effects of long-term benzodiazepine use effects of long-term benzodiazepine use the effects of long-term benzodiazepine use include drug dependence and neurotoxicity as well as the possibility of adverse effects on cognitive function, physical health, and mental health. long-term use is sometimes described as use not shorter than three months. benzodiazepines are generally effective when used therapeutically in the short term, but even then the risk of dependency can be significantly high. there are significant physical, mental and social risks associated with the long-term use of benzodiazepines. although anxiety can temporarily increase as a withdrawal symptom, there is evidence that a reduction or withdrawal from benzodiazepines can lead in the long run to a reduction of anxiety symptoms. due to these increasing physical and mental symptoms from long-term use of benzodiazepines, slow withdrawal is recommended for long-term users. not everyone, however, experiences problems with long-term use. benzodiazepinesthe core structure of benzodiazepines. "r" labels denote common locations of side chains, which give different benzodiazepines their unique properties. pronunciation: /ˌbɛnzoʊdaɪˈæzəpiːn/ benzodiazepine list of benzodiazepines benzodiazepine overdose benzodiazepine dependence benzodiazepine misuse benzodiazepine withdrawal syndrome effects of long-term benzodiazepine use some of the symptoms that could possibly occur as a result of a withdrawal from benzodiazepines after long-term use include emotional clouding, flu-like symptoms, suicide, nausea, headaches, dizziness, irritability, lethargy, sleep problems, memory impairment, personality changes, aggression, depression, social deterioration as well as employment difficulties, while others never have any side effects from long-term benzodiazepine use. abruptly or rapidly stopping benzodiazepines can be dangerous; when withdrawing a gradual reduction in dosage is recommended, under professional supervision. while benzodiazepines are highly effective in the short term, adverse effects associated with long-term use, including impaired cognitive abilities, memory problems, mood swings, and 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, especially in individuals that have a "drug-seeking" behavior; further, a physical dependence can develop after a few weeks or months of use. many of these adverse effects associated with long-term use of benzodiazepines begin to show improvements three to six months after withdrawal. other concerns about the effects associated with long-term benzodiazepine use, in some, include dose escalation, benzodiazepine use disorder, tolerance and benzodiazepine dependence and benzodiazepine withdrawal problems. both physiological tolerance and dependence can be associated with worsening the adverse effects associated with 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 available research has been conducted in prescribed users, even less is known about illicit misusers. the long-term use of benzodiazepines is controversial and has generated significant debate 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. symptoms effects of long-term benzodiazepine use 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. 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. the use of benzodiazepines for the treatment of anxiety has been found to lead to a significant increase in healthcare costs due to accidents and other adverse effects associated with the long-term use of benzodiazepines. 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. 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 deficits that were detectable after several weeks but not after 3.5 years. effect on sleep sleep architecture can be adversely affected by benzodiazepine dependence. possible adverse effects on sleep include induction or worsening of sleep disordered breathing. like alcohol, benzodiazepines are commonly used to treat insomnia in the short term (both prescribed and self-medicated), but worsen sleep in the long term. although benzodiazepines can put people to sleep, while asleep, the drugs disrupt sleep architecture, decreasing sleep time, delayed and decreased rem sleep, increased alpha and beta activity, decreased k complexes and delta activity, and decreased deep slow-wave sleep (i.e., nrem stages 3 and 4, the most restorative part of sleep for both energy and mood). mental and physical health the long-term use of benzodiazepines may have a similar effect on the brain as alcohol, and is also implicated in depression, anxiety, post-traumatic stress disorder (ptsd), mania, psychosis, sleep disorders, sexual dysfunction, delirium, and neurocognitive disorders. however a 2016 study found no association between long-term usage and dementia. as with alcohol, the effects of benzodiazepine on neurochemistry, such as decreased levels of serotonin and norepinephrine, are believed to be responsible for their effects on mood and anxiety. additionally, benzodiazepines can indirectly cause or worsen other psychiatric symptoms (e.g., mood, anxiety, psychosis, irritability) by worsening sleep (i.e., benzodiazepine-induced sleep disorder). these effects are paradoxical to the use of benzodiazepines, both clinically and non-medically, in management of mental health conditions. long-term benzodiazepine use may lead to the creation or exacerbation of physical and mental health conditions, which improve after six or more months of abstinence. after a period of about 3 to 6 months of abstinence after completion of a gradual-reduction regimen, marked improvements in mental and physical wellbeing become apparent. for example, one study of hypnotic users gradually withdrawn from their hypnotic medication reported after six 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 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 precede alcohol or benzodiazepine dependence but the alcohol or benzodiazepine dependence often acts to keep the anxiety disorders going and often progressively makes them worse. many people who are addicted to alcohol or prescribed benzodiazepines decide to quit when it is explained to them they have a choice between ongoing ill mental health or quitting and recovering from their symptoms. it was noted that because every individual has an individual sensitivity level to alcohol or sedative hypnotic drugs, what one person can tolerate without ill health will cause another to develop very ill health, and that even moderate drinking in sensitive individuals can cause rebound anxiety syndromes and sleep disorders. a person who experiences 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. 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, after several years of chronic benzodiazepine use, a large portion of patients developed 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 one 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 are not unique but occur 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 fetuses of 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, have 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 use of prescribed benzodiazepines is associated with an increased rate of suicide or attempted suicide. the prosuicidal effects of benzodiazepines are suspected to be due to a psychiatric disturbance caused by side effects or withdrawal symptoms. 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 alcohol use disorder and substance use disorder. benzodiazepine misuse or misuse of