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Long-term effects of benzodiazepines

    Benzodiazepine dependence has a number of potential or suspected long term effects on cognitive physical and mental health Individuals who successfully discontinue hypnotic therapy have less severe sleep and anxiety problems are less distressed and have a general feeling of improved health Some of the symptoms which may occur in long term users of benzodiazepines include dependence nausea headaches dizziness irritability lethargy memory impairment personality changes aggression and depression

    Cognitive status

    Long-term benzodiazepine use leads 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 may exist although their impact on patient's daily functioning might be 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

    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 - 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in mental and physical wellbeing become apparent For example one study of hypnotic users who were gradually withdrawn from their hypnotic medication reported after 6 months of abstinence that they had less severe sleep and anxiety problems were less distressed and had a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 who remained of hypnotic medication had no improvements in their insomnia anxiety or general health ratingsmental 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 benzodiazepines tends to take a lot longer than recovery from alcohol but people can regain their previous good health
    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 where as only 53% of patients receiving psychotherapy developed violent or aggressive behavioural patterns 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 as well as 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 that 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 only two of the patients having 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 stable prescribed doses being taken Another theory is that chronic benzodiazepine use causes subtle increasing toxicity which in turn leads to increasing psychopathology in long term users of benzodiazepines Chronic use of benzodiazepines is a risk factor for blepharospasm Long term use of benzodiazepines can induce perceptual disturbances and depersonalisationin some people even in those who are taking a stable daily dosage and it can also become a protracted withdrawal feature of the benzodiazepine withdrawal syndrome Chronic use of benzodiazepines seemed to cause significant immunological disorders in a study of selected outpatients attending a psychopharmacology department Drug induced symptoms which resemble withdrawal like effects can occur on a set dosage as a result of prolonged use have also been 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 ie alcohol and barbiturates

    Carcinogenicity

    In the second national cancer study in 1982 the American Cancer Society conducted a survey of over 1.1 million participents A marked increased risk of cancer was found in the users of sleepings pills mainly benzodiazepines There have been 15 epidemiologic studies which have shown that 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 Not only are benzodiazepines associated with an increased risk of cancer the benzodiazepine receptor agonist Z-drugs also are associated with cancer in humans in these studies Initially the US Food and Drug Administration reviewers did not want to approve the nonbenzodiazepine Z drugs due to concerns of cancer but ultimately changed their mind and approved the drugs despite the concerns The data shows that trial subjects receiving hypnotic drugs had an increased risk of developing cancer The review author concluded saying; "the likelihood of cancer causation is sufficiently strong now that physicians and patients should be warned that hypnotics possibly place patients at higher risk for cancer"

    Brain damage controversy

    Several clinical studies have tried to establish if benzodiazepines cause structural brain damage and have come to different findings Evidence of structural brain damage is strongest but still not definitive for high dose prescribed users and high dose benzodiazepine drug abusers although evidence exists from clinical studies of a degree of brain shrinkage even in chronic low dose benzodiazepine users but this has been disputed in other clinical studies While some of the studies controlled for factors such as alcohol use others didn't Some studies were too small or in one case was only a single case report Medical opinion on whether long term prescribed benzodiazepines cause structural brain damage differs
    High dose abusers of benzodiazepines have shown enlarged cerebrospinal fluid spaces with associated brain shrinkage Neuropsychological function can be permanently affected in chronic high dose abusers of benzodiazepines with brain damage similar to alcoholic brain damage as was shown in a 4 to 6 year follow-up study of benzodiazepine abusers by Borg and others of the Karolinska Institute 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 An earlier study by Borg et al. found evidence of cerebral disorder in those that exclusively abused benzodiazepines suggesting that cerebral disorder was not the result of other substances of abuse Withdrawal from high dose abuse of nitrazepam have caused severe hypoperfusion of the whole brain with diffuse slow activity on EEG After withdrawal abnormalities in hypofrontal brain wave patterns persist beyond the withdrawal syndrome which suggested organic brain damage occurs from chronic high dose abuse of benzodiazepinesSome studies have demonstrated brain damage 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 Two publications have suggested that lorazepam is more toxic than diazepam Permanent brain damage may result from chronic use of benzodiazepines similar to alcohol related brain damage The brain damage reported is similar to but less severe than that seen in chronic alcoholics Brain damage reportedly appeared to be dose dependent with low dose users having less brain shrinkage than higher dose users However two studies found no evidence of brain shrinkage in prescribed benzodiazepine users
    Professor Ashton a leading expert on benzodiazepines from Newcastle University Institute of Neuroscience has been cautious in jumping to any firm conclusions and is an advocate for further research into long lasting or possibly permanent symptoms of long term use of benzodiazepines 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 have never been used to investigate the question of whether benzodiazepines cause functional or structural brain damage Professor Ashton tried to acquire funding to perform scans using more detailed scanning technologies such as PET scans and MRI scans but was turned down for research funding At present the question of whether benzodiazepines cause structural or functional brain damage remains unanswered definitively A recent government inquiry by the British Government parliamentary inquiry recommended that research into the long term effects of benzodiazepines needs to be carried out

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