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Dr salman kareem
1st yr junior resident
Dept of Psychiatry
Meaning?
 symptoms that are experienced on stopping
prescribing drugs that are not drugs of dependence.
 Occurs after stopping many drugs , including anti
depressants
 d/f between discontinuation and withdrawal
symptoms – latter implies “ addiction”.
 Explained in context of “RECEPTOR REBOUND” eg :
an anti depressant in potent anti cholinergic side
effects may be associated with diarrohea on
discontinuation.
 depends on the elimination half-life of the drug and
the patient's metabolism.
 can mimic serious illness and can be very distressing
and intensely uncomfortable
Various
 Roughly divided into six categories
 Affective : Irritability
 Gastrointestinal : Nausea
 Neuromotor : Ataxia
 Vasomotor : diaphoresis
 Neurosensory: Paraesthesia
 Other neurological : increased day dreaming.
Diagnostic criteria
 duration symptoms are experienced by at least a third of
patients.
 Onset of symptoms – 5 days of stopping treatment
(depends on half life)
 Occasionally during taper or after missed doses.
 Symptoms can vary in form and intensity and occur in any
combination.
 symptoms cause clinically significant distress or
impairment and are not due to a general medical condition
or recurrence of a mental disorder
 Normally mild and self limiting but occasionally be severe
and prolonged.
Theories?
 electrophysiological changes in the brain (particularly
on the 5-HT receptor)
 electrophysiological changes in the body (nerve
growth factor) in the absence of the SSRI,
 dopamine dependency
 over-excited immune system
 Quantifies using discontinuation – emergent signs and
symptoms scale (DESS)
 Some symptoms are more likely with individual drugs.
Antidepressant
class
Drugs most
commonly
associated with
discontinuation
symptoms
Common
symptoms
Occasional
symptoms
MAOIs All
Tranylcypromine
is partly
metabolised to
amfetamine and is
therefore
associated with a
true ‘withdrawal
syndrome’
Agitation,
irritability, ataxia,
movement
disorders,
insomnia,
somnolence , vivid
dreams, cognitive
impairment,
slowed speech,
pressured speech.
Hallucinations,
paranoid
delusions.
Antidepressant
class
Drugs most
commonly
associated with
discontinuation
symptoms
Common
symptoms
Occasional
symptoms
TCAs Amitriptyline
lmipramine
Flu-like symptoms
( chills, myalgia,
excessive
sweating,
headache,
nausea),
insomnia,
excessive
dreaming
Movement
disorders, mania,
cardiac
arrhythmia
Antidepressant
class
Drugs most
commonly
associated with
discontinuation
symptoms
Common
symptoms
Occasional
symptoms
SSRIs and SNRIs
Buproprian
Paroxetine
Venlafaxine
Flu-like
symptoms,’ shock-
like’ sensations,
dizziness
exacerbated by
movement,
insomnia,
excessive(vivid)
dreaming,
irritability , crying
spells
Movement
disorders ,
problem with
concentration and
memory
Agomelatine None Few , if any
Mirtazapine Anxiety
, insomnia, nausea
Clinical relevance
 Symptoms may be mistaken for a relapse of illness or
the emergence of new physical illness.
 Symptoms may be some enough to interfere with daily
functioning.
 Evidence showing emerging suicidal thoughts on
discontinuation with “Paroxetine”.
 discontinuation of SSRIs may result in sexual
dysfunction
Who is most at risk?
 Risk is increased in those short half life drugs e.g.
paroxetine , venlafaxine particularly if not taken
regularly.
 Those who have been taking anti depressant for 8 wks
or longer.
 Those who develop symptoms of anxiety at the start of
the therapy.
 Centrally acting medication.
 Child and adolescents.
 Those who experienced discontinuation symptoms.
 Common in neonates born to woman taking
antidepressants and possibly breast feeding.*
*Drug Saf. 2001;24(3):183-97 Antidepressant discontinuation syndromes. Haddad PM
How to avoid
 Anti depressant therapy should be discontinued over
at least a 4 week period.
 Patient over MAOI’s need to be tapered over a long
period.
 At risk patients may need slow tapering.
 Psycho education about the symptoms.
How to treat
 Pragmatic
 If symptoms are mild – reassurance
 Reintroduce the original anti depressant (another with
a long half life from the same class) and taper
gradually while monitoring the dose.
 Evidence suggestive use of anti cholinergic agents in
tricyclic withdrawal of fluoxetine for symptoms
associated with stopping clomipramine and
venlafaxine.
Discontinuation syndrome

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Discontinuation syndrome

  • 1. Dr salman kareem 1st yr junior resident Dept of Psychiatry
  • 2. Meaning?  symptoms that are experienced on stopping prescribing drugs that are not drugs of dependence.  Occurs after stopping many drugs , including anti depressants  d/f between discontinuation and withdrawal symptoms – latter implies “ addiction”.
  • 3.  Explained in context of “RECEPTOR REBOUND” eg : an anti depressant in potent anti cholinergic side effects may be associated with diarrohea on discontinuation.  depends on the elimination half-life of the drug and the patient's metabolism.  can mimic serious illness and can be very distressing and intensely uncomfortable
  • 4. Various  Roughly divided into six categories  Affective : Irritability  Gastrointestinal : Nausea  Neuromotor : Ataxia  Vasomotor : diaphoresis  Neurosensory: Paraesthesia  Other neurological : increased day dreaming.
  • 5. Diagnostic criteria  duration symptoms are experienced by at least a third of patients.  Onset of symptoms – 5 days of stopping treatment (depends on half life)  Occasionally during taper or after missed doses.  Symptoms can vary in form and intensity and occur in any combination.  symptoms cause clinically significant distress or impairment and are not due to a general medical condition or recurrence of a mental disorder  Normally mild and self limiting but occasionally be severe and prolonged.
  • 6. Theories?  electrophysiological changes in the brain (particularly on the 5-HT receptor)  electrophysiological changes in the body (nerve growth factor) in the absence of the SSRI,  dopamine dependency  over-excited immune system
  • 7.  Quantifies using discontinuation – emergent signs and symptoms scale (DESS)  Some symptoms are more likely with individual drugs.
  • 8. Antidepressant class Drugs most commonly associated with discontinuation symptoms Common symptoms Occasional symptoms MAOIs All Tranylcypromine is partly metabolised to amfetamine and is therefore associated with a true ‘withdrawal syndrome’ Agitation, irritability, ataxia, movement disorders, insomnia, somnolence , vivid dreams, cognitive impairment, slowed speech, pressured speech. Hallucinations, paranoid delusions.
  • 9. Antidepressant class Drugs most commonly associated with discontinuation symptoms Common symptoms Occasional symptoms TCAs Amitriptyline lmipramine Flu-like symptoms ( chills, myalgia, excessive sweating, headache, nausea), insomnia, excessive dreaming Movement disorders, mania, cardiac arrhythmia
  • 10. Antidepressant class Drugs most commonly associated with discontinuation symptoms Common symptoms Occasional symptoms SSRIs and SNRIs Buproprian Paroxetine Venlafaxine Flu-like symptoms,’ shock- like’ sensations, dizziness exacerbated by movement, insomnia, excessive(vivid) dreaming, irritability , crying spells Movement disorders , problem with concentration and memory Agomelatine None Few , if any Mirtazapine Anxiety , insomnia, nausea
  • 11. Clinical relevance  Symptoms may be mistaken for a relapse of illness or the emergence of new physical illness.  Symptoms may be some enough to interfere with daily functioning.  Evidence showing emerging suicidal thoughts on discontinuation with “Paroxetine”.  discontinuation of SSRIs may result in sexual dysfunction
  • 12. Who is most at risk?  Risk is increased in those short half life drugs e.g. paroxetine , venlafaxine particularly if not taken regularly.  Those who have been taking anti depressant for 8 wks or longer.  Those who develop symptoms of anxiety at the start of the therapy.  Centrally acting medication.  Child and adolescents.
  • 13.  Those who experienced discontinuation symptoms.  Common in neonates born to woman taking antidepressants and possibly breast feeding.* *Drug Saf. 2001;24(3):183-97 Antidepressant discontinuation syndromes. Haddad PM
  • 14. How to avoid  Anti depressant therapy should be discontinued over at least a 4 week period.  Patient over MAOI’s need to be tapered over a long period.  At risk patients may need slow tapering.  Psycho education about the symptoms.
  • 15. How to treat  Pragmatic  If symptoms are mild – reassurance  Reintroduce the original anti depressant (another with a long half life from the same class) and taper gradually while monitoring the dose.  Evidence suggestive use of anti cholinergic agents in tricyclic withdrawal of fluoxetine for symptoms associated with stopping clomipramine and venlafaxine.