and may be...
and insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
. Depletion of certain neurotransmitters and cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
levels and alterations in immune function and biological markers can also occur. Elderly individuals who have been long-term users of benzodiazepines have been found to have a higher incidence of post-operative confusion. Benzodiazepines have been associated with increased body sway in the elderly, which can potentially lead to fatal accidents including falls. Discontinuation of benzodiazepines leads to improvement in the balance of the body and also leads to improvements in cognitive functions in the elderly benzodiazepine hypnotic
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
users without worsening of insomnia.
A review of the evidence has found that whilst long-term use of benzodiazepines impairs memory, its association with causing dementia is not clear and requires further research. A more recent study found that benzodiazepines are associated with an increased risk of dementia and it is recommended that benzodiazepines are avoided in the elderly.
Mental and physical health
Long-term benzodiazepine use may lead to the creation or exacerbation of physical and mental health conditions, which improve after 6 or more months of abstinence. After a period of about 3 to 6 months of abstinence after completion of a gradual-reduction regime, marked improvements in mental and physical wellbeing become apparent. For example, one study of hypnotic users gradually withdrawn from their hypnotic medication reported after 6 months of abstinence that they had less severe sleep and anxiety problems, were less distressed, and had a general feeling of improved health. Those having remained on hypnoticHypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
medication had no improvements in their insomnia, anxiety, or general health ratings. A study found that individuals having withdrawn from benzodiazepines showed a marked reduction in use of medical and mental health services.
Approximately half of patients attending mental health services for conditions including anxiety disorders such as panic disorder
Panic disorder
Panic disorder is an anxiety disorder characterized by recurring severe panic attacks. It may also include significant behavioral change lasting at least a month and of ongoing worry about the implications or concern about having other attacks. The latter are called anticipatory attacks...
or social phobia
Social anxiety disorder
Social anxiety disorder , also known as social phobia, is an anxiety disorder characterized by intense fear in social situations causing considerable distress and impaired ability to function in at least some parts of daily life...
may be the result of alcohol or benzodiazepine dependence. Sometimes anxiety disorders pre-existed alcohol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
or benzodiazepine dependence but the alcohol or benzodiazepine dependence
Benzodiazepine dependence
Benzodiazepine dependence or benzodiazepine addiction is a condition during which a person is dependent on benzodiazepine drugs. Dependence can be either a psychological dependence, physical dependence, or a combination of the two...
often act to keep the anxiety disorders going and often progressively making them worse. Many people who are addicted to alcohol or prescribed benzodiazepines when it is explained to them they have a choice between ongoing ill mental health or quitting and recovering from their symptoms decide on quitting alcohol and or their benzodiazepines. It was noted that every individual has an individual sensitivity level to alcohol or sedative hypnotic drugs and what one person can tolerate without ill health another will suffer very ill health and that even moderate drinking can cause rebound anxiety syndromes and sleep disorders. A person who is suffering the toxic effects of alcohol or benzodiazepines will not benefit from other therapies or medications as they do not address the root cause of the symptoms. Recovery from benzodiazepine dependence tends to take a lot longer than recovery from alcohol but people can regain their previous good health. A review of the literature regarding benzodiazepine hypnotic
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
drugs concluded that these drugs cause an unjustifiable risk to the individual and to public health. The risks include dependence
Substance dependence
The section about substance dependence in the Diagnostic and Statistical Manual of Mental Disorders does not use the word addiction at all. It explains:...
, accidents and other adverse effects. Gradual discontinuation of hypnotics leads to improved health without worsening of sleep.
Chronic long-term use of benzodiazepines is associated with an increased risk of impulsive
Impulsive
Impulsive may refer to:*Impulsive *Impulsivity*Impulsion*Impulse function...
, aggressive
Aggressive
“Aggressive” is a New York-based Grammy award-winning music video and commercial directing team of Alex Topaller and Daniel Shapiro.Aggressive has been described by Movie Creation Mag as “having a fascination with the wonderful, in the likes of the surrealist Rafal Olbinski” and “tenacious about...
, and violent behaviour. A study showed that 53% of long-term benzodiazepine users showed violent characteristics, whereas only 5.3% of patients receiving psychotherapy developed violent or aggressive behavioural patterns, though controlled studies are needed to confirm this data. Daily users of benzodiazepines are also at a higher risk of experiencing psychotic symptomatology such as delusions and hallucinations. A medical paper published findings that of 42 patients treated with alprazolam, up to a third of long-term users of the benzodiazepine drug alprazolam (Xanax) develop depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
. Studies have shown that long-term use of benzodiazepines and the benzodiazepine receptor agonist nonbenzodiazepine
Nonbenzodiazepine
The nonbenzodiazepines, also called benzodiazepine-like drugs, are a class of psychoactive drugs pharmacologically resembling the benzodiazepines, with similar benefits, side effects and risks, despite having dissimilar or entirely different chemical structures.-Classes:There are currently three...
Z drugs are associated with causing depression as well as a markedly raised suicide risk and an overall increased mortality
Mortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
risk.
A study of 50 patients who attended a benzodiazepine withdrawal clinic found that long-term use of benzodiazepines causes a wide range of psychological and physiological disorders. It was found that, after several years of chronic benzodiazepine use, a large portion of patients developed various mental and physical health problems including agoraphobia
Agoraphobia
Agoraphobia is an anxiety disorder defined as a morbid fear of having a panic attack or panic-like symptoms in a situation from which it is perceived to be difficult to escape. These situations can include, but are not limited to, wide-open spaces, crowds, or uncontrolled social conditions...
, irritable bowel syndrome
Irritable bowel syndrome
Irritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...
, paraesthesiae, increasing anxiety, and panic attacks, which were not preexisting. The mental health and physical health symptoms induced by long-term benzodiazepine use gradually improved significantly over a period of a year following completion of a slow withdrawal. Three of the 50 patients had wrongly been given a preliminary diagnosis of multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
when the symptoms were actually due to chronic benzodiazepine use. Ten of the patients had taken drug overdoses whilst on benzodiazepines, despite the fact that only two of the patients had any prior history of depressive symptomatology. After withdrawal, no patients took any further overdoses after 1 year post-withdrawal. The cause of the deteriorating mental and physical health in a significant proportion of patients was hypothesised to be caused by increasing tolerance where withdrawal type symptoms emerged, despite the administration of stable prescribed doses. Another theory is that chronic benzodiazepine use causes subtle increasing toxicity, which in turn leads to increasing psychopathology in long-term users of benzodiazepines.
Long-term use of benzodiazepines can induce perceptual disturbances and depersonalisation in some people, even in those taking a stable daily dosage, and it can also become a protracted withdrawal feature of the benzodiazepine withdrawal syndrome
Benzodiazepine withdrawal syndrome
Benzodiazepine withdrawal syndrome—often abbreviated to benzo withdrawal—is the cluster of symptoms which appear when a person who has taken benzodiazepines long term and has developed benzodiazepine dependence stops taking benzodiazepine drug or during dosage reductions...
.
In addition, chronic use of benzodiazepines is a risk factor for blepharospasm
Blepharospasm
A blepharospasm , is any abnormal contraction or twitch of the eyelid....
. Drug-induced symptoms that resemble withdrawal-like effects can occur on a set dosage as a result of prolonged use, also documented with barbiturate
Barbiturate
Barbiturates are drugs that act as central nervous system depressants, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, as hypnotics, and as anticonvulsants...
-like substances, as well as alcohol and benzodiazepines. This demonstrates that the effects from chronic use of benzodiazepine drugs is not unique but occurs with other GABAergic sedative hypnotic drugs, i.e., alcohol and barbiturates.
Immune system
Chronic use of benzodiazepines seemed to cause significant immunological disorders in a study of selected outpatients attending a psychopharmacology department. Diazepam and clonazepam have been found to have long-lasting, but not permanent, immunotoxic effects in the fetus of pregnant rats. However, single very high doses of diazepam have been found to cause life-long immunosuppression in neonatal rats. No studies have been done to assess the immunotoxic effects of diazepam in humans; however, high prescribed doses of diazepam, in humans, has been found to be a major risk of pneumonia, based on a study of people with tetanus. It has been proposed that diazepam may cause long-lasting changes to the GABAA receptors with resultant long-lasting disturbances to behaviour, endocrine function and immune functionSuicide and self-harm
Benzodiazepine use is highly associated with suicideSuicide
Suicide is the act of intentionally causing one's own death. Suicide is often committed out of despair or attributed to some underlying mental disorder, such as depression, bipolar disorder, schizophrenia, alcoholism, or drug abuse...
. Care should be taken when prescribing especially to at risk patients. Depressed adolescents who were taking benzodiazepines were found to have a greatly increased risk of self harm or suicide
Suicide
Suicide is the act of intentionally causing one's own death. Suicide is often committed out of despair or attributed to some underlying mental disorder, such as depression, bipolar disorder, schizophrenia, alcoholism, or drug abuse...
, although the sample size was small. The effects of benzodiazepines in individuals under the age of 18 requires further research. Additional caution is required in using benzodiazepines in depressed adolescents. Benzodiazepine dependence
Benzodiazepine dependence
Benzodiazepine dependence or benzodiazepine addiction is a condition during which a person is dependent on benzodiazepine drugs. Dependence can be either a psychological dependence, physical dependence, or a combination of the two...
often results in an increasingly deteriorating clinical picture, which includes social deterioration leading to comorbid alcoholism
Alcoholism
Alcoholism is a broad term for problems with alcohol, and is generally used to mean compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinker's health, personal relationships, and social standing...
and drug abuse
Drug abuse
Substance abuse, also known as drug abuse, refers to a maladaptive pattern of use of a substance that is not considered dependent. The term "drug abuse" does not exclude dependency, but is otherwise used in a similar manner in nonmedical contexts...
. Suicide is a common outcome of chronic benzodiazepine dependence. Benzodiazepine misuse or misuse of other CNS depressants increases the risk of suicide in drug misusers. 11% of males and 23% of females with a sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
hypnotic
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
misuse habit commit suicide.
Carcinogenicity
There has been some controversy around the possible link between benzodiazepine use and development of cancer; early cohort studies in the 1980s suggested a possible link, but follow-up case-control studies have found no link between benzodiazepines and cancer. In the second U.S. national cancer study in 1982, the American Cancer SocietyAmerican Cancer Society
The American Cancer Society is the "nationwide community-based voluntary health organization" dedicated, in their own words, "to eliminating cancer as a major health problem by preventing cancer, saving lives, and diminishing suffering from cancer, through research, education, advocacy, and...
conducted a survey of over 1.1 million participants. A marked increased risk of cancer was found in the users of sleeping pills, mainly benzodiazepines. There have been 15 epidemiologic studies that have suggested that benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
or nonbenzodiazepine
Nonbenzodiazepine
The nonbenzodiazepines, also called benzodiazepine-like drugs, are a class of psychoactive drugs pharmacologically resembling the benzodiazepines, with similar benefits, side effects and risks, despite having dissimilar or entirely different chemical structures.-Classes:There are currently three...
hypnotic
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
drug use is associated with increased mortality
Mortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
, mainly due to increased cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
deaths in humans. The cancers included cancer of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
, bowel, breast
Breast
The breast is the upper ventral region of the torso of a primate, in left and right sides, which in a female contains the mammary gland that secretes milk used to feed infants.Both men and women develop breasts from the same embryological tissues...
, and bladder
Bladder
Bladder usually refers to an anatomical hollow organBladder may also refer to:-Biology:* Urinary bladder in humans** Urinary bladder ** Bladder control; see Urinary incontinence** Artificial urinary bladder, in humans...
, and other neoplasms. It has been hypothesised that either depressed immune function or the viral infections themselves were the cause of the increased rates of cancer. While initially U.S. Food and Drug Administration reviewers expressed concerns about approving the nonbenzodiazepine
Nonbenzodiazepine
The nonbenzodiazepines, also called benzodiazepine-like drugs, are a class of psychoactive drugs pharmacologically resembling the benzodiazepines, with similar benefits, side effects and risks, despite having dissimilar or entirely different chemical structures.-Classes:There are currently three...
Z drugs due to concerns of cancer, ultimately they changed their minds and approved the drugs. A recent case-control study, however, found no link between use of benzodiazepines and cancers of the breast, lung, large bowel, lung, uterine lining, ovaries, testes, thyroid, liver, or Hodgkin's Disease, melanoma, or non-Hodgkin's lymphoma. More specific case-control studies since 2000 have shown no link between benzodiazepine use and breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
. One study found an association between self-reported benzodiazepine use and development of ovarian cancer
Ovarian cancer
Ovarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses....
, whereas another study found no relationship.
Brain damage controversy
Some studies have demonstrated brain damage in therapeutic dose users whereas other studies have refuted that benzodiazepines caused structural brain damage. The evidence seems to suggest some form of brain damage but whether the long-term effects of benzodiazepines are due to structural brain damage or functional brain damage remains to be determined conclusively.In a study in 1980 in a group of 55 consecutively admitted patients having abused exclusively sedatives or hypnotics, neuropsychological performance was significantly lower and signs of intellectual impairment significantly more often diagnosed than in a matched control group taken from the general population. These results suggested a relationship between abuse of sedatives or hypnotics and cerebral disorder.
A publication has asked in 1981 if lorazepam
Lorazepam
Lorazepam is a high-potency short-to-intermediate-acting 3-hydroxy benzodiazepine drug that has all five intrinsic benzodiazepine effects: anxiolytic, amnesic, sedative/hypnotic, anticonvulsant, antiemetic and muscle relaxant...
is more toxic than diazepam
Diazepam
Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
.
In a study in 1984, 20 patients having taken long-term benzodiazepines were submitted to brain CT scan examinations. Some scans appeared abnormal. The mean ventricular/brain area measured by planimetry was increased over mean values in an age- and sex-matched group of control subjects but was less than that in a group of alcoholics. There was no significant relationship between CT scan appearances and the duration of benzodiazepine therapy. The clinical significance of the findings was unclear.
In 1986, it was presumed that permanent brain damage may result from chronic use of benzodiazepines similar to alcohol related brain damage.
In 1987, 17 high-dose inpatient abusers of benzodiazepines have anecdotally shown enlarged cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
spaces with associated brain shrinkage.
Brain shrinkage reportedly appeared to be dose dependent with low-dose users having less brain shrinkage than higher-dose users.
However, a CT study in 1987 found no evidence of brain shrinkage in prescribed benzodiazepine users.
In 1989, in a 4- to 6-year follow-up study of 30 inpatient benzodiazepine abusers, Neuropsychological function was found to be permanently affected in some chronic high-dose abusers of benzodiazepines . Brain damage
Brain damage
"Brain damage" or "brain injury" is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors...
similar to alcoholic brain damage was observed. The CT scan abnormalities showed dilatation of the ventricular system. However, unlike alcoholics, sedative hypnotic abusers showed no evidence of widened cortical sulci
Sulcus (neuroanatomy)
In neuroanatomy, a sulcus is a depression or fissure in the surface of the brain.It surrounds the gyri, creating the characteristic appearance of the brain in humans and other large mammals....
. The study concluded that, when cerebral disorder is diagnosed in sedative hypnotic benzodiazepine abusers, it is often permanent.
A CT study in 1993 investigated brain damage in benzodiazepine users and found no overall differences to a healthy control group.
A study in 2000 found that long-term benzodiazepine therapy does not result in brain abnormalities.
Withdrawal from high-dose abuse of nitrazepam
Nitrazepam
Nitrazepam is a type of benzodiazepine drug and is marketed in English-speaking countries under the following brand names: Alodorm, Arem, Insoma, Mogadon, Nitrados, Nitrazadon, Ormodon, Paxadorm, Remnos, and Somnite...
anecdotally was alleged in 2001 to have caused severe hypoperfusion of the whole brain with diffuse slow activity on EEG
EEG
EEG commonly refers to electroencephalography, a measurement of the electrical activity of the brain.EEG may also refer to:* Emperor Entertainment Group, a Hong Kong-based entertainment company...
in one patient after 25 years of abuse. After withdrawal, abnormalities in hypofrontal brain wave patterns persisted beyond the withdrawal syndrome, which suggested to the authors that organic brain damage occurred from chronic high-dose abuse of nitrazepam.
Professor Ashton, a leading expert on benzodiazepines from Newcastle University Institute of Neuroscience, has been cautious in jumping to any firm conclusions and was an advocate for further research into long-lasting or possibly permanent symptoms of long-term use of benzodiazepines as of 1996. She has stated that she believes that the most likely explanation for lasting symptoms is persisting but slowly resolving functional changes at the GABAA benzodiazepine receptor level. Newer and more detailed brain scanning technologies such as PET scans and MRI scans had as of 2002 to her knowledge never been used to investigate the question of whether benzodiazepines cause functional or structural brain damage. As of 2002, the question of whether benzodiazepines cause structural or functional brain damage remained unanswered to her knowledge.
Neonatal effects
Benzodiazepines have been found to cause teratogenic malformations. The literature concerning the safety of benzodiazepines in pregnancy is unclear and controversial. Initial concerns regarding benzodiazepines in pregnancy began with alarming findings in animals but these do not necessarily cross over to humans. Conflicting findings have been found in babies exposed to benzodiazepines. A recent analysis of the Swedish Medical Birth Register found an association with preterm births, low birth weight and a moderate increased risk for congental malformations. An increase in pylorostenosis or alimentary tract atresiaAtresia
Atresia is a condition in which a body orifice or passage in the body is abnormally closed or absent.Examples of atresia include:* Imperforate anus - malformation of the opening between the rectum and anus....
was seen. An increase in orofacial clefts was not demonstrated however and it was concluded that benzodiazepines are not major teratogens.
Neurodevelopmental disorders
Neurodevelopmental Disorders
A neurodevelopmental disorder, or disorder of neural development, is an impairment of the growth and development of the brain or central nervous system. A narrower use of the term refers to a disorder of brain function that affects emotion, learning ability and memory and that unfolds as the...
and clinical symptoms are commonly found in babies exposed to benzodiazepines in utero
In utero
In utero is a Latin term literally meaning "in the womb". In biology, the phrase describes the state of an embryo or fetus. In legal contexts, the phrase is used to refer to unborn children. Under common law, unborn children are still considered to exist for property transfer purposes.-See also:*...
. Benzodiazepine-exposed babies have a low birth weight
Low birth weight
Low birth weight is defined as a birth weight of a liveborn infant of less than 2,500 g. regardless of gestational age-Causes:LBW is either the result of preterm birth or of the infant being small for gestational age , or a combination of...
but catch up to normal babies at an early age, but smaller head circumferences found in benzo babies persists. Other adverse effects of benzodiazepines taken during pregnancy are deviating neurodevelopmental and clinical symptoms including craniofacial
Craniofacial
Craniofacial may be used to describe certain congenital malformations, injuries, surgeons who subspecialize in this area, multi-disciplinary medical-surgical teams that treat and do research on disorders affecting this region, and organizations with interest in...
anomalies, delayed development of pincer grasp, deviations in muscle tone
Muscle tone
In physiology, medicine, and anatomy, muscle tone is the continuous and passive partial contraction of the muscles, or the muscle’s resistance to passive stretch during resting state. It helps maintain posture, and it declines during REM sleep.-Purpose:Unconscious nerve impulses maintain the...
and pattern of movements. Motor impairments in the babies are impeded for up to 1 year after birth. Gross motor development impairments take 18 months to return to normal but fine motor function impairments persist. In addition to the smaller head circumference found in benzodiazepine-exposed babies mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
, functional deficits, long-lasting behavioural anomalies, and lower intelligence occurs.
Benzodiazepines, like many other sedative hypnotic drugs causes apoptotic neuronal cell death. However, benzodiazepines do not cause as severe apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
to the developing brain as alcohol does. The prenatal toxicity of benzodiazepines is most likely due to their effects on neurotransmitter systems, cell membranes and protein synthesis. This however, is complicated in that neuropsychological or neuropsychiatric effects of benzodiazepines, if they occur, may not become apparent until later childhood
Childhood
Childhood is the age span ranging from birth to adolescence. In developmental psychology, childhood is divided up into the developmental stages of toddlerhood , early childhood , middle childhood , and adolescence .- Age ranges of childhood :The term childhood is non-specific and can imply a...
or even adolescence
Adolescence
Adolescence is a transitional stage of physical and mental human development generally occurring between puberty and legal adulthood , but largely characterized as beginning and ending with the teenage stage...
. A review of the literature found data on long-term follow-up regarding neurobehavioural outcomes is very limited. However, a study was conducted that followed up 550 benzodiazepine-exposed children, which found that, overall, most children developed normally. There was a smaller subset of benzodiazepine-exposed children who were slower to develop, but by four years of age most of this subgroup of children had normalised. There were a small number benzodiazepine-exposed children who had continuing developmental abnormalities at 4-year follow-up, but it was not possible to conclude whether these deficits were the result of benzodiazepines or whether social and environmental factors explained the continuing deficits.
Concerns regarding whether benzodiazepines during pregnancy cause major malformations, in particular cleft palet have been hotly debated in the literature. A meta analysis of the data from cohort studies found no link but meta analysis of case control studies did find a significant increase in major malformations (however, the cohort studies were homogenous and the case control studies were heterogeneous, thus reducing the strength of the case control results). There have also been several reports that suggest that benzodiazepines have the potential to cause a syndrome similar to fetal alcohol syndrome
Fetal alcohol syndrome
Fetal alcohol syndrome is a pattern of mental and physical defects that can develop in a fetus in association with high levels of alcohol consumption during pregnancy. Current research also implicates other lifestyle choices made by the prospective mother...
, but this has been disputed by a number of studies. As a result of conflicting findings use of benzodiazepines during pregnancy is controversial. The best available evidence suggests that benzodiazepines are not a major cause of birth defects, i.e. major malformations or cleft lip or cleft palet.
Political controversy
The Medical Research Council in 1980 recommended that research be conducted into the effects of long-term use of benzodiazepines A 2009 British Government parliamentary inquiryParliamentary inquiry
A parliamentary inquiry is a question directed to the presiding officer of a deliberative assembly to obtain information on a matter of parliamentary law or the rules of the organization bearing on the business at hand...
recommended that research into the long-term effects of benzodiazepines must be carried out. The view of the Department of Health is that they have made every effort to make doctors aware of the problems associated with the long-term use of benzodiazepines, as well as the dangers of benzodiazepine drug addiction.
In 1980, the Medicines and Healthcare products Regulatory Agency
Medicines and Healthcare products Regulatory Agency
The Medicines and Healthcare products Regulatory Agency is the UK government agency which is responsible for ensuring that medicines and medical devices work and are acceptably safe....
's Committee on the Safety of Medicines
Committee on the Safety of Medicines
The Committee on the Safety of Medicines was an independent advisory committee that for 40 years advised the UK Licensing Authority on the quality, efficacy and safety of medicines....
issued guidance restricting the use of benzodiazepines to short-term use and updated and strengthened these warnings in 1988. When asked by Phil Woolas
Phil Woolas
Philip James Woolas was a British Labour Party politician who was the Member of Parliament for Oldham East and Saddleworth from his election in 1997 to 2010. He was the Minister of State for Borders and Immigration in the Home Office, as well as being the Minister of State for the Treasury...
in 1999 whether the Department of Health had any plans to conduct research into the long-term effects of benzodiazepines, the Department replied, saying they have no plans to do so, as benzodiazepines are already restricted to short-term use and monitored by regulatory bodies. In a House of Commons debate, Phil Woolas has claimed that there has been a cover-up with regard to the problems associated with benzodiazepines because they are of too large of a scale for governments, regulatory bodies, and the pharmaceutical industry to deal with. John Hutton
John Hutton (Labour MP)
John Matthew Patrick Hutton, Baron Hutton of Furness is a British Labour Party politician who was the Member of Parliament for Barrow and Furness in Cumbria from 1992 to 2010, and has served in a number of Cabinet offices, including Defence Secretary and Business Secretary...
stated in response that the Department of Health take the problems of benzodiazepines extremely seriously and are not sweeping the issue under the carpet. In 2010, the All-Party Parliamentary Group on Involuntary Tranquilliser Addiction filed a complaint with the Equality and Human Rights Commission under the Disability Discrimination Act 1995
Disability Discrimination Act 1995
The Disability Discrimination Act 1995 is an Act of the Parliament of the United Kingdom which has now been repealed and replaced by the Equality Act 2010 , except in Northern Ireland where the Act still applies...
against the Department of Health and the Department for Work and Pensions
Department for Work and Pensions
The Department for Work and Pensions is the largest government department in the United Kingdom, created on June 8, 2001 from the merger of the employment part of the Department for Education and Employment and the Department of Social Security and headed by the Secretary of State for Work and...
alleging discrimation against people with a benzodiazepine prescription drug dependence as a result of denial of specialised treatment services, exclusion from medical treatment, non-recognition of the protracted benzodiazepine withdrawal syndrome
Benzodiazepine withdrawal syndrome
Benzodiazepine withdrawal syndrome—often abbreviated to benzo withdrawal—is the cluster of symptoms which appear when a person who has taken benzodiazepines long term and has developed benzodiazepine dependence stops taking benzodiazepine drug or during dosage reductions...
, as well as denial of rehabilitation and back to work schemes. Additionally the APPGITA complaint alleged that there is a "virtual prohibition" on the collection of statistical information on benzodiazepines across government departments, whereas with other controlled drugs there are enormous volumes of statistical data. The complaint alleged that the discrimination is deliberate, large scale and that government departments are aware of what they are doing.
Declassified Medical Research Council meeting
The Medical Research Council (UK)Medical Research Council (UK)
The Medical Research Council is a publicly-funded agency responsible for co-ordinating and funding medical research in the United Kingdom. It is one of seven Research Councils in the UK and is answerable to, although politically independent from, the Department for Business, Innovation and Skills...
held a closed meeting among top UK medical doctors and representatives from the pharmaceutical industry between the dates of 30 October 1980 and 3 April 1981. The meeting was classified under the Public Records Act 1958
Public Records Act 1958
The Public Records Act 1958 is an Act of the Parliament of the United Kingdom forming the main legislation governing public records in the United Kingdom....
until 2014 but became available in 2005 as a result of the Freedom of Information Act. The meeting was called due to concerns that 10–100,000 people could be dependent; this estimate was later revised by the Chairman Professor Malcolm Lader, of the meeting to approximately half a million members of the British public were suspected of being dependent on therapeutic dose levels of benzodiazepines, about half of those on long-term benzodiazepines. It was reported that benzodiazepines may be the third- or fourth-largest drug problem in the UK (the largest being alcohol and tobacco). The Chairman of the meeting followed up after the meeting with additional information, which was forwarded to the Medical Research Council neuroscience board, raising concerns regarding tests that showed definite cortical atrophy in 2 of 14 individuals tested and borderline abnormality in five others. He felt that, due to the methodology used in assessing the scans, the abnormalities were likely an underestimate, and more refined techniques would be more accurate. Also discussed were findings that tolerance to benzodiazepines can be demonstrated by injecting diazepam into long-term users; in normal subjects, increases in growth hormone
Growth hormone
Growth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...
occurs, whereas in benzodiazepine-tolerant individuals this effect is blunted. Also raised were findings in animal studies that showed the development of tolerance in the form of a 15 percent reduction in binding capacity of benzodiazepines after seven days administration of high doses of the partial agonist benzodiazepine drug flurazepam
Flurazepam
Flurazepam is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. It produces a metabolite with a very long half-life , which may stay in the bloodstream for up to four days...
and a 50 percent reduction in binding capacity after 30 days of a low dose of diazepam. The Chairman was concerned that papers soon to be published would "stir the whole matter up" and wanted to be able to say that the Medical Research Council "had matters under consideration if questions were asked in parliament". The Chairman felt that it "was very important, politically that the MRC should be 'one step ahead" and recommended epidemiological studies be funded and carried out by Roche Pharmaceuticals and MRC sponsored research conducted into the biochemical effects of long-term use of benzodiazepines. The meeting aimed to identify issues that were likely to arise, alert the Department of Health to the scale of the problem and identify the pharmacology and nature of benzodiazepine dependence and the volume of benzodiazepines being prescribed. The World Health Organisation was also interested in the problem and it was felt the meeting would demonstrate to the WHO that the MRC was taking the issue seriously. Among the psychological effects of long-term use of benzodiazepines discussed was a reduced ability to cope with stress. The Chairman stated that the "withdrawal symptoms from valium were much worse than many other drugs including, e.g., heroin". It was stated that the likelihood of withdrawing from benzodiazepines was "reduced enormously" if benzodiazepines were prescribed for longer than four months. It was concluded that benzodiazepines are often prescribed inappropriately, for a wide range of conditions and situations. Dr Mason (DHSS) and Dr Moir (SHHD), felt it important to determine the effectiveness and toxicity of benzodiazepines due to the large numbers of people using benzodiazepines for long periods of time before deciding what regulatory action to take.
Controversy resulted in 2010 when the previously secret files came to light over the fact that the Medical Research Council was warned that benzodiazepines prescribed to millions of patients appeared to cause brain shrinkage similar to alcohol abuse in some patients and failed to carry out larger and more rigorous studies. The Independent on Sunday reported allegations that "scores" of the 1.5 million the UK public who use benzodiazepines long-term have symptoms that are consistent with brain damage. It has been described as a 'huge scandal' by Jim Dobbin, and legal experts and MPs have predicted a class action lawsuit. A solicitor said she was aware of the past failed litigation against the drug companies and the relevance the documents had to that court case and said it was strange that the documents were kept 'hidden' by the MRC.
Professor Lader, who chaired the MRC meeting, declined to speculate as to why the MRC declined to support his request to set up a unit to further research benzodiazepines and why they did not set up a special safety committee to look into these concerns. Professor Lader stated that he regrets not being more proactive on pursuing the issue, stating that he did not want to be labeled as the guy who pushed only issues with benzos. Professor Ashton also submitted proposals for grant-funded research using MRI, EEG, and cognitive testing in a ramdomised controlled trial to assess whether benzodiazepines have permanent damage to the brain, but similar to Professor Lader got turned down by the MRC.
The MRC spokesperson said they accept the conclusions of Professor Lader's research and said that they fund only research that meets required quality standards of scientific research, and stated that they were and continue to remain receptive to applications for research in this area. No explanation was reported for why the documents were sealed by the Public Records Act.
Jim Dobbin, who chairs the All-Party Parliamentary Group for Involuntary Tranquilliser Addiction, stated that:
"Many victims have lasting physical, cognitive and psychological problems even after they have withdrawn. We are seeking legal advice because we believe these documents are the bombshell they have been waiting for. The MRC must justify why there was no proper follow-up to Professor Lader's research, no safety committee, no study, nothing to further explore the results. We are talking about a huge scandal here."
The legal director of Action Against Medical Accidents said urgent research must be carried out and said that, if the results of larger studies confirm professor Lader's research, the government and MRC could be faced with one of the biggest group actions for damages the courts have ever seen given the large number of people potentially affected. People who report enduring symptoms post-withdrawal such as neurological pain, headaches, cognitive impairment, and memory loss have been left in the dark as to whether these symptoms are drug-induced damage or not due to the MRC's inaction, it was reported. Professor Lader reported that the results of his research did not surprise his research group given that it was already known that alcohol could cause permanent brain changes.
Class-action lawsuit
Benzodiazepines have a unique history in that they were responsible for the largest-ever class-action lawsuit against drug manufacturers in the United Kingdom, in the 1980s and early 1990s, involving 14,000 patients and 1,800 law firms that alleged the manufacturers knew of the dependence potential but intentionally withheld this information from doctors. At the same time, 117 general practitioners and 50 health authorities were sued by patients to recover damages for the harmful effects of dependenceBenzodiazepine dependence
Benzodiazepine dependence or benzodiazepine addiction is a condition during which a person is dependent on benzodiazepine drugs. Dependence can be either a psychological dependence, physical dependence, or a combination of the two...
and withdrawal
Withdrawal
Withdrawal can refer to any sort of separation, but is most commonly used to describe the group of symptoms that occurs upon the abrupt discontinuation/separation or a decrease in dosage of the intake of medications, recreational drugs, and alcohol...
. This led some doctors to require a signed consent form from their patients and to recommend that all patients be adequately warned of the risks of dependence and withdrawal before starting treatment with benzodiazepines. The court case against the drug manufacturers never reached a verdict; legal aid
Legal aid
Legal aid is the provision of assistance to people otherwise unable to afford legal representation and access to the court system. Legal aid is regarded as central in providing access to justice by ensuring equality before the law, the right to counsel and the right to a fair trial.A number of...
had been withdrawn, leading to the collapse of the trial, and there were allegations that the consultant psychiatrists, the expert witnesses, had a conflict of interest. This litigation led to changes in the British law, making class action law suits more difficult.
See also
- Long-term effects of alcoholLong-term effects of alcoholThe long term effects of alcohol range from possible health benefits for low levels of alcohol consumption to severe detrimental effects in cases of chronic alcohol abuse...
- Benzodiazepine withdrawal syndromeBenzodiazepine withdrawal syndromeBenzodiazepine withdrawal syndrome—often abbreviated to benzo withdrawal—is the cluster of symptoms which appear when a person who has taken benzodiazepines long term and has developed benzodiazepine dependence stops taking benzodiazepine drug or during dosage reductions...
- Benzodiazepine dependenceBenzodiazepine dependenceBenzodiazepine dependence or benzodiazepine addiction is a condition during which a person is dependent on benzodiazepine drugs. Dependence can be either a psychological dependence, physical dependence, or a combination of the two...