Detoxification from Benzodiazepines' Why, when and how

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Detoxification from Benzodiazepines.Why, when
and how

• Lucy Cockayne
• Lead Clinician

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Key points

• It is possible
• It is worth doing
• It needs the right time, the right support and
  the right regimen
• Relapse happens but should not be a reason not to
  try and keep trying!

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Not every one needs a detox

• Even with long term use mot everyone develops
  dependency.
• More likely when
• Longer durations of treatment
• Higher doses
• More potent benzodiazepines
• Shorter-acting drugs
• A history of anxiety problems
• (Kan et al 2004)

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ADDICTION IS A BRAIN DISEASE
AND IT MATTERS !!
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Drug addiction is a chronic, relapsing brain
disease
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Why detoxify

• Long term use
• Affects thinking and memory
• Reduces emotional responsiveness
• Increased depression and anxiety
• Most actually feel better after coming off the
  drugs the net curtain lifted
• Even short term consequences can be dire!! (look
  away if you are squeamish))

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BENZODIAZEPINES !!
temazepam injecting necrotizing fasciitis
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If the only tool you own is a hammer,
everything starts tolook like a nail
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Is it possible

• Evidence for brief interventions
• Evidence for various graded withdrawal regimens
  but no robust comparison (Sweetmen,
  Lingord-/hughes)
• Slow seems better (Ashton 1987) but cohort study

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Withdrawals depend on speed of reduction

• Most people only experience mild withdrawal
  symptoms when withdrawal is slow and tapered to
  their needs Ashton, 2002d.
• Severe withdrawal symptoms are associated with
  the following Kan et al, 2004
• Rapid withdrawal
• Prolonged use of benzodiazepines
• High-dose use
• Short-acting, potent benzodiazepines
• People with a history of anxiety problems
• Withdrawal symptoms characteristically vary in
  severity and type from day to day and from week
  to week. As some symptoms resolve, others may
  take their place. These symptoms gradually become
  less severe and less frequent with time Ashton,
  2002d.

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What has been tried?

• NO EVIDENCE for-
• Anticonvulsants
• Antipsychotics makes it worse!!
• Antidepressants
• Beta blockers
• Buspirone
• SOME evidence for propranolol
• Lingford- Hughes et al 2004

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Hard facts!

• Most people will become dependent after gt 6 weeks
  continuous use
• Only 30 of benzodiazepine dependent people ever
  get off them completely
• Methadone patients at high risk of
  benzodiazepine abuse (25 - 65)

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Why is it so hard to come off?

• Reducing causes increased excitation throughout
  the brain which causes the symptoms of
  withdrawal, including agitation, anxiety, and
  insomnia.
• The number of GABA receptors is slowly restored
  in response to benzodiazepine cessation or dose
  reduction.. The rate of withdrawal of treatment
  needs to allow time for GABA receptors to
  regenerate if withdrawal symptoms are to be
  minimized.

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Common problems when detoxing.

• Symptoms of depression
• Symtopms of anxiety
• Insomnia
• Worsening of pre-existing mental health problems
• OCD
• Panickattacks
• Psychotic symptoms

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Anxiety symptoms

• Common to all anxiety
• Agitation
• panic attacks
• agoraphobia
• Insomnia
• nightmares
• Depression
• Poor memory,
• loss of concentration

• Specific to withdrawal
• Perceptual distortions, depersonalization
• Hallucinations (visual and auditory)
• Tingling and loss of sensation, formication (a
  feeling of ants crawling over the skin)
• Sensory hypersensitivity
• Muscle twitches and fasciculations
• Psychotic symptoms, confusion, convulsions (rare)

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How long do symptoms last?

• Up to 15 of people develop protracted withdrawal
  symptoms (months or years)
• Anxiety- Gradually diminishes over 1 year
• Insomnia- Gradually diminishes over 62 months
• Depression- May last a few months
• responds to antidepressants
• Cognitive impairment- Gradually improves, but
  may last for gt1 year
• Perceptual symptoms (e.g.tinnitus, paraesthesia,
  pain (usually in limbs) Gradually recedes, but
  may last for at least 1 year and occasionally
  persist indefinitely
• Motor symptoms (e.g.muscle pain, weakness,
  tension, painful tremor, jerks) Usually gradually
  recede, but may last for gt1 year
• Gastrointestinal symptoms-Gradually recede, but
  may last for at least 1 year and occassionally
  persist indefinitely

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GABA BRAIN CIRCUITRY
60 - 75 OF ALL BRAIN SYNAPSES ARE GABAERGIC
natural tranquilliser
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Some people dont need benzos!
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Different detoxes for different types of
addiction?

• Therapeutic dose dependence.
• Prescribed high dose dependence
• More flexibility in reduction
• Recreational use of benzodiazepines
• to increase the "kick" obtained from illicit
  drugs
• alleviate the withdrawal symptoms of other drugs
  of abuse
• Tend to be fixed withdrawal why?

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Suggested principles.

• Where possible change to a long acting drug
  usually diazepam
• Avoid extra medication
• Antidepressants only useful for clinical
  depression or panic attacks
• SUPPORT.. SUPPORT.. SUPPORT!
• Family, friends, helplines, addiction or GP staff

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Why use diazepam?

• Withdrawal is most easily managed from diazepam
  because
• Diazepam and its metabolites (desmethyldiazepam
  and nordiazepam) have long half-lives (between
  20 hours and 200 hours), which ensures a gradual
  fall in blood concentrations. The blood level of
  its longest active metabolite for each dose falls
  by a half in about 8 days Micromedex, 2006

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When to detox?

• Sometimes required to get on a script
• Usually only short term success
• Well prepared
• Good physicaland psychological health
• Stable on other drugs e.g. methadone or anti
  depressants
• Stable personal circumstances

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Detox regimens

• Be flexible in following the schedule
• For people taking 40 mg per day of diazepam or
  less, a typical withdrawal schedule that is
  tolerated by most people would be to
• Reduce by 2 mg to 4 mg every 12 weeks to 20 mg
  per day
• Reduce by 1 mg to 2 mg every 12 weeks to 10 mg
  per day
• Reduce by 1 mg every 12 weeks to 5 mg per day
• Reduce by 0.5 mg to 1 mg every 12 weeks until
  completely stopped.
• Total withdrawal time from diazepam 40 mg per day
  might be 3060 weeks withdrawal from diazepam
  20 mg per day might take 2040 weeks.
• Stopping the last few milligrams is often seen by
  patients as being particularly difficult but this
  is usually an unfounded fear derived from
  long-term psychological dependence on
  benzodiazepines.

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RCGP new guidelines

• Highlight benefits of stopping
• Recommend FLEXIBLE, GRADUAL reduction, tailored
  to individual
• consider the need for psychological support
• When symptoms arise
• Explain
• Slow or suspend withdrawal

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New developments
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FLUMAZENIL

• benzodiazepine receptor antagonist (high
  affinity, low agonist action)
• attenuates withdrawal and reduces withdrawal
  symptoms signs
• normalizes and upregulates BZD receptors
• restores GABA receptor allosteric structure and
  inhibits BZD induced uncoupling
• reverses tolerance
• reduces craving

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Intravenous flumazenil versus oxazepam in the
treatment of benzodiazepinewithdrawal a
randomized, placebo-controlled study

• Gerra G et al
• Addiction Biology 7385 -395, 2002

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Single-blind, randomized, placebo- controlled
trial

• (n 20) IV flumazenil 1mg in 500ml normal saline
  over 4hrs x twice daily (0900 - 1300 1430 -
  1830) for 8 days (oxazepam 30mg,15mg, 7.5mg
  nocte x 3 days)
• (n 20) tapering oxazepam 105mg - 7.5mg over 8
  days
• (n 10) placebo tablets and saline infusion

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Intravenous flumazenil in the treatment of
benzodiazepine dependence

• reduced withdrawal symptoms signs
• reduced craving
• reduced post detoxification relapse rates

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Intravenous flumazenil in the treatment of
benzodiazepine dependence

• reduced post detoxification relapse rates
• DAY 30
• FLUMAZENIL 40
• OXAZEPAM 70

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Westmead protocol

• IV flumazenil 1mg in 500mg normal saline per 6
  hours continuous infusion for 4 - 5 days
• No benzodiazepine supplementation
• 24 hours post infusion observation

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BENZODIAZEPINE ABSTINENCE AT LONG TERM FOLLOW-UP

• I MONTH
• Abstinent 75
• Known Relapse 11
• Relapse lost to follow up 25
• 3 MONTHS
• Abstinent 54
• Known Relapse 34
• Relapse lost to follow up 46

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References

• Ashton, C.H. (1987) Benzodiazepine withdrawal
  outcome in 50 patients. British Journal of
  Addiction 82(6), 665-671.
• Ashton, C.H. (2002a) Benzodiazepines how they
  work and how to withdraw. The Ashton Manual.
  University of Newcastle. www.benzo.org.uk
  Accessed 16/03/2006. Free Full-text
• Ashton, C.H. (2002b) How to withdraw from
  benzodiazepines after long-term use. The Ashton
  Manual. University of Newcastle. www.benzo.org.uk
  Accessed 31/03/2006. Free Full-text
• Ashton, C.H. (2002c) Slow withdrawal schedules.
  The Ashton Manual. University of Newcastle.
  www.benzo.org.uk Accessed 31/03/2006. Free
  Full-text
• Ashton, C.H. (2002d) Benzodiazepine withdrawal
  symptoms, acute and protracted. The Ashton
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• Ashton, C.H. (2004a) Protracted withdrawal
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References (cont)

• BNF 51 (2006) British National Formulary. 51st
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References (cont)

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