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Is it dangerous to use benzodiazepines for life?
1. Menan Abd El Maksoud Rabie,
MBBCh, Msc, Arab Board, MD,
Assistant Professor of Psychiatry, Faculty of Medicine, Ain Shams
University,
Member of the Egyptian Psychiatric Association (EPA),
International Member of the American Psychiatric Association (APA),
Associate Member of the International Federation of Psychiatric
Epidemiology
(IFPE),
Managing editor at the journal of Middle East Current Psychiatry
(MECPych)
3. The chronic use of BDZ is becoming
accepted in some cultures, as it is
unfortunately not as stigmatizing as
chronic use of cannabis, alcohol or
heroin.
When a psychiatrist advises a chronic
BDZ user about the hazards of its
prolonged use, what is the most
subjectively annoying symptom to the
patient?
4. Benzodiazepine withdrawal syndrome is the
cluster of symptoms which appear when a person
who has taken benzodiazepines long term & has
developed benzodiazepine dependence stops
taking benzodiazepine drug(s) or reduces the
dosage too rapidly.
Chronic exposure to benzodiazepines causes
physical adaptations in the brain to counteract the
drug's effects. This is known as a tolerance and
physical dependence.
5. 50-80% of people who have taken
benzodiazepines continually for 6
months or longer will experience
withdrawal symptoms when reducing
the dose.
People who have been taking
benzodiazepines regularly for many
years can have symptoms of
withdrawal most of the time, even
when they have not reduced the dose.
Often they are unaware that their poor
physical and mental health is related
to their long term use of the
benzodiazepines
6. the higher the dose (DOSAGE SIZE )
the longer a benzodiazepine is used
(LENGTH OF USE)
the more rapidly a benzodiazepine is
discontinued (RATE OF TAPERING)
the more likely severe withdrawal
symptoms will occur.
…and possibly genetic factors play a role
7. Severe withdrawal symptoms can still
occur during gradual dose reduction or
from relatively low doses
Long term use of benzodiazepines may
lead to withdrawal like symptoms
emerging despite a constant therapeutic
dose.
Withdrawal symptoms are an adverse
effect and result of drug tolerance.
8. In certain selected patient groups the occurrence
of withdrawal symptoms are as high as 100%,
whereas more than 50% of subjects are able to
discontinue benzodiazepines with mild or even no
withdrawal symptoms.
It is not known for sure why there is such a
variation between patients but recent research in
animals suggests that withdrawal may be
influenced by a genetic component.
9. Withdrawal symptoms may persist for weeks or months
after cessation of benzodiazepines.
In a smaller subset of patients withdrawal symptoms may
continue at a sub acute level for many months or even a
year or more.
Apart from the length of time taking
benzodiazepines and the dose, there are no
predictors for the severity or otherwise of the
withdrawal. Slowly reducing the dose of the drug
minimises the severity of the withdrawal
symptoms.
10. Patients who are physically dependent on short
acting anxiolytic benzodiazepines.
Interdose withdrawal are withdrawal symptoms
which occur between doses when the previous
dose wears off. This can lead to symptoms such as
rebound anxiety between doses and craving for the
next dose.
The ability to determine the difference between
relapse and rebound is very important during the
withdrawal phase and can often lead to a
misdiagnosis.
11. GABA is the second most common
neurotransmitter in the CNS (after glutamate) and
the most abundant inhibitory neurotransmitter;
roughly 1/4 to 1/3 of synapses use GABA.
The use of benzodiazepines has an effect on
almost every aspect of brain and body function,
either directly or indirectly.
14. GABA site
BZ site
picrotoxin site
alcohol site
barbiturate
site
8-20 Stahl S M, Essential
Psychopharmacology (2000)
15. Benzodiazepines cause a decrease in
norepinephrine, serotonin, acetylcholine and
dopamine.
These neurotransmitters are needed for
normal memory,
mood,
muscle tone and coordination,
emotional responses,
endocrine gland secretions,
heart rate and blood pressure control.
A number of people have observed changes
in their cognitive abilities following long
term benzodiazepine use. Research
undertaken by the School of Psychology at
LaTrobe University has shown that many
people who have been taking
benzodiazepines long term have problems
with concentration, learning and memory.
16. With chronic benzodiazepine use, tolerance
develops rapidly to most of its effects, so that when
benzodiazepines are withdrawn, various
neurotransmitter systems go into overdrive due to
the lack of inhibitory GABA-ergic activity.
Withdrawal symptoms then emerge as a result,
and persist until the nervous system physically
reverses the physical dependence which have
occurred in the CNS.
17. Withdrawal symptoms typically consist of a mirror
image of the drug's effects:
sedative effects and suppression of REM and SWS
stages of sleep can be replaced by insomnia,
nightmares, and hypnogogic hallucinations;
antianxiety effects with anxiety and panic;
muscle relaxant effects are replaced with muscular
spasms or cramps;
anticonvulsant effects with seizures, especially in
cold turkey or overly-rapid withdrawal.
19. Studies in mice have found that discontinuation of
benzodiazepines leads to decreased agonist affinity
and increased inverse agonist affinity of the
benzodiazepine receptors, essentially causing the
receptors to reverse their natural function.
This may explain the cause of the benzodiazepine
withdrawal effects, down regulation of other sub
receptor types.
20. A. Cessation of (or reduction in) sedative, hypnotic, or anxiolytic use that has
been heavy and prolonged.
B. Two (or more) of the following, developing within several hours to a few
days after criterion A:
(1) autonomic hyperactivity (e.g., sweating or pulse rate greater than 100)
(2) increased hand tremor
(3) insomnia
(4) nausea or vomiting
(5) transient visual, tactile, or auditory hallucinations or illusions
(6) psychomotor agitation
(7) anxiety
(8) grand mal seizures
C. The symptoms in criterion B cause clinically significant distress or
impairment in social, occupational, or other important areas of functioning.
D. The symptoms are not due to a general medical condition and are not better
accounted for by another mental disorder.
Specify if:
With perceptual disturbances
21. Withdrawal state
G1. There must be clear evidence of recent cessation or reduction of
substance use after repeated, and usually prolonged and/or high-dose,
use of that substance.
G2. Symptoms and signs are compatible with the known features of a
withdrawal state from the particular substance or substances (see
below).
G3. Symptoms and signs are not accounted for by a medical disorder
unrelated to substance use, and not better accounted for by another
mental or behavioral disorder.
The diagnosis of withdrawal state may be further specified by using the
following:
Uncomplicated
With convulsions
22. Sedative or hypnotic withdrawal state
A. The general criteria for withdrawal state must be met.
B. Any three of the following signs must be present:
(1) tremor of the tongue, eyelids, or outstretched hands
(2) nausea or vomiting
(3) tachycardia
(4) postural hypotension
(5) psychomotor agitation
(6) headache
(7) insomnia
(8) malaise or weakness
(9) transient visual, tactile, or auditory hallucinations or illustrations
(10) paranoid ideation
(11) grand mal convulsions
Comment
If delirium is present, the diagnosis should be sedative or hypnotic withdrawal state with
delirium.
23. 1. Electric shock sensations
2. Muscular spasms, cramps or fasiculations
3. Insomnia
4. Blurred vision
5. Dizziness
6. Dry mouth
7. Aches and pains
8. Hearing disturbances
9. Taste and smell disturbances
10. Chest pain
11. Flu like symptoms
12. Impaired memory and concentration
13. Increased sensitivity to sound
14. Increased urinary frequency
15. Numbness and tingling
16. Hot and cold flushes
17. Headache
18. Rebound REM sleep
19. Stiffness
20. Fatigue and weakness
21. Restless legs syndrome
22. Metallic taste
23. Photophobia
24. Paranoia
25. Hypnagogic-hallucinations
26. Nausea and vomiting
27. Nightmares
28. Agitation and restlessness
29. Anxiety and panic attacks
30. Hypochondriasis
31. Impaired concentration
32. Elevation in blood pressure
33. Tachycardia
34. Hypertension
35. Postural hypotension
36. Depression possible suicidal ideation
37. Tremor
38. Perspiration
39. Loss of appetite and weight loss
40. Dysphoria
41. Depersonalization
42. Derealisation (Feelings of unreality)
43. Obsessive compulsive disorder
44. Tinnitus
45. Paraesthesia
46. Visual disturbances
47. Mood swings
48. Indecision
49. Irritable bowel syndrome
24. Convulsions, which may result in death
Catatonia, which may result in death
Coma(rare)
Hyperthermia
Organic brain syndrome
Confusion
Suicide, Attempted suicide and Suicidal ideation
Self harm
Delusions and other psychotic features
Homicidal ideation
Urges to shout, throw, break things or to harm
someone
Violence
Post Traumatic Stress Disorder
Mania
Neuroleptic malignant syndrome like event (rare)
delirium tremens
25. Benzodiazepine withdrawal represents in part
excitotoxicity to brain neurons.
Repeated benzodiazepines withdrawals may lead
to sensitisation or kindling of the CNS, possibly
leading to worsening cognition and
symptomatology and making each subsequent
withdrawal period worse.
Long term use of benzodiazepines causes
cognitive, neurological and intellectual
impairments, with attentional and visuospatial
functional impairments.
After one year of abstinence ,withdrawal from
benzodiazepines can lead to improved alertness
and decreased forgetfulness in the elderly. There
were some cognitive abilities which did not
improve which are sensitive to benzodiazepines as
well as age such as epsiodic memory
26. The main Hypothesis of this study was that chronic
users of benzodiazepines experience many withdrawal
symptoms, if they try to decrease the dose.
Research questions were about age, gender &
diagnoses of the users & the effects on type of drug,
duration of use, withdrawal symptoms and
discontinuation rate.
27. To describe the characteristics of chronic
benzodiazepine (BDZ) users and to identify the Most
Annoying Withdrawal Symptom (MAWS) which may
play a key role in hindering the discontinuation of the
drug, and delaying abstinence.
28. 547 BDZ chronic users were subjected to Psychiatric
history and examination,
They were diagnosed according to DSM-IV diagnostic
criteria and they were advised to decrease the doses of
BDZ gradually (1/4 dose every 4 weeks)
In subsequent visits they were asked to check in a list of
withdrawal symptoms & they were asked to specify the
most annoying symptom from their subjective point of
view.
29.
30. Males with SAD, GAD, MAD, Panic D, MDD,
Adjustment D with depressive symptoms, PTSD,
Insomnia, BD & Schizophrenia were more prone than
females with the same diagnoses to use BDZ.
Females with OCD, Adjustment D with anxiety
symptoms, Alzheimer’s D, were more commonly using
BDZ
32. 0 20 40 60 80 100 120
SAD
GAD
MAD
Panic
OCD
Sp Phobia
PTSD
MDD
Schiz
BD
Alz
Adj D Anx
Adj D Dep
Adj D Anx Dep
Insomnia
ICD
FEMALE
MALE
33. Males suffering from Impulse Control Disorder
were using BDZ for the longest Duration
(M100 ms)
Females suffering from Panic D, Adjustment D
with depressive symptoms & Alzheimer’s D
80-100 ms
Males suffering from Schizophrenia, BD, Panic
D & MDD 60-80 ms
Females suffering from MAD, OCD, GAD, SAD
60-80 ms
35. Despite withdrawal symptoms,
42.1% of OCD pts,
36.8% of schizophrenia pts,
34.2% of MDD pts,
28.6 % of BD pts,
28.6% of Adj D dep pts,
18.8% of Adj D anx dep pts,
16.7% of Adj D anx pts
were able to D/C BDZ doses within 3 months,
with the aid of non BDZ psychiatric ttt and
supportive psychotherapy
40. Withdrawal Symptoms were most prevalent (100%)
with Alzheimer’s D and Imp Cont D.
They were least prominent in cases suffering from
Specific phobia (60%), PTSD (75%) & Adj D anx s
(75%)
42. Sedative, hypnotic, or anxiolytic dependence is
influenced by several factors: the most important is
the pharmacology of drugs.
Dependence is also affected by the beliefs and values
of physicians, who must be aware of their attitudes
toward dispensing drugs of this class.
Finally, patients, and society at large, are influenced by
the moral, economic, and political views of the time.
Taken together these factors influence medical care,
sometimes to the detriment of patients, who may be
denied appropriate medication because of such biases.
43. The gender, age and diagnosis, the type of BDZ and the
duration of its use significantly affect the perception of
the patient about the withdrawal symptoms.
Insomnia is the most subjectively annoying withdrawal
symptom, followed by irritability and dysphoria.
It is not impossible to D/C BDZ for your patient as
soon as they are willing to start living their lives
without dependence.
