PMM Comorbid diseases

Medication Misuse and Comorbid Disorders

In the following lecture I will present the list of disorders frequently found among medication misusers and present evidence of their relationship.

ObjectivesUnderstand which disorders are frequently found among medication misusersUnderstand the impact of these disorders on pain treatmentUnderstand prescription medications can be used to self medicate Know resources available for help for patients

Prescription Medication Misuse DefinitionTaking medications for non-intended uses, differently than prescribed, without a prescription or with interacting substances.

Medication misuse is taking a drug for something it wasnt intended for, taking more of a drug, or taking it more frequently than prescribed, using it without a prescription, or taking it with interacting substances.

3PMM and Co-morbid Psychiatric DisordersPatients may attempt to self medicate through symptoms of depression or anxietyKhantzian E. The self medication theory of addictive disorders: focus on heroin and cocaine dependence. Am J Psychiatry 1985; 142: 1259-64.Survey showing only a small percentage of medication misuse is for recreational reasons only - 13% (civilian data no data on Service Members)McCabe S, Boyd C, Teter C. Subtypes of nonmedical prescription drug use. Drug and Alcohol Dependence. 2009, 102: 63-70.May also be due to shared vulnerability for depression or anxiety or a combination of both

There are several psychiatric disorders frequently found among medication misusers. A possible explanation for this is that individuals may be self medicating through symptoms or alternatively they have a shared vulnerability for the two disorders. The evidence to support one theory over another is limited, but the self medication theory has more evidence to support it.

4Disorders Frequently Found In Patients Who Misuse Prescription Medication -Potential Triggers for Self MedicationPost traumatic stress disorderAnxiety disorderDepressionBipolar Disorder

Several psychiatric disorders are frequently found among medication misusers. The most common are PTSD and anxiety disorders as well as mood disorders. Individuals with these disorders also appear to have a higher incidence of medication misuse.

5PTSD and PMMEvidence of a RelationshipHigher rates of PTSD among medication misusersHigher rates of PMM among individuals with PTSDSimultaneous increases in PTSD and PMM rates among Service Members Certain groups of Service Members are higher risk for both PMM and PTSD

Medication misusers have a high incidence of PTSD and vice versa. In the following slides I am going to review the available evidence of the relationship between the two.

6PTSD Among Medication MisusersData from Service Members survey not reported for US population (only reported as serious mental illness and depression in civilian survey)Higher possible PTSD rate among Service Members who misuse medications than those who dontPossible PTSD rate in medication misusers is 19%Possible PTSD rate in other Service Members is 8.5%2008 Department of Defense Survey of Health Related Behaviors among Active Duty Military Personnel. Research Triangle Institute, Research Triangle Park NC 2009Possible PTSD rate in Service Members who misuse medications was comparable to possible PTSD rate among heavy drinkers and smokers PTSD rate in heavy drinkers 18.1% vs. 7.9% in non-drinkersPTSD rate in heavy smokers 22% vs. 7.9% in non-smokers2008 Department of Defense Survey of Health Related Behaviors among Active Duty Military Personnel. Research Triangle Institute, Research Triangle Park NC 2009 Table 4.43

In a recent survey of active duty troops, individuals who endorse misusing medications had a nineteen percent incidence of symptoms consistent with post traumatic stress disorder while only eight and a half percent of Service Members who did not misuse medications did. It was a similar difference in the incidence of possible PTSD among heavy drinkers compared to abstainers and heavy smokers compared to non smokers. Medication misusers and heavy drinkers and heavy smokers had similar incidence rates of possible post traumatic stress disorder. PTSD should be considered a motivation for medication misuse in the same way it is thought of as a motivation for other self destructive behaviors such as heavy drinking and heavy smoking.

7PMM Among Patients with PTSDIndividuals with PTSD are at higher risk for misusing medications - observational study of pain patients in civilian health care systemsOR 2.45 (CI 1.88-3.19) White AG, Birnbaum HG, Shiller M, Tang J, Katz NP. Analytic models to identify patients at risk for prescription opioid abuse. Am J Manag Care. 2009; 15: 897-906.High rate of SUD (including PMM) among civilian patients with PTSD - 21-46% Jacobsen LK, Southwick SM, Kosten TR. Substance Use Disorders in Patients With Posttraumatic Stress Disorder: A Review of the Literature Am J Psychiatry 2001; 158: 11841190Higher rate with combat related PTSD - 75%Kulka RA, Schlenger WE, Fairbank JA, Hough RL, Jordan BK, Marmar CR, Weiss DS: Trauma and the Vietnam War Generation: Report of Findings From the National Vietnam Veterans Readjustment Study. New York, Brunner/Mazel, 1990

Other evidence suggests individuals with post traumatic stress disorder have a high incidence of medication misuse. Civilian chronic pain patients with post traumatic stress disorder had over two times the hazard ratio for medication misuse. Individuals with post traumatic stress disorder also have a high incidence of substance use disorder. Particularly patients with combat related PTSD. Nearly 75% of Vietnam veterans with post traumatic stress disorder had a substance use disorder in their lifetime. The current generation of veterans has chosen medication misuse over illicit substance abuse and we will likely see a similar rate of medication misuse among them as we saw illicit substance abuse among the Vietnam veterans.

8PTSD and PMM Rates Rising in Service Members Evidence of a RelationshipPMM rates increasing since 20021.8% in 200211.1% in 2008Possible PTSD prevalence among Service Members increasing as well 10.4% of Service Members may have PTSD on 2008 surveyUp from 6.7% in 20052008 Department of Defense survey of health related behaviors among military personnel, Research Triangle Institute, Research Triangle Park NC 2009, Table 4.22

In addition to the high degree of comorbidity of post traumatic disorder and medication misuse, the rise in the incidence of both among US service members in recent years suggests a relationship between the two.9PTSD and PMM Service Member Selective Sub-groupings Show a Possible RelationshipDeployed vs. non-deployedFemales at higher risk for both

There are two sub-groupings of service members that appear to be at higher risk for medication misuse as well as post traumatic stress disorder. The relationship in these two groups also suggest a strong link between PTSD and medication misuse, either through self medication or through a shared vulnerability.

10Higher Rates of PTSD and PMM Among Service Members Who Have Been Deployed Also Suggests A RelationshipHigher rate of PMM in Service Members who have been deployed to Iraq or Afghanistan12% higher PMM rates in SMs who have been deployed (17% in SMs who have not deployed, 19% in SMs who have deployed)2008 Department of Defense survey of health related behaviors among military personnel, Research Triangle Institute, Research Triangle Park NC 2009Up to 17 percent of troops screened after deployment may have PTSD (compared to 10% of all SMs)Hogue C, Castro C, Messer S, McGurk D, Cotting D, and Koffman R. Combat duty in Iraq and Afghanistan, Mental Health Problems, and Barriers to Care. NEJM. 2004; 351: 13-22.

The higher incidence of both post traumatic stress disorder and medication misuse among service members who have been deployed compared to those who have not deployed suggest a link, probably through self medication.

11Higher Rates of PTSD and PMM Among Female Service Members Also Suggests RelationshipFemale Service Members at increased risk for PTSDOR 2.33, CI 1.8-3.03LeardMann CA, Smith TC, Smith B, Wells TS, Ryan MA. Baseline self reported functional health and vulnerability to post-traumatic stress disorder after combat deployment: prospective US military cohort study. BMJ. 2009; 338: b1273.Female Service Members also had higher rate of PMM13.2% of female Service Members11.2% of male Service Members3.2% of females in the US population2008 Department of Defense survey of health related behaviors among military personnel, Research Triangle Institute, Research Triangle Park NC 2009

The higher incidence of both post traumatic stress disorder and medication misuse among female service members also strongly suggest a link between the two. The interesting part of this fact is that the higher incidence of medication misuse among female service members compared to male service members runs contrary to the gender ratios of substance abuse or misuse seen in every other population for every other drug studied. Female service members may be a select subgroup of the population that have a shared vulnerability for both post traumatic stress disorder and medication misuse or they may also just be driven by self medication.

12PTSD and PMMEvidence suggests a link between the twoCausal?Bidirectional?Likely self medication of PTSD with medications

The relationship between post traumatic stress disorder and medication misuse seems clear, but the exact direction and the basis for its relationship is unclear.There may be a unidirectional relationship with PTSD triggering medication misuse, but it is likely bi-directional with each one impacting the other.

13PTSD and PMMDoes treating PTSD reduce the risk for PMM?Unknown possible based on data on treating ISA and PTSD treatment

An interesting question this raises is does treating post traumatic stress disorder impact medication misuse? Currently there is not any data on the subject but it is possibly true. Treating post traumatic stress disorder reduced illicit substance abuse and it is possible that it would have the same impact on medication misuse.

14Treating PTSD and the Potential Effect on PMM RatesTreating PTSD may be beneficial in reducing PMM based on evidence of impact with illicit substance abuse (ISA)PTSD responsive to treatment renders patients less prone to substance abuseOuimette P, Brown P, Najavits L. Course and treatment of patients with both substance use and posttraumatic stress disorders. Addict Behav 1998; 23:785795Substance abusers with unremitting PTSD had more relapses and felt less able to prevent relapsesOuimette P, Coolhart D, Funderburk J, Wade M, Brown P. Precipitants of first substance use in recently abstinent substance use disorder patients with PTSD. Addict Behav. 2007. 32(8):1719-27.

Individuals successfully treated for post traumatic stress disorder felt less prone to substance abuse, while other individuals with PTSD unresponsive to treatment felt more prone to relapses. If the same holds true for medication misuse, then treating PTSD may reduce it. 15PTSD TreatmentSpecific serotonin reuptake inhibitors (SSRIs) are effective Viewig, WV; Et al. Posttraumatic stress disorder: clinical features, pathophysiology, and treatment. Am J Med 2006; 119: 383-390.Most effective when continued for 9-12 months after symptom remission. Ursano RJ, Bell C, Eth S, et al. Practice guideline for the treatment of patients with acute stress disorder and posttraumatic stress disorder. Am J Psychiatry 2004;161:331.Cognitive behavioral therapy (CBT) lead by a consulting psychiatrist is also effective. Stein DJ, van der Kolk BA, Austin C, et al. Efficacy of sertraline in posttraumatic stress disorder secondary to interpersonal trauma or childhood abuse. Ann Clin Psychiatry 2006;18: 2439.

Treatment for post traumatic stress disorder usually consists of an SSRI and cognitive behavioral therapy.

16PTSD and PMMPatients with active PTSD are high risk for PMM and should only be managed in close consultation with a psychiatrist and preferentially by the appropriate specialist (pain management, psychiatrist, etc.)PCMs must still be engaged in patient care and aware of medical interactions which could impact the pharmacology of potentially misused medicationsPCMs must also be able to identify PTSD and properly risk stratify patients

Individuals with active post traumatic stress disorder should be managed either in close consultation with or primarily by a psychiatrist. Primary care providers should still remain engaged in the care of the patient and should remember to screen for PTSD prior to prescribing a potentially misused medication.

17Depression and PMMDepressive symptoms may trigger PMMReview evidence of a direct linkReview possible evidence of an indirect link through the interaction of depression with PTSD and chronic pain

Depression is another disorder commonly found with medication misuse.

18Direct Link between Depression and PMMPatients with depression are at an increased risk for PMM (civilian data from chronic pain patients receiving chronic opioid therapy)Probable Depression increases the risk for PMMOR 2.4 (CI 1.6-3.4)MDD increases the OR to 3.2 (CI 2.9-3.6)Any mood disorder increases the risk for PMMOR 3.5 (CI 3.1-3.9) Major references on depression and PMM:Becker W, Fiellin D, Gallagher R, Barth K, Ross J, Oslin D. The association between chronic pain and prescription drug abuse in Veterans. Pain Medicine 2009; 10: 531-536.Martins S, Keyes K, Storr C, Zhu H, Chilcoat H. Pathways between nonmedical opioid use/dependence and psychiatric disorders: Results from the National Epidemiologic Survey on Alcohol and Related Conditions Drug and Alcohol Dependence. 2009: 1624.Survey data (National Survey on Drug Use and Health) shows a strong relationship between a major depressive episode and PMM

There appears to be a direct relationship between depression and medication misuse. Patients with depression have a significantly higher hazard ratio for medication misuse and medication misusers have a higher incidence of depression as well.

19Indirect Relationship Between Depression and PMM Through Chronic PainDepression may indirectly increase PMM through its interactions with chronic painPatients with depression experience more severe pain and pain catastrophizing and are more likely to develop an SUDJamison R, Link C, and Marceau L. Do pain patients at high risk for substance misuse experience more pain? A longitudinal outcomes study. Pain Med. 2009 Sep;10(6):1084-94.Patients with chronic pain and comorbid depression have worse outcomes and potentially greater drive to self medicateEicsson M, Poston W, Linder J, Taylor J, Haddock C, and Foreyt J. Depression predicts disability in long term chronic pain patients. Disabil Rehabil 2002; 24: 334-340.Providers must be aware that depression and comorbid pain may increase the risk of suicidal ideation/attempts Spiegel B, Schoenfeld P, Naliboff B. Systematic review: the prevalence of suicidal behaviour in patients with chronic abdominal pain and irritable bowel syndrome. Aliment Pharmacol Ther. 2007 Jul 15;26(2):183-93.

Depression may also have an indirect relationship with medication misuse. Individuals with depression and chronic pain experience more pain catastrophizing and have worse outcomes and may have a greater drive for self medication than patients with chronic pain without depression. Providers should also be aware that patients with chronic pain and depression are at increased risk for higher suicidal behavior and ideation. This should always be considered when prescribing a potentially misused medication.

20Treating Depression Impact on PMMTreating depression will possibly reduce PMMImpact on PMM inferred from studies on the impact of treating depression in illicit substance useAdherence to depression treatment leads to a lowered rate of substance abuse among drug usersStein M, Herman D, Solomon D, Anthony J, Anderson B, Ramsey S, and Miller I. Adherence to treatment of depression in active injection drug users: the Minerva study. J Subst Abuse Treat. 2004. 26(2):87-93.Nunes E and Levin F. Treatment of depression in patients with alcohol or other drug dependence: a meta-analysis. JAMA 2004; 291 (15): 1887-1896

Treating depression could reduce a patients risk for medication misuse, but like post traumatic stress disorder, there is no evidence to support this. This is just a conclusion based on the impact that treating depression has on illicit substance abuse rates.

21Depression and PMMThese patients are high risk for PMM and should be managed by a specialist in the appropriate discipline in conjunction with a psychiatrist and the PCMProviders must be able to screen for depression to identify need for specialty careProviders must know interactions between medications prescribed to avoid interactions

Patients with active depression should also be managed in close consultation with or primarily by a psychiatrist. Primary care providers should still be involved in their care and should definitely be aware to screen for depression in patients who are prescribed potentially misused medications.

22TBI and PMMService Members who have sustained a TBI in combat may be at increased risk for PMMNo studies existAnecdotal evidencePersonal communicationsMedia reportsSome evidence that patients with a combat related TBI may have an increased drive for self medication due to increased incidence of chronic pain, PTSD and depression

Though no direct evidence currently exists in the literature, many of the DoD and VA providers have seen medication misuse among TBI patients.

23TBI and PMMCivilians may suffer a TBI as a result of intoxication and then have a decrease in substance abuse ratesPonsford J, Whelan R, Bahar-Fuchs A. Alcohol and drug use following traumatic brain injury: a prospective study. Brain Inj. 2007. (21):13851392Military TBI patients have different circumstances leading to the injury

There is literature on substance abuse rates among civilian TBI patients. But they are very likely a different subset of patients from service members who sustained a TBI.

24TBI and PMM Suicide RiskTBI patients have a 2-4 fold increased suicide rate, particularly with depression or substance use disorders danger for fatal prescription medication misuseSimpson G, Tate R. Suicidality after traumatic brain injury: demographic, injury and clinical correlates. Psychol Med. 2002;32:687697.Irresponsibly prescribed medications may be the equivalent of a loaded gun

TBI patients are at increased risk for suicidal behavior. Potentially misused medications must be prescribed very cautiously to them and with close follow up and a minimal pill burden.

25ConclusionMany gaps but evidence suggestive that PTSD, depression, chronic pain, and TBIs may predispose patients to PMMThese patients are high risk for PMMPCMs must be able to identify these disordersPCMs must interact with specialists involved in caring for these patients to ensure optimal careNo audio recorded for this slide. 26Patient Scenario Sam Coleman Present ComplaintA 35 year old female patient with an unremarkable physical exam presents complaining of chronic headaches.

She also complains of insomnia, waking frequently and difficulty falling asleep five nights a week.

She avoids eye contact, sits low in the chair and is tearful in between heavy sighing. The patient would like a refill for oxycodone which was prescribed to her for a recent sprained ankle, since it helps with her headache pain.

Sam Coleman History

The patient has had insomnia for 2 years.She is in a difficult custody battle for a young daughter, who lives with her ex-husband. He was mentally and physically abusive during their marriage. She alludes to possible sexual assaults by her husband as well. She has not seen her daughter in two years.

She is a lab director working long hours under high pressure. She has little time for friends and her current husband.

The patient does not drink alcohol, but smokes one pack of cigarettes per day.

Sam Coleman - QuestionsWhat are her risk factors for prescription medication misuse?Do you think this patient might also suffer from depression? If so, what treatment plan would you consider? Medications? Therapy? Complementary medicine?What are the symptoms of depression?What are the symptoms of post-traumatic stress disorder?What impact do depression and/or PTSD have on pain?Would you refill her oxycodone?How would you treat the insomnia?

Military Resources

Military Homefront Support800-342-9647www.militaryonesource.comBranch Specific Support is also available:Army Substance Abuse Program (ASAP)Navy Alcohol and Drub Abuse Prevention (NADAP)Marine Substance Abuse Combat Center (SACC)Air Force Alcohol and Drub Abuse Prevention and Treatment (ADAPT)Non-Military Resources

Substance Abuse and Mental Health Services Administration (SAMSHA) www.findtreatment.samsha.gov1-800-662-HELPNational Suicide Prevention Lifeline 800-273-TALKNational Alliance on Mental Illness www.nami.orgMental Health America www.mentalhealthamerica.netAmerican Academy of Addiction Psychiatry www.aaap.orgAmerican Academy of Child and Adolescent Psychiatry www.aacap.orgNational Drug Abuse Clinical Trials www.drugabuse.gov/CTN/ or www.clinicaltrials.govNarcotics Anonymous www.na.org/Alcoholics Anonymous www.aa.org

Medication misuse can chronically lead to addiction. Acutely, it could lead to death either directly through overdose or as a contributory factor to another mechanism of death. It has been a well documented increase in death rate related to medication overdose in recent years in the United States.

Some of this may have been the result of taking medication exactly as prescribed, but clearly a significant percentage of this was a result of medication misuse.Chart16.7510.411.1

PTSDPMM

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