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Some good info about this sensitive subject :
[link to www.benzobuddies.org]
[link to en.wikipedia.org (secure)]
[link to en.wikipedia.org (secure)]
From Wikipedia :
Long-term use of benzodiazepines leads to increasing physical and mental health problems, and as a result, discontinuation is recommended for many long-term users. The withdrawal syndrome from benzodiazepines can range from a mild and short-lasting syndrome to a prolonged and severe syndrome. Withdrawal symptoms leads to continued use of benzodiazepines for many years, long after the original reason for taking benzodiazepines has passed. Many patients know that the benzodiazepines no longer work for them but are unable to discontinue benzodiazepines because of withdrawal symptoms.
Withdrawal symptoms can emerge despite slow reduction but can be reduced by a slower rate of withdrawal. As a result, withdrawal rates have been recommended to be customized to each individual patient. The time needed to withdraw can vary from a couple of months to a year or more and often depends on length of use, dosage taken, lifestyle, health, and social and environmental stress factors.
Diazepam is often recommended due to its long elimination half-life and also because of its availability in low potency doses. The non-benzodiazepine Z drugs such as zolpidem, zaleplon, and zopiclone should not be used as a replacement for benzodiazepines, as they have a similar mechanism of action and can induce a similar dependence. The pharmacological mechanism of benzodiazepine tolerance and dependence is the internalization (removal) of receptor site in the brain and changes in gene transcription codes in the brain.
With long-term use and during withdrawal of benzodiazepines, treatment-emergent depression and emotional blunting may emerge and sometimes also suicidal ideation. There is evidence that the higher the dose used the more likely it is benzodiazepine use will induce these feelings. Reducing the dose or discontinuing benzodiazepines may be indicated in such cases. Withdrawal symptoms can persist for quite some time after discontinuing benzodiazepines. Some common protracted withdrawal symptoms include anxiety, depression, insomnia, and physical symptoms such as gastrointestinal, neurologic, and musculoskeletal effects. The protracted withdrawal state may still occur despite slow titration of dosage. It is believed that the protracted withdrawal effects are due to persisting neuroadapations
Cognitive status
Long-term benzodiazepine use can lead to a generalised impairment of cognition, 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.
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 hypnotic 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 in sensitive individuals 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.
There is some evidence that 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 study found 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.
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 lifelong 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 function
Suicide and self-harm
Because benzodiazepines in general may be associated with increased suicide risk, 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.
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 Society 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.
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