The chemistry and psychiatry of tapering - PowerPoint Presentation

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 painYawningSlide15
Slide16

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)