Jane C Ballantyne University of Washington Seattle Dr Ballantyne has no conflicts of interest or disclosures Consider the role of endogenous opioid systems Current theories about the ID: 743880
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Slide1
The chemistry and psychiatry of tapering
Jane C
Ballantyne
University of Washington, SeattleSlide2
Dr
Ballantyne
has no conflicts of interest or disclosuresSlide3
Consider the role of endogenous opioid systemsSlide4
Current theories about the
purposes
of the endogenous opioid
system suggest two important categories:
to provide stress-related pain relief and pain enhancement (injury-related “physical pain”)to facilitate maternal-infant and other attachmentsDisruption of social attachments, particularly maternal-infant attachments is one of the primary causes of “social and emotional pain”The suffering of chronic pain patients encompasses both physical and emotional pain that has often been refractory to treatment other than opioids
Top down viewpoint
Dysphoric social dimension
Contributes as much
as
nociception
Accepts that mechanisms at the cellular level have evolved through evolutionary processes over millions of years Slide5
Neuroadaptations
are
integrated
biological adaptations that underlie the clinical manifestations of analgesia,
hyperalgesia
, tolerance, dependence and addictionway
to avoid iatrogenic addictionOpioid adaptationsSlide6
Opioid induced
hyperalgesia
Tolerance, dependence and withdrawal
hyperalgesia
Enduring adaptations – role of memory - irreversible Slide7
Opioid induced
hyperalgesiaSlide8
Model of
neuroadaptive
changes underlying expression and recovery of opioid-induced
hyperalgesia
Angst & Clark Anesthesiology 2006;104:570Slide9
Tolerance, dependence and withdrawal
hyperalgesiaSlide10
Psychological
Associative (learned) tolerance
Environmental clues
Psychological factors
Pharmacological
Nonassociative
(adaptive) toleranceCellular processReceptor down-regulation
turnover rate
number
Receptor desensitization
NMDA linked
Tolerance has an
important psychological componentSlide11
Pharmacological (but not psychological) tolerance can be partly overcome by
opioid rotation
Confocal microscopy of MOR-1 and MOR-1C in the dorsal horn of the spinal cord
Rotation to another opioid overcomes tolerance to some degree. Clinically, can reduce to ½ MED to achieve same analgesia.
Pasternak Neuroscientist 2001;7:220-31Slide12
Physical – regions of control of somatic function - locus
ceruleus
(noradrenergic nucleus)
upregulation of cAMP arousal, agitation, diarrhea, rhinorrhea, piloerectionEmotional/psychological – reward centers hedonia and anhedonia
Pain pathways analgesia and
hyperalgesiaBallantyne & LaForge, Pain 2007;129:235Ballantyne et al, Arch Int Med 2012;172:1342
Dependence is inevitable with continuous useSlide13
NORMAL
EUPHORIA
ANALGESIA
DYSPHORIA
HYPERALGESIA
Opioid dependence is
an adaptation
PAIN
PAIN RELIEF
WORSE PAINSlide14
Manifestations of withdrawal
Note: Withdrawal symptoms are not necessarily explosive and obvious. They may be insidious and even imperceptible.
Hyperalgesia
– whole body aches and pains
Dysphoria and distressRestlessnessAnxietyTearing upRunny noseSweatingNausea and vomitingAbdominal painYawningSlide15Slide16
Enduring adaptations
Explain relapse
Result of complex interactions between drugs themselves and the circumstances under which they are taken
Neuroadaptation occurs through gene regulation, remodeling of circuits, changes in intrinsic excitability, increased in synaptic strength, actual morphological changes
These adaptations may also alter analgesia and tolerance Slide17
Cami
, J. et al. N
Engl
J Med 2003;349:975-986
Metabotropic Mechanisms of Action of Drugs of AbuseSlide18
What is addiction?Slide19
Ballantyne &
LaForge
Pain 2007;129:235-55 Slide20
DSM V Behavioral criteria for Substance Use Disorder
A maladaptive pattern of substance use leading to clinically significant impairment or distress as manifested by 2 or more of the following:
Failure to fulfill major role obligations at work, school or home
Continue in situations in which it is physically hazardous (eg driving)Persistent or recurrent social or interpersonal problems Substance taken in larger amounts or longer than was intended Persistent desire or unsuccessful efforts to cut downGreat deal of time spent in activities necessary to obtain substance, use substance or recover from substance use Important social, occupations or recreational activities given up or reduced Continued use despite knowledge of harmCravingSlide21
How we think of addiction
How we think
of dependence on pain medication
Are
they biologically any different?Slide22
GRAY ZONE
ADDICTED
NOT ADDICTED
Meets DSM criteria for addiction
No lost prescriptions
No ER visitsNo early prescriptionsNo requests for dose escalationNo UDT aberranciesNo doctor shopping (PMP)Slide23
Dependence/addiction develops through pain treatment
Dependence/addiction develops through recreational drug use
DSM Criteria
Social Disruption
Loss of control over useContinued use despite knowledge of harm(Craving) (may not be manifest until off)Pestering reluctant doctorsUsing opioid to treat painPredominant symptom of withdrawal - painOpioid seeking behaviors
Need to procure opioidOften use paraphernaliaPredominant symptom of withdrawal - anhedonia
Do not accept that anything is wrong other than painAccept that they are addictedSlide24
What happens when you taper?Slide25
Withdrawal symptoms can be insidious and last for months
Withdrawal
hyperalgesia
can trick the mind into believing opioids were needed
The difficulty of overcoming withdrawal symptoms often hampers efforts to taper opioidsThe most difficult to overcome is psychological dependenceEnduring adaptations may mean risk of relapse after successful tapering (this applies to prescription opioid dependence as well as opioid use disorder)