Managing Patients With Substance Use Disorders: A Case-Based Approach (page 265 in syllabus) William M. Sauvé, MD Clinical Director of Military Programs Poplar Springs Hospital Sponsored by the Neuroscience Education Institute Additionally sponsored by the American Society for the Advancement of Pharmacotherapy This activity is supported solely by the sponsor, Neuroscience Education Institute.
Individual Disclosure Statement Faculty Editor / Presenter William M. Sauvé, MD, is the clinical director of military programs at Poplar Springs Hospital in Petersburg, VA. Speakers Bureau: Pfizer
Learning Objective Apply appropriate management strategies for patients with psychiatric illness and comorbid substance use disorder
Substance Use Disorder Treatment in Psychiatric Patients Greater psychiatric severity tends to predict worse substance use outcomes Compared to substance use patients, patients with substance use AND a psychiatric disorder were less satisfied with the substance use treatment and found the program less supportive saw fewer benefits to quitting and reported less self-efficacy and reliance on approach coping reported more psychiatric symptoms at 1- and 5-year follow-ups did as well as substance use only patients on 1- and 5-year substance use outcomes Boden, Moos. J Subst Abuse Treatment 2009;19;Epub ahead of print.
PATIENT CASE The Case: Depressed woman with chronic pain and escalating opiate use
Patient Intake and History 30-year-old woman with a long history of depression currently being treated with psychotherapy, no medication She is married and has one daughter She works full time as an office administrator A year ago, she suffered a back injury; she had surgery 6 months ago and was prescribed hydrocodone-acetaminophen combination for pain control (7.5 mg/325 mg every 6 hours) short term
Patient Intake and History Her husband contacts her therapist with concerns that she may be abusing her drugs Interview reveals that she has continued to use hydrocodone, obtaining it from the Internet and friends and escalating to more than 200 mg/day She states that if she stops or decreases her dose, she becomes more depressed and gets sick (nausea, muscle aches, sweating, diarrhea, insomnia)
Poll Question 1 Based on what you ve been told so far about this patient, how would you characterize her use of opioids? 1. Abuse 2. Addiction 3. Pseudoaddiction 4. Dependence
Definitions Term Misuse Abuse Aberrant behavior Addiction Pseudoaddiction Dependence Tolerance Definition Use of a medication other than as directed, whether willful or not Use of a drug/medication for nonmedical purposes (e.g., getting high) Medication-related behaviors that depart from adherence to the prescription plan Chronic neurobiological disease characterized by impaired control over drug use, compulsive use, continued use despite harm, and/or craving Mimics true addiction, but symptoms resolve with adequate pain relief Pharmacological adaptation characterized by drug class-specific withdrawal State of adaptation in which exposure to a given dose of a drug induces biologic changes that result in its diminished effects over time; often leads to dose escalation
Screening for Opioid Misuse Warning signs: vague, inconsistent, or incomplete information in history; difficulty establishing rapport; doctor shopping Acute intoxication: constricted pupils, slurred speech, itching, euphoria or agitation, dry mouth, drowsiness, impaired judgment Withdrawal: dysphoric mood, nausea or vomiting, muscle aches, runny nose and eyes, dilated pupils, goose bumps, sweating, diarrhea, yawning, fever, insomnia Dodrill CL et al. Am J Psychiatry 2011;168(5):466-71.
Screening for Opioid Misuse Self-report Current Opioid Misuse Measure Opioid Risk Tool Comprehensive Drug Abuse Screening Test CAGE-AID UNCOPE Drug and Alcohol Problem Assessment for Primary Care Dodrill CL et al. Am J Psychiatry 2011;168(5):466-71.
Attending s Notes Screening and interview reveal that the patient experiences withdrawal when opiates are stopped She does not complain of ongoing or worsened pain when opiates are stopped She is clearly dependent, and her behavior pattern suggests that she may be addicted
Poll Question 2 Which treatment strategy would you most likely choose to address this patient s opioid dependence? 1. Methadone 2. Buprenorphine 3. Naltrexone 4. Medically supervised withdrawal with or without naltrexone 5. Nonpharmacological treatment only
Treatment: Buprenorphine Partial opioid agonist Take-home medication: less stigma, better adherence Convenient, flexible dosing, ease of discontinuation, low abuse potential Patient must experience at least mild withdrawal symptoms before beginning treatment Practitioners require special training in order to prescribe buprenorphine Requires DEA Data 2000 waiver Training on treatment plans, goals, rules, and monitoring of urine and pill counts Dodrill CL et al. Am J Psychiatry 2011;168(5):466-71.
Maintenance (based on patient s needs) Stabilization (up to 2 months) Initiation (7 days) Buprenorphine/Naloxone Treatment Stages Stage Typical Dosage Visits Goal Patient must be in mild withdrawal state before starting Day 1: 8 mg B/2 mg N Day 2: add l 4 mg/1 mg up to 16 mg/4 mg Days 3 7: increase in units of 4 mg/1 mg until withdrawal symptoms cease; maximum 32 mg/8 mg Generally range from 8 mg/2 mg up to 24 mg/6 mg Dose as determined during stabilization At least 2 hours observation with initial dose, then 1 2 visits in first week 1/week Biweekly or monthly Dodrill CL et al. Am J Psychiatry 2011;168(5):466-71. Achieve lowest dose that eliminates withdrawal symptoms and illicit opioid use Eliminate withdrawal symptoms, side effects, and illicit drug use Address lifestyle changes and social and psychological needs; if desired, plan for medically supervised withdrawal
Considerations for Patients With Ongoing Chronic Pain Buprenorphine/naloxone can provide pain relief, but may not be sufficient for all patients Pain relief strategies may include Other medications (SNRIs, TCAs, alpha 2 delta ligands, NSAIDs, acetaminophen) Aerobic exercise
Treatment: Naltrexone Opioid antagonist; blocks pleasurable effects of opioid agonists No abuse potential Patients must be completely withdrawn and abstinent for 5 days (short-acting opioid) to 7 days (long-acting opioid) Requires 0.8 mg IM test dose to ensure that patient is no longer dependent on opioids before starting treatment Usual dose is 50 mg/day or 100 mg Mon and Wed and 150 mg Fri Side effects: dysphoria, anxiety, GI distress After discontinuing naltrexone: increased sensitivity to opioid effects; risk that overdose will lead to respiratory depression APA. Am J Psychiatry 2007;164(4):1-124.
Treatment: Other Options Methadone Regulated programs Most effective for suppressing use in the most highly-dependent patients Medically supervised withdrawal In residential drug-free program During naltrexone maintenance Inpatient detoxification units Outpatient detoxification programs Behavioral Brief reinforcement-based therapy with contingency management Acceptance and commitment therapy Dodrill CL et al. Am J Psychiatry 2011;168(5):466-71.
Case Outcomes The patient is enrolled in a substance dependence treatment program and is prescribed buprenorphine/naloxone She is eventually stabilized on 24 mg/6 mg She continues in psychotherapy for her depression Three years later, despite attempts, she has not been able to decrease the buprenorphine/naloxone dose She is not using any other opioids She is experiencing life stress (divorce), and she continues in psychotherapy Is this a positive outcome?
PATIENT CASE The Case: The pained man who soaked up opiates like a sponge
Patient Intake and History 58-year-old man with a history of chronic pain He is married and has one daughter He does not smoke, drink alcohol, or use illicit drugs He is an engineer and a successful entrepreneur Relatively well until 6 years ago, when he developed painful tinnitus in his right ear No diagnosable problem Also diagnosed with Dercum s Disease and has had over 50 lipomas surgically resected from all over his body Hydrocodone 15 mg/day worked for 3 4 years, then he required 30 mg/day up until last year
Patient History Developed unusual pain in his lower legs and had to increase hydrocodone to 60 80 mg/day Orthopedic evals suggest degenerative disc disease that may ultimately require surgery To avoid surgery, he has escalated opiate use to 80 120 mg/day Too sedating, he cannot concentrate or do his work; but with less than 80 mg/day, he s in too much pain to work He is distressed by his pain, but clinical evaluation suggests that he is not depressed and has no history of depression
Medication History Numerous TCAs not tolerated (urinary retention, constipation, sedation) and did not work on his pain Gabapentin too sedating, but seemed to cause increased tinnitus, paresthesias, and gastrointestinal pain when he stopped it Numerous SSRIs not effective, caused burning sensation in upper and lower distal extremities Quetiapine very sedating, even at low doses
Current Medications Levothyroxine 75 mcg Duloxetine (Cymbalta) 60 mg Atomoxetine (Strattera) 40 mg Hydrocodone up to 120 mg/day Zolpidem 10 mg for sleep Ezetimibe for hypercholesterolemia Uses CPAP (continuous positive airway pressure) machine most nights for obstructive sleep apnea
Based on what you have been told so far about this patient s history and various pain conditions, what do you think is his diagnosis? 1. Pain secondary to Dercum s disease plus degenerative lumbar disc disease 2. Pain disorder, somatoform 3. Somatization disorder 4. Depression 5. Fibromyalgia 6. Other Poll Question 3
Attending s Notes No obvious psychosocial stressors His multiple, vague, and widespread pain complaints without an obvious medical explanation seem excessive Dercum s Disease is a rare and controversial condition, and many people have lipomas that are not painful It seems possible that his pain all over is fibromyalgia instead, but his referring physician is unclear about that Orthopedic reports do not suggest that degenerative disc disease is very severe or advanced or that it will imminently need surgery
Attending s Notes The patient is escalating his opiate use in a somewhat concerning manner It may be useful to explore psychological factors in follow-up visits and even get psychological testing Working diagnosis could be a somatoform disorder (namely, pain disorder) that impairs functioning and has pain in multiple sites of severity to warrant medical attention Unconfirmed suspicion that psychological factors may play an important role; this must be investigated further He does not appear to have somatization disorder because his complaints did not start before age 30 and he only has pain, not other somatic symptoms He does not seem excessively depressed
What would be your first priority in treating this patient? 1. Increase duloxetine dose 2. Increase atomoxetine dose 3. Suggest reduction in opiate dose; maybe switch to long-acting formulations, but lower total daily dose 4. Referral to insight-oriented psychotherapy 5. Referral to biofeedback 6. Referral to CBT 7. Other Poll Question 4
Treatment Recommendations Advised to increase duloxetine to 120 mg/day Suggested discontinuing atomoxetine Suggested low-dose pregabalin (less sedating than gabapentin, which he did not tolerate previously) If duloxetine and pregabalin are somewhat effective, advised to attempt to lower hydrocodone dose Consider modafinil augmentation for both opiateinduced impairment in concentration/sedation and sleepiness/executive dysfunction, which may result from his obstructive sleep apnea
Case Outcomes 6 months later: has not reduced his total daily opiate dose; now taking sustained-release oxycodone 40 mg 3 times/day and feels that pain is under control Now taking two sedative hypnotics for sleep Taking only 40 60 mg/day duloxetine because higher doses increase his blood pressure Pregabalin and modafinil have been helpful Advised to try milnacipran and/or increase pregabalin since he cannot tolerate higher doses of duloxetine Does not want to consider reducing hypnotic dose or opiate dose
Case Outcomes 18 months later: his pain is worse Current medications Oxycodone 120 mg 3 times/day Hydrocodone 7.5 mg plus ibuprofen 200 mg or hydrocodone 10 mg plus acetaminophen 500 mg, up to 8 times/day Duloxetine 120 mg/day unless blood pressure rises Modafinil 400 mg/morning and 200 mg/afternoon Pregabalin 50 mg 4 times/day as needed, but never more than 3 days in a row because of side effects Zolpidem 10 mg plus eszopiclone 6 mg
What would you do? 1. Trial of trazodone to reduce sedative hypnotics 2. Trial of quetiapine again to reduce sedative hypnotics 3. Referral to opiate detoxification program in a pain specialty clinic 4. Insist on a psychotherapy evaluation 5. Psychological/personality testing 6. Report the referring physician to the medical board 7. Resign from the case 8. Other Poll Question 5
Attending s Notes Patient is now opiate-dependent and reaching a dangerous ceiling on dosing, particularly with his concomitant medications and history of OSA Warn about potential overdose implications of continuing his opiates at these doses and the possibility of respiratory depression or respiratory arrest He is not actually abusing the opiates because he is not taking more than prescribed, and he is not having daytime sedation by history or examination This may be as much a problem of a compassionate but enabling opiate-prescribing physician as it is opiate dependence on the patient s part
Attending s Notes Medications are not the way out of this dilemma, and the patient should be told that Strongly advised to decrease opiate dose; referred to a new pain center for reduction but not elimination of opiates Strongly suggested psychotherapy Advised trazodone in lieu of zolpidem/zopiclone
Case Outcomes He has attacks of pain Did not follow up on opiate reduction program or psychotherapy Wife left him Is in litigation with disability insurance company Current medications Oxycodone SR 80 mg, 3 4 times/day (240 320 mg/day) Oxycodone IR 15 mg, 6 8 times/day (90 120 mg/day) Hydrocodone/ibuprofen 7.5 mg/200 mg, 2 4 times/day Pregabalin 100 mg most days Alprazolam 1 mg up to 2 times/day Duloxetine 120 mg/day Zolpidem 20 30 mg/night Modafinil 200 mg/morning and 100 mg/afternoon
Case Debrief This man has a mixture of many painful conditions, the sum of which cause him great misery and disability Avoidant of psychological issues, psychotherapy, and psychological interpretations of pain Always chasing a solution in another drug At high risk for premature death from accidental or deliberate overdose High risk of suicide Poor outcome is likely Part of the problem is the physician who is prescribing the opiates Psychological factors are likely to have an important role in this patient s pain
PATIENT CASE The Case: Comorbid bipolar disorder and stimulant abuse
Patient Intake 32-year-old female with a chief complaint of depression and current stimulant abuse Well until age 19, became manic after delivering her son Untreated mania/hypomania postpartum for a year and a half, then suddenly crashed into depression Age 21: treated with unknown antidepressants, ineffective, then had a suicide attempt Then treated with sertraline and lorazepam with incomplete recovery Received ECT, which saved [her] life Diagnosed with bipolar II, but treated with various antidepressants and no mood stabilizers
Patient Intake Did well, got married, stopped medications Began to experiment with drugs of abuse, including marijuana and especially cocaine, yet finished college Developed social anxiety; treated with paroxetine without notable results, so stopped it Eventually, stimulant abuse became severe, and she was hospitalized for substance abuse treatment Given paroxetine again, and it flipped her into mania, which was rapidly reconstituted with risperidone Next 10 years: mood continued up and down She recently relapsed into using stimulants to self-medicate depression
Poll Question 6 What would be your treatment recommendation for this patient? 1. Stabilize her current mood episode first 2. Address her stimulant abuse first 3. Use integrated treatment to simultaneously address her depression and stimulant abuse
Attending s Notes Can be necessary to get acute mood symptoms in check In general, medication adherence is better if you address substance use first Little evidence for pharmacological treatment of stimulant dependence or withdrawal Cognitive behavioral therapy is effective, particularly for more severe cases and those with comorbid disorders Twelve-step facilitation and individual drug counseling can be effective Limited, mostly uncontrolled data evaluating mood stabilizers in comorbid patients Teeter CJ et al. Psychiatry Res 2011;Epub ahead of print; APA. Am J Psychiatry 2007;164(4):1 124.
Patient Outcomes She agrees to enter treatment for her stimulant abuse and take medication for her bipolar depression She is successful in her treatment to stop using stimulants, but crashes into deep and unremitting depression Sees a number of psychiatrists, takes a number of medications (most recently, duloxetine, lithium, olanzapine), without notable results Receives another 13 ECT treatments, with no therapeutic response but notable memory loss Aborts her own attempt to drive a car off the road to commit suicide while alone; her husband discovers this and brings her in
Patient Outcomes Her medications are adjusted Duloxetine 60 mg twice/day Ziprasidone 80 mg twice/day Lamotrigine slowly titrated up to 100 mg/day Quetiapine titrated up to 200 mg/day After 8 weeks, rates herself "50% better" No more suicidal thoughts, sleeping better "Tingling" occurs occasionally during the day; for her, this is a sign of anxiety and incipient mania Told to increase quetiapine to 300 or 400 mg qhs with an additional 100 mg in the day as necessary for incipient manic symptoms
Patient Outcomes 3 months later: rates herself 3/10 (10 worst), but still lying around in bed Continue medication adjustments over the next several months to address daytime sedation, tingling, and anxiety Now taking lamotrigine 200 mg/day, quetiapine 250 mg qhs and 100 mg in the day, ziprasidone 160 mg, and duloxetine 90 mg 4 months later: taking only 60 mg bid of ziprasidone, 200 mg quetiapine qhs, plus lamotrigine 200 mg and duloxetine 90 mg No longer lying around, no more daytime quetiapine Still lacks some motivation, but now rates herself 2/10 The case continues
Case Debrief Bipolar disorder complicated by long-term stimulant abuse that has become resistant to ECT and many medications; can still be treatable Antipsychotic polypharmacy may be justified in such cases It is possible that a slow reversal of long-term stimulantinduced dopamine neuronal "burnout" may be contributing to her recovery and may continue for another year or two if she remains abstinent It is possible that the antidepressant should be discontinued in order to prevent possible cycling again Long-term recovery can obviously take a long time
Summary Treating comorbid psychiatric illness and substance use is complicated and not well studied Prescription drug abuse is now a significant issue nationwide Abstinence is the ultimate goal, but for patients who are unwilling or unable, minimizing use (harm reduction) can be beneficial
Poll Question 7 On average, how many patients with substance use disorders do you see each week? 1. None 2. 1-2 3. 3-4 4. 5-6 5. 7-8 6. 9-10 7. 11-12 8. 13-15 9. More than 15