[10] Some of the symptoms that could possibly occur as a result of a withdrawal from benzodiazepines after long-term use include emotional clouding,[1] flu-like symptoms,[5] suicide,[11] 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.
[22] 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.
[23] 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.
[24] 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.
[44][45] 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.
[15] A study found that individuals having withdrawn from benzodiazepines showed a marked reduction in use of medical and mental health services.
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.
[55] 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.
[59][60] 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.
[70] In 1987, 17 inpatient people who used high doses of benzodiazepines non-medically have anecdotally shown enlarged cerebrospinal fluid spaces with associated cerebral atrophy.
[75] Withdrawal from high-dose use of nitrazepam anecdotally was alleged in 2001 to have caused severe shock of the whole brain with diffuse slow activity on EEG in one patient after 25 years of use.
[77] 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.
[78] A 2018 review of the research found a likely causative role between the use of benzodiazepines and an increased risk of dementia,[79] but the exact nature of the relationship is still a matter of debate.
[80] 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.
[93] In a House of Commons debate, Phil Woolas claimed that there had been a cover-up of problems associated with benzodiazepines because they are of too large of a scale for governments, regulatory bodies, and the pharmaceutical industry to deal with.
[94] 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 discrimination 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.
The meeting was called due to concerns that 10–100,000 people could be dependent; meeting chairman Professor Malcolm Lader later revised this estimate to include approximately half a million members of the British public suspected of being dependent on therapeutic dose levels of benzodiazepines, with about half of those on long-term benzodiazepines.
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 Independent on Sunday reported allegations that "scores" of the 1.5 million members of the UK public who use benzodiazepines long-term have symptoms that are consistent with brain damage.
[96] Jim Dobbin, who chaired 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.
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.
At the same time, 117 general practitioners and 50 health authorities were sued by patients to recover damages for the harmful effects of dependence and withdrawal.
[97] 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.
[102] In addition to the smaller head circumference found in benzodiazepine-exposed babies mental retardation, functional deficits, long-lasting behavioural anomalies, and lower intelligence occurs.
[113][114] 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, depersonalization, sleepwalking, aggressivity, orthostatic hypotension and insomnia.
[116] Benzodiazepines have been associated with increased body sway in the elderly, which can potentially lead to fatal accidents including falls.
[117] 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.