Prescription

 Drug  Misuse  2018  

Darius  A.  Rastegar,  MD  

Learning  Objectives  

After  completing  this  module,  the  learner  will:  

1. Describe  the  epidemiology  and  public  health  impact  of  prescription  drug  misuse  
 
2. Identify  misused  prescription  medications  
 
3. Describe  risk  factors  for  prescription  drug  misuse.  
 
4. Implement  strategies  for  preventing,  identifying,  and  managing  prescription  drug  misuse  in  their  
clinical  practice.  
a. Patient  assessment  
b. Treatment  Plan  
c. Monitoring    
 
Objective  1:  Overview  of  prescription  drug  misuse  

Case   1:   A   20   year-­‐old   college   student   comes   for   a   routine   check   up.     He   is   not   on   any   prescribed  
medications,  but  admits  that  he  occasionally  gets  amphetamines  from  classmates  to  help  him  stay  up  to  
finish  projects.    He  has  not  had  any  ill  effects  from  taking  the  amphetamines.  

Which  one  of  the  following  terms  best  characterizes  this  pattern  of  use?  

a. Amphetamine  dependence.  
b. Amphetamine  misuse  
c. Therapeutic  use  of  amphetamine  
d. Amphetamine  addiction.  

Pop  up  answers:  

a. Incorrect.  This  pattern  of  use  does  not  meet  criteria  for  dependence.  
b. Correct!  This  pattern  of  use  does  not  meet  criteria  for  misuse.  
c. Incorrect.     Using   psychoactive   substances   for   purposes   or   by   persons   other   than   intended  
would  generally  be  considered  “misuse”    
 d. Incorrect.   There   is   not   sufficient   evidence   from   this   description   to   say   that   the   patient   is  
addicted.  

Summary  Answer:  The  correct  answer  is  C:  Using  prescription  medication  in  any  manner  other  than  that  
prescribed/intended  by  a  practitioner  is  referred  to  as  “misuse”.    “Addiction”  and  “dependence”  refer  to  
levels  of  misuse  that  have  not  been  met  in  the  description  of  this  case.  

Introduction:  

Prescription   drugs   of   a   number   of   different   classes   may   be   misused,   but   prescription   opioids   in  
particular   have   become   cause   for   major   public   health   concern,   as   rates   of   nonmedical   use   have  
increased,   causing   significant   morbidity,   mortality,   and   social   costs.   The   increase   in   nonmedical   use  
parallels   an   increase   in   prescribing   opioids   (1)   with   more   aggressive   treatment   of   chronic   pain   in   the  
primary  care  setting  over  the  last  20-­‐30  years  (2).    

The  following  figure  shows  the  parallel  increases  in  sales  of  prescription  opioids,  deaths  from  overdose  
and  entry  into  treatment.  

SOURCE:  CDC,  Prescription  Painkiller  Overdoses  in  the  US,  11/1/2011  

This   module   will   present   an   overview   of   nonmedical   use   of   prescription   drugs   and   prescription   drug   use  
disorders   including   epidemiology,   a   review   of   specific   classes   of   drugs,   risk   factors,   and   strategies   for  
prevention,  identification,  and  management.  
Definitions  

Substance   use,   including   prescription   drug   use,   exists   along   a   spectrum,   ranging   from   aberrant   or  
unhealthy  use  to  substance  use  disorders  (SUD)  as  classified  in  the  Diagnostic  and  Statistical  Manual  of  
Mental  Disorders  (DSM  5)  (4).  Please  refer  to  the  “Addiction:  Illicit  Drugs”  module  for  a  discussion  of  the  
DSM  5  criteria.      
 
The  terms  ‘prescription  drug  abuse’  or  ‘prescription  drug  misuse’  are  also  often  used  as  broad  terms  to  
refer  to  problematic,  unhealthy,  or  non-­‐prescribed  use  of  prescription  drugs.  This  may  lead  to  confusion  
and  ambiguity  about  whether  one  is  referring  to  a  substance  use  disorder,  or  referring  to  problematic  
medication-­‐taking  behavior.    The  Substance  Abuse  and  Mental  Health  Services  Administration  (SAMHSA)  
defines   prescription   drug   misuse   as   “use   in   any   way   not   directed   by   a   doctor,   including   use   without   a  
prescription  of  one’s  own;  use  in  greater  amounts,  more  often,  or  longer  than  told  to  take  a  drug;  or  use  
in  any  other  way  not  directed  by  a  doctor.”  

For  the  purposes  of  this  module,  we  will  use  the  terms  ‘substance  use  disorder’  (SUD)  or  'prescription  
drug  use  disorder'  to  refer  specifically  to  prescription  drug  use  meeting  DSM  5  criteria,  and  will  use  the  
term  ‘misuse.’  to  refer  more  broadly  to  problematic  prescription  drug  use  or  that  does  not  necessarily  
meet  DSM  criteria  for  substance  use  disorders.      
 
Another  frequently  used  term  is  aberrant  drug-­‐related  behaviors  (ADRB)  (sometimes  also  referred  to  as  
aberrant   drug-­‐taking   behaviors   or   aberrant   medication-­‐taking   behaviors).     ADRB   are   a   spectrum   of  
patient   behaviors   that   may   reflect   misuse,   but   in   themselves   do   not   necessarily   establish   misuse   or   a  
substance  use  disorder  (5,  6).    A  pattern  of  aberrant  medication  taking  behaviors,  or  severe  or  persistent  
ADRB  should  trigger  further  evaluation  for  misuse  or  a  substance  use  disorder.    

Some  examples  of  ADRB  may  include:  

• Requests  for  early  refills  (e.g.,  running  out  of  medication  earlier  than  expected)  
• Reporting  lost  or  stolen  medication  
• Obtaining  prescription  medications  from  multiple  clinicians  
• Taking  more  medication  than  prescribed/recommended  
• Borrowing  or  stealing  another  person’s  medications  
 • Using  medication  for  the  purpose  of  affecting  one’s  mood  
• Illicit  drug  use  or  nonmedical  use  of  other  prescription  drugs  
• Illegal  activities  such  as  forging  prescriptions  or  diversion  of  medication  

Of   course,   these   behaviors   are   not   equally   problematic   or   concerning;   for   example,   forging   a  
prescription  would  be  a  strong  indication  of  a  problem,  while  taking  a  few  extra  doses  of  medication  is  
of  less  concern.  
 

Objective  2:  The  epidemiology  and  public  health  impact  of  prescription  drug  misuse  

CASE  2:  Ms.  S  is  a  67  year-­‐old  woman  with  history  of  chronic  low  back  pain,  hypertension,  and  history  of  
depression.   She   is   brought   into   the   emergency   room   via   EMS   after   being   found   somnolent   and  
minimally   responsive   by   her   daughter.   She   responded   well   to   intramuscular   naloxone   administered   in  
the   field.     Prescription   bottles   found   on   the   kitchen   counter   include   extended-­‐release   oxycodone,  
hydrocodone/acetaminophen,  and  lorazepam.      
Which  of  the  following  is  a  risk  factor  for  overdose  among  patients  being  prescribed  opioids?  

a. Higher  dose  
b. Female  gender  
c. History  of  back  pain  
d. Use  of  combination  formulation  hydrocodone/acetaminophen  
Pop-­‐up  answers:  
a. Correct!     Several   studies   have   demonstrated   that   the   risk   of   fatal   and   nonfatal   overdose  
increases  with  higher  prescribed  doses  of  opioids.    
b. Incorrect.     There   is   no   evidence   for   an   association   between   gender   and   prescribed   opioid  
overdose.  
c. Incorrect.     There   is   no   evidence   for   an   association   between   back   pain   and   prescribed   opioid  
overdose.  
d. Incorrect.   There   are   no   data   to   suggest   that   the   use   of   acetaminophen   containing  
formulations  of  opioid  analgesics  increase  the  risk  of  overdose.    However,  in  2011  the  FDA  
added   a   black   box   warning   to   prescription   medications   containing   acetaminophen  
underscoring  the  potential  for  severe  liver  injury  with  acetaminophen-­‐containing  products.    
 
Summary  answer:  The  correct  answer  is  A:  the  risk  of  overdose  increases  with  the  dose  prescribed.    The  
other  factors  have  not  been  shown  to  increase  overdose  risk.  

The  epidemiology  and  public  health  impact  of  prescription  drug  misuse  

According  to  the  2015  NSDUH,  an  estimated  119  million  Americans  aged  12  or  older  used  prescription  
psychotherapeutic   drugs   in   the   past   year;   this   is   44.5%   of   the   population.     An   estimated   18.9   million  
persons  aged  12  and  older  in  the  US  (7.1%  of  the  population)  misused  prescription  medications  in  the  
past   year   (3).   An   estimated   2.7   million   Americans   had   a   prescription   drug   use   disorder   (1.0%   of   the  
population   aged   12   or   older).     The   most   commonly   misused   prescription   drugs   were   pain   relievers  
(opioids)  followed  by  tranquilizers  (mainly  benzodiazepines),  stimulants,  and  then  sedatives  (1).    

Sources  

As   shown   in   the   figure   below,   according   to   the  NSDUH,   in   2010-­‐11,   among   those   who   used   prescription  
analgesics  non-­‐medically  in  the  past  year,  54%  obtained  the  pain  relievers  they  most  recently  used  from  
a   friend   or   relative   for   free   and   approximately  17%   bought   or   took   them   from   a   friend   or   relative.     In  
81%  of  the  instances  where  nonmedical  users  obtained  the  drugs  from  a  friend  or  relative  for  free,  the  
individuals  indicated  that  their  friend  or  relative  had  obtained  the  drugs  from  just  one  doctor.      

 
Figure  2.  Source  Where  Pain  Relievers  Were  Obtained  for  Most  Recent  Nonmedical  Use  among  Past  Year  
Users  Aged  12  or  Older:  2010-­‐2011  (SAMHSA  2012).  

This  shows  that  physician  prescriptions  are  the  primary  source  of  prescription  opioids  that  are  used  non-­‐
medically.  

Public  health  burden  

As   opioid   prescribing   has   increased,   morbidity   and   mortality   from   opioid   overdose   has   increased  
substantially   in   the   United   States   over   the   last   decade   (7-­‐12).   In   2009,   over   500,000   emergency  
department   visits   in   the   United   States   involved   the   nonmedical   use   of   pain   relievers,   over   400,000   of  
which  were  opioid  analgesics  (13).    According  to  the  Centers  for  Disease  Control  and  Prevention  (CDC),  
drug   overdose   death   rates   in   the   United   States   have   more   than   tripled   since   1990   and   are   at   an   all-­‐time  
high.  (14).  
 

The   problem   of   increased   overdose   morbidity   and   mortality   is   complex   and   multifactorial.     A   study   of  
unintentional   prescription   medication   overdose   deaths   in   West   Virginia   (a   state   that   had   a   550%  
increase   in   unintentional   poisoning   deaths   from   1999-­‐2004)   found   that   63%   of   unintentional  
prescription   medication   overdose   deaths   in   2006   were   associated   with   diversion   of   prescription  
medications  and  that  21%  were  associated  with  doctor  shopping  (defined  as  having  five  more  clinicians  
prescribing   controlled   substances   in   the   prior   year).   The   majority   of   cases   involved   opioids   (93%)   but  
other   potentially   contributing   substances   were   present   in   79%.     Additionally,   among   those   who   died,  
78%  had  a  history  of  substance  use  disorder.  (7)  

The  dose  of  opioids  prescribed  is  another  important  factor  in  the  risk  of  overdose.    A  study  of  over  9,000  
health  maintenance  organization  patients  found  that  in  comparison  with  patients  receiving  1-­‐20  mg/day  
of   morphine   equivalents,   those   receiving   50-­‐99   mg   of   morphine   equivalents   per   day   had   a   3.7-­‐fold  
increased   in   overdose   risk   and   those   receiving   100   mg   or   more   morphine   equivalents   per   day   had   a   8.9-­‐
fold  increased  in  overdose  risk.    Patients  who  recently  received  sedative-­‐hypnotic  medications  were  also  
at  increased  risk  for  overdose  (15).      

Finally,   the   type   of   opioid   prescribed   appears   to   be   factor   and   long-­‐acting   opioids,   particularly  
methadone  prescribed  for  chronic  pain,  have  been  associated  with  a  higher  risk  of  fatal  overdose  than  
other  opioids.  (16)  
Objective  3.  Prescription  medications  with  the  potential  for  misuse.      

CASE  3:    A  23  year-­‐old  medical  student  comes  in  your  office  for  a  routine  check-­‐up.    Other  than  a  history  
of  ADHD,  he  reports  no  medical  or  psychiatric  history.    His  physical  exam  is  normal.  On  the  way  out  the  
door  he  asks  for  a  refill  of  his  ‘Adderall’  usually  prescribed  by  his  family  physician  in  his  hometown.      
Which  of  the  following  is  NOT  a  potential  adverse  effect  associated  with  amphetamine-­‐type  stimulants?  
a. Seizures  
b. Cardiac  arrhythmias  
c. Hypersomnolence  
d. Agitation  
Pop-­‐up  answers:  
a. Incorrect.   Medical   consequences   of   amphetamine-­‐type   stimulant   use   may   include  
hyperthermia,  cardiac  arrhythmias,  and  seizures  
b. Incorrect.   Acute   effects   of   stimulant   use   include   hypertension,   tachycardia,   tachypnea,  
anorexia,   and   insomnia.     Medical   consequences   of   amphetamine-­‐type   stimulant   use   may  
also  include  cardiac  arrhythmias.  
c. Correct!     Hypersomnolence   is   NOT   an   adverse   effect   associated   with   stimulant   use.    
Insomnia  is  an  acute  effect  of  stimulant  use.  
d. Incorrect.  Psychiatric  side  effects  of  stimulants  include  agitation,  paranoia,  or  hostility  with  
repeated  doses  over  short  periods  of  time.        
Summary   answer:   The   correct   answer   is   C.     Stimulants   increase   alertness   and   do   not   cause  
hypersomnolence.    Other  adverse  effects  include  seizures,  cardiac  arrhythmias  and  agitation.  
 
Prescription  Medications  with  the  Potential  for  Misuse.      

Opioid  analgesics    

Of   the   almost   19   million   persons   in   the   US   reporting   misuse   of   prescription   medications,   the   majority  
used   pain   relievers   (prescription   opioids).   (1).   With   chronic   use   of   opioids,   even   when   taken   as  
prescribed,  physiological  dependence,  including  manifestations  of  tolerance  and  withdrawal  is  expected.  
It  is  important  to  distinguish  this  physiologic  dependence  from  a  substance  use  disorder.  Available  data  
suggests  that  the  rates  of  opioid  use  disorders  among  chronic  pain  patients  on  long-­‐term  opioid  therapy  
ranges   from   3%   to   20%,   depending   on   the   patient   population   and   how   the   problem   is   defined   (17).    
Moreover,  when  compared  to  those  not  taking  opioids,  those  receiving  long-­‐term  prescription  opioids  
do  have  higher  rates  of  substance  use  disorders  (18,  19).  

Prescription  Stimulants    

Prescriptions  stimulants,  including  amphetamine  and  methylphenidate,  are  approved  by  the  FDA  for  the  
treatment  of  attention-­‐deficit/hyperactivity  disorder  (ADHD),  but  have  also  been  demonstrated  to  have  
misuse   liability   (20).     Reasons   cited   for   misuse   of   prescription   stimulants   include   to   increase  
concentration  and  alertness,  as  well  as  for  their  euphoric  properties  (21).    

In   addition   to   the   risks   of   developing   substance   use   disorder,   there   are   a   number   of   medical   and  
psychiatric   consequences   of   stimulant   misuse.     Acute   effects   of   stimulant   use   include   hypertension,  
tachycardia,   tachypnea,   anorexia,   and   insomnia.     Withdrawal   symptoms   from   stimulants   may   include  
fatigue,  depression,  and  sleep  disturbances.    Other  consequences  from  stimulant  use  include  psychiatric  
side   effects   including   agitation,   paranoia,   or   hostility   with   repeated   doses   over   short   periods   of   time.    
Medical  consequences  may  include  hyperthermia,  cardiac  arrhythmias,  and  seizures.  
 

Sedative-­‐hypnotics  

Sedatives,   hypnotics,   and   anxiolytic   medications   are   examples   of   central   nervous   system   (CNS)  
depressants  that  have  misuse  potential.    Benzodiazepines  have  largely  replaced  barbiturates  and  related  
drugs   as   the   prescribed   sedative-­‐hypnotics   of   choice,   as   the   benzodiazepines   have   a   better   safety  
profile.     Benzodiazepines   are   used   as   sedative-­‐hypnotics,   anxiolytics,   in   the   treatment   of   alcohol  
withdrawal,   as   anticonvulsants,   and   as   muscle   relaxants.     Other   drugs   in   the   class   include   the   non-­‐
benzodiazepine  hypnotics,  zolpidem,  zaleplon,  and  eszopiclone.    

Benzodiazepines   are   reinforcing   and   have   abuse   potential   as   well   as   produce   physiologic   dependence  
with   a   sedative-­‐hypnotic   type   withdrawal   syndrome.   They   have   additive   effects   with   other   CNS  
depressants,   among   other   drug   interactions;   they   also   have   deleterious   effects   on   memory,   cognition,  
and   psychomotor   function.     Despite   their   addictive   potential,   benzodiazepines   were   the   primary  
substance   of   misuse   for   less   than   1%   of   people   admitted   for   addiction   treatment   in   the   US   between  
1995   and   2005.     Most   of   these   treatment   admissions   also   reported   misuse   of   alcohol   or   opioids   in  
addition  to  benzodiazepines.  (22)  
 
Other  Medications      

Other  prescription  drugs  with  potential  misuse  liability  include:    

• Dissociative  anesthetics  (e.g.,  ketamine)  

•  Muscle  relaxers  (e.g.,  carisoprodol)    
• Anti-­‐emetics  (e.g.,  promethazine)  
• Gabapentinoids  (e.g.,  pregabalin)  
• Atypical  antipsychotics  (e.g.,  quetiapine)  
• Bupropion  
• Anabolic-­‐androgenic  steroids  (AAS).    

A   detailed   discussion   of   all   misused   drugs   is   beyond   the   scope   of   this   module.     We   will   focus   on   opioids,  
which   is   the   most   commonly   misused   class   and   the   one   responsible   for   the   most   harm.     Many   of   the  
principles  discussed  will  also  apply  to  other  classes  of  drugs.    

Objective  4.  Risk  factors  for  prescription  drug  use  disorders  

CASE  4:    Mr.  B  is  a  57  year-­‐old  man  with  hypertension,  hyperlipidemia,  COPD,  and  obesity.    He  smokes  
one-­‐half   pack   per   day   after   cutting   back   from   two   packs   a   day   for   years.     He   has   a   history   of   motor  
vehicle  accident  five  years  ago  and  has  had  chronic  back  pain  since  then.    He  has  not  had  any  further  
work  up  since  the  initial  accident,  and  recently  transferred  to  your  care  from  another  provider.    He  has  
tried  NSAIDS  with  little  relief.    He  started  physical  therapy  at  your  request  two  weeks  ago,  which  he  feels  
is  not  helping.    He  is  now  requesting  a  prescription  for  extended-­‐release  oxycodone,  which  he  thinks  will  
help   him   get   through   the   day.     He   especially   has   trouble   with   stairs   and   he   lives   alone   in   a   walk-­‐up  
apartment.    Which  of  the  following  is  the  best  next  step?  

a. Write   a   prescription   for   a   one   month   supply   of   extended-­‐release   oxycodone   and   see   him  
back  in  a  month,  since  he  has  never  demonstrated  any  prior  history  of  aberrant-­‐drug  related  
behaviors.  
b. Obtain   records   from   his   prior   health   care   provider.   Prescribe   a   limited   supply   of   immediate-­‐
release  oxycodone  for  breakthrough  pain  and  see  him  back  in  two  weeks.  
c. Refer  to  a  chronic  pain  specialist  for  further  management.      
d. Refuse   to   prescribe   any   analgesics   other   than   NSAIDS,   unless   he   completes   a   course   of  
physical  therapy  first.  
Pop-­‐up  answers:  

a. Incorrect.    While  he  may  be  a  candidate  for  opioid  analgesic  therapy,  he  has  at  least  one  risk  
factor   for   prescription   drug   misuse   (tobacco   dependence).     Further   evaluation   of   the  
etiology  of  his  pain  and  assessments  of  the  relative  risks/benefits  of  opioid  therapy  would  
be  indicated  first.    
b. Correct!    Obtaining   a   thorough   medical  history,  including  prior  medical  records  is  important  
to   understand   the   etiology   of   his   pain,   what,   if   any,   diagnostic   workup   has   been   performed,  
and   if   there   is   any   history   of   other   risk   factors   or   aberrant   medication-­‐taking   behaviors.    
Imaging  would  be  appropriate  if  no  recent  imaging  has  been  performed.  Encouraging  him  to  
continue  physical  therapy  in  order  to  obtain  maximal  benefit  would  be  important  as  well.    A  
trial   of   opioid   therapy   may   be   reasonable   in   this   patient,   with   clear   treatment   goals   and  
close  follow  up.  
c. Incorrect.     A   chronic   pain   specialist   may   be   appropriate   in   the   future   for   this   patient.  
However,  at  this  point,  further  history  and  diagnostic  workup  is  warranted.  
d. Incorrect.     The   patient’s   pain   clearly   impacts   his   day-­‐to-­‐day   functioning   and   must   be  
addressed.     Encouraging   him   to   continue   physical   therapy   is   likely   warranted.     However,  
additional  therapeutic  options  should  be  considered  and  explored.  

Summary   answer:   The   correct   answer   is   B.     Obtaining   a   medical   history,   including   prior   medical   records  
is  important  to  understand  the  etiology  of  his  pain,  what,  if  any,  diagnostic  workup  has  been  performed,  
and  if  there  is  any  history  aberrant  medication-­‐taking  behaviors.  Encouraging  him  to  continue  physical  
therapy  in  order  to  obtain  maximal  benefit  would  be  important  as  well.    A  trial  of  opioid  therapy  may  be  
reasonable  in  this  patient,  with  clear  treatment  goals  and  close  follow  up.    It  would  not  be  appropriate  
to  start  with  long-­‐acting  opioid  at  this  point.  

Risk  factors  for  prescription  drug  use  disorders  

As  described  earlier,  there  is  a  range  of  behaviors  along  the  spectrum  of  prescription  drug  use,  ranging  
from  therapeutic  use,  to  aberrant  drug-­‐related  behaviors  (ADRB)  of  varying  severity,  and  to  substance  
use   disorder.   The   most   consistent   risk   factor   for   misuse   of   prescription   drugs   is   a   personal   history   of  
substance  use  disorders  (23)  including  tobacco  use  (24).    Additional  risk  factors  that  have  been  identified  
are:   family   history   of   substance   use   disorders   (25)   psychiatric   illness   (26)   and   history   of   incarceration  
(25).    
A   study   of   prescription   drug   use   disorders   among   patients   with   chronic   pain   who   were   taking   analgesics  
in  an  urban  primary  care  clinic  found  that:    

• 18%  met  criteria  for  lifetime  prescription  drug  use  disorder  

• 25%  met  the  criteria  for  another  lifetime  substance  use  disorder  diagnosis.      
• Of   those   with   a   prescription   drug   use   disorder,   90%   also   had   another   substance   use  
disorder.      
Other   risk   factors   associated   with   a   prescription   drug   use   disorder   included   history   of   incarceration,  
greater   limitations   from   pain,   smoking,   family   history   of   substance   use   disorder,   male   gender,   and  
history   of   post-­‐traumatic   stress   disorder.     The   investigators   also   found   that   all   patients   with   a  
prescription   drug   use   disorder   had   at   least   2   risk   factors,   and   among   those   with   six   or   more   risk   factors,  
over  90%  had  a  prescription  drug  use  disorder  (24).        

In   another   study   that   evaluated   nonmedical   use   of   prescription   opioids   from   the   NSDUH   2002-­‐2004  
surveys   for   correlates,   found   that   non-­‐medical   use   in   the   previous   year   was   associated   with   panic,  
depressive   and   social   phobic/agoraphobic   symptoms.     Of   those   with   non-­‐medical   use,   13%   met   the  
criteria   for   a   substance   use   disorder   (26).     Another   study   of   veterans   referred   for   behavioral   health  
evaluation   by   their   primary   care   physicians   found   that   younger   age,   depressive   symptoms,   smoking,  
illicit  drug  use,  and  chronic  pain  were  associated  with  non-­‐medical  use  of  prescription  drugs  (27).    

These   studies   suggest   that   certain   identifiable   risk   factors   can   help   alert   the   practitioner   to   which  
patients   might   be   most   at   risk   for   developing   a   prescription   drug   use   disorder.   This   should   prompt  
clinicians  to  prescribe  mindfully  and  monitor  carefully  and  to  take  this  into  account  when  weighing  the  
benefits  and  risks  of  prescribing  a  controlled  substance.    In  the  next  section,  we  will  discuss  strategies  
for  prevention,  as  well  as  identification  and  management  of  patients  who  misuse  prescription  opioids.    

Objective  5.    Strategies  for  preventing  and  addressing  prescription  drug  misuse.  

CASE  5:    A  55  year-­‐old  man  who  transferred  into  your  care  a  few  months  ago,  has  chronic  leg  pain  due  
to   venous   stasis   ulcers.     He   is   under   the   care   of   a   wound   specialist,   but   you   are   his   primary   care  
provider.     He   came   to   you   on   a   regimen   of   extended-­‐release   oxycodone   20   mg   every   12   hours,   plus  
oxycodone/acetaminophen   10/325,   one   tablet   three   times   a   day   as   needed   for   breakthrough   pain.     You  
continued   this   regimen,   as   he   had   been   on   it   for   several   years   and   was   reluctant   to   change.     He   calls  
your  office  and  has  run  out  of  his  oxycodone/acetaminophen  early,  because  he  has  been  taking  two  or  
three  tablets  three  times.      

Which  of  the  following  is  the  best  course  of  action?  

a. Give   him   a   new   prescription   for   a   one-­‐month   supply   of   oxycodone/acetaminophen   to   be  

taken  two  tablets  every  eight  hours.  
b. Taper  him  off  opioids  and  discontinue  opioid  therapy.  
c. Increase   his   extended-­‐release   oxycodone   dose,   provide   a   limited   supply   of   a   short-­‐acting  
opioid  for  breakthrough  pain  and  see  him  back  in  two  weeks.    
d. Switch  to  methadone  for  chronic  pain  

Pop-­‐up  answers:  

a. Incorrect.     The   patient   is   on   both   long   and   short-­‐acting   oxycodone,   but   is   using   the   short-­‐
acting   formulation   around-­‐the-­‐clock   rather   than   for   breakthrough   pain.   While   there   is   no  
one   correct   approach,   an   adjustment   of   his   extended-­‐release   oxycodone   might   be  
warranted  for  better  around-­‐the-­‐clock  coverage.    In  addition,  two  tablets  every  eight  hours  
of   oxycodone/acetaminophen   might   be   inadequate,   as   he   is   sometimes   taking   even   more  
than  this.    He  should  be  evaluated  for  causes  for  the  need  of  escalation,  and  monitored  for  
adverse  effects.      
b. Incorrect.     We   should   do   our   best   to   help   this   patient   with   his   pain.     Running   out   of  
medication   is   concerning,   but   may   simply   be   due   to   inadequate   treatment.   Discontinuing  
therapy  would  not  be  appropriate  at  this  time.  
c. Correct!     While   there   is   no   single   correct   answer,   after   assessing   him   for   etiology   of  
increased   pain,   and   assessing   for   side   effects,   an   adjustment   of   his   extended-­‐release   dose  
might   be   warranted   if   he   is   getting   inadequate   pain   control.     A   limited   supply   of   medication  
for   breakthrough   pain   is   reasonable,   and   short   interval   follow   up   is   indicated   for   close  
monitoring.  
d. Incorrect.     While   methadone   is   a   therapeutic   option   for   treatment   of   chronic   pain,   and   may  
be   a   future   option   for   this   patient,   it   would   not   be   the   best   choice   now.   With   its   complex  
pharmacokinetics   and   pharmacodynamics,   methadone   must   be   initiated   and   titrated   very  
carefully.    His  recent  behavior  of  taking  higher  than  prescribed  doses  suggests  that  he  would  
be  at  risk  for  overdose.    
Summary   answer:   The   correct   answer   is   C.   A   trial   of   an   increased   dose   of   the   long-­‐acting   opioid   with  
close  monitoring  would  be  the  most  appropriate  of  the  choices  offered.  

Strategies  for  preventing  and  addressing  prescription  drug  misuse  in  clinical  practice.  

We   will   discuss   some   strategies   to   address   prescription   drug   misuse.     The   discussion   will   focus   on  
opioids,  because  this  class  is  responsible  for  the  majority  of  the  problem,  but  the  principles  also  apply  to  
prescription   sedatives   and   stimulants.     When   thinking   of   strategies   to   address   prescription   drug   misuse,  
there  are  four  overlapping  populations  to  consider:    
1. Those  who  are  not  taking  controlled  substances  (either  prescribed  or  non-­‐medically).  
2. Those  who  are  taking  these  medications  therapeutically.  
3. Those  who  have  a  prescription  drug  use  disorder.  
4. Those  who  are  diverting  prescription  drugs.  
 
Primary  prevention  

For   those   who   are   not   taking   controlled   substances,   our   goal   should   be   to   prevent   them   from  
developing  a  prescription  drug  use  disorder  (PDUD).    The  simplest  way  to  do  this  is  to  avoid  exposure  to  
these   drugs.     Increasingly,   individuals   with   opioid   use   disorders   are   introduced   to   opioids   through  
prescriptions   rather   than   recreational   use.     Therefore,   medications   with   misuse   liability   should   not   be  
prescribed   unless   they   are   indicated   and   patients   should   be   counseled   on   their   risks.     While   studies  
suggest  that  a  minority  of  individuals  who  are  exposed  to  opioids  will  develop  a  PDUD,  initiation  of  these  
drugs  will  lead  to  some  becoming  persistent  users  (28)  and  others  to  develop  a  PDUD  (17).  Why  some  
individuals   who   are   exposed   to   opioids   become   addicted   while   most   others   do   not   is   not   completely  
understood,   but   is   probably   at   least   partly   mediated   by   differences   in   the   subjective   effects   of   these  
drugs  (29).  
 

While  opioids  may  be  indicated  for  treatment  of  acute  severe  pain,  they  are  not  indicated  for  treatment  
of  mild  or  moderate  pain.    Studies  have  shown  that  400  mg  of  ibuprofen  is  a  more  effective  analgesic  
than  5  mg  of  oxycodone  after  minor  surgery  or  dental  procedures.  (30)  When  treating  individuals  with  
chronic  pain,  it  is  important  to  keep  in  mind  that  the  efficacy  of  opioids  for  chronic  pain  has  not  been  
established   (31)   and   is   modest   at   best   (32).     In   fact,   there   is   evidence   that   taking   opioids   chronically  
decreases  pain  tolerance  (“opioid-­‐induced  hyperalgesia”)  (33)  and  that  these  changes  may  persist  long  
after  opioids  are  discontinued  (34).  
Secondary  Prevention  

When  prescribing  controlled  substances,  particularly  opioids  for  chronic  pain,  we  must  balance  benefit  
and   risk.     As   noted   earlier,   the   available   data   suggests   that   the   rates   of   opioid   use   disorders   among  
chronic   pain   patients   on   long-­‐term   opioid   therapy   ranges   from   3%   to   20%,   depending   on   the   patient  
population   and   how   the   problem   is   defined   (17).   There   are   a   number   of   strategies   to   reduce   opioid  
misuse   and   the   harms   associated   with   it,   including   screening   instruments,   development   and  
dissemination  of  treatment  guidelines,  limiting  the  dosage  of  medication,  pharmaceutical  strategies  and  
monitoring  strategies.  
 

Instruments  

Among   patients   being   prescribed   opioids   for   chronic   pain,   it   can   be   difficult   to   distinguish   between  
appropriate   and   inappropriate   use.     There   is   no   gold   standard   for   assessment   of   prescription   drug  
misuse.    Some  instruments  that  have  been  evaluated  for  the  identification  of  prescription  drug  misuse  
among  persons  being  prescribed  opioids  for  chronic  pain  include  (35):  

• The  Prescription  Drug  Use  Questionnaire  (PDUQ)  (36);    

• The   Screener   and   Opioid   Assessment   for   patients   with   Pain   (SOAPP)   and   a   revised   version  
(SOAPP-­‐R)  (37,  38)    
• The  Current  Opioid  Misuse  Measure  (COMM)  (7)    
• Opioid  Risk  Tool  (39)      

A  systematic  review  of  risk  stratification  instruments  found  very  limited  evidence  for  their  efficacy.    They  
concluded  that  the  evidence  for  prediction  and  identification  was   limited,  and  that  there  is  a  need  for  
high-­‐quality,  prospective  studies  evaluating  these  instruments  (35).      

Guidelines  

In   2016,   the   CDC   disseminated   guidelines   on   the   use   of   opioids   for   chronic   pain   (41)   The   authors  
acknowledge   that   the   evidence   for   most   of   these   recommendations   is   weak,   and   note   that   more  
prospective   studies   are   needed   to   address   the   appropriate   initiation   and   monitoring   of   chronic   opioid  
therapy  for  chronic  pain.    A  full  review  of  their  recommendations  is  beyond  the  scope  of  this  module,  
but  a  summary  of  certain  key  recommendations  is  presented  below:  
1.  Nonpharmacologic  therapy  and  nonopioid  pharmacotherapy  are  preferred  for  chronic  pain.    Opioids  
should  only  be  used  when  the  benefits  for  pain  and  function  are  anticipated  to  outweigh  the  risks.  
2.  Before  starting  opioid  therapy  for  chronic  pain,  treatment  goals  for  pain  and  function  should  be  
established.    Clinicians  should  only  continue  opioid  therapy  if  there  is  a  clinically  meaningful  
improvement  in  pain  and  function  that  outweighs  the  risks  to  patient  safety.  
3.  Before  starting  and  periodically  during  opioid  therapy,  clinicians  should  discuss  risks  and  realistic  
benefits  of  therapy,  as  well  as  patient  and  clinician  responsibilities  for  managing  therapy  
4.  When  starting  opioid  therapy  for  chronic  pain,  clinicians  should  prescribed  immediate-­‐release  opioids  
rather  than  long-­‐acting  opioids.  
5.    When  opioids  are  started,  clinicians  should  prescribed  the  lowest  effective  dosage  and  show  use  
caution  when  prescribing  more  than  50  mg  morphine  mg  equivalents  (MME)/day  and  avoid  prescribing  
more  than  90  MME/day  
6.    When  opioids  are  used  for  acute  pain,  clinicians  should  prescribe  the  lowest  effective  dose  and  for  no  
greater  quantity  than  the  expected  duration  of  pain;  3  days  or  less  is  often  sufficient;  more  than  7  days  
rarely  needed.  
7.  Clinicians  should  evaluate  the  benefits  and  harms  with  1-­‐4  weeks  of  therapy  and  should  reassess  at  
least  once  every  3  months.    If  benefits  do  not  outweigh  harms,  clinicians  should  work  with  patients  to  
optimize  other  treatments  and  taper  opioids  to  lower  dosages  or  to  discontinue  opioids.  
8.  Before  starting  and  periodically  during  opioid  therapy,  clinicians  should  evaluate  risk  factors  for  
opioid-­‐related  harms.    Clinicians  should  adopt  strategies  to  mitigate  risk,  including  prescribing  naloxone,  
when  factors  that  increase  the  risk  of  overdose  are  present.  
9.  Clinicians  should  review  the  patient’s  history  of  controlled  substance  prescriptions  using  the  state  
prescription  drug-­‐monitoring  program  (PDMP)  before  initiating  and  periodically  during  opioid  therapy.  
10.  Clinicians  should  use  urine  drug  testing  before  starting  opioid  therapy  and  consider  drug  testing  at  
least  annually  to  assess  for  prescribed  medications  and  other  controlled  substances.  
11.  Clinicians  should  avoid  prescribing  opioids  and  benzodiazepines  concurrently  whenever  possible.  
12.  Clinicians  should  offer  or  arrange  evidence-­‐based  treatment  (usually  medication-­‐assisted  treatment  
with  buprenorphine  or  methadone)  for  patients  with  opioid  use  disorder.  
 
The  CDC  website  has  these  guidelines,  along  with  useful  handouts  and  summaries.  

 
Limiting  Dosage    

Another  strategy  to  decrease  the  harm  associated  with  opioids  is  to  limit  the  dose  that  is  prescribed.    As  
noted   earlier,   studies   have   found   an   association   between   the   dosage   and   overdose   risk.     This   has   led  
some   to   recommend   limiting   the   dose   prescribed;   for   example,   2007   Washington   state   guidelines  
recommend   that   the   “total   daily   dose   of   opioids   should   not   be   increased   above   120   mg   oral   MED  
[morphine  equivalent  daily]  without  either  the  patient  demonstrating  improvement  in  function  and  pain  
or  first  obtaining  a  consultation  from  a  practitioner  qualified  in  chronic  pain  management.”  (42)  These  
guidelines  appear  to  have  had  an  effect  on  prescribing  practices.  (43)  However,  the  guidelines  have  not  
led  to  a  significant  reduction  in  the  rate  of  opioid  overdoses;  in  one  analysis,  most  overdoses  occurred  
among   individuals   who   were   prescribed   doses   lower   than   120   mg   MED   or   were   not   being   prescribed  
opioids.  (44)    The  2016  CDC  guidelines  (summarized  above)  also  recommend  limiting  the  dose  of  opioids  
prescribed.  (41)  

Monitoring  Strategies  

Strategies  employed  in  the  monitoring  of  patients  on  chronic  opioid  therapy  include  urine  drug  testing  
(UDT),  written  treatment  agreements,  and  prescription  drug  monitoring  programs  (PDMPs).  

Urine  Drug  Testing  

Despite   a   lack   of   evidence   (45),   guidelines   recommend   the   use   of   UDT   to   monitor   patients   who   are  
prescribed  opioids,  particularly  those  at  high  risk  for  misuse  and  those  who  exhibit  ADRBs.    UDT  can  be  
used   to   verify   that   the   patient   is   taking   the   prescribed   medication   and   not   taking   other   illicit   or   non-­‐
prescribed  substances.    As  with  any  test,  it  is  important  to  be  aware  of  the  performance  characteristics  
of   the   test-­‐-­‐   i.e.,   what   the   test   tells   you   and   what   it   cannot   tell   you.     It   is   also   important   to   interpret   the  
results  in  the  context  of  other  factors.  

There   are   two   types   of   urine   drugs   tests:   1)   enzyme-­‐linked   immunoassay   (EIA)   and   2)   gas  
chromatography/mass  spectrometry  (GC/MS).    EIA  is  generally  used  for  initial  screening  and  GC/MS  for  
confirmation  of  positive  EIA  results.    EIA  testing  identifies  the  presence  of  a  specific  substance  at  levels  
above  a  threshold.    GC/MS  can  provide  more  specific  information  on  the  type  of  substance  and  the  level  
at   which   it   is   present.     For   example,   EIA   testing   may   identify   the   presence   of   benzodiazepines   in   a   urine  
specimen  and  GC/MS  can  be  used  to  identify  the  specific  benzodiazepine.    The  EIA  test  is  sufficient  for  
most  situations;  the  GC/MS  is  much  more  expensive  and  should  be  reserved  for  special  cases.  
It   is   important   to   realize   that   many   urine   drug   test   panels   are   designed   to   identify   illicit   drugs   rather  
than   prescription   drugs.     Most   standard   panels   test   for   the   presence   of   opiates,   which   includes  
morphine,   heroin   (which   is   metabolized   to   morphine),   codeine,   hydrocodone   and   hydromorphone.    
Other   opioids,   such   as   oxycodone,   methadone,   buprenorphine   and   fentanyl   generally   do   not   trigger   a  
positive  opiate  test  result  and  specific  tests  are  needed  to  detect  their  presence.  

Another   factor   to   consider   when   using   urine   drug   testing   is   the   possibility   of   false   positive   results.     A  
number  of  substances  may  trigger  positive  EIA  results.    The  following  table  provides  a  list  of  some  that  
have  been  reported.    It  should  be  noted  that  these  substances  do  not  always  cause  positive  results  and  
that  false  positive  EIA  rates  often  depend  on  the  type  of  assay  used.  
 
Substances  that  may  cause  a  false  positive  EIA  result  

Drug/Substance   Other  drugs/substances  that  may  cause  a  positive  EIA  result  

Opiates   Poppy  seeds,  Quinolones,  Rifampin  

Methadone   Diphenhydramine,  Verapamil,  Quetiapine  

Buprenorphine   Tramadol  

Cocaine   Coca  leaf  tea,  Topical  anesthetics  containing  cocaine  

Amphetamines   Pseudoephedrine,  Buproprion,  Ranitidine,  Phenylpropanolamine  

PCP   Dextramethorphan,  Tramadol  

Cannabinoids   Dronabinol,  Efavirenz  

Benzodiazepines   Sertraline  

Adapted  from:  Moeller  KE,  et  al.  Urine  drug  screening:  practical  guide  for  clinicians.  Mayo  Clin  Report  
2008;83:66-­‐76  (and  other  reports).  

Drug  testing  should  be  done  in  an  open  manner.    Telling  a  patient  prior  to  prescribing  opioids  that  drug  
testing   is   routine   can   help   reduce   the   stigma.   When   an   unexpected   result   occurs   (either   positive   or  
negative),   this   should   lead   to   a   non-­‐judgmental   discussion   with   the   patient   about   the   results.     If   there   is  
a   suspicion   of   a   false   positive   result,   GC/MS   testing   can   be   performed   to   confirm   the   EIA   results.   The  
clinician  should  express  her/his  concerns  over  the  results  and  always  do  what  s/he  believes  is  best  for  
the   patient.     If   a   test   is   unexpectedly   negative   for   a   prescribed   medication,   one   strategy   is   to   ask   the  
patient   to   return   with   their   medication   for   a   pill   count   to   make   sure   they   are   not   diverting   the  
medication.  

Patient  Agreements  

Patient  agreements  (sometimes  referred  to  as  “pain  contracts”)  are  written  documents  that  outline  the  
goals   and   expectations   prior   to   prescribing   controlled   substances.   The   general   components   of   an  
agreement   include   outlining   the   goals   of   treatment,   warning   the   patient   of   the   risks   and   advising   the  
patient   on   aberrant   behaviors.     While   these   agreements   have   not   been   shown   to   prevent   or   reduce  
misuse,  their  use  is  recommended  in  expert  guidelines.  

Prescription  Drug  Monitoring  Programs  

Finally,   another   monitoring   strategy   is   prescription   drug   monitoring   programs   (PDMPs),   which   provide  
clinicians  access  to  records  of  controlled  substance  prescriptions.  Most  states  in  the  United  States  have  
PDMPs,  but  the  programs  vary  from  state  to  state  and  are  evolving  over  time.    While  these  programs  are  
theoretically   a   useful   tool   to   reduce   misuse,   there   are   a   number   of   limitations.     One   limitation   is   that  
clinicians   often   do   not   use   these   programs.     Some   programs   are   not   user-­‐friendly   or   up   to   date.     The  
programs   are   generally   state-­‐based   and   individuals   can   circumvent   them   by   crossing   state   borders.    
Finally,   these   programs   only   identify   a   minority   of   individuals   who   are   using   prescription   drugs   non-­‐
medically;  most  obtain  the  drugs  from  family  or  friends  or  from  a  single  clinician.      

A   study   of   US   data   from   1999-­‐2005   found   that   states   with   PDMPs   did   not   have   lower   rates   of   drug  
overdose  mortality  or  opioid  consumption  (46).  On  the  other  hand,  in  Florida,  which  had  high  rates  of  
prescription  drug  overdose  deaths,  a  number  of  state  policy  changes,  including  establishment  of  a  PDMP  
in  2011,  was  associated  with  a  decline  in  overdose  deaths.(47)  Increasing  the  use  of  these  systems  may  
enhance   their   effectiveness;   many   states   are   mandating   the   use   of   these   programs   when   prescribing  
controlled  substances.  (48)  

 
Objective  6.  Addressing  Aberrant  Drug  Related  Behaviors  and  Prescription  Opioid  Misuse  

Case  6.  A  50  year-­‐old  patient  of  yours  had  a  total  knee  replacement  2  months  ago.    When  she  last  saw  
you  a  month  ago,  she  told  you  that  she  ran  out  the  oxycodone  that  had  been  prescribed  for  pain  and  
you   provided   a   prescription   for   her.     She   has   been   going   to   physical   therapy   and   has   been   gradually  
increasing  her  activity  level.    She  asks  you  for  a  refill  on  the  oxycodone  at  this  visit.    You  see  from  a  note  
that  she  also  obtained  oxycodone  from  the  orthopedic  surgeon  since  her  last  visit  with  you.    The  patient  
acknowledges  that  this  was  the  case.  
Which  of  the  following  is  the  most  appropriate  response  to  this  situation?  
a. Do  not  prescribe  oxycodone  and  advise  the  orthopedic  surgeon  to  do  the  same.  
b. Do   not   prescribe   oxycodone   and   tell   the   patient   that   she   will   need   to   get   all   future  
prescriptions  for  oxycodone  from  the  orthopedic  surgeon.  
c. Educate   the   patient   on   the   dangers   of   obtaining   controlled   substances   from   multiple  
providers   and   tell   her   that   you   are   willing   to   prescribe   oxycodone   with   the   understanding  
that  she  will  only  be  getting  this  from  you.  
d. Prescribe  acetaminophen  with  codeine  instead  of  oxycodone.  
Pop-­‐up  answers:  
a. Incorrect.  The  best  option  is  to  educate  the  patient  and  to  make  sure  that  she  only  obtains  
opioids   from   a   single   clinician   who   can   monitor   her   use.     If   she   continues   to   do   this   after  
being  educated  and  advised,  than  discontinuation  may  be  appropriate.  
b. Incorrect.  The  best  option  is  to  educate  the  patient  and  to  make  sure  that  she  only  obtains  
opioids   from   a   single   clinician   who   can   monitor   her   use.     If   she   continues   to   do   this   after  
being  educated  and  advised,  than  discontinuation  may  be  appropriate.  
c. Correct!  The  best  option  is  to  educate  the  patient  and  to  make  sure  that  she  only  obtains  
opioids   from   a   single   clinician   who   can   monitor   her   use.     If   she   continues   to   do   this   after  
being  educated  and  advised,  than  discontinuation  may  be  appropriate.  
d. Incorrect.  The  best  option  is  to  educate  the  patient  and  to  make  sure  that  she  only  obtains  
opioids   from   a   single   clinician   who   can   monitor   her   use.     If   she   continues   to   do   this   after  
being   educated   and   advised,   than   discontinuation   may   be   appropriate.     Prescribing   a   lower-­‐
potency  opioid  does  not  address  the  problem.  
Summary  answer:    The  correct  answer  is  C.  The  best  option  is  to  educate  the  patient  and  to  make  sure  
that  she  only  obtains  opioids  from  a  single  clinician  who  can  monitor  her  use.    If  she  continues  to  do  this  
after  being  educated  and  advised,  than  discontinuation  may  be  appropriate.  
Addressing  Aberrant  Drug  Related  Behaviors  and  Prescription  Opioid  Misuse  

When   treating   patients,   we   must   always   balance   benefit   and   risk   and   to   be   prepared   to   change   the  
therapeutic   plan   when   the   risks   outweigh   the   benefits,   even   if   the   patient   does   not   agree   with   this  
decision.   While   clinicians   are   trained   to   work   with   patients   to   develop   a   mutually-­‐agreed   upon   plan,   the  
prescribing   of   controlled   substances   is   one   situation   where   this   may   not   always   be   the   case   and  
clinicians   need   to   confront   patients   when   they   feel   there   is   a   problem   and   to   say   “no”   when   the   risk  
outweighs   the   benefit.     It   is   important   to   keep   in   mind   that   opioids   are   effective   for   the   treatment   of  
acute  pain,  but  their  effectiveness  for  treatment  of  chronic  pain  has  not  been  established  and  they  carry  
serious  risks.  
 

The  basic  approach  to  dealing  with  aberrant  drug  related  behaviors  (ADRB)  is  to  match  the  response  to  
the  behavior.    For  example,  if  the  patient  does  not  understand  that  he  or  she  should  not  to  be  obtaining  
opioids  concurrently  from  more  than  one  clinician,  then  patient  education  is  an  appropriate  response;  
this  can  be  documented  in  a  treatment  agreement  (sometimes  called  a  “pain  contract”).    If  the  patient  is  
running  out  of  medication  early  because  her/his  pain  is  inadequately  controlled,  than  it  would  be  best  to  
revisit   and   adjust   the   treatment   plan   accordingly   or   make   appropriate   referrals.     For   more   serious  
behaviors,   such   as   forging   prescriptions,   diverting   medication   or   overdose,   discontinuation   of   the  
opioids  is  generally  the  most  appropriate  response.    Other  strategies  to  deal  with  ADRBs  include  closer  
monitoring  with  urine  drug  testing  or  pill  counts,  providing  smaller  quantities  of  medication  and  seeing  
the  patient  more  frequently,  or  referral  to  a  pain  management  specialist.  
 

Patients   who   meet   the   criteria   for   prescription   opioid   use   disorder   should   be   offered   treatment   or  
referred  to  treatment  for  these  conditions.    While  it  is  generally  appropriate  to  stop  prescribing  opioids  
to   these   individuals,   it   is   important   to   keep   in   mind   that   this   alone   will   not   solve   their   problem   and   that  
it  is  our  duty  to  try  to  help  them.    Often,  the  most  difficult  task  is  to  get  the  patient  to  acknowledge  that  
they   have   a   problem.     It   is   best   to   approach   the   patient   in   a   supportive   and   nonjudgmental   manner.  
Treatment  may  include  medically  supervised  withdrawal  or  ‘detoxification’  from  opioids,  which  is  often  
followed  by  any  of  a  number  of  forms  of  non-­‐pharmacologic  treatment  (e.g.  twelve  step  groups,  formal  
group   or   individual   therapy,   formal   treatment   programs);   another   option   is   opioid   maintenance  
treatment  with  methadone  or  buprenorphine.      
 
For   patients   with   opioid   dependence,   opioid   agonist   treatment   with   methadone   or   buprenorphine   is  
generally   the   most   effective   therapeutic   option.     Methadone   is   a   synthetic,   long-­‐acting   full   opioid  
agonist.     Methadone   treatment   for   opioid   dependence   in   the   US   is   limited   to   regulated,   specialized  
treatment  centers.  Buprenorphine  is  a  partial  opioid  agonist  also  approved  for  the  treatment  of  opioid  
dependence  and  can  be  prescribed  by  physicians  who  have  fulfilled  an  eight-­‐hour  training  requirement  
for  the  treatment  of  opioid  dependence  in  the  office-­‐based  setting.    
 

Naltrexone,  an  opioid  antagonist,  is  another  option  for  the  treatment  of  opioid  dependence.  However,  
its  use  has  generally  been  limited  in  the  US.    Alone,  oral  naltrexone  has  limited  effectiveness  compared  
to   placebo,   largely   because   of   poor   adherence.    An   extended–release   formulation   for   monthly  
intramuscular  injection  appears  to  be  more  effective.    Patients  must  be  free  of  opioids  prior  to  initiation  
of   naltrexone   treatment.     The   Addiction:   Illicit   Drugs   module   includes   further   discussion   of   treatment  
options  for  opioid  dependence.  

In  summary,  prescription  drug  misuse  -­‐  and  the  harms  associated  with  it  -­‐  are  growing  problems  in  the  
United  States.    Physicians  need  to  be  judicious  and  vigilant  when  prescribing  these  drugs  and  as  with  any  
treatment,   balance   the   benefits   and   risks   before   prescribing,   and   when   prescribing,   monitor   patients  
closely,  particularly  those  who  are  at  risk.  
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